Life-threatening coma and full-thickness sunburn in a patient treated with transdermal fentanyl patches: a case report

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Sindali Katia

2012-07-01

Full Text Available Abstract Introduction Fentanyl transdermal patches have been widely used in the treatment of chronic pain and in palliative care settings since 1991 in cases where prolonged opioid use is often necessary. Transdermal drug delivery is deemed safe and effective with the advantages of delivering a steady dose of the drug and improving patient compliance due to its ease of use. However, intentional and unintentional misuse and overdose using transdermal opioid patches has been widely reported in the literature. Case presentation We describe the case of a 77-year-old Caucasian woman who developed severe opioid toxicity while sun tanning, likely due to altered fentanyl transdermal patch function in a heated environment. As a result of prolonged sun exposure due to an opioid-induced coma she then sustained hyperthermia and severe burns to her abdomen and lower limbs. This inadvertent fentanyl overdose necessitated initial treatment in intensive care and follow on care in a specialist burn unit. Conclusion Patients who are using fentanyl patches and their relatives should be educated about how to use the patch safely. Healthcare practitioners should warn patients about the possibility of overdosing on transdermally delivered drugs if used incorrectly. They should avoid strenuous activities and external heat sources such as warming blankets, hot water bottles, saunas, hot tubs or sunbathing and should seek medical attention if they develop a fever. Additionally, any burns sustained in the context of altered consciousness levels such as in this case with opioid overdose should raise suspicion about a potential deeper burn injury than is usually observed.

Comparison of an Additional Transdermal Fentanyl Patch Compared to Intravenous NSAID and Opioid Analgesics within 24 Hours of an Uterine Artery Embolization for Myoma and Adenomyosis

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Song, Suk Yun; Kang, Byung Chul; Rho, Kyung Min [Dept. of Radiology, Mokdong Hospital, Ewha Womans University School of Medicine, Seoul (Korea, Republic of)

2011-05-15

To evaluate the effectiveness of an additional transdermal fentanyl patch compared to intravenous analgesics in pain control during the 24-hour period following uterine artery embolization (UAE) for myoma and adenomyosis. Between September 2009 and August 2010, 42 patients underwent UAE for myoma or adenomyosis. Of these, 21 received an intravenous opioid (pethidine) and a nonsteroidal anti-inflammatory drug (group A), and 21 received an additional transdermal fentanyl patch (group B). Pain perception levels were established verbally on a 0-10 scale during the 24-hour period following UAE. Differences in pain trends, mean dose of intravenous pethidine, and adverse effects were compared between the two groups. Pain perception was most severe at 6 hours after UAE and the mean pain level of group B at that time was 6.3 {+-} 0.7, which was significantly lower than that of group A, 8.2 {+-} 0.7 (p<0.05). The mean dose of intravenous pethidine was 114.3 {+-} 59.5 mg in group A and 90.5 {+-} 49.0 mg in group B, while the incidence of nausea was 67% in group A and 77% in group B. In both cases, the differences were not significantly different (p>0.05), and no evidence of respiratory distress was demonstrated. The addition of a transdermal fentanyl patch to intravenous analgesics is effective in reducing post-embolization pain during the 24-hour period after UAE.

Transdermal fentanyl for pain caused by radiotherapy in head and neck cancer patients treated in an outpatient setting. A multicenter trial in Taiwan

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Chang, J.T.C.; Lin Chienyu; Wang Hungming; Lin Jinching; Lee Moonsing; Chen Yujen

2010-01-01

This study evaluated the efficacy and safety of transdermal fentanyl in the outpatient treatment of head and neck cancer patients with pain caused by radiotherapy. Patients with a visual analogue scale score ≥4 were invited to participate in the study. The following variables were collected: visual analogue scale, the Brief Pain Inventory, concomitant pain medications and adverse effects. A total of 163 head and neck cancer patients were enrolled (148 males and 15 females; median age, 53 years; age range, 21-72 years). Seventy-two (44%) patients had a visual analogue scale score >6 at enrollment, despite the use of non-steroidal anti-inflammatory drugs or weak opioids. Ninety-four (57.7%) patients received concurrent chemotherapy. A total of 88 patients completed the study, whereas 55 underwent a drop-out by side effects. The most frequently reported adverse events were vomiting (23.9%) and nausea (16.6%). Treatment with transdermal fentanyl resulted in a significant decrease in visual analogue scale and Brief Pain Inventory scores that persisted during treatment. In the overall efficacy evaluation, the pain-alleviating effect, the easiness of application and the overall impression of transdermal fentanyl were rated as good by 54.5%, 65.9% and 59.1% of the completers, respectively. Effects of transdermal fentanyl were rated as good by 64.8% of the investigators. Our data provide evidence that transdermal fentanyl is effective and relatively easy to use for outpatient treatment of pain control in head and neck cancer patients following radiotherapy in selected patients. Reduction of side effects and effective pain management need to be paramount in the management of head and neck cancer patients undergoing radiotherapy. (author)

Fentanyl Transdermal Patch

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Fentanyl patches are used to relieve severe pain in people who are expected to need pain medication ... and who cannot be treated with other medications. Fentanyl is in a class of medications called opiate ( ...

Fatal Overdose due to Confusion of an Transdermal Fentanyl Delivery System

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Ingo Voigt

2013-01-01

Full Text Available Background. The use of transdermal fentanyl systems has increased over recent years, especially in patients with chronic pain. Large misuse potential and fatal outcomes have been described. Case Presentation. A 58-year-old patient presenting with clinical signs of opioid poisoning (hypoventilation, bradycardia, hypotension, and miosis was admitted to our ICU. The first body check revealed a 75 mcg per hour fentanyl patch at the patient's right scapula. Some months ago, patient's aunt died after suffering from an oncological disease. During breaking up of her household, the patches were saved by the patient. Not knowing the risk of this drug, he mistook it as a heat plaster. Investigations. Laboratory test showed an impaired renal function and metabolic acidosis. Urine drug test was negative at admittance and 12 h later. CCT scan presented a global hypoxic brain disease. Treatment and Outcome. The patient was discharged 30 days after admittance in a hemodynamic stable condition but a vegetative state and transferred to a rehabilitation center. Learning Points. With the ongoing increase in fentanyl patch prescriptions for therapeutic reasons, it is likely that misuse cases will become more relevant. Conventional urine drug screening tests are not able to exclude the diagnosis fentanyl intoxication. History taking should include family member's drug prescriptions.

Design and functionality of a smart fentanyl iontophoretic transdermal system for the treatment of moderate-to-severe postoperative pain.

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Joshi, Nitin; Lemke, John; Danesi, Hassan

2016-04-01

Fentanyl iontophoretic transdermal system (ITS) is a patient-controlled analgesia system used for the management of acute postoperative pain. The first-generation fentanyl ITS was an integrated one-piece system; however, corrosion that could limit reliability was detected in a small number of systems. A second-generation fentanyl ITS was designed to separate the hydrogels in the Drug Unit from the electronic circuit of the Controller during manufacture and storage, removing the primary cause of corrosion and thereby improving reliability. No evidence of corrosion has been observed in over 10,000 systems tested in real-time aging studies for the second generation fentanyl ITS. The second generation fentanyl ITS design features combine to ensure safe operation of the system with high reliability.

Foetal Fentanyl Exposure and Ion Trapping after Intravenous and Transdermal Administration to the Ewe.

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Heikkinen, Emma M; Kokki, Hannu; Heikkinen, Aki; Ranta, Veli-Pekka; Räsänen, Juha; Voipio, Hanna-Marja; Kokki, Merja

2017-02-01

Opioids given to pregnant and parturient women are relatively freely transferred across the placenta. Spinal, epidural and intravenous fentanyl has been studied in pregnant women and neonates, but foetal safety of fentanyl dosing with transdermal patch during pregnancy and labour is not sufficiently studied. Foetal pH is physiologically lower than maternal pH, and thus, opioids, which are weak bases, are ionized and may cumulate to foetus. Foetal asphyxia may further worsen acidosis, and ion trapping induced by low pH is assumed to increase the foetal exposure to opioids. Here, we show that no correlation between foetal acidosis and ion trapping of fentanyl could be found. In three experiments, 29 pregnant sheep were administered fentanyl with 2 μg/kg/h patch supplemented with IV boluses/infusion. Foetal exposure to fentanyl was extensive, median 0.34 ng/ml (quartiles 0.21, 0.42), yet drug accumulation to foetus was not observed, and median of foetal/maternal concentration (F/M) ratio was 0.63 (0.43, 0.75) during the first hours after the fentanyl administration. Low foetal pH and pH difference between ewe and the foetus did not correlate with fentanyl concentration in the foetus or F/M ratio. At steady-state during the second patch worn, foetal plasma fentanyl was low, 0.13 ng/ml, and the median of F/M ratio was 0.69. Our results demonstrate that drug accumulation to foetus caused by ion trapping seen with some weak base opioids may not be that significant with fentanyl. These results have a clinical relevance when fentanyl is dosed to pregnant woman and the foetus is acidemic. © 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

"INTRODUCING A FULL VALIDATED ANALYTICAL PROCEDURE AS AN OFFICIAL COMPENDIAL METHOD FOR FENTANYL TRANSDERMAL PATCHES"

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Amir Mehdizadeh

2005-04-01

Full Text Available A simple, sensitive and specific HPLC method and also a simple and fast extraction procedure were developed for quantitative analysis of fentanyl transdermal patches. Chloroform, methanol and ethanol were used as extracting solvents with recovery percent of 92.1, 94.3 and 99.4% respectively. Fentanyl was extracted with ethanol and the eluted fentanyl through the C18 column was monitored by UV detection at 230 nm. The linearity was at the range of 0.5-10 µg/mL with correlation coefficient (r2 of 0.9992. Both intra and inter-day accuracy and precision were within acceptable limits. The detection limit (DL and quantitation limit (QL were 0.15 and 0.5 µg/mL, respectively. Other validation characteristics such as selectivity, robustness and ruggedness were evaluated. Following method validation, a system suitability test (SST including capacity factor (k´, plate number (N, tailing factor (T, and RSD was defined for routine test.

Innate Immune Signalling Genetics of Pain, Cognitive Dysfunction and Sickness Symptoms in Cancer Pain Patients Treated with Transdermal Fentanyl

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Barratt, Daniel T.; Klepstad, Pål; Dale, Ola; Kaasa, Stein; Somogyi, Andrew A.

2015-01-01

Common adverse symptoms of cancer and chemotherapy are a major health burden; chief among these is pain, with opioids including transdermal fentanyl the mainstay of treatment. Innate immune activation has been implicated generally in pain, opioid analgesia, cognitive dysfunction, and sickness type symptoms reported by cancer patients. We aimed to determine if genetic polymorphisms in neuroimmune activation pathways alter the serum fentanyl concentration-response relationships for pain control, cognitive dysfunction, and other adverse symptoms, in cancer pain patients. Cancer pain patients (468) receiving transdermal fentanyl were genotyped for 31 single nucleotide polymorphisms in 19 genes: CASP1, BDNF, CRP, LY96, IL6, IL1B, TGFB1, TNF, IL10, IL2, TLR2, TLR4, MYD88, IL6R, OPRM1, ARRB2, COMT, STAT6 and ABCB1. Lasso and backward stepwise generalised linear regression were used to identify non-genetic and genetic predictors, respectively, of pain control (average Brief Pain Inventory fentanyl concentrations did not predict between-patient variability in these outcomes, nor did genetic factors predict pain control, sickness response or opioid adverse event complaint. Carriers of the MYD88 rs6853 variant were half as likely to have cognitive dysfunction (11/111) than wild-type patients (69/325), with a relative risk of 0.45 (95% CI: 0.27 to 0.76) when accounting for major non-genetic predictors (age, Karnofsky functional score). This supports the involvement of innate immune signalling in cognitive dysfunction, and identifies MyD88 signalling pathways as a potential focus for predicting and reducing the burden of cognitive dysfunction in cancer pain patients. PMID:26332828

The effect of inhalant anesthetic and body temperature on peri-anesthetic serum concentrations of transdermally administered fentanyl in dogs.

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Pettifer, Glenn R; Hosgood, Giselle

2004-04-01

To determine whether moderate hypothermia during anesthesia significantly affects the serum concentration of transdermally delivered fentanyl and whether halothane or isoflurane affect these concentrations. Randomized cross-over experimental trial. Six mature, healthy Beagles (three males, three females) weighing 10.6 +/- 0.43 kg. A 50-microg hour(-1) fentanyl patch was applied 36 hours prior to anesthesia. Anesthesia was induced at time 0 (t = 0). Each dog received four treatments: isoflurane + normothermia (ISO-NORM), isoflurane + hypothermia (ISO-HYPO), halothane + normothermia (HAL-NORM), and halothane + hypothermia (HAL-HYPO). Dogs were intubated and maintained at 1.5 times MAC. Animals in the hypothermia treatments were cooled to 35 degrees C during anesthesia. Serum fentanyl analysis was performed at -36, -24, -12, 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9, 10, 18, and 26 hours. Direct arterial blood pressures and arterial blood gases were monitored. The mean body temperatures (+/-SEM) during the anesthetic period for the four treatments were: ISO-NORM = 37.7 +/- 0.07 degrees C, ISO-HYPO = 35.8 +/- 0.1 degrees C, HAL-NORM = 37.7 +/- 0.06 degrees C, and HAL-HYPO = 35.8 +/- 0.13 degrees C. The mean (+/-SEM) serum fentanyl concentrations (SFC) for both hypothermia treatments were significantly lower than baseline concentrations at t = 1 hour and persisted for the duration of anesthesia for the ISO-HYPO treatment but only from t = 1 to 2 hours for the HAL-HYPO treatment. Serum fentanyl concentrations returned to baseline within one hour of the end of anesthesia, regardless of body temperature. There were no significant differences between treatments for systolic or diastolic blood pressure but mean blood pressures were higher during normothermia versus hypothermia during the last hour of anesthesia. Hypothermia during inhalation anesthesia produced a significant reduction in SFC using transdermal administration and was more protracted with isoflurane

On the Road to Development of an in Vitro Permeation Test (IVPT) Model to Compare Heat Effects on Transdermal Delivery Systems: Exploratory Studies with Nicotine and Fentanyl.

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Shin, Soo Hyeon; Ghosh, Priyanka; Newman, Bryan; Hammell, Dana C; Raney, Sam G; Hassan, Hazem E; Stinchcomb, Audra L

2017-09-01

At elevated temperatures, the rate of drug release and skin permeation from transdermal delivery systems (TDS) may be higher than at a normal skin temperature. The aim of this study was to compare the effect of heat on the transdermal delivery of two model drugs, nicotine and fentanyl, from matrix-type TDSs with different formulations, using in vitro permeation tests (IVPT). IVPT experiments using pig skin were performed on two nicotine and three fentanyl TDSs. Both continuous and transient heat exposures were investigated by applying heat either for the maximum recommended TDS wear duration or for short duration. Continuous heat exposure for the two nicotine TDSs resulted in different effects, showing a prolonged heat effect for one product but not the other. The J max enhancement ratio due to the continuous heat effect was comparable between the two nicotine TDS, but significantly different (p drug from the skin depot after TDS removal differently for two drugs, with fentanyl exhibiting a longer heat effect. This exploratory work suggests that an IVPT study may be able to discriminate differences in transdermal drug delivery when different TDS are exposed to elevated temperatures. However, the clinical significance of IVPT heat effects studies should be further explored by conducting in vivo clinical studies with similar study designs.

Inappropriate Fentanyl Prescribing Among Nursing Home Residents in the United States.

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Fain, Kevin M; Castillo-Salgado, Carlos; Dore, David D; Segal, Jodi B; Zullo, Andrew R; Alexander, G Caleb

2017-02-01

We quantified transdermal fentanyl prescribing in elderly nursing home residents without prior opioid use or persistent pain, and the association of individual and facility traits with opioid-naïve prescribing. Cross-sectional study. Linked Minimum Data Set (MDS) assessments; Online Survey, Certification and Reporting (OSCAR) records; and Medicare Part D claims. From a cross-section of all long-stay US nursing home residents in 2008 with an MDS assessment and Medicare Part D enrollment, we identified individuals (≥65 years old) who initiated transdermal fentanyl, excluding those with Alzheimer disease, severe cognitive impairment, cancer, or receipt of hospice care. We used Medicare Part D to select beneficiaries initiating transdermal fentanyl in 2008 and determined whether they were "opioid-naïve," defined as no opioid dispensing during the previous 60 days. We obtained resident and facility characteristics from MDS and OSCAR records and defined persistent pain as moderate-to-severe, daily pain on consecutive MDS assessments at least 90 days apart. We estimated associations of patient and facility attributes and opioid-naïve fentanyl initiation using multilevel mixed effects logistic regression modeling. Among 17,052 residents initiating transdermal fentanyl, 6190 (36.3%) were opioid-naïve and 15,659 (91.8%) did not have persistent pain. In the regression analysis with adjustments, residents who were older (ages ≥95 odds ratio [OR] 1.69, 95% confidence interval [CI] 1.46-1.95) or more cognitively impaired (moderate-to-severe cognitive impairment, OR 1.99, 95% CI 1.73-2.29) were more likely to initiate transdermal fentanyl without prior opioid use. Most nursing home residents initiating transdermal fentanyl did not have persistent pain and many were opioid-naïve. Changes in prescribing practices may be necessary to ensure Food and Drug Administration warnings are followed, particularly for vulnerable subgroups, such as the cognitively impaired

Innate Immune Signalling Genetics of Pain, Cognitive Dysfunction and Sickness Symptoms in Cancer Pain Patients Treated with Transdermal Fentanyl.

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Daniel T Barratt

Full Text Available Common adverse symptoms of cancer and chemotherapy are a major health burden; chief among these is pain, with opioids including transdermal fentanyl the mainstay of treatment. Innate immune activation has been implicated generally in pain, opioid analgesia, cognitive dysfunction, and sickness type symptoms reported by cancer patients. We aimed to determine if genetic polymorphisms in neuroimmune activation pathways alter the serum fentanyl concentration-response relationships for pain control, cognitive dysfunction, and other adverse symptoms, in cancer pain patients. Cancer pain patients (468 receiving transdermal fentanyl were genotyped for 31 single nucleotide polymorphisms in 19 genes: CASP1, BDNF, CRP, LY96, IL6, IL1B, TGFB1, TNF, IL10, IL2, TLR2, TLR4, MYD88, IL6R, OPRM1, ARRB2, COMT, STAT6 and ABCB1. Lasso and backward stepwise generalised linear regression were used to identify non-genetic and genetic predictors, respectively, of pain control (average Brief Pain Inventory < 4, cognitive dysfunction (Mini-Mental State Examination ≤ 23, sickness response and opioid adverse event complaint. Serum fentanyl concentrations did not predict between-patient variability in these outcomes, nor did genetic factors predict pain control, sickness response or opioid adverse event complaint. Carriers of the MYD88 rs6853 variant were half as likely to have cognitive dysfunction (11/111 than wild-type patients (69/325, with a relative risk of 0.45 (95% CI: 0.27 to 0.76 when accounting for major non-genetic predictors (age, Karnofsky functional score. This supports the involvement of innate immune signalling in cognitive dysfunction, and identifies MyD88 signalling pathways as a potential focus for predicting and reducing the burden of cognitive dysfunction in cancer pain patients.

Meta-Analysis of the Ease of Care From the Nurses' Perspective Comparing Fentanyl Iontophoretic Transdermal System (ITS) Vs Morphine Intravenous Patient-Controlled Analgesia (IV PCA) in Postoperative Pain Management.

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Pestano, Cecile R; Lindley, Pam; Ding, Li; Danesi, Hassan; Jones, James B

2017-08-01

The aim of this meta-analysis was to compare the ease of care (EOC) of fentanyl iontophoretic transdermal system (ITS) vs the morphine intravenous patient-controlled analgesia (IV PCA) as assessed by the nurse. Meta-analysis of three phase 3B randomized active-comparator trials. This meta-analysis according to Cochrane's approach assessed EOC using a validated nurse questionnaire (22 items grouped into three subscales, which include time efficiency, convenience, and satisfaction) in adult patients treated with fentanyl ITS or morphine IV PCA for postoperative pain management. The weighted mean difference (WMD) between treatments was calculated. EOC analyses were based on responses to questionnaires from 848 (fentanyl ITS) and 761 (morphine IV PCA) nurses. Fentanyl ITS was reported to provide significant advantages compared with morphine IV PCA in terms of nurses' overall EOC (WMD = -0.57, P PCA. Copyright © 2016 American Society of PeriAnesthesia Nurses. Published by Elsevier Inc. All rights reserved.

Fentanyl Formulations in the Management of Pain: An Update.

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Schug, Stephan A; Ting, Sonya

2017-05-01

Fentanyl is a synthetic, highly selective opioid with many desirable physicochemical properties, including a high lipophilicity and predictable pharmacokinetics. These properties have an established record in the management of pain in a variety of settings, particularly acute pain and breakthrough cancer pain. Fentanyl was initially developed for parenteral use; however, this is invasive and impractical in the outpatient setting. Unfortunately, the high first-pass metabolism of fentanyl makes oral formulations unfeasible. However, its high lipophilicity allows fentanyl to be absorbed via a number of other routes. Thus new formulations were designed to allow non-invasive methods of administration. Transmucosal and transdermal fentanyl formulations are well established, and have proven useful in the settings of breakthrough cancer pain, emergencies and in the paediatric population. The iontophoretic transdermal system was developed to provide a needle-free system of delivering bolus doses of fentanyl on demand, a novel way of delivering patient-controlled opioid analgesia. Transpulmonary administration of fentanyl remains experimental. The aim of this review is to provide an update on current non-parenteral fentanyl formulations, with attention to their particular pharmacokinetics and features relevant to clinical use in pain management.

A retrospective study on the influence of nutritional status on pain management in cancer patients using the transdermal fentanyl patch.

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Takahashi, Hiroaki; Chiba, Takeshi; Tairabune, Tomohiko; Kimura, Yusuke; Wakabayashi, Go; Takahashi, Katsuo; Kudo, Kenzo

2014-01-01

It is unknown whether nutritional status influences pain intensity in cancer patients receiving a transdermal fentanyl patch (FP). This study aimed to determine whether nutritional status is associated with pain intensity and to evaluate the influence of changes in nutritional status on pain intensity in cancer patients receiving transdermal FP treatment. We included 92 patients receiving transdermal FP treatment for the first time with switching from oxycodone. The patients were classified into low- and normal-nutrition groups based on their nutritional status, which was assessed according to the Nutrition Risk Screening 2002 (NRS 2002) parameters. The pain intensity of each patient was evaluated by a numeric rating scale (11-point scale from 0 to 10). NRS 2002 score and pain intensity were obtained on day 3 after the FP was applied to the skin. Pain intensities were significantly higher among patients in the low-nutrition group than among patients in the normal-nutrition group. NRS 2002 scores showed a significant positive correlation with the pain intensities. In 52 of 92 patients, who were evaluated using the NRS 2002 score and pain intensity on day 30 after FP application, the changes in NRS 2002 scores were significantly related to changes in pain intensities (odds ratio, 30.0; 95% confidence interval, 4.48-200.97; p=0.0005). These results suggest that an increase in the NRS 2002 score is a risk factor for an increase in pain intensity in cancer patients receiving FP treatment. Malnutrition may lead to poor pain management in cancer patients receiving FP treatment.

Use of Fentanyl Iontophoretic Transdermal System (ITS) (IONSYS®) in the Management of Patients with Acute Postoperative Pain: A Case Series.

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Poplawski, Steven; Johnson, Matthew; Philips, Philip; Eberhart, Leopold H J; Koch, Tilo; Itri, Loretta M

2016-12-01

Fentanyl iontophoretic transdermal system (ITS) [IONSYS ® , The Medicines Company, Parsippany, NJ, USA] is a needle-free, patient-controlled, postoperative opioid pain management treatment. It is indicated for the short-term management of acute postoperative pain in adults requiring opioid analgesia in the hospital. The safety and effectiveness of fentanyl ITS for acute postoperative pain management has been demonstrated in a range of surgery and patient types studied in seven phase 3 trials (three placebo-controlled trials and four active-comparator trials). The majority of the patients in the phase 3 trials had undergone either abdominal/pelvic, orthopedic, or thoracic surgery. Consistent with the prescribing information, physicians in clinical practice may treat patients with this system following any type of surgery including those that may not have been included in the phase 3 trials. The purpose of this case series is to illustrate how fentanyl ITS is being utilized for postoperative pain management in real-world clinical practice following a variety of surgeries and in current pain management protocols that may have evolved since the completion of the phase 3 program. There are seven cases from three clinical centers described within this case series, each using fentanyl ITS according to the prescribing information. The surgery types included are bariatric (N = 3), prostate (N = 2), colorectal (N = 1), and perirectal abscess drainage (N = 1). A systematic review of each patient chart was conducted via a standardized retrospective assessment by the clinicians who managed each patient. Additionally, each healthcare professional was interviewed regarding their overall experience and key learnings using fentanyl ITS. Overall, fentanyl ITS was effective and well tolerated in these case reports in current-day clinical practice settings. These case studies are informative about fentanyl ITS use shortly after product approval and set the stage for

Multicenter clinical study for evaluation of efficacy and safety of transdermal fentanyl matrix patch in treatment of moderate to severe cancer pain in 474 chinese cancer patients.

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Zhu, Yu-Lin; Song, Guo-Hong; Liu, Duan-Qi; Zhang, Xi; Liu, Kui-Feng; Zang, Ai-Hua; Cheng, Ying; Cao, Guo-Chun; Liang, Jun; Ma, Xue-Zhen; Ding, Xin; Wang, Bin; Li, Wei-Lian; Hu, Zuo-Wei; Feng, Gang; Huang, Jiang-Jin; Zheng, Xiao; Jiao, Shun-Chang; Wu, Rong; Ren, Jun

2011-12-01

Although a new matrix formulation fentanyl has been used throughout the world for cancer pain management, few data about its efficacy and clinical outcomes associated with its use in Chinese patients have been obtained. This study aimed to assess the efficacy and safety of the new system in Chinese patients with moderate to severe cancer pain. A total of 474 patients with moderate to severe cancer pain were enrolled in this study and were treated with the new transdermal fentanyl matrix patch (TDF) up to 2 weeks. All the patients were asked to record pain intensity, side effects, quality of life (QOL), adherence and global satisfaction. The initial dose of fentanyl was 25 μg/h titrated with opioid or according to National Comprehensive Cancer Network (NCCN) guidelines. Transdermal fentanyl was changed every three days. After 2 weeks. The mean pain intensity of the 459 evaluated patients decreased significantly from 5.63±1.26 to 2.03±1.46 (P<0.0001). The total remission rate was 91.29%, of which moderate remission rate 53.16%, obvious remission rate 25.49% and complete remission rate 12.64%. The rate of adverse events was 33.75%, 18.78% of which were moderate and 3.80% were severe. The most frequent adverse events were constipation and nausea. No fatal events were observed. The quality of life was remarkably improved after the treatment (P<0.0001). The new TDF is effective and safe in treating patients with moderate to severe cancer pain, and can significantly improve the quality of life.

Safety of fentanyl initiation according to past opioid exposure among patients newly prescribed fentanyl patches

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Friesen, Kevin J.; Woelk, Cornelius; Bugden, Shawn

2016-01-01

Background: Although a convenient opioid delivery system, transdermal fentanyl patches have caused several deaths and resulted in safety warnings reminding prescribers that fentanyl patches should be prescribed only for patients who have adequate prior exposure to opioids. We conducted a longitudinal analysis of the safety of fentanyl initiation by examining past opioid exposure among patients newly prescribed fentanyl patches. Methods: We identified all patients in the province of Manitoba who were newly prescribed fentanyl patches between Apr. 1, 2001, and Mar. 31, 2013. We converted all prior opioid use to oral morphine equivalents and determined the average daily dose in the 7–30 days before initial fentanyl patch use. Fentanyl initiation was considered unsafe if the patient’s pre-fentanyl opioid exposure was below the recommended level. Results: We identified 11 063 patients who began using fentanyl patches during the study period. Overall, fentanyl initiation was deemed unsafe in 74.1% of cases because the patient’s prior opioid exposure was inadequate. Women and patients 65 years of age and older were more likely than men and younger patients, respectively, to have inadequate prior opioid exposure (p fentanyl patches decreased significantly over the study period, from 87.0% in 2001 to 50.0% in 2012 (p fentanyl initiation improved over the study period, but still half of fentanyl patch prescriptions were written for patients with inadequate prior opioid exposure. Review of prior opioid exposure may be a simple but important way to improve the safe use of fentanyl patches. PMID:27044480

Effects of smoking and body mass index on the exposure of fentanyl in patients with cancer.

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Kuip, Evelien J M; Oldenmenger, Wendy H; Thijs-Visser, Martine F; de Bruijn, Peter; Oosten, Astrid W; Oomen-de Hoop, Esther; Koolen, Stijn L W; Van der Rijt, Carin C D; Mathijssen, Ron H J

2018-01-01

The transdermal fentanyl patch is widely used to treat cancer-related pain despite its wide inter- and intrapatient variability in pharmacokinetics. The aim of this study was to investigate whether smoking and body size (i.e. body mass index) influence fentanyl exposure in patients with cancer. These are factors that typically change during treatment and disease trajectories. We performed an explorative cohort study in patients with cancer using transdermal fentanyl patches (Durogesic®), by taking a blood sample for pharmacokinetic analysis one day after applying a patch in patients with a stable fentanyl dose. A total of 88 patients were evaluable. Although no statistically significant difference was found, the plasma concentrations of non-smokers was 28% (95% CI [-14%; +89-%]) higher than those of smokers normalizing for a dose of 25μg/min. Patients with a low BMI ( 25 kg/m2). A wider variation in fentanyl plasma concentrations was found in this study than anticipated. Due to this variation, studies in larger patient cohorts are needed to further investigate the effect of smoking on plasma concentration of fentanyl and thereby clarify the clinical significance of our findings.

78 FR 44432 - New Animal Drugs; Change of Sponsor; Fentanyl; Iron Injection

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2013-07-24

... for an NADA from Nexcyon Pharmaceuticals, Inc. to Elanco Animal Health, A Division of Eli Lilly & Co..., NADA 141-337 for RECUVYRA (fentanyl) Transdermal Solution to Elanco Animal Health, A Division of Eli Lilly & Co., Lilly Corporate Center, [[Page 44433

Fentanyl Iontophoretic Transdermal System (IONSYS(®)) can be Safely used in the Hospital Environment with X-Rays, Computerized Tomography and Radiofrequency Identification Devices.

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Lemke, John; Sardariani, Edmond; Phipps, Joseph Bradley; Patel, Niki; Itri, Loretta M; Caravelli, James; Viscusi, Eugene R

2016-09-01

Fentanyl iontophoretic transdermal system (fentanyl ITS, IONSYS(®)) is a patient-controlled analgesia system used for the management of acute postoperative pain, designed to be utilized in a hospital setting. The objective of the two studies was to determine if fentanyl ITS could be safely used with X-rays, computerized tomography (CT) scans and radiofrequency identification (RFID) devices. The ITS system has two components: controller and drug unit; the studies utilized ITS systems without fentanyl, referred to as the ITS Placebo system. The first study evaluated the effect of X-radiation on the operation of an ITS Placebo system. Five ITS Placebo systems were exposed to X-rays (20 and 200 mSv total radiation dose-the 200 mSv radiation dose represents a tenfold higher exposure than in clinical practice) while operating in the Ready Mode and five were exposed while operating in the Dose Mode. The second study evaluated the effect of RFID (worst-case scenario of direct contact with an RFID transmitter) on the operation of an ITS Placebo system. During these tests, observations of the user interface and measurements of output voltage confirmed proper function throughout all operational modes (Ready Mode, Dose Mode, End-of-Use Mode, and End-of-Life Mode). The ITS Placebo system met all specifications and no functional anomalies were observed during and following X-ray exposure at two radiation dose levels or exposure at six different combinations of RFID frequencies and field strengths. The performance of the ITS system was unaffected by X-ray exposure levels well beyond those associated with diagnostic X-rays and CT scans, and by exposure to radiofrequency field strengths typically generated by RFID devices. These results provide added confidence to clinicians that the fentanyl ITS system does not need to be removed during diagnostic X-rays and CT scans and can also be utilized in close proximity to RFID devices. The studies and writing of this manuscript were

Postoperative fentanyl patch versus subacromial bupivacaine infusion in arthroscopic shoulder surgery.

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Merivirta, Riika; Äärimaa, Ville; Aantaa, Riku; Koivisto, Mari; Leino, Kari; Liukas, Antti; Kuusniemi, Kristiina

2013-07-01

The purpose of our study was to compare the effectiveness of subacromial bupivacaine infusion and a transdermal fentanyl patch in the treatment of postoperative pain after arthroscopic shoulder surgery. Sixty patients with rotator cuff disease scheduled for elective arthroscopic shoulder surgery were enrolled in the study. For the treatment of postoperative pain, 30 patients constituted group F and received a 12.0-μg/h fentanyl patch for 72 hours and saline solution infusion in a subacromial manner at the rate of 4 mL/h. The remaining 30 patients constituted group B and received a placebo patch and an infusion of 2.5-mg/mL bupivacaine in a subacromial manner for 72 hours. The primary outcome measure was the postoperative numerical rating scale pain score. The consumption of opioids, ibuprofen, and acetaminophen was also recorded. The Constant scores and general recovery were followed up until the 90th postoperative day. There was no statistically significant difference in the numerical rating scale scores (P = .60) between the groups. No differences in the use of rescue analgesic were observed except that the patients receiving bupivacaine used more ibuprofen (median, 1,200 mg v 600 mg) during the day of surgery (P = .042). No difference was found in general recovery between the groups. A fentanyl patch delivering 12-μg/h fentanyl offers an easy and safe treatment option as a part of multimodal analgesia with few adverse effects in the treatment of postoperative pain in a carefully selected patient group after arthroscopic shoulder surgery. Level I, randomized controlled trial. Copyright © 2013 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

A comparison between the administration of oral prolonged-release oxycodone-naloxone and transdermal fentanyl in patients with moderate-to-severe cancer pain: a propensity score analysis

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Roberto A

2017-09-01

Full Text Available A Roberto,1 MT Greco,2 L Legramandi,3 F Galli,3 M Galli,4 O Corli1 1Pain and Palliative Care Research Unit, Oncology Department, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy, 2Department of Clinical Sciences and Community, University of Milan, Milan, Italy, 3Methodology for Clinical Research Laboratory, Oncology Department, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy, 4Scientific Medical Communication srl, Novara, Italy Background: Opioids are the most important pharmacological treatment for moderate-to-severe cancer pain, but side effects limit their use. Transdermal fentanyl (TDF and oral prolonged-release oxycodone-naloxone (OXN-PR are effective in controlling chronic pain, with less constipation compared to other opioids. However, TDF and OXN-PR have never been directly compared.Patients and methods: Cancer patients with moderate-to-severe chronic pain were consecutively enrolled in two prospective 28-day trials, received either TDF or OXN-PR, and were assessed at baseline and after 7, 14, 21, and 28 days. The primary endpoint was 28-day analgesic response rate (average pain intensity decrease ≥30% from baseline. Other outcome measures included opioid daily dose changes over time; need for adjuvant analgesics; number of switches; premature discontinuation; presence and severity of constipation; and other adverse drug reactions. To compare the efficacy and the safety of TDF and OXN-PR, we used the propensity score analysis to adjust for heterogeneity between the two patient groups.Results: Three hundred ten out of 336 patients originally treated (119 TDF and 191 OXN-PR were included in the comparative analysis. The amount of responders was comparable after TDF (75.3% and OXN-PR administration (82.9%, not significant [NS]. The final opioid daily dose expressed as morphine equivalent was 113.6 mg for TDF and 44.5 mg for OXN-PR (p<0.0001. A daily opioid dose escalation >5% was less common after

Disaster after the plaster. Fentanyl withdrawal symptoms in a curable hospice patient.

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Maathuis, M.H.; Dijkstra, D.D.

2011-01-01

Opioids have been used for thousands of years for pain relief. Transdermal fentanyl (TDF) is a synthetic opioid that is prescribed for the treatment of chronic pain. This clinical lesson demonstrates that TDF may be easy to start but sometimes difficult to stop. Like any other opioid there is a

COMPARATIVE STUDY OF EPIDURAL FENTANYL AND FENTANYL PLUS MAGNESIUM SULPHATE FOR POSTOPERATIVE ANALGESIA

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Shiva

2015-11-01

Full Text Available AIMS AND OBJECTIVES Magnesium has antinociceptive effects in animal and human models of pain. It is found that the addition of Magnesium sulphate to postoperative Epidural infusion of Fentanyl may decrease the need for Fentanyl. We undertook a study to compare the duration of postoperative analgesia after Epidural Fentanyl and Epidural Fentanyl plus Magnesium sulphate administered postoperatively, along with side effects. MATERIALS AND METHODS 50 patients undergoing elective lower limb and abdominal surgeries were randomized into one of the two groups with 25 patients in each group. Combined Spinal Epidural Anaesthesia was used for all patients. Spinal anaesthesia with 2.5 cc of 0.5% Hyperbaric Bupivacaine was given. When sensory blockade regressed to L1, patients were given either 50 µg of Fentanyl (diluted to 6cc with normal saline, Group F or 50 µg of Fentanyl plus 50 mg Magnesium sulphate (diluted to 6cc with normal saline, Group FM. Parameters like blood pressure, pulse rate, respiratory rate and oxygen saturation were monitored, and other side effects were noted. Data were analysed by using Student t test and Chi-square/ Fisher Exact tests. RESULTS There was significant difference in duration of analgesia between Group F (107 min and Group FM (143 min. Hemodynamic parameters were stable in both the groups with minimal side effects. CONCLUSION Co-administration of Magnesium sulphate with Fentanyl for postoperative Epidural analgesia results in prolongation of Fentanyl analgesia without significant side-effects.

Consumption of three strong opioids (morphine, oxycodone and fentanyl) in seven European countries during seven years (2003-2009).

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Hudec, R; Tisonova, J; Foltan, V; Kristova, V

2013-01-01

The aim was to analyse the consumption of selected strong opioid analgesics during a seven-year period of 2003-2009 in order to compare Slovak consumption with that in six other European countries and to determine our position. Drug consumption data from the State Institute for Drug Control in Slovak Republic were used. As to the data from other countries, annual health statistics published on websites were used in comparison. Obviously the consumption of one of studied opioid drugs with transdermal aplication route, particularly fentanyl, tended to increase in all countries during the observed period. Oxycodone tends to yield a rapid increase in consumption as well. As opposed to the latter drugs, the consumption of morphine was decreasing throughout the observed period. The consumption of these drugs in Slovakia remains low (except for that of fentanyl). Our analysis confirmed a clear shift from oral to transdermal therapy as well as usage of newer drugs. Drug consumption data are a relatively new source of information for health research. Our analysis showed increasing trends in fentanyl (patch opioid) consumption in all compared countries as well as an increasing consumption of oxycodone and decreasing consumption of morphine (Fig. 3, Ref. 17).

A review: Fentanyl and non-pharmaceutical fentanyls.

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Suzuki, Joji; El-Haddad, Saria

2017-02-01

Fentanyl and non-pharmaceutical fentanyls (NPFs) have been responsible for numerous outbreaks of overdoses all over the United States since the 1970s. However, there has been a growing concern in recent years that NPFs are contributing to an alarming rise in the number of opioid-related overdoses. The authors conducted a narrative review of the published and grey literature on fentanyl and NPFs in PubMed, Google Scholar, and Google using the following search terms: "fentanyl", "non-pharmaceutical fentanyl", "fentanyl analogs", "fentanyl laced heroin" and "fentanyl overdose". References from relevant publications and grey literature were also reviewed to identify additional citations for inclusion. The article reviews the emergence and misuse of fentanyl and NPFs, their clinical pharmacology, and the clinical management and prevention of fentanyl-related overdoses. Fentanyl and NPFs may be contributing to the recent rise in overdose deaths in the United States. There is an urgent need to educate clinicians, researchers, and patients about this public health threat. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The Effectiveness of Transdermal Opioid in the Management Multiple Rib Fractures: Randomized Clinical Trial

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Okan Solak

2013-09-01

Full Text Available Background: The most commonly observed pathology in chest traumas is rib fracture, and the most important clinical symptom is severe pain. Aims: To investigate the effectiveness of intramuscular opioid (IMO, intravenous patient-controlled analgesia (IVPCA and the Fentanyl transdermal therapeutic system (TTS in the management of rib fracture pain. Study Design: Prospective randomized clinical trial. Methods: In our prospective and randomised study, we included 45 patients with a diagnosis of multiple rib fractures. There were three groups and intercostal nerve blockage (ICB in the first day and oral paracetamol for five days was administered to each group as standard. In Group IMO (n=15, 4x40 mg pethidine HCl was administered to the patients, while in Group IVPCA (n=15 this was 5 µg/mL continuous intravenous fentanyl and was 50 µg fentanyl TTS in Group TTS (n=15. The demographics, injury data and vital signs of the patients were recorded. Pain was scored using Visual Analogue Scale (VAS. The pain during lying down (VASl and mobilisation (VASm was detected. Results: There were no differences between the three groups regarding age, sex, the trauma pattern, the number and distribution of costal fracture localisations, the presence of additional pathology, complications, thoracal catheter and the duration of thoracal catheter. No significant difference between the groups regarding systolic and diastolic arterial tension, number of breaths and beats in a minute was observed (p>0.05. We observed an improvement in the mean VAS score after treatment in all three groups. The mean VASl score significantly decreased after treatment in each group (p0.05. Conclusion: In the analgesia of patients with multiple rib fractures, TTS administration with ICB showed similar effectiveness with IVPCA administration with ICB. In the management of pain due to multiple rib fractures, TTS administration is a safe, non-invasive and effective procedure.

The effectiveness of transdermal opioid in the management multiple rib fractures: randomized clinical trial.

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Solak, Okan; Oz, Gürhan; Kokulu, Serdar; Solak, Ozlem; Doğan, Gökçen; Esme, Hıdır; Ocalan, Kubilay; Baki, Elif Doğan

2013-09-01

The most commonly observed pathology in chest traumas is rib fracture, and the most important clinical symptom is severe pain. To investigate the effectiveness of intramuscular opioid (IMO), intravenous patient-controlled analgesia (IVPCA) and the Fentanyl transdermal therapeutic system (TTS) in the management of rib fracture pain. Prospective randomized clinical trial. In our prospective and randomised study, we included 45 patients with a diagnosis of multiple rib fractures. There were three groups and intercostal nerve blockage (ICB) in the first day and oral paracetamol for five days was administered to each group as standard. In Group IMO (n=15), 4×40 mg pethidine HCl was administered to the patients, while in Group IVPCA (n=15) this was 5 μg/mL continuous intravenous fentanyl and was 50 μg fentanyl TTS in Group TTS (n=15). The demographics, injury data and vital signs of the patients were recorded. Pain was scored using Visual Analogue Scale (VAS). The pain during lying down (VASl) and mobilisation (VASm) was detected. There were no differences between the three groups regarding age, sex, the trauma pattern, the number and distribution of costal fracture localisations, the presence of additional pathology, complications, thoracal catheter and the duration of thoracal catheter. No significant difference between the groups regarding systolic and diastolic arterial tension, number of breaths and beats in a minute was observed (p>0.05). We observed an improvement in the mean VAS score after treatment in all three groups. The mean VASl score significantly decreased after treatment in each group (p0.05). In the analgesia of patients with multiple rib fractures, TTS administration with ICB showed similar effectiveness with IVPCA administration with ICB. In the management of pain due to multiple rib fractures, TTS administration is a safe, non-invasive and effective procedure.

Opioids Switching with Transdermal Systems in Chronic Cancer Pain

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Barbarisi M

2009-05-01

Full Text Available Abstract Background Due to tolerance development and adverse side effects, chronic pain patients frequently need to be switched to alternative opioid therapy Objective To assess the efficacy and tolerability of an alternative transdermally applied (TDS opioid in patients with chronic cancer pain receiving insufficient analgesia using their present treatment. Methods A total of 32 patients received alternative opioid therapy, 16 were switched from buprenorphine to fentanyl and 16 were switched from fentanyl to buprenorphine. The dosage used was 50% of that indicated in equipotency conversion tables. Pain relief was assessed at weekly intervals for the next 3 weeks Results Pain relief as assessed by VAS, PPI, and PRI significantly improved (p Conclusion Opioid switching at 50% of the calculated equianalgesic dose produced a significant reduction in pain levels and rescue medication. The incidence of side effects decreased and no new side effects were noted. Further studies are required to provide individualized treatment for patients according to their different types of cancer.

A retrospective analysis of nebulized versus intravenous fentanyl for renal colic.

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Imamoglu, Melih; Aygun, Ali; Bekar, Omer; Erdem, Erkan; Cicek, Mustafa; Tatli, Ozgur; Karaca, Yunus; Sahin, Aynur; Turkmen, Suha; Turedi, Suleyman

2017-05-01

To assess the effectiveness of nebulized fentanyl used for analgesia in renal colic. This research was planned as a randomized, blinded study in which prospectively collected data were analyzed retrospectively to compare nebulized and intravenous (iv) fentanyl therapies. Patients with renal colic with 'moderate' or worse pain on a four-point verbal pain score (VPS) or with pain of 20mm or above on a 100-mm visual analogue score (VAS) at time of presentation were randomized into iv fentanyl (n=62) or nebulized fentanyl (n=53) study groups. Decreases in VAS and VPS scores at 15 and 30min compared to baseline, rescue analgesia requirements and side-effects between the groups were compared. Both iv fentanyl and nebulized fentanyl provided effective analgesia in renal colic patients at the end of 30min. However, iv fentanyl provided more rapid and more effective analgesia than nebulized fentanyl. Patients receiving iv fentanyl had lower rescue analgesia requirements than those receiving nebulized fentanyl (37.1% vs 54.7%), although the difference was not statistically significant (p=0.058). In addition, side-effects were more common in the iv fentanyl group compared to the nebulized fentanyl group (22.1% vs 9.4%), although the difference was also not significant (p=0.058). Nebulized fentanyl provides effective analgesia in patients with renal colic. However, iv fentanyl exhibits more rapid and more powerful analgesic effects than nebulized fentanyl. Nonetheless, due to its ease of use and few potential risks and side-effects the nebulized form can be used as an alternative in renal colic. Copyright © 2017 Elsevier Inc. All rights reserved.

Pheniramine Maleate is more effective than Lidocaine on Fentanyl Induced Cough.

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Ozmen, Ozgur; Kara, Duygu; Karaman, Emine Uzlas; Karakoc, Fatma; Karakaya, Muhammet Ahmet; Arslan, Zakir

2016-01-01

Fentanyl is frequently used during anesthesia induction. The use of fentanyl can cause cough through different mechanisms. Here, we aimed to investigate effects of pheniramine maleate (PM), an antihistaminic agent, and compare it with lidocaine on fentanyl induced cough. This is a randomized double-blind prospective clinical study of ASA I-II, 120 patients scheduled for elective abdominal surgery. Patients were administered drugs intravenously and randomly allocated into three groups: Group C (2 ml 0.9 % normal saline), Group L (1mg/kg lidocaine), and Group F (PM 45.5 mg). 90 seconds after administration, 2µ/kg fentanyl was applied in three seconds to all patients. Severity of cough (mild: 1-2, moderate: 3-5, severe> 5), time of the cough and vital parameters were recorded 90 seconds after fentanyl injection. Eight patients (25%) in Group C had fentanyl induced cough whereas three patients (7.5%) in Group L and one patient (2.5%) in Group F experienced this phenomenon. There was statistically significant difference between Group F and Group C (p0.05). Pheniramine Maleate 45.5 mg is better that placebo and as effective as lidocaine to prevent fentanyl induced cough.

Neurotoxic effects of levobupivacaine and fentanyl on rat spinal cord

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Yesim Cokay Abut

2015-02-01

Full Text Available BACKGROUND: The purpose of the study was to compare the neurotoxic effects of intrathecally administered levobupivacaine, fentanyl and their mixture on rat spinal cord. METHODS: In experiment, there were four groups with medication and a control group. Rats were injected 15 µL saline or fentanyl 0.0005 µg/15 µL, levobupivacaine 0.25%/15 µL and fentanyl 0.0005 µg + levobupivacaine 0.25%/15 µL intrathecally for four days. Hot plate test was performed to assess neurologic function after each injection at 5th, 30th and 60th min. Five days after last lumbal injection, spinal cord sections between the T5 and T6 vertebral levels were obtained for histologic analysis. A score based on subjective assessment of number of eosinophilic neurons - Red neuron - which means irreversible neuronal degeneration. They reflect the approximate number of degenerating neurons present in the affected neuroanatomic areas as follows: 1, none; 2, 1-20%; 3, 21-40%; 4, 41-60%; and 5, 61-100% dead neurons. An overall neuropathologic score was calculated for each rat by summating the pathologic scores for all spinal cord areas examined. RESULTS: In the results of HPT, comparing the control group, analgesic latency statistically prolonged for all four groups.In neuropathologic investment, the fentanyl and fentanyl + levobupivacaine groups have statistically significant high degenerative neuron counts than control and saline groups. CONCLUSIONS: These results suggest that, when administered intrathecally in rats, fentanyl and levobupivacaine behave similar for analgesic action, but fentanyl may be neurotoxic for spinal cord. There was no significant degeneration with levobupivacaine, but fentanyl group has had significant degeneration.

[Low-dose hypobaric spinal anesthesia for anorectal surgery in jackknife position: levobupivacaine-fentanyl compared to lidocaine-fentanyl].

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de Santiago, J; Santos-Yglesias, J; Girón, J; Jiménez, A; Errando, C L

2010-11-01

To compare the percentage of patients who were able to bypass the postoperative intensive care recovery unit after selective spinal anesthesia with lidocaine-fentanyl versus levobupivacaine-fentanyl for anorectal surgery in jackknife position. Randomized double-blind clinical trial comparing 2 groups of 30 patients classified ASA 1-2. One group received 18 mg of 0.6% lidocaine plus 10 microg of fentanyl while the other group received 3 mg of 0.1% levobupivacaine plus 10 microg of fentanyl. Intraoperative variables were time of start of surgery, maximum extension of sensory blockade, requirement for rescue analgesics, and hemodynamic events. The level of sensory blockade was recorded at 5, 10, and 15 minutes after the start of surgery and at the end of the procedure. The degrees of postoperative motor blockade and proprioception were recorded, as were the results of the Romberg test and whether or not the patient was able to bypass the postoperative recovery unit. Also noted were times of start of ambulation and discharge, complications, and postoperative satisfaction. Intraoperative variables did not differ significantly between groups, and all patients in both groups bypassed the postoperative recovery unit. Times until walking and discharge home, complications, and overall satisfaction after surgery were similar in the 2 groups. Both spinal anesthetic solutions provide effective, selective anesthesia and are associated with similar rates of recovery care unit bypass after anorectal surgery in jackknife position.

Changes in blood glucose level during and after light sedations using propofol-fentanyl and midazolam-fentanyl in diabetic patients who underwent cataract surgery.

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Khalighinejad, Pooyan; Rahimi, Mojtaba; Naghibi, Khosro; Niknam, Negar

2015-01-01

Surgeries may trigger the stress response which leads to changes in blood glucose level, and studies suggest that different sedation and anesthesia methods have different effects on blood glucose level. The aim of this study was to investigate changes of blood glucose levels in diabetic patients and compare them in two sedation methods of propofol + fentanyl and midazolam + fentanyl. Totally, 80 diabetic candidates for cataract surgery who had all the inclusion criteria, underwent cataract surgery using two methods of propofol (1 mg/kg/h) + fentanyl (2 μg/kg) (Group P) and midazolam (0.03 mg/kg) + fentanyl (2 μg/kg) (Group M) for light sedation. In the end, 70 patients (Group P n = 35 and Group M n = 35) remained in the study. Patients' blood glucose levels, vital signs, and hemodynamic data were assessed 30 min prior to the surgery, each 15 min during surgery and at the end of surgery. Hemodynamic parameters did not have a statistically significant difference between the two groups mean blood glucose level in Group M was 149.15 mg/dl and in Group P was 149.2 mg/dl, and based on repeated measures analysis of variance test, significant differences were not observed between the two groups (P = 0.99). T-test showed no significant differences in the blood glucose level at any time of the study between the two groups. Light sedation methods of propofol + fentanyl and midazolam + fentanyl did not have any differences in alteration of blood glucose level.

Myocardial protection induced by fentanyl in pigs exposed to high-dose adrenaline.

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da Luz, Vinicius Fernando; Otsuki, Denise Aya; Gonzalez, Maria Margarita Castro; Negri, Elnara Marcia; Caldini, Elia Garcia; Damaceno-Rodrigues, Nilsa Regina; Malbouisson, Luiz Marcelo Sá; Viana, Bruno Gonçalves; Vane, Matheus Fachini; Carmona, Maria Jose Carvalho

2015-10-01

The use of high doses of adrenaline is common in critical patients, especially during cardiac arrest. During these situations, myocardial dysfunction can be a result of multiple factors, including adrenaline use. In addition, opioids have been shown to have anti-arrhythmic and anti-ischemic mechanisms that may confer cardiac protection. This study aimed to evaluate the effects of fentanyl on myocardial function in pigs exposed to high-dose adrenaline. After institutional ethics committee approval, 26 pigs were randomly allocated to receive either 20 μg/kg fentanyl (n = 10; fentanyl group) administered 5 min before five doses of adrenaline (20 μg/kg), equivalent-volume saline (n = 10; saline group) using the same adrenaline dosing protocol, or neither fentanyl nor adrenaline (n = 6; sham group). The fentanyl group showed lower levels of troponin at the end of the sixth hour compared with the saline group (1.91 ± 1.47 vs 5.44 ± 5.35 ng/mL, P = 0.019). Transmission electron microscopy and immunohistochemistry also showed less myocardial injury in the fentanyl group. The conclusion was reached that fentanyl attenuates myocardial injury caused by high-dose adrenaline without blunting the hemodynamic effect of adrenaline. © 2015 Wiley Publishing Asia Pty Ltd.

Hypobaric bupivacaine spinal anesthesia for cystoscopic intervention: the impact of adding fentanyl.

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Atallah, Mohamed M; Helal, Mostafa A; Shorrab, Ahmed A

2003-10-01

Addition of fentanyl to hyperbaric bupivacaine spinal anesthesia prolonged the duration of sensory block. This study seeks to test the hypothesis that adding fentanyl to small dose hypobaric spinal anesthesia will improve intraoperative patients and surgeon satisfaction without delay in recovery. Patients (n = 80) subjected to minor cystoscopic surgery were randomly assigned to have spinal anesthesia with either 5 mg bupivacaine 0.1% or 5 mg bupivacaine 0.1% mixed with 20 micrograms fentanyl. The main outcome measures included intraoperative patient and endoscopist satisfaction, sedative/analgesic supplementation, postoperative side effects and time to ambulation. Patients in the bupivacaine group needed more analgesic supplementation. Analgesia was more adequate in the bupivacaine-fentanyl group. Pruritus was the main side effect in the bupivacaine fentanyl group. Ambulation and discharge of patients were nearly the same in both groups. Spinal anesthesia with small dose (5 mg) hypobaric (0.1%) bupivacaine mixed with fentanyl (20 micrograms) produced adequate anesthesia for short cystoscopic procedures with minimal side effects and without delay in ambulation.

Deaths Involving Fentanyl, Fentanyl Analogs, and U-47700 - 10 States, July-December 2016.

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O'Donnell, Julie K; Halpin, John; Mattson, Christine L; Goldberger, Bruce A; Gladden, R Matthew

2017-11-03

Preliminary estimates of U.S. drug overdose deaths exceeded 60,000 in 2016 and were partially driven by a fivefold increase in overdose deaths involving synthetic opioids (excluding methadone), from 3,105 in 2013 to approximately 20,000 in 2016 (1,2). Illicitly manufactured fentanyl, a synthetic opioid 50-100 times more potent than morphine, is primarily responsible for this rapid increase (3,4). In addition, fentanyl analogs such as acetylfentanyl, furanylfentanyl, and carfentanil are being detected increasingly in overdose deaths (5,6) and the illicit opioid drug supply (7). Carfentanil is estimated to be 10,000 times more potent than morphine (8). Estimates of the potency of acetylfentanyl and furanylfentanyl vary but suggest that they are less potent than fentanyl (9). Estimates of relative potency have some uncertainty because illicit fentanyl analog potency has not been evaluated in humans. This report describes opioid overdose deaths during July-December 2016 that tested positive for fentanyl, fentanyl analogs, or U-47700, an illicit synthetic opioid, in 10 states participating in CDC's Enhanced State Opioid Overdose Surveillance (ESOOS) program.* Fentanyl analogs are similar in chemical structure to fentanyl but not routinely detected because specialized toxicology testing is required. Fentanyl was detected in at least half of opioid overdose deaths in seven of 10 states, and 57% of fentanyl-involved deaths also tested positive for other illicit drugs, such as heroin. Fentanyl analogs were present in >10% of opioid overdose deaths in four states, with carfentanil, furanylfentanyl, and acetylfentanyl identified most frequently. Expanded surveillance for opioid overdoses, including testing for fentanyl and fentanyl analogs, assists in tracking the rapidly changing illicit opioid market and informing innovative interventions designed to reduce opioid overdose deaths.

Comparison between Infusion Pumps: Fentanyl/Ketamine and Fentanyl/Paracetamol in Pain control Following Tight and Leg Surgeries

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Behnam Mahmoodiyeh

2016-08-01

Full Text Available Background: Adjuvants such as ketamine, promethazine and paracetamol could bring up patients satisfaction and control harmful effects of opioids besides lessening their needed doses, as seen by fentanyl/paracetamol and fentanyl/ketamine combination before. The current study headed to compare paracetamol and ketamine in addition to fentanyl applied by infusion pumps in order to pain relief following major surgery.Methods: Through a double blinded randomized clinical trial, patients between18 and 65 with elective surgery for tight or leg fractures with ASA Class 1 and 2 referring to a university hospital in Arak, a town in central region of Iran, were recruited and used infusion pump for their postoperative pain control. The participants were divided into cases and controls regarding using ketamine/fentanyl (KF or paracetamol/fentanyl (PF infusion pumps.Results: The mean pain score was totally 3.87 with higher value in KF (5.06 and lower in PF (4.5 immediately after finishing surgery and getting conscious when started using infusion pump. There was no statistical difference between the groups in this regard. Concerning the side effects of the applied medications, blood pressure and heart rate had no differences comparing the groups.Conclusion: This study showed that paracetamol used in infusion pump can be brilliant in pain control after major surgeries like what done in lower extremities and joint replacement while lessens opioid use. Although paracetamol was more effective than ketamine in the current trial, more qualified studies at bigger size and in other fields of surgery beside orthopedic ones would be useful to support the effects if applicable.Keywords: Infusion pump, Ketamine, Paracetamol, Fentanyl, Postoperative pain

Administration order of midazolam/fentanyl for moderate dental sedation.

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Lobb, Douglas; Clarke, Alix; Lai, Hollis

2018-02-01

The purpose of this study is to investigate the effects of administration order when a sedative drug (midazolam) and an opioid analgesic drug (fentanyl) is applied for moderate intravenous (IV) sedation in dentistry. A retrospective chart review was conducted in one dental clinic during its transition from a midazolam-first to a fentanyl-first protocol for dental procedures requiring moderate IV sedation. Physiological parameters, drug administration times, patient recovery times, drug dosages, and patient recall and satisfaction were investigated for differences. A total of 76 charts (40 midazolam-first and 36 fentanyl-first administrations), were used in the analysis. Administering midazolam first resulted in an average 4.38 min (52%) decrease in administration times (P 0.05). Oxygen saturation levels did not drop below 90% for either group; however, 5 cases in the fentanyl-first group fell to between 90% and 92%, compared with 0 cases in the midazolam-first group. The administration order of fentanyl and midazolam may have different effects on patients and the sedation procedure. Findings from this study should be used to facilitate discussion among dental practitioners and to guide additional research investigating this topic.

Intrathecal isobaric ropivacaine-fentanyl versus intrathecal isobaric bupivacaine-fentanyl for labor analgesia: A controlled comparative double-blinded study

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Meenoti Pramod Potdar

2014-01-01

Full Text Available Context: Neuraxial analgesia and walking epidural is the popular method of practicing labor analgesia. The combination of local anesthetic and opioid is advantageous as it prolongs the duration of labor analgesia. Ropivacaine is the newer local anesthetic agent having lesser motor effects and toxic effects hence would be preferred for labor analgesia. Aims: The primary objective of the study was to assess the duration of analgesia of the intrathecal drug. The secondary objective was the assessment of onset, fixation of analgesia, motor weakness, ambulation, sedation, incidence of side-effects, maternal, and neonatal outcomes. Settings and Design: This is prospective, randomized, controlled, double-blinded, study of 120 patients consenting for labor analgesia. Subjects and Methods: A total of 120 primiparas with a singleton pregnancy in active labor who were given combined spinal epidural (CSE were included in the study. These patients were randomly allocated to three groups of 40 each and received CSE. Group F-received 25 μcg fentanyl intrathecally. Group BF-received 25 μcg fentanyl with 2.5 mg isobaric bupivacaine intrathecally. Group RF-received 25 μcg fentanyl with 2.5 mg isobaric ropivacaine intrathecally. Statistical Analysis Used: Correlations among different measurements were assessed using Pearson′s correlation coefficients, P <0.05 was considered to be statistically significant. Results: The three groups show comparable demographic data and obstetric parameters. The duration of spinal analgesia was significantly greater with Group RF 106.63 ± 17.99 min and Group BF 111.75 ± 23.58 min than the control Group F which was 60 ± 10.39 min with P = 0.001, but were comparable for Group BF and RF. The secondary outcome was comparable in all the three groups. Conclusions: The addition of bupivacaine or ropivacaine to fentanyl intrathecally increased duration and quality of analgesia, did not affect ambulation and bearing down. The

Epidural versus intravenous fentanyl for postoperative analgesia following orthopedic surgery: randomized controlled trial

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Marcelo Soares Privado

Full Text Available CONTEXT AND OBJECTIVE: Controversy exists regarding the site of action of fentanyl after epidural injection. The objective of this investigation was to compare the efficacy of epidural and intravenous fentanyl for orthopedic surgery. DESIGN AND SETTING: A randomized double-blind study was performed in Hospital São Paulo. METHODS: During the postoperative period, in the presence of pain, 29 patients were divided into two groups: group 1 (n = 14 received 100 µg of fentanyl epidurally and 2 ml of saline intravenously; group 2 (n = 15 received 5 ml of saline epidurally and 100 µg of fentanyl intravenously. The analgesic supplementation consisted of 40 mg of tenoxicam intravenously and, if necessary, 5 ml of 0.25% bupivacaine epidurally. Pain intensity was evaluated on a numerical scale and plasma concentrations of fentanyl were measured simultaneously. RESULTS: The percentage of patients who required supplementary analgesia with tenoxicam was lower in group 1 (71.4% than in group 2 (100%: 95% confidence interval (CI = 0.001-0.4360 (P = 0.001, Fisher's exact test; relative risk, RR = 0.07. Epidural bupivacaine supplementation was also lower in group 1 (14.3% than in group 2 (53.3%: 95% CI = 0.06-1.05 (P = 0.03, Fisher's exact test; RR = 0.26. There was no difference in pain intensity on the numerical scale. Mean fentanyl plasma concentrations were similar in the two groups. CONCLUSION: Intravenous and epidural fentanyl appear to have similar efficacy for reducing pain according to the numerical scale, but supplementary analgesia was needed less frequently when epidural fentanyl was used. CLINICAL TRIAL REGISTRATION NUMBER: NCT00635986

Intrathecal sufentanil versus fentanyl for lower limb surgeries - A randomized controlled trial

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Poonam Motiani

2011-01-01

Full Text Available Background:To compare the efficacy and safety of intrathecal sufentanil or fentanyl as adjuvants to hyperbaric bupivacaine in patients undergoing major orthopaedic lower limb surgeries in terms of onset and duration of sensory block, motor block and post-operative pain relief. Patients & Methods: Ninety patients were recruited in this Prospective, randomized double blind study to receive either intrathecal sufentanil 5 μg (Group S, fentanyl 25 μg (Group F or normal saline 0.5 ml (Group C as adjuvants to 15 mg of 0.5% hyperbaric bupivacaine. The onset and duration of sensory and motor block were assessed intraoperatively. The pain scores were assessed postoperatively. Duration of complete and effective analgesia was recorded. The incidence of side effects such as nausea, vomiting, pruritus, shivering and PDPH was recorded. Results: The Demographic data, hemodynamic and respiratory parameters were comparable in the three groups. There was a significantly earlier onset and prolonged duration of sensory block in the sufentanil and fentanyl groups. The duration of complete and effective analgesia were also significantly prolonged in the fentanyl and sufentanil groups. Pruritus was noticed in the study groups (Groups S&F. Conclusions: Intrathecal sufentanil (5 μg and fentanyl (25 μg, as adjuvants lead to an earlier onset and prolonged duration of sensory block. The duration of effective analgesia with intrathecal sufentanil and fentanyl as adjuvants to hyperbaric bupivacaine is longer than that of bupivacaine alone.

Transdermal hyoscine induced unilateral mydriasis.

LENUS (Irish Health Repository)

Hannon, Breffni

2012-03-20

The authors present a case of unilateral mydriasis in a teenager prescribed transdermal hyoscine hydrobromide (scopolamine) for chemotherapy induced nausea and vomiting. The authors discuss the ocular side-effects associated with this particular drug and delivery system and the potential use of transdermal hyoscine as an antiemetic agent in this group.

A COMPARATIVE STUDY OF INTRATHECAL DEXMEDETOMIDINE AND FENTANYL AS ADJUVANTS TO BUPIVACAINE

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Gollapalli Hanumanth

2016-02-01

Full Text Available INTRODUCTION Uncontrolled postoperative pain may produce a range of detrimental acute and chronic effects. Spinal anaesthesia provided by bupivacaine may be too short for providing postoperative analgesia. This study is conducted to evaluate the efficacy of intrathecal fentanyl and intrathecal dexmedetomidine as an adjuvant to hyperbaric bupivacaine with regards to the onset and duration of sensory and motor blockade, as well as postoperative analgesia and adverse effects. Hundred patients aged 18-55 years were randomly divided into two groups, each group consisting of 50 patients of either sex belonging to ASA class I and II posted for elective lower abdominal surgeries were given spinal anaesthesia using bupivacaine 0.5%, heavy 2.5 ml with either fentanyl 25µg (group F or 5µg of preservative free dexmedetomidine (group D. Assessment of the sensory and motor blockade were done at the end of each minute till the maximum level achieved. Measurement of blood pressure, pulse rate, respiratory rate and arterial oxygen saturation were obtained. Postoperatively the patients were observed for the duration of analgesia, time taken for complete regression of sensory blockade to S1 and time taken for complete recovery of motor power. RESULTS Our results showed a statistically highly significant prolongation of sensory and motor blockade, and postoperative analgesia in the dexmedetomidine group compared to the fentanyl group. In dexmedetomidine group four out of fifty patients, and in fentanyl group two out of fifty patients developed hypotension. In dexmedetomidine group five out of fifty patients, and in fentanyl group two out of fifty patients developed bradycardia. Incidence of pruritis is significantly high in fentanyl group.

Characterizing fentanyl use in methadone-maintained clients.

Science.gov (United States)

Arfken, Cynthia L; Suchanek, Jessica; Greenwald, Mark K

2017-04-01

Deaths attributed to fentanyl have increased in the United States. However, little is known about fentanyl use among substance abuse treatment clients. To fill this gap, we assessed prevalence of fentanyl exposure, characteristics of clients testing positive for fentanyl, other substances detected concurrently or simultaneously with fentanyl, and clients' perception of how many people are actively seeking to use fentanyl. A retrospective chart review was conducted of all clients at one methadone maintenance treatment clinic between January 2015 and May 2016 in Wayne County, Michigan. Urine drug screens (UDS) including fentanyl (and its metabolite norfentanyl) were conducted clinically. To obtain additional data, 113 clients in this clinic subsequently completed an anonymous survey. Of 368 unique clients with UDS, 38.0% had at least one and 26.1% had ≥2 fentanyl-positive UDS results. None had a fentanyl prescription. Clients ever testing positive for fentanyl were significantly (pFentanyl-positive UDS results coincided most commonly with metabolites of cocaine- and heroin-positive UDS results. Of the anonymously surveyed clients, most (67.3%) reported they did not know anyone seeking fentanyl, a proportion significantly higher than for heroin, cocaine, alprazolam, hydrocodone and morphine. Fentanyl was commonly detected during this period with some clients having multiple fentanyl-positive UDS. Most clients did not know anyone seeking to obtain fentanyl. Regardless, the high exposure underscores that naloxone training and distribution is needed. Copyright © 2017 Elsevier Inc. All rights reserved.

COMPARISON OF INTRAMUSCULAR FENTANYL-MIDAZOLAM, FENTANYL-MIDAZOLAM-KETAMINE, AND KETAMINE-MEDETOMIDINE FOR IMMOBILIZATION OF JAPANESE MACAQUES ( MACACA FUSCATA).

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Ølberg, Rolf-Arne; Sinclair, Melissa; Barker, Ian K; Crawshaw, Graham

2018-03-01

The combination of fentanyl and midazolam is commonly used as a sedative in humans. The objective of this study was to evaluate the sedative properties and physiological effects of fentanyl-midazolam and fentanyl-midazolam-ketamine compared with medetomidine-ketamine given intramuscularly in Japanese macaques ( Macaca fuscata). In a randomized crossover design, eight Japanese macaques were hand-injected with either 30 μg/kg fentanyl + 0.3 mg/kg midazolam (FM), 15 μg/kg fentanyl + 0.3 mg/kg midazolam + 5.0 mg/kg ketamine (FMK), or 0.05 mg/kg medetomidine + 5.0 mg/kg ketamine (MedK). Heart rate; indirect systolic, mean, and diastolic arterial pressure; respiratory rate; blood gas concentrations; rectal temperature; and duration of immobilization were recorded. Mixed linear models were used to evaluate the effects of drug treatment on all continuous variables, with a significance level of P < 0.05. Only three of seven animals receiving FM were successfully immobilized. All eight animals in both the FMK and MedK treatment groups had a rapid, smooth induction and were successfully immobilized. Both FMK and MedK treatments resulted in significant hypoxia and the animals required supplemental oxygen via face mask. The mean duration of FMK immobilization was 42 ± 10 min, significantly shorter than the 65 ± 14 min for the animals receiving MedK. Immobilization with MedK resulted in significantly lower heart rates, and significantly higher arterial pressure compared with FMK. Hypoventilation was significantly more pronounced in FMK-treated animals compared with MedK treatments. Immobilization with FMK resulted in a gradual, slow recovery whereas MedK-treated animals woke up more rapidly. Fentanyl-midazolam alone is not a useful sedative in Japanese macaques. A combination of fentanyl and midazolam with ketamine can be used as an alternative to medetomidine-ketamine in this species.

Avaliação do efeito antinociceptivo do fentanil transdérmico no controle da dor lombar pós-operatória Evaluación del efecto antinociceptivo del fentanil transdérmico en el control del dolor lumbar postoperatorio Efficacy of fentanyl transdermal delivery system for acute postoperative pain after posterior laminectomy

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Gabriela Rocha Lauretti

2009-12-01

ía posterior sobre anestesia general estandarizada. Los adhesivos transdérmicos fueron colocados en los pacientes diez horas antes del inicio de la cirugía y removidos 24 horas después de haber terminado la misma. Cetoprofeno por vía venosa fue administrado por vía venosa en el inicio de la cirugía. Dipirona estaba disponible para analgesia de rescate, si era necesario, a intervalos mínimos de seis horas. RESULTADOS: los pacientes que recibieron F transdérmico presentaron reducción de 60% en el consumo de dipirona en el periodo postoperatorio (pObjectives: patients who are submitted to posterior laminectomy often complain of severe pain that is difficult to treat. The transdermal application of the potent opioid fentanyl results in its continuous liberation and consequently could be useful in controlling the pain. This study evaluated the efficacy of transdermal fentanyl (F delivery system for acute postoperative pain after posterior laminectomy. METHODS: the study was approved by the local Ethic Committee and conducted in the Teaching Hospital. After the patient's consent, 24 patients were randomized to either transdermic F 25 mg/h (n=12 or transdermic placebo (n=12. All patients were submitted to posterior laminectomy under a standard general anesthesia. Transdermic systems were placed during 10 hours preoperatively and removed 24 hours later; 20 minute IV ketoprofen, 2.5 mg/kg was administered following traqueal intubation with propofol, alfentanil and atracurium. IV 20 mg/kg dipyrone act as rescue at a minimum six hours interval. Data was recorded for 36 hours. RESULTS: the transdermic F Group showed 60% of reduction in the rescue dipyrone consumption (p<0.05; and displayed lesser VAS scores after the 12th hour, which was maintained until the 36th hour (p<0.02. All physiological parameters fluctuated within normal range and no differences were observed between the treatments. The incidence of adverse events was similar between the groups, there was local erythema

Chronological age affects the permeation of fentanyl through human skin in vitro

DEFF Research Database (Denmark)

Holmgaard, R; Benfeldt, E; Sorensen, J A

2013-01-01

AIM: To study the influence of chronological age on fentanyl permeation through human skin in vitro using static diffusion cells. Elderly individuals are known to be more sensitive to opioids and obtain higher plasma concentrations following dermal application of fentanyl compared to younger...... individuals. The influence of age - as an isolated pharmacokinetic term - on the absorption of fentanyl has not been previously studied. METHOD: Human skin from 30 female donors was mounted in static diffusion cells, and samples were collected during 48 h. Donors were divided into three age groups: ... and old age groups: 5,922 and 4,050 ng, respectively). Furthermore, the lag time and absorption rate were different between the three groups, with a significantly higher rate in the young participants versus the oldest participants. CONCLUSION: We demonstrate that fentanyl permeates the skin of young...

Clinical efficacy of dexmedetomidine in the diminution of fentanyl dosage in pediatric cardiac surgery.

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Sun, Yingying; Ye, Hongwu; Xia, Yin; Li, Yuanhai; Yuan, Xianren; Wang, Xing

2017-06-01

This study aims to explore the clinical efficacy of dexmedetomidine (DEX) in the diminution of fentanyl dosage in pediatric cardiac surgery based on some clinical and biochemical parameters. Fifty pediatric patients (American Society of Anesthesiologists II), 1-6 years old, were randomly allocated into two groups: group F (control group), in which patients received normal saline and high dosage of fentanyl (30 μg/kg), and group D, in which patients were given DEX and low dosage of fentanyl (15 μg/kg). Some hemodynamic and clinical parameters of the two groups were recorded. Furthermore, stress hormone (serum cortisol, norepinephrine, blood glucose) levels and cytokine (interleukin 6, tumor necrosis factor alpha) levels in the two groups were compared with each other. Stress hormone levels, cytokine levels, hemodynamic parameters and the consumption of sevoflurane did not differ between the two groups. Meanwhile, the extubation time was significantly shorter in Group D than F (Pfentanyl supplemented with DEX almost had the same anesthesia effects and inflammation extent compared with high dose of fentanyl, which suggested that infusion DEX might decrease fentanyl consumption in pediatric cardiac surgery.

An LC-MS-MS Method for the Analysis of Carfentanil, 3-Methylfentanyl, 2-Furanyl Fentanyl, Acetyl Fentanyl, Fentanyl and Norfentanyl in Postmortem and Impaired-Driving Cases.

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Sofalvi, Szabolcs; Schueler, Harold E; Lavins, Eric S; Kaspar, Claire K; Brooker, Ian T; Mazzola, Carrie D; Dolinak, David; Gilson, Thomas P; Perch, Steve

2017-07-01

In July of 2016, carfentanil (CF) emerged in Northeast Ohio resulting in over 25 deaths within a 30-day period. A total of 125 deaths have occurred in Summit County and Cuyahoga County has reported 40 deaths, relating to the presence of CF either alone, or in combinations with heroin and fentanyl. Prior to this surge in CF cases, positive fentanyl enzyme-linked immunosorbent assay (ELISA) screening results were increasing in number. Many were negative for fentanyl confirmation by gas chromatography-mass spectrometry. Fentanyl analogs such as CF, acetyl fentanyl (AF), 2-furanyl fentanyl (2-Fu-F) and 3-methylfentanyl (3-MF) may be present in these cases. Some fentanyl analogs like CF and 3-MF do not cross-react with the Immunalysis ELISA fentanyl assay. With the emergence of potent synthetic fentanyl analogs, questions arose as to how to interpret their very low concentrations or absence in the blood in relation to cause of death. Driving under the influence of drugs (DUID) blood specimens had also tested positive for CF by reference laboratories. A liquid chromatography-tandem mass spectrometry method was developed to identify and quantify fentanyl, norfentanyl (NF) and four analogs: AF, 2-Fu-F, 3-MF and CF. The method has been utilized to quantify these fentanyl analogs in blood and vitreous humor in authentic antemortem and postmortem cases. Calibration curves were established between 0.10-4.0 ng/mL (NF, AF, 3-MF, 2-Fu-F and CF) and 1.0-40 ng/mL for fentanyl. In total, 98 postmortem cases analyzed produced the following blood concentration ranges: CF (0.11-0.88 ng/mL), 3-MF (0.15-1.7 ng/mL), 2-Fu-F (0.15-0.30 ng/mL), AF (0.14-0.16 ng/mL), fentanyl (1.1-15 ng/mL) and NF (0.10-3.7 ng/mL). Only CF, fentanyl and NF were detected in a statistically significant subset DUID population of 26 cases producing concentration ranges between 0.11 and 0.47 ng/mL, 1.0 and 9.8 ng/mL, and 0.11 and 3.5 ng/mL, respectively. © The Author 2017. Published by Oxford University Press

Effect of fentanyl on 125I-β-CIT uptake in mice brain

International Nuclear Information System (INIS)

Liu Xingdang; Lin Xiangtong

2003-01-01

Objective: To investigate the effect of fentanyl on 125 I-2β-carbomethoxy-3β-(4-iodophenyl) tropane ( 125 I-β-CIT) uptake in mice brain. Methods: 1) KM mice groups of five were given different doses of fentanyl, and 10 min or 1 h later were given a dose of 125 I-β-CIT. 2)Two groups of animals were killed at 2 h after injection of 125 I-β-CIT. 3)One group of animals were killed at 1 h after injection of 125 I-β-CIT. Results: 1)In the striatum, frontal cortex, hippocampus, brain stem, cerebellum and whole brain, a dose-dependent increase in uptake (%ID/g or %ID) of 125 I-β-CIT was detected at the fentanyl doses ranging from 125 to 300 μg/kg, and the uptakes of hippocampus and cerebellum were higher than that of the controls. There was a great difference in the value of %ID/g or %ID between the group treated with 250 μg/kg fentanyl and the control group; while at the doses from 12.5 to 100 μg/kg, a dose-dependent decrease in uptake in the same regions was observed and all the uptake levels were lower (hippocampus: except 62.5 and 12.5 μg/kg groups; brain stem: except 62.5 μg/kg group) than that of the controls. 2)The uptakes of 125 I-β-CIT in the striatum, frontal cortex, hippocampus, brain stem, cerebellum and whole brain in the groups injected with 125 I-β-CIT 10 min after fentanyl treatment were higher than that in the groups injected with 125 I-β-CIT 1 h after fentanyl treatment. 3)The binding of 125 I-β-CIT in the striatum, frontal cortex, hippocampus, brain stem, cerebellum and whole brain in the groups killed at 1 h after injection of 125 I-β-CIT was higher than that in the control group, but without significant difference. Conclusion: Fentanyl may have different effects on 125 I-β-CIT at various time points and doses

Danish pain specialists' rationales behind the choice of fentanyl transdermal patches and oral transmucosal systems-A Delphi study

DEFF Research Database (Denmark)

Jacobsen, Ramune; Møldrup, Claus; Christrup, Lona

2009-01-01

survey. Response rates were 45% in the brainstorming and 88% in the rating phases, respectively. Statistical analysis with SPSS for Windows 15.00 included descriptive statistics and factor analysis. Results. The most important rationale to choose fentanyl patches was that patients' clinical condition did...

Postmortem Toxicology Findings of Acetyl Fentanyl, Fentanyl, and Morphine in Heroin Fatalities in Tampa, Florida

OpenAIRE

Pearson, Julia; Poklis, Justin; Poklis, Alphonse; Wolf, Carl; Mainland, Mary; Hair, Laura; Devers, Kelly; Chrostowski, Leszek; Arbefeville, Elise; Merves, Michele

2015-01-01

In the last two years, an epidemic of 40 fatal heroin overdose cases has occurred in the Tampa area of Florida. Of these cases, 14 involved fentanyl and acetyl fentanyl. Victim demographics, case histories, toxicology findings, and causes and manners of death for all 40 deaths are presented. In 26 deaths in which acetyl fentanyl or fentanyl were not involved, free and total peripheral blood morphine concentrations were consistent with fatal heroin intoxications, averaging 0.16 mg/L and 0.35 m...

Heroin and fentanyl overdoses in Kentucky: Epidemiology and surveillance.

Science.gov (United States)

Slavova, Svetla; Costich, Julia F; Bunn, Terry L; Luu, Huong; Singleton, Michael; Hargrove, Sarah L; Triplett, Jeremy S; Quesinberry, Dana; Ralston, William; Ingram, Van

2017-08-01

The study aims to describe recent changes in Kentucky's drug overdose trends related to increased heroin and fentanyl involvement, and to discuss future directions for improved drug overdose surveillance. The study used multiple data sources (death certificates, postmortem toxicology results, emergency department [ED] records, law enforcement drug submissions, and prescription drug monitoring records) to describe temporal, geographic, and demographic changes in drug overdoses in Kentucky. Fentanyl- and heroin-related overdose death rates increased across all age groups from years 2011 to 2015 with the highest rates consistently among 25-34-year-olds. The majority of the heroin and fentanyl overdose decedents had histories of substantial exposures to legally acquired prescription opioids. Law enforcement drug submission data were strongly correlated with drug overdose ED and mortality data. The 2016 crude rate of heroin-related overdose ED visits was 104/100,000, a 68% increase from 2015 (62/100,000). More fentanyl-related overdose deaths were reported between October, 2015, and September, 2016, than ED visits, in striking contrast with the observed ratio of >10 to 1 heroin-related overdose ED visits to deaths. Many fatal fentanyl overdoses were associated with heroin adulterated with fentanyl; fentanyl and other synthetic drugs. In order to inform coordinated public health and safety responses, drug overdose surveillance must move from a reactive to a proactive mode, utilizing the infrastructure for electronic health records. Copyright © 2017 Elsevier B.V. All rights reserved.

Acetyl Fentanyl Toxicity: Two Case Reports.

Science.gov (United States)

Fort, Chelsea; Curtis, Byron; Nichols, Clay; Niblo, Cheryl

2016-11-01

Acetyl fentanyl is an illicit fentanyl analog recently appearing in forensic casework. A quantitative method was created for measuring acetyl fentanyl in various biological matrices acquired post-mortem due to recent positive screening results in casework. Initial detection by immunoassay and standard gas chromatography mass spectrometry (GC/MS) methods have been previously reported for acetyl fentanyl and are examined further here. A Selective Ion Monitoring (SIM) method was created using a GC/MS for quantitation. In two separate cases, acetyl fentanyl was found to be in similar concentrations to those previously reported and ruled to be the cause of death. Acetyl fentanyl concentrations were determined in blood samples, liver, brain, vitreous humor, and urine. Individual 1 had acetyl fentanyl concentrations as follows: heart blood-285 ng/mL, femoral blood-192 ng/mL, liver-1,100 ng/g, brain-620 ng/g, and urine-3,420 ng/mL. Individual 2 had acetyl fentanyl concentrations as follows: heart blood-210 ng/mL, femoral blood-255 ng/mL, urine-2,720 ng/mL and vitreous humor-140 ng/mL. Experimental conditions for screening and quantitation are provided, using immunoassay and GC/MS methods. Due to the recent emergence of acetyl fentanyl, more data will need to be generated to fully differentiate recreational and fatal concentrations of acetyl fentanyl to assist toxicologists accurately understanding its physiological impact. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Perspectives on Transdermal Electroporation

Science.gov (United States)

Ita, Kevin

2016-01-01

Transdermal drug delivery offers several advantages, including avoidance of erratic absorption, absence of gastric irritation, painlessness, noninvasiveness, as well as improvement in patient compliance. With this mode of drug administration, there is no pre-systemic metabolism and it is possible to increase drug bioavailability and half-life. However, only a few molecules can be delivered across the skin in therapeutic quantities. This is because of the hindrance provided by the stratum corneum. Several techniques have been developed and used over the last few decades for transdermal drug delivery enhancement. These include sonophoresis, iontophoresis, microneedles, and electroporation. Electroporation, which refers to the temporary perturbation of the skin following the application of high voltage electric pulses, has been used to increase transcutaneous flux values by several research groups. In this review, transdermal electroporation is discussed and the use of the technique for percutaneous transport of low and high molecular weight compounds described. This review also examines our current knowledge regarding the mechanisms of electroporation and safety concerns arising from the use of this transdermal drug delivery technique. Safety considerations are especially important because electroporation utilizes high voltage pulses which may have deleterious effects in some cases. PMID:26999191

Isoflurane minimum alveolar concentration reduction by fentanyl.

Science.gov (United States)

McEwan, A I; Smith, C; Dyar, O; Goodman, D; Smith, L R; Glass, P S

1993-05-01

Isoflurane is commonly combined with fentanyl during anesthesia. Because of hysteresis between plasma and effect site, bolus administration of fentanyl does not accurately describe the interaction between these drugs. The purpose of this study was to determine the MAC reduction of isoflurane by fentanyl when both drugs had reached steady biophase concentrations. Seventy-seven patients were randomly allocated to receive either no fentanyl or fentanyl at several predetermined plasma concentrations. Fentanyl was administered using a computer-assisted continuous infusion device. Patients were also randomly allocated to receive a predetermined steady state end-tidal concentration of isoflurane. Blood samples for fentanyl concentration were taken at 10 min after initiation of the infusion and before and immediately after skin incision. A minimum of 20 min was allowed between the start of the fentanyl infusion and skin incision. The reduction in the MAC of isoflurane by the measured fentanyl concentration was calculated using a maximum likelihood solution to a logistic regression model. There was an initial steep reduction in the MAC of isoflurane by fentanyl, with 3 ng/ml resulting in a 63% MAC reduction. A ceiling effect was observed with 10 ng/ml providing only a further 19% reduction in MAC. A 50% decrease in MAC was produced by a fentanyl concentration of 1.67 ng/ml. Defining the MAC reduction of isoflurane by all the opioids allows their more rational administration with inhalational anesthetics and provides a comparison of their relative anesthetic potencies.

In vivo real-time monitoring system of electroporation mediated control of transdermal and topical drug delivery.

Science.gov (United States)

Blagus, Tanja; Markelc, Bostjan; Cemazar, Maja; Kosjek, Tina; Preat, Veronique; Miklavcic, Damijan; Sersa, Gregor

2013-12-28

Electroporation (EP) is a physical method for the delivery of molecules into cells and tissues, including the skin. In this study, in order to control the degree of transdermal and topical drug delivery, EP at different amplitudes of electric pulses was evaluated. A new in vivo real-time monitoring system based on fluorescently labeled molecules was developed, for the quantification of transdermal and topical drug delivery. EP of the mouse skin was performed with new non-invasive multi-array electrodes, delivering different amplitudes of electric pulses ranging from 70 to 570 V, between the electrode pin pairs. Patches, soaked with 4 kDa fluorescein-isothiocyanate labeled dextran (FD), doxorubicin (DOX) or fentanyl (FEN), were applied to the skin before and after EP. The new monitoring system was developed based on the delivery of FD to and through the skin. FD relative quantity was determined with fluorescence microscopy imaging, in the treated region of the skin for topical delivery and in a segment of the mouse tail for transdermal delivery. The application of electric pulses for FD delivery resulted in enhanced transdermal delivery. Depending on the amplitude of electric pulses, it increased up to the amplitude of 360 V, and decreased at higher amplitudes (460 and 570 V). Topical delivery steadily enhanced with increasing the amplitude of the delivered electric pulses, being even higher than after tape stripping used as a positive control. The non-invasive monitoring of the delivery of DOX, a fluorescent chemotherapeutic drug, qualitatively and quantitatively confirmed the effects of EP at 360 and 570 V pulse amplitudes on topical and transdermal drug delivery. Delivery of FEN at 360 and 570 V pulse amplitudes verified the observed effects as obtained with FD and DOX, by the measured physiological responses of the mice as well as FEN plasma concentration. This study demonstrates that with the newly developed non-invasive multi-array electrodes and with the

Intravenous ketamine is as effective as midazolam/fentanyl for procedural sedation and analgesia in the emergency department.

Science.gov (United States)

Jamal, S M; Fathil, S M; Nidzwani, M M; Ismail, A K; Yatim, F M

2011-08-01

The study compared the effectiveness of ketamine and midazolam/fentanyl as procedural sedation and analgesia agents for reduction of fractures and dislocated joints. Forty-one adult patients were enrolled by convenience sampling. They were randomized to receive ketamine or midazolam/fentanyl. Depth of sedation, pain score, procedural outcome and memory of the procedure were documented. The ketamine group had deeper sedation, but there was no statistical difference in other variables between the two groups. Three patients in the midazolam/fentanyl group had oxygen desaturation. More adverse effects were associated with ketamine. Intravenous ketamine is as effective as midazolam/fentanyl for procedural sedation.

Transdermal nitroglycerine enhances postoperative analgesia of intrathecal neostigmine following abdominal hysterectomies

Directory of Open Access Journals (Sweden)

Fareed Ahmed

2010-01-01

Full Text Available This study was carried out to assess the effect of nitroglycerine (transdermal on intrathecal neostigmine with bupivacaine on postoperative analgesia and note the incidence of adverse effects, if any. After taking informed consent, 120 patients of ASA Grade I and II were systematically randomised into four groups of 30 each. Patients were premedicated with midazolam 0.05 mg/kg intravenously and hydration with Ringer′s lactate solution 10ml/kg preoperatively in the holding room. Group I patients received Intrathecal injection of 15 mg bupivacaine with 1ml of normal saline and transdermal placebo patch. Group II patients received Intrathecal injection of 15 mg bupivacaine with 5 mcg of neostigmine and transdermal placebo patch. Group III patients received Intrathecal injection of 15 mg bupivacaine with 1ml of normal saline with transdermal nitroglycerine patch (5 mg/24 hours. Group IV patients received Intrathecal injection of 15 mg bupivacaine with 5mcg of neostigmine and transdermal nitroglycerine patch (5 mg/24 hours, applied on a non anaesthetised area after 20 minutes. Groups were demographically similar and did not differ in intraoperative characteristics like sensory block, motor block, haemodynamic parameters and SpO 2 . The mean duration of analgesia was 202.17 minutes, 407.20 minutes, 207.53 minutes and 581.63 minutes in control group (I, neostigmine group (II, nitroglycerine group (III and nitroglycerine neostigmine group (IV respectively (P< 0.01. To conclude, our results show that transdermal nitroglycerine itself does not show any analgesic potential but it enhances the analgesic potential of intrathecal neostigmine.

Pharmacokinetics and safety of fentanyl sublingual spray and fentanyl citrate intravenous: a multiple ascending dose study in opioid-naïve healthy volunteers.

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Rauck, Richard L; Oh, D Alexander; Singla, Neil; Koch, Christian; Parikh, Neha; Nalamachu, Srinivas; Wilson, Daniel; Yu, Jin; Vetticaden, Santosh

2017-11-01

Fentanyl sublingual spray, with its rapid onset for pain relief, may be efficacious in the management of acute or post-operative pain. Because patients in these settings may be opioid-naïve, the study was conducted to determine the safety, tolerability, and pharmacokinetics of multiple dose administration of fentanyl sublingual spray in an opioid-naïve population. Fentanyl sublingual spray (100 mcg, 200 mcg, and 400 mcg) and fentanyl citrate intravenous (IV; 50 mcg) were administered every 0.5, 1.0, 2.0, and 4.0 h for up to three doses per cohort in opioid-naïve subjects (ClinicalTrials.gov identifier: NCT02641340). Eight subjects in each cohort were randomly assigned (six subjects received fentanyl sublingual spray; two subjects received fentanyl citrate IV). Pharmacokinetic and safety-related pharmacodynamic assessments were performed through 24 h post-first dose. Safety assessments were collected through Day 7. Ninety-six opioid-naïve subjects, aged 20-55 years, with a body mass index of 18.7-31.5 kg/m 2 , participated in the study. Multiple doses of fentanyl sublingual spray (100, 200, and 400 mcg) were generally well tolerated. Hypoxia, observed in the 200-mcg and 400-mcg dose groups, increased with increasing doses and higher dosing frequency, but was readily managed by nasal cannula oxygenation. Overall, nausea increased with increasing doses, and ∼52.6% (10 out of 19) cases of nausea that occurred at the highest dose of 400 mcg were treated with concomitant medication. Overall, the reported adverse events were consistent with the known safety profile of fentanyl. Fentanyl sublingual spray (100 mcg, 200 mg, and 400 mcg) administered every 0.5, 1, 2, and 4 h was generally well tolerated in an opioid-naïve population. The results suggest that doses of 200 mcg or lower may be safe for use in an opioid-naïve population.

Knee strength retention and analgesia with continuous perineural fentanyl infusion after total knee replacement: randomized controlled trial.

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Mangar, Devanand; Karlnoski, Rachel A; Sprenker, Collin J; Downes, Katheryne L; Taffe, Narrene; Wainwright, Robert; Gustke, Kenneth; Bernasek, Thomas L; Camporesi, Enrico

2014-04-01

Despite providing adequate pain relief, a femoral nerve block can induce postoperative muscle weakness after total knee arthoplasty (TKA). Fentanyl has been shown to have peripheral effects but has not been used as a perineural infusate alone after TKA. Sixty patients scheduled for TKA were randomized to one of three blinded groups: a continuous 24 h infusion of either fentanyl 3 μg/ml, ropivacaine 0.1%, or 0.9% normal saline through a femoral nerve sheath catheter at 10 ml/h. The main outcome was maximum voluntary isometric contraction (MVIC) in the quadriceps femoris (knee extension), measured by a handheld dynamometer (Nm/kg). Other variables assessed were preoperative and postoperative visual analog scale (VAS) scores, hamstrings MVIC (knee flexion), active range of motion of the operative knee, distance ambulated, incidence of knee buckling, supplemental morphine usage, postoperative side effects, and serum fentanyl levels. Quadriceps MVIC values were significantly greater in the fentanyl group compared to the group that received ropivacaine (median values, 0.08 vs. 0.03 Nm/kg; p = 0.028). The incidence of postoperative knee buckling upon ambulation was higher in the ropivacaine group compared to the fentanyl group, although not statistically significant (40% vs. 15 %, respectively; p = 0.077). VAS scores while ambulating were not significantly different between the fentanyl group and the ropivacaine group (p = 0.270). Postoperative morphine consumption, nausea and vomiting, and resting VAS scores were similar among the three groups. A continuous perineural infusion of fentanyl produced greater strength retention than ropivacaine post-TKA.

Demonstration of analgesic effect of intranasal ketamine and intranasal fentanyl for postoperative pain after pediatric tonsillectomy.

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Yenigun, Alper; Yilmaz, Sinan; Dogan, Remzi; Goktas, Seda Sezen; Calim, Muhittin; Ozturan, Orhan

2018-01-01

Tonsillectomy is one of the oldest and most commonly performed surgical procedure in otolaryngology. Postoperative pain management is still an unsolved problem. In this study, our aim is to demonstrate the efficacy of intranasal ketamine and intranasal fentanyl for postoperative pain relief after tonsillectomy in children. This randomized-controlled study was conducted to evaluate the effects of intranasal ketamine and intranasal fentanyl in children undergoing tonsillectomy. Tonsillectomy performed in 63 children were randomized into three groups. Group I received: Intravenous paracetamol (10 mg/kg), Group II received intranasal ketamine (1.5 mg/kg ketamine), Group III received intranasal fentanyl (1.5 mcg/kg). The Children's Hospital of Eastern Ontario Pain Scale (CHEOPS) and Wilson sedation scale scores were recorded at 15, 30, 60 min, 2 h, 6hr, 12 h and 24 h postoperatively. Patients were interviewed on the day after surgery to assess the postoperative pain, nightmares, hallucinations, nausea, vomiting and bleeding. Intranasal ketamine and intranasal fentanyl provided significantly stronger analgesic affects compared to intravenous paracetamol administration at postoperative 15, 30, 60 min and at 2, 6, 12 and 24 h in CHEOPS (p ketamine administration group. No such sedative effect was seen in the groups that received intranasal fentanyl and intravenous paracetamol in Wilson Sedation Scale (p ketamine and intranasal fentanyl were more effective than paracetamol for postoperative analgesia after pediatric tonsillectomy. Sedative effects were observed in three patients with the group of intranasal ketamine. There was no significant difference in the efficacy of IN Ketamine and IN Fentanyl for post-tonsillectomy pain. Copyright © 2017 Elsevier B.V. All rights reserved.

Crystallographic and theoretical studies of an inclusion complex of β-cyclodextrin with fentanyl.

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Ogawa, Noriko; Nagase, Hiromasa; Loftsson, Thorsteinn; Endo, Tomohiro; Takahashi, Chisato; Kawashima, Yoshiaki; Ueda, Haruhisa; Yamamoto, Hiromitsu

2017-10-15

The crystal structure of an inclusion complex of β-cyclodextrin (β-CD) with fentanyl was determined by single crystal X-ray diffraction analysis. The crystal belongs to the triclinic space group P1 and the complex comprises one fentanyl, two β-CD, and several water molecules. β-CD and fentanyl form a host-guest inclusion complex at a ratio of 2:1 and the asymmetric unit of the complex contains two host molecules (β-CDs) in a head-to-head arrangement that form dimers through hydrogen bonds between the secondary hydroxyl groups of β-CD and one guest molecule. Fentanyl is totally contained within the β-CD cavity and the structure of the phenylethyl part of fentanyl inside the dimeric cavity of the complex is disordered. Furthermore, theoretical molecular conformational calculations were conducted to clarify the mobility of the guest molecule in the β-CD cavity using CONFLEX software. Crystal optimization and crystal energy calculations were also conducted. The results of the theoretical calculations confirmed that the conformation of disorder part 1, which was high in occupancy by crystal structure analysis, was more stable. The phenylethyl part of fentanyl existed in several stable conformations. Copyright © 2017 Elsevier B.V. All rights reserved.

The fentanyl concentration required for immobility under propofol anesthesia is reduced by pre-treatment with flurbiprofen axetil.

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Kodaka, Mitsuharu; Tsukakoshi, Mikiko; Miyao, Hideki; Tsuzaki, Koichi; Ichikawa, Junko; Komori, Makiko

2013-12-01

We hypothesized that nonsteroidal anti-inflammatory drugs decrease the plasma fentanyl concentration required to produce immobility in 50% of patients in response to skin incision (Cp50incision) compared with placebo under target-controlled infusion (TCI) propofol anesthesia. Sixty-two unpremedicated patients scheduled to undergo gynecologic laparoscopy were randomly assigned to receive placebo (control group) or flurbiprofen axetil 1 mg·kg(-1) (flurbiprofen group) preoperatively. General anesthesia was induced with fentanyl and propofol, and intubation was performed after succinylcholine 1 mg·kg(-1). Propofol was administered via a target-controlled infusion (TCI) system (Diprifusor™) set at an effect-site concentration of 5 μg·mL(-1). Fentanyl was given by a TCI system using the STANPUMP software (Schafer model). The concentration for the first patient was set at 3 ng·mL(-1) and modified in each group according to the up-down method. Skin incision was performed after more than ten minutes equilibration time. Serum fentanyl concentration, bispectral index (BIS), and hemodynamic parameters were measured two minutes before and after skin incision. The Cp50incision of fentanyl was derived from the mean of the crossovers (i.e., the serum fentanyl concentrations of successive participants who responded and those who did not or vice versa). Ten and 11 independent crossover pairs were collected in the control and flurbiprofen groups, respectively, representing 42 of 62 enrolled patients. The mean (SD) fentanyl Cp50incision was less in the flurbiprofen group [0.84 (0.63) ng·mL(-1)] than in the control group [1.65 (1.15) ng·mL(-1)]; P = 0.007; however, there were no differences in BIS, blood pressure, or heart rate, between groups. Preoperative flurbiprofen axetil decreased the Cp50incision of fentanyl by 49% during propofol anesthesia without changing the BIS or hemodynamic variables.

Fentanyl Ameliorates Severe Acute Pancreatitis-Induced Myocardial Injury in Rats by Regulating NF-κB Signaling Pathway.

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Wang, Yayun; Chen, Manhua

2017-07-06

BACKGROUND Acute pancreatitis (AP) is a sudden inflammation of the pancreas. It results in multiple, severe complications, and 15-20% of patients develop severe acute pancreatitis (SAP) with mortality as high as 30%. Consequently, it is imperative to develop an effective therapy for SAP. MATERIAL AND METHODS We used 30 adult male Sprague Dawley (SD) rats. Rats were randomly divided into 3 groups - sham, SAP, and fentanyl+SAP - with 10 rats in each group. An automatic biochemical analyzer was used to analyze the concentration of creatine kinase isoenzyme (CK-MB) and lactate dehydrogenase (LDH). Terminal-deoxynucleotidyl transferase-mediated nick-end labeling (TUNEL) assay was applied to assess the cell apoptosis rate. Pathological changes in pancreas/heart were detected with hematoxylin and eosin (HE) staining. Western immunoblot assay was used to analyze protein levels of interleukin (IL)-1β, IL-6, and IκB. RESULTS Fentanyl pre-treatment inhibits SAP-induced elevation of CK-MB/LDH concentrations in serum. Compared with the sham group, SAP generates a higher brown/yellow staining rate, which is abated by fentanyl. In the pancreas, SAP generated more serious interstitial edema/hemorrhage and fat necrosis than in the sham group, which are attenuated by fentanyl. Likewise, compared to the sham group, SAP generates swelled/disordered myocardial fibers and congested blood vessels in myocardium, which are ameliorated by fentanyl. In the sham group, there was little IL-1β/IL-6, and fentanyl significantly inhibited SAP-induced up-regulation of IL-1β/IL-6 levels. Compared with the sham group, SAP significantly reduced IκB level, which was rescued by fentanyl. CONCLUSIONS Fentanyl effectively alleviates SAP-induced pancreas and heart injuries through regulating the nuclear factor-κB (NF-κB) signaling pathway.

COMPARATIVE STUDY OF EFFECT OF INTRAVENOUS MAGNESIUM SULPHATE AND INTRAVENOUS FENTANYL IN ATTENUATING THE HAEMODYNAMIC RESPONSES TO LARYNGOSCOPY AND INTUBATION

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Patta

2016-07-01

Full Text Available AIM To compare the haemodynamic response to laryngoscopy and intubation with intravenous MgSO4 and intravenous fentanyl. METHODS Fifty adult patients were divided into two groups randomly into group M and group F. Patients of group M received 30 mg/kg body weight of IV MgSO4 and group F received IV fentanyl 1.5 µg/kg 5 minutes before intubation. RESULTS IV Fentanyl showed greater degree of haemodynamic stability i.e. rise in heart rate, mean arterial pressure during laryngoscopy and intubation compared to IV MgSO4. IV fentanyl showed side effects like respiratory depression, nausea and vomiting. CONCLUSION IV fentanyl is a better drug in controlling haemodynamic response to laryngoscopy and intubation.

Postmortem Tissue Distribution of Acetyl Fentanyl, Fentanyl and their Respective Nor-Metabolites Analyzed by Ultrahigh Performance Liquid Chromatography with Tandem Mass Spectrometry

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Poklis, Justin; Poklis, Alphonse; Wolf, Carl; Mainland, Mary; Hair, Laura; Devers, Kelly; Chrostowski, Leszek; Arbefeville, Elise; Merves, Michele; Pearson, Julia

2015-01-01

In the last two years, an epidemic of fatal narcotic overdose cases has occurred in the Tampa area of Florida. Fourteen of these deaths involved fentanyl and/or the new designer drug, acetyl fentanyl. Victim demographics, case histories, toxicology findings and causes and manners of death, as well as, disposition of fentanyl derivatives and their nor-metabolites in postmortem heart blood, peripheral blood, bile, brain, liver, urine and vitreous humor are presented. In the cases involving only acetyl fentanyl (without fentanyl, n=4), the average peripheral blood acetyl fentanyl concentration was 0.467 mg/L (range 0.31 to .60 mg/L) and average acetyl norfentanyl concentration was 0.053 mg/L (range 0.002 to 0.086 mg/L). In the cases involving fentanyl (without acetyl fentanyl, n=7), the average peripheral blood fentanyl concentration was 0.012 mg/L (range 0.004 to 0.027 mg/L) and average norfentanyl blood concentration was 0.001 mg/L (range 0.0002 to 0.003 mg/L). In the cases involving both acetyl fentanyl and fentanyl (n=3), the average peripheral blood acetyl fentanyl concentration was 0.008 mg/L (range 0.006 to 0.012 mg/L), the average peripheral blood acetyl norfentanyl concentration was 0.001 mg/L (range 0.001 to 0.002 mg/L), the average peripheral blood fentanyl concentration was 0.018 mg/L (range 0.015 to 0.021 mg/L) and the average peripheral blood norfentanyl concentration was 0.002 mg/L (range 0.001 mg/L to 0.003 mg/L). Based on the toxicology results, it is evident that when fentanyl and/or acetyl fentanyl were present, they contributed to the cause of death. A novel ultrahigh performance liquid chromatography (UPLC) tandem mass spectrometry (MS/MS) method to identify and quantify acetyl fentanyl, acetyl norfentanyl, fentanyl and norfentanyl in postmortem fluids and tissues is also presented. PMID:26583960

Fentanyl

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Perioperative analgesia after intrathecal fentanyl and morphine or morphine alone for cesarean section: A randomized controlled study.

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Weigl, Wojciech; Bieryło, Andrzej; Wielgus, Monika; Krzemień-Wiczyńska, Świetlana; Kołacz, Marcin; Dąbrowski, Michał J

2017-12-01

Intrathecal morphine is used in the postoperative management of pain after caesarean section (CS), but might not be optimal for intraoperative analgesia. We hypothesized that intrathecal fentanyl could supplement intraoperative analgesia when added to a local anesthetic and morphine without affecting management of postoperative pain. This prospective, randomized, double-blind, parallel-group study included 60 parturients scheduled for elective CS. Spinal anesthesia consisted of bupivacaine with either morphine 100 μg (M group), or fentanyl 25 μg and morphine 100 μg (FM group). The frequency of intraoperative pain and pethidine consumption in the 24 hours postoperatively was recorded. Fewer patients in the FM group required additional intraoperative analgesia (P fentanyl and morphine may provide better perioperative analgesia than morphine alone in CS and could be useful when the time from anesthesia to skin incision is short. However, an increase in PONV and possible acute spinal opioid tolerance after addition of intrathecal fentanyl warrants further investigation using lower doses of fentanyl.

A sensitive radioimmunoassay for fentanyl

International Nuclear Information System (INIS)

Michiels, M.; Hendriks, R.; Heykants, J.

1977-01-01

Antiserum to fentanyl was obtained in rabbits repeatedly injected with carboxyfentanyl conjugated to bovine serum albumin. Using the antiserum, a highly sensitive radioimmunoassay has been developed, based on the dextran-coated charcoal method. It proved possible to assay the drug directly in plasma, in amounts as small as 30 picogram in 0.5 ml. The antibody was highly specific for fentanyl and no cross-reaction was observed with its major metabolites. This sensitive and specific radioimmunoassay method was employed to determine fentanyl in plasma from six volunteers after an intravenous bolus of 0.2 mg, and in plasma from dogs treated both intravenously and subcutaneously with 0.02 mg/kg. The plasma level of fentanyl could be followed for up to 6 h after a therapeutic dose in dogs and man. (orig.) [de

Intrathecal fentanyl abolishes the exaggerated blood pressure response to cycling in hypertensive men

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Barbosa, Thales C; Vianna, Lauro C; Fernandes, Igor A

2016-01-01

. In the present study, we tested whether the attenuation of these neural signals in hypertensive patients could normalize their abnormal increase in blood pressure during physical activity. Attenuation of the neural signals from the leg muscles with intrathecal fentanyl injection reduced the blood pressure...... of fentanyl, a μ-opioid receptor agonist, aiming to attenuate the central projection of opioid-sensitive group III and IV muscle afferent nerves. The cardiovascular response to exercise of these subjects was compared with that of six normotensive men. During cycling, the hypertensive group demonstrated...... an exaggerated increase in blood pressure compared to the normotensive group (mean ± SEM: +17 ± 3 vs. +8 ± 1 mmHg, respectively; P 0.05). Fentanyl inhibited the blood pressure response to exercise...

Functionality Effect of Pressure Sensitive Adhesives on In Vitro Drug Release Behavior of Fentanyl Drug in an Adhesive Patch

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S.M. Taghizadeh

2009-12-01

Full Text Available Some formulations of drug in adhesive transdermal drug delivery systems (TDDSs( with different functional and non-functional acrylic pressure sensitive adhesives PSAs( were prepared. For this purpose fentanyl was used as a drug component. The effects of PSAs type on skin permeation and in vitro drug release from devices were evaluated using hydrodynamically well-characterized Chien permeation system fitted with excised rat abdominal skin. The adhesion properties of devices (peel strength and tack values( were obtained. It was found that TDDS with –COOH functional PSA had the lowest steady state flux. Drug release was followed by Higuchi's kinetic model. Adhesion properties of the samples were improved by addition of functional PSA in the formulations.

The median effective concentration (EC50) of propofol with different doses of fentanyl during colonoscopy in elderly patients.

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Li, Shiyang; Yu, Fang; Zhu, Huichen; Yang, Yuting; Yang, Liqun; Lian, Jianfeng

2016-04-21

Propofol and fentanyl are the most widely administered anesthesia maintaining drugs during colonoscopy. In this study, we determined the median effective concentration (EC50) of propofol required for colonoscopy in elderly patients, and the purpose of this study was to describe the pharmacodynamic interaction between fentanyl and propofol when used in combination for colonoscopy in elderly patients. Ninety elderly patients scheduled for colonoscopy were allocated into three groups in a randomized, double-blinded manner as below, F0.5 group (0.5 μg.kg(-1) fentanyl), F1.0 group (1.0 μg.kg(-1) fentanyl) and saline control group. Anaesthesia was achieved by target-controlled infusion of propofol (Marsh model, with an initial plasma concentration of 2.0 μg.ml(-1)) and fentanyl. Colonoscopy was started 3 min after the injection of fentanyl. The EC50 of propofol for colonoscopy with different doses of fentanyl was measured by using an up-and-down sequential method with an adjacent concentration gradient at 0.5 μg.ml(-1) to inhibit purposeful movements. Anaesthesia associated adverse events and recovery characters were also recorded. The EC50 of propofol for colonoscopy in elderly patients were 2.75 μg.ml(-1) (95% CI, 2.50-3.02 μg.ml(-1)) in F0.5 group, 2.05 μg.ml(-1) (95% CI, 1.98-2.13 μg.ml(-1)) in F1.0 group and 3.08 μg.ml(-1) (95% CI, 2.78-3.42 μg.ml(-1)) in control group respectively (P fentanyl up to 1.0 μg.kg(-1) reduces the propofol EC50 required for elderly patients undergoing colonoscopy, and there was no significant difference in anaesthesia associated adverse events but prolonged awake and discharge time. Chinese Clinical Trial Registry ChiCTR15006368. Date of registration: May 3, 2015.

Molecular modeling of fentanyl analogs

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LJILJANA DOSEN-MICOVIC

2004-11-01

Full Text Available Fentanyl is a highly potent and clinically widely used narcotic analgesic. A large number of its analogs have been synthesized, some of which (sufentanil and alfentanyl are also in clinical use. Theoretical studies, in recent years, afforded a better understanding of the structure-activity relationships of this class of opiates and allowed insight into the molecular mechanism of the interactions of fentanyl analogs with their receptors. An overview of the current computational techniques for modeling fentanyl analogs, their receptors and ligand-receptor interactions is presented in this paper.

Postoperative analgesia in children when using clonidine or fentanyl with ropivacaine given caudally

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Usha Shukla

2011-01-01

Full Text Available Background: The aim of the study was to compare the efficacy of clonidine and fentanyl as an additive to ropivacaine given via single shot caudal epidural in pediatric patients for postoperative pain relief. Materials and Methods: In the present double blind study, 90 children of ASA-I-II aged 3-8 years scheduled for infraumblical surgical procedures were randomly allocated to two groups to receive either ropivacaine 0.25% 1 ml/kg+clonidine 2 μg/kg (group I or ropivacaine 0.25% 1 μl/kg+fentanyl 1 μg/kg (group II. Caudal block was performed after the induction of general anesthesia. Postoperatively patients were observed for analgesia, sedation, hemodynamics, and side effects/complications. Results: Both the groups were similar with respect to patient and various block characteristics. The analgesic properties and hemodynamics were also comparable in both groups (P > 0.05. Side effects such as respiratory depression, vomiting bradycardia were significantly less in group I than group II (P < 0.05 ensuing more patient comfort. Conclusions: The analgesic properties of clonidine and fentanyl as additives to ropivacaine in single shot caudal epidural in children are comparable but clonidine offers a more favorable side effect profile. The use of clonidine as additive to ropivacaine in caudal epidural is superior choice to fentanyl because of lack of unwanted side effects and increased patient comfort.

Correlation of ADRB1 rs1801253 Polymorphism with Analgesic Effect of Fentanyl After Cancer Surgeries

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Wei, Wei; Tian, Yanli; Zhao, Chunlei; Sui, Zhifu; Liu, Chang; Wang, Congmin; Yang, Rongya

2015-01-01

Background Our study aimed to explore the association between β1-adrenoceptor (ADRB1) rs1801253 polymorphism and analgesic effect of fentanyl after cancer surgeries in Chinese Han populations. Material/Methods Postoperative fentanyl consumption of 120 patients for analgesia was recorded. Genotype distributions were detected by allele specific amplification-polymerase chain reaction (ASA-PCR) method. Postoperative pain was measured by visual analogue scale (VAS) method. Differences in postoperative VAS score and postoperative fentanyl consumption for analgesia in different genotype groups were compared by analysis of variance (ANOVA). Preoperative cold pressor-induced pain test was also performed to test the analgesic effect of fentanyl. Results Frequencies of Gly/Gly, Gly/Arg, Arg/Arg genotypes were 45.0%, 38.3%, and 16.7%, respectively, and passed the Hardy-Weinberg Equilibrium (HWE) test. The mean arterial pressure (MAP) and the heart rate (HR) had no significant differences at different times. After surgery, the VAS score and fentanyl consumption in Arg/Arg group were significantly higher than in other groups at the postoperative 2nd hour, but the differences were not obvious at the 4th hour, 24th hour, and the 48th hour. The results suggest that the Arg/Arg homozygote increased susceptibility to postoperative pain. The preoperative cold pressor-induced pain test suggested that individuals with Arg/Arg genotype showed worse analgesic effect of fentanyl compared to other genotypes. Conclusions In Chinese Han populations, ADRB1 rs1801253 polymorphism might be associated with the analgesic effect of fentanyl after cancer surgery. PMID:26694722

Epidural Labor Analgesia-Fentanyl Dose and Breastfeeding Success: A Randomized Clinical Trial.

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Lee, Amy I; McCarthy, Robert J; Toledo, Paloma; Jones, Mary Jane; White, Nancy; Wong, Cynthia A

2017-10-01

Breastfeeding is an important public health concern. High cumulative doses of epidural fentanyl administered for labor analgesia have been reported to be associated with early termination of breastfeeding. We tested the hypothesis that breastfeeding success is adversely influenced by the cumulative epidural fentanyl dose administered for labor analgesia. The study was a randomized, double-blind, controlled trial of parous women at greater than 38 weeks gestation who planned to breastfeed, had successfully breastfed a prior infant, and who received neuraxial labor analgesia. Participants were randomized to receive one of three epidural maintenance solutions for labor analgesia (bupivacaine 1 mg/ml, bupivacaine 0.8 mg/ml with fentanyl 1 μg/ml, or bupivacaine 0.625 mg/ml with fentanyl 2 μg/ml). The primary outcome was the proportion of women breastfeeding at 6 weeks postpartum. Maternal and umbilical venous blood fentanyl and bupivacaine concentration at delivery were measured. A total of 345 women were randomized and 305 had complete data for analysis. The frequency of breastfeeding at 6 weeks was 97, 98, and 94% in the groups receiving epidural fentanyl 0, 1, and 2 μg/ml, respectively (P = 0.34). The cumulative fentanyl dose (difference: 37 μg [95% CI of the difference, -58 to 79 μg], P = 0.28) and maternal and umbilical cord venous fentanyl and bupivacaine concentrations did not differ between women who discontinued breastfeeding and those who were still breastfeeding at 6 weeks postpartum. Labor epidural solutions containing fentanyl concentrations as high as 2 μg/ml do not appear to influence breastfeeding rates at 6 weeks postpartum.

Two Fatal Intoxications Involving Butyryl Fentanyl

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Poklis, Justin; Poklis, Alphonse; Wolf, Carl; Hathaway, Cindie; Arbefeville, Elise; Chrostowski, Leszek; Devers, Kelly; Hair, Laura; Mainland, Mary; Merves, Michele; Pearson, Julia

2016-01-01

We present the case histories, autopsy findings and toxicology findings of two fatal intoxications involving the designer drug, butyryl fentanyl. The quantitative analysis of butyryl fentanyl in postmortem fluids and tissues was performed by an ultrahigh-performance liquid chromatography tandem mass spectrometry method. In the first case, butyryl fentanyl was the only drug detected with concentrations of 99 ng/mL in peripheral blood, 220 ng/mL in heart blood, 32 ng/mL in vitreous humor, 590 ng/mL in gastric contents, 93 ng/g in brain, 41 ng/g in liver, 260 ng/mL in bile and 64 ng/mL in urine. The cause of death was ruled fatal intoxication by butyryl fentanyl. In the second case, butyryl fentanyl was detected along with acetyl fentanyl, alprazolam and ethanol. The butyryl fentanyl concentrations were 3.7 ng/mL in peripheral blood, 9.2 ng/mL in heart blood, 9.8 ng/mL in vitreous humor, 4,000 ng/mL in gastric contents, 63 ng/g in brain, 39 ng/g in liver, 49 ng/mL in bile and 2 ng/mL in urine. The acetyl fentanyl concentrations were 21 ng/mL in peripheral blood, 95 ng/mL in heart blood, 68 ng/mL in vitreous humor, 28,000 ng/mL in gastric contents, 200 ng/g in brain, 160 ng/g in liver, 330 ng/mL in bile and 8 ng/mL in urine. In addition, the alprazolam concentration was 40 ng/mL and the ethanol concentration was 0.11 g/dL, both measured in peripheral blood. The cause of death in the second case was ruled a mixed drug intoxication. In both cases, the manner of death was accident. PMID:27339481

3-alkyl fentanyl analogues: Structure-activity-relationship study

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Vučković, Sonja; Savić-Vujović, Katarina; Srebro, Dragana; Ivanović, Milovan; Došen-Mićović, Ljiljana; Stojanović, Radan; Prostran, Milica

2012-01-01

Introduction. Fentanyl belongs to 4-anilidopiperidine class of synthetic opioid analgesics. It is characterized by high potency, rapid onset and short duration of action. A large number of fentanyl analogues have been synthesized so far, both to establish the structure-activity-relationship (SAR) and to find novel, clinically useful analgesic drugs. Objective. In this study, newly synthesized 3-alkyl fentanyl analogues were examined for analgesic activity and compared with fentanyl. Methods. ...

Comparison of efficacy of bupivacaine and fentanyl with bupivacaine and sufentanil for epidural labor analgesia

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Kalra Sumit

2010-01-01

Full Text Available Objectives: A study to compare the efficacy between fentanyl and sufentanil combined with low concentration (0.0625% of bupivacaine for epidural labor analgesia in laboring women. Materials and Methods: Fifty full term parturients received an initial bolus dose of a 10 ml solution containing 0.125% bupivacaine. The patients were randomly divided into two: group F received 0.0625% bupivacaine with 2.5 mcg/ml fentanyl and group S received 0.0625% bupivacaine with 0.25 mcg/ml sufentanil. Verbal analogue pain scores, need of supplementary/rescue boluses dose of bupivacaine consumed, mode of delivery, maternal satisfaction, and neonatal Apgar scores were recorded. No significant difference was observed between both groups. Results: Both the groups provided equivalent labor analgesia and maternal satisfaction. The chances of cesarean delivery were also not increased in any group. No difference in the cephalad extent of sensory analgesia, motor block or neonatal Apgar score were observed. Although mean pain scores throughout the labor and delivery were similar in both groups, more patients in fentanyl group required supplementary boluses though not statistically significant. Conclusion: We conclude that both 0.0625% bupivacaine-fentanyl (2.5 μg/ml and 0.0625% bupivacaine-sufentanil (0.25 μg/ml were equally effective by continuous epidural infusion in providing labor analgesia with hemodynamic stability achieving equivalent maternal satisfaction without serious maternal or fetal side effects. We found that sufentanil was 10 times more potent than fentanyl as an analgesic for continuous epidural labor analgesia.

Bronchoscopic diagnosis of peripheral pulmonary lung cancer employing sedation with fentanyl and midazolam.

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Minami, Daisuke; Nakasuka, Takamasa; Ando, Chihiro; Iwamoto Md, Yoshitaka; Sato, Ken; Fujiwara, Keiichi; Shibayama, Takuo; Yonei Md PhD, Toshirou; Sato, Toshio

2017-09-01

Sedation with fentanyl and midazolam during bronchoscopic examination is commonly employed by pulmonary physicians in the USA and Europe. We assessed the efficacy of such sedation in the bronchoscopic diagnosis of peripheral lung cancer. We retrospectively evaluated data from 102 patients who underwent transbronchial biopsies (TBB) for diagnosis of peripheral lung cancer. Bronchoscopies with and without fentanyl were performed in 61 (group A) and 41 (group B) patients, respectively. Midazolam was administered to all patients. Medical records were retrieved, and between-group comparisons were made using unpaired Student's t-tests. The mean fentanyl dose was 49.5 μg (range: 10-100 μg), and midazolam doses in groups A and B were 4.29mg (range: 1-14mg) and 5.54mg (range: 1-12mg), respectively. Diagnostic histological specimens were obtained from 75.4% and 65.8% of group A and B patients, respectively (P = 0.30). The diagnostic sensitivities for lung cancer, via at least one of TBB, cytological brushing, or bronchial washing, in groups A and B were 88.5% and 70.4%, respectively (P = 0.035). Moreover, lesion diagnostic sensitivities, via at least one of TBB, cytological brushing, and bronchial washing, in groups A and B were 98.1% and 68.0%, respectively (P = 0.01). Fentanyl and midazolam sedation during bronchoscopy facilitated the diagnosis of peripheral pulmonary lung cancers. Copyright © 2017 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

21 CFR 522.800 - Droperidol and fentanyl citrate injection.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Droperidol and fentanyl citrate injection. 522.800... § 522.800 Droperidol and fentanyl citrate injection. (a) Specifications. Droperidol and fentanyl citrate injection is a sterile solution containing 20 milligrams of droperidol and 0.4 milligram of fentanyl citrate...

Stability of Fentanyl Citrate in Polyolefin Bags.

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Donnelly, Ronald F

2016-01-01

Fentanyl is used to manage pain because it is a potent lipophilic opiate agonist. The stability of fentanyl in polyolefin bags when diluted to either 10 µg/mL or 50 µg/mL with sodium chloride 0.9% has not been studied. The chemical stability of fentanyl 50 µg/mL packaged in polyvinyl chloride bags has been studied, however, the stability in polyolefin bags is lacking. Polyolefin bags were aseptically filled with either 10-µg/mL or 50-µg/mL fentanyl solution. Containers were then stored at either 5°C and protected from light or 22°C and exposed to light for 93 days. Fentanyl peaks were monitored using a stability-indicatin high-performance liquid chromatographic method. Changes to color, clarity, and pH were also monitored. There were no signs of chemical degradation of fentanyl packaged in polyolefin bags at either 5°C or 22°C after storage for 93 days. Over the course of the study, all solutions remained colorless and clear. The pH showed a slight decrease during the 93 days of storage. The stability of both undiluted (50-µg/mL) and diluted (10-µg/mL) fentanyl solutions when packaged in polyolefin bags was 93 days when stored at either 5°C or 22°C. Copyright© by International Journal of Pharmaceutical Compounding, Inc.

Population Pharmacokinetics of Fentanyl in the Critically Ill

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Choi, Leena; Ferrell, Benjamin A; Vasilevskis, Eduard E; Pandharipande, Pratik P; Heltsley, Rebecca; Ely, E Wesley; Stein, C Michael; Girard, Timothy D

2016-01-01

Objective To characterize fentanyl population pharmacokinetics in patients with critical illness and identify patient characteristics associated with altered fentanyl concentrations. Design Prospective cohort study. Setting Medical and surgical ICUs in a large tertiary care hospital in the United States. Patients Patients with acute respiratory failure and/or shock who received fentanyl during the first five days of their ICU stay. Measurements and Main Results We collected clinical and hourly drug administration data and measured fentanyl concentrations in plasma collected once daily for up to five days after enrollment. Among 337 patients, the mean duration of infusion was 58 hours at a median rate of 100 µg/hr. Using a nonlinear mixed-effects model implemented by NONMEM, we found fentanyl pharmacokinetics were best described by a two-compartment model in which weight, severe liver disease, and congestive heart failure most affected fentanyl concentrations. For a patient population with a mean weight of 92 kg and no history of severe liver disease or congestive heart failure, the final model, which performed well in repeated 10-fold cross-validation, estimated total clearance (CL), intercompartmental clearance (Q), and volumes of distribution for the central (V1) and peripheral compartments (V2) to be 35 (95% confidence interval: 32 to 39) L/hr, 55 (42 to 68) L/hr, 203 (140 to 266) L, and 523 (428 to 618) L, respectively. Severity of illness was marginally associated with fentanyl pharmacokinetics but did not improve the model fit after liver and heart disease were included. Conclusions In this study, fentanyl pharmacokinetics during critical illness were strongly influenced by severe liver disease, congestive heart failure, and weight, factors that should be considered when dosing fentanyl in the ICU. Future studies are needed to determine if data-driven fentanyl dosing algorithms can improve outcomes for ICU patients. PMID:26491862

The effect of nitrous oxide in comparison to oxygen combined with fentanyl on the hospitalization time and pain reduction in renal colic patients at emergency department

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Omid Ahmadi

2018-01-01

Full Text Available Background: Renal colic is a painful medical emergency, needs urgent intervention to reduce pain. Nonsteroidal anti-inflammatory drugs, opioids, and entonox are pain-relieving agents. This study was aimed to compare fentanyl + entonox (nitrous oxide + O2 versus fentanyl + oxygen. Materials and Methods: One hundred and twenty patients with acute renal colic presenting to the emergency department were enrolled. First, 50 μg fentanyl was infused for all patients. Then, patients divided into two groups receiving masks of entonox and oxygen, respectively. Quantitative measurement of pain was performed by visual analog scale, before the intervention, after 3, 5, 10, and 30 min of that. If the pain was not relieved after 30 min, 50 μg fentanyl was infused. If the pain was still continued, ketorolac and ketamine were used. Hospitalization duration and severity of pain at specified times were compared between patients in two groups. Results: The mean (standard deviation time of hospitalization was 211 (59 and 236 (61 min in fentanyl + entonox and fentanyl + O2 groups, respectively (P = 0.024. The decrease in pain severity after 10 and 30 min in fentanyl + entonox group were significantly greater than fentanyl + O2 group (P = 0.002 and 0.001, respectively. Mean (standard error of needed time for renal colic pain to get better was 11.27 (1.23 and 20.47 (1.71 min in fentanyl + entonox and fentanyl + O2 groups, respectively (P < 0.001. Proportion of patients relief from pain in fentanyl + entonox in the second, third, and fourth measurements were significantly more than fentanyl + O2 group (P = 0.036, P < 0.001, and P < 0.001, respectively. Conclusion: Entonox is more effective to decrease the duration of hospitalization and reduction of pain than O2 in renal colic patients.

Granisetron Transdermal Patch

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Granisetron transdermal patches are used to prevent nausea and vomiting caused by chemotherapy. Granisetron is in a class of medications called 5HT3 ... Granisetron transdermal comes as a patch to apply to the skin. It is usually applied 24 to ...

Effect of Fentanyl Nasal Packing Treatment on Patients With Acute Postoperative Pain After Nasal Operation: A Randomized Double-Blind Controlled Trial.

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Kim, Kwan-Sub; Yeo, Nam-Kyung; Kim, Seong-Su; Park, Woong-Sub; Kwak, Su-Hyun; Cho, Sang-Hyeon; Sung, Gyu-Wan; Kim, Hae-Sook; Yi, Sang-Wook; Cho, Hae Jun

2018-05-01

Nasal packing is an option for bleeding control after endoscopic sinus surgery and septoplasty. Although new packing materials have been developed, patients still suffer from pain and require additional analgesics treatments. In this study, a prospective, randomized, and double-blind controlled trial was designed to evaluate the effect of fentanyl-soaked packing on pain after endoscopic sinus surgery and septoplasty. One hundred fifty-two patients who underwent nasal surgeries due to chronic rhinosinusitis or nasal septal deviation were enrolled in this study. At the end of operation, 50 mcg fentanyl-soaked biodegradable synthetic polyurethane foams packing Nasopore or Merocel were applied to a group of 79 patients, and saline-soaked ones were applied to another group of 73 patients. To evaluate the influence of fentanyl on postoperative nasal pain, patients' conditions were assessed via means of Numeric Rating Scale, patient satisfaction, and Ramsay Sedation Scale. In addition, symptoms of headache or sore throat and any signs of cardiopulmonary-relevant indicators were monitored. The fentanyl group had significantly decreased Numeric Rating Scale and increased patient satisfaction in every operation type for the majority of postoperative time periods ( P fentanyl group showed a higher score on Ramsay Sedation Scale than the control group ( P .05). Fentanyl group showed significantly reduced postoperative pain without serious adverse effects. We suggest that topical fentanyl application to nasal packs can be a useful method to reduce pain during the early postoperative period after endoscopic sinus surgery and septoplasty.

TRANSDERMAL DRUG DELIVERY SYSTEM: REVIEW

OpenAIRE

Vishvakarama Prabhakar; Agarwal Shivendra; Sharma Ritika; Saurabh Sharma

2012-01-01

Various new technologies have been developed for the transdermal delivery of some important drugs. Today about 74% of drugs are taken orally and are found not to be as effective as desired. To improve such characters transdermal drug delivery system was emerged. Drug delivery through the skin to achieve a systemic effect of a drug is commonly known as transdermal drug delivery and differs from traditional topical drug delivery. Transdermal drug delivery systems (TDDS) are dosage forms involve...

A COMPARATIVE STUDY OF INTRATHECAL DEXMEDETOMIDINE AND FENTANYL AS ADJUVANTS TO BUPIVACAINE FOR LOWER ABDOMINAL SURGERIES

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Hari Kishore

2015-01-01

Full Text Available INTRODUCTION: Various adjuvants have been used with local anesthetics in spinal anesthesia to improve the quality of block and to provide prolonged postoperative analgesia. Dexmedetomidine, the new highly selective α2 - agonist drug, is now being used as a neuraxial adju vant. AIM: The aim of this study was to evaluate the onset and duration of sensory and motor block, hemodynamic effect, postoperative analgesia, and adverse effects of dexmedetomidine or fentanyl given intrathecally with hyperbaric 0.5% bupivacaine. METHOD OLOGY: Fifty patients classified in American Society of Anesthesiologists classes I and II scheduled for lower abdominal surgeries were included in this prospective cohort study at Amala Institute of Medical Sciences. Patients received either 15 mg hyperba ric bupivacaine plus 25 μg fentanyl (group 1, n = 25 or 15 mg hyperbaric bupivacaine plus 5 μg dexmedetomidine (group 2, n = 25 intrathecally . RESULTS : Patients in dexmedetomidine group (2 had a significantly longer duration of motor and sensory block t han patients in fentanyl group . (1 The mean time regression of motor block to reach Bromage 0 was 17 6 . 2± 5.71 min in d exmeditomid ine group and 16 6 . 36 ± 5.97 min in fentanyl group (P<0.05. Duration of analgesia was 2 39.52 ± 9.05 min in D exmed i tomidine gro up and 189.96 ± 5.35 min in fentanyl group ( p< 0.05. A significant decrease in heart rate was noted in dexmedetomidine group. CONCLUSION : Intrathecal dexmedetomidine is associated with prolonged duration of analgesia and motor block along with significant dec rease in heart rate.

Intrathecal tramadol versus intrathecal fentanyl for visceral pain ...

African Journals Online (AJOL)

Intrathecal tramadol versus intrathecal fentanyl for visceral pain control during bupivacaine subarachnoid block for open appendicectomy. ... Visual analog scale scores and frequency of subjective symptoms among patients in the three groups formed the primary outcome measure of this study. Results: Effective ...

Clinical Pharmacology of Fentanyl in Preterm Infants. A Review

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Gian Maria Pacifici

2015-06-01

Full Text Available Fentanyl is a synthetic opioid that is very important in anesthetic practice because of its relatively short time to peak analgesic effect and the rapid termination of action after small bolus doses. The objective of this survey is to review the clinical pharmacology of fentanyl in preterm infants. The bibliographic search was performed using PubMed and EMBASE databases as search engines. In addition, the books Neofax: A manual of drugs used in neonatal care and Neonatal formulary were consulted. Fentanyl is N-dealkylated by CYP3A4 into the inactive norfentanyl. Fentanyl may be administered as bolus doses or as a continuous infusion. In neonates, there is a remarkable interindividual variability in the kinetic parameters. In neonates, fentanyl half-life ranges from 317 minutes to 1266 minutes and in adults it is 222 minutes. Respiratory depression occurs when fentanyl doses are >5 μg/kg. Chest wall rigidity may occur in neonates and occasionally is associated with laryngospasm. Tolerance to fentanyl may develop after prolonged use of this drug. Significant withdrawal symptoms have been reported in infants treated with continuous infusion for 5 days or longer. Fentanyl is an extremely potent analgesic and is the opioid analgesic most frequently used in the neonatal intensive care unit.

Comparative evaluation of femoral nerve block and intravenous fentanyl for positioning during spinal anaesthesia in surgery of femur fracture

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Ashok Jadon

2014-01-01

Full Text Available Background: Spinal anaesthesia is the preferred technique to fix fracture of the femur. Extreme pain does not allow ideal positioning for this procedure. Intravenous fentanyl and femoral nerve block are commonly used techniques to reduce the pain during position for spinal anaesthesia however; results are conflicting regarding superiority of femoral nerve block over intravenous fentanyl. Aims: We conducted this study to compare the analgesic effect provided by femoral nerve block (FNB and intra- venous (IV fentanyl prior to positioning for central neuraxial block in patients undergoing surgery for femur fracture. Patients and Methods: In this randomized prospective study 60 patients scheduled for fracture femur operation under spinal were included. Patients were distributed in two groups through computer generated random numbers table; Femoral nerve block group (FNB and Intravenous fentanyl group (FENT. In FNB group patients received FNB guided by a peripheral nerve stimulator (Stimuplex; B Braun, Melsungen, AG 5 minutes prior to positioning. 20mL, 1.5% lidocaine with adrenaline (1:200,000 was injected incrementally after a negative aspiration test. Patients in the fentanyl group received injection fentanyl 1 μg/kg IV 5 mins prior to positioning. Spinal block was performed and pain scores before and during positioning were recorded. Statistical analysis was done with Sigmaplot version-10 computer software. Student t-test was applied to compare the means and P < 0.05 was taken as significant. Results: VAS during positioning in group FNB: 0.57 ± 0.31 versus FENT 2.53 ± 1.61 (P = 0.0020. Time to perform spinal anesthesia in group FNB: 15.33 ± 1.64 min versus FENT 19.56 ± 3.09 min (P = 0.000049. Quality of patient positioning for spinal anesthesia in group FNB 2.67± 0.606 versus FENT 1.967 ± 0.85 (P = 0.000027. Patient acceptance was less in group FENT (P = 0.000031. Conclusion: Femoral nerve block provides better analgesia, patient

Intranasal Fentanyl Intoxication Leading to Diffuse Alveolar Hemorrhage.

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Ruzycki, Shannon; Yarema, Mark; Dunham, Michael; Sadrzadeh, Hossein; Tremblay, Alain

2016-06-01

Increasing rates of opioid abuse, particularly fentanyl, may lead to more presentations of unusual effects of opioid toxicity. Diffuse alveolar hemorrhage is a rare complication of fentanyl overdose. A 45-year-old male presented in hypoxic respiratory failure secondary to diffuse alveolar hemorrhage requiring intubation. Comprehensive drug screening detected fentanyl without exposure to cocaine. Further history upon the patient's recovery revealed exposure to snorted fentanyl powder immediately prior to presentation. Diffuse alveolar hemorrhage is a potential, though rare, presentation of opioid intoxication. Recognition of less common complications of opioid abuse such as diffuse alveolar hemorrhage is important in proper management of overdoses.

Schedules of Controlled Substances: Temporary Placement of ortho-Fluorofentanyl, Tetrahydrofuranyl Fentanyl, and Methoxyacetyl Fentanyl Into Schedule I. Temporary amendment; temporary scheduling order.

Science.gov (United States)

2017-10-26

The Administrator of the Drug Enforcement Administration is issuing this temporary scheduling order to schedule the synthetic opioids, N-(2-fluorophenyl)-N-(1-phenethylpiperidin-4-yl)propionamide (ortho-fluorofentanyl or 2-fluorofentanyl), N-(1-phenethylpiperidin-4-yl)-N-phenyltetrahydrofuran-2-carboxamide (tetrahydrofuranyl fentanyl), and 2-methoxy-N-(1-phenethylpiperidin-4-yl)-N-phenylacetamide (methoxyacetyl fentanyl), into Schedule I. This action is based on a finding by the Administrator that the placement of ortho-fluorofentanyl, tetrahydrofuranyl fentanyl, and methoxyacetyl fentanyl into Schedule I of the Controlled Substances Act is necessary to avoid an imminent hazard to the public safety. As a result of this order, the regulatory controls and administrative, civil, and criminal sanctions applicable to Schedule I controlled substances will be imposed on persons who handle (manufacture, distribute, reverse distribute, import, export, engage in research, conduct instructional activities or chemical analysis, or possess), or propose to handle, ortho-fluorofentanyl, tetrahydrofuranyl fentanyl, and methoxyacetyl fentanyl.

The effects of secondhand smoke on postoperative pain and fentanyl consumption.

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Aydogan, Mustafa Said; Ozturk, Erdogan; Erdogan, Mehmet Ali; Yucel, Aytac; Durmus, Mahmut; Ersoy, Mehmet Ozcan; Colak, Cemil

2013-08-01

Although the need for increased postoperative analgesia in smokers has been described, the effect of secondhand smoke on postoperative analgesia requirements has not been studied. We examined the effects of secondhand smoke on fentanyl consumption and postoperative pain. In this study, 101 patients (American Society of Anesthesiology physical status I and II) who underwent abdominal hysterectomy were divided into 3 groups according to history of exposure to cigarette smoke as per medical records which was retrospectively confirmed by measurement of serum cotinine: smokers (n = 28), nonsmokers (n = 31), and secondhand smokers (n = 32). All patients received propofol-remifentanil total intravenous anesthesia and used fentanyl patient controlled analgesia for postoperative pain. The fentanyl consumption visual analogue scale-pain intensity (VAS-PI) score and side effects were recorded in the postanesthesia care unit (PACU) and at 2, 4, 6, and 24 h after surgery. Fentanyl consumption at all the evaluation time points was significantly higher in secondhand smokers than in nonsmokers (P secondhand smokers was lower than that in smokers in the PACU and at 24 h (P secondhand smokers than in nonsmokers (P effects such as nausea, vomiting, and dizziness (P > 0.05). Secondhand smoking was associated with increased postoperative fentanyl consumption, and increased VAS-PI scores. These findings may be beneficial for managing postoperative pain in secondhand smokers.

Detection of illicit online sales of fentanyls via Twitter.

Science.gov (United States)

Mackey, Tim K; Kalyanam, Janani

2017-01-01

A counterfeit fentanyl crisis is currently underway in the United States.  Counterfeit versions of commonly abused prescription drugs laced with fentanyl are being manufactured, distributed, and sold globally, leading to an increase in overdose and death in countries like the United States and Canada.  Despite concerns from the U.S. Drug Enforcement Agency regarding covert and overt sale of fentanyls online, no study has examined the role of the Internet and social media on fentanyl illegal marketing and direct-to-consumer access.  In response, this study collected and analyzed five months of Twitter data (from June-November 2015) filtered for the keyword "fentanyl" using Amazon Web Services.  We then analyzed 28,711 fentanyl-related tweets using text filtering and a machine learning approach called a Biterm Topic Model (BTM) to detect underlying latent patterns or "topics" present in the corpus of tweets.  Using this approach we detected a subset of 771 tweets marketing the sale of fentanyls online and then filtered this down to nine unique tweets containing hyperlinks to external websites.  Six hyperlinks were associated with online fentanyl classified ads, 2 with illicit online pharmacies, and 1 could not be classified due to traffic redirection.  Importantly, the one illicit online pharmacy detected was still accessible and offered the sale of fentanyls and other controlled substances direct-to-consumers with no prescription required at the time of publication of this study.   Overall, we detected a relatively small sample of Tweets promoting illegal online sale of fentanyls.  However, the detection of even a few online sellers represents a public health danger and a direct violation of law that demands further study.

Fentanyl supplement expedites the onset time of sensory and motor blocking in interscalene lidocaine anesthesia

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RS Moharari

2010-12-01

Full Text Available Background and the purpose of the study: Opioids are usually used in regional anesthesia, with or without local anesthetics to improve the regional block or postoperative pain control. Since no data are available on fentanyl's effect on the onset time of lidocaine interscalene anesthesia, the purpose of this study was to examine its effect on the onset time of sensory and motor blockade during interscalene anesthesia.  Methods: In a prospective, randomized, double-blind study, ninety patients scheduled for elective shoulder, arm and forearm surgeries under an  interscalene brachial plexus block .They were randomly allocated to receive either 30 ml of  1.5 % lidocaine with 1.5 ml of isotonic saline  (control group, n = 39 or 30 ml of 1.5%  lidocaine with 1.5 ml (75µg of  fentanyl (fentanyl group,n=41. Then the onset time of sensory and motor blockades of the shoulder, arm and forearm were evaluated every 60 sec. The onset time of the sensory and motor blockades was defined as the time between the last injection and the total abolition of the pinprick response and complete paralysis. The duration of sensory blocks were considered as the time interval between the administration of the local anesthetic and the first postoperative pain sensation. Results: Ten patients were excluded because of unsuccessful blockade or unbearable pain during the surgery. The onset time of the sensory block was significantly faster in the fentanyl group (186.54± 62.71sec compared with the control group (289.51± 81.22, P < 0.01. The onset times of the motor block up to complete paralysis in forearm flexion was significantly faster in the fentanyl group (260.61± 119.91sec than the control group (367.08± 162.43sec, P < 0.01 There was no difference in the duration of the sensory block between two groups. Conclusion: Results of the study showed that the combination of 75 µg fentanyl and 1.5% lidocaine solution accelerated the onset of sensory and motor

Follow-up at the corrected age of 24 months of preterm newborns receiving continuous infusion of fentanyl for pain control during mechanical ventilation.

Science.gov (United States)

Ancora, Gina; Lago, Paola; Garetti, Elisabetta; Pirelli, Anna; Merazzi, Daniele; Pierantoni, Luca; Ferrari, Fabrizio; Faldella, Giacomo

2017-05-01

The neurodevelopmental impact of fentanyl given to preterm newborns for pain control is still unknown. The aim of this study was to assess the neurodevelopmental impact of 2 regimens of fentanyl administration by a prospective follow-up evaluation. In our previous multicenter, double-blind, randomized controlled trial, 131 mechanically ventilated newborns (gestational age ≤32 weeks) were randomized to fentanyl (continuous infusion of fentanyl + open label boluses of fentanyl) or placebo (continuous infusion of placebo + open label boluses of fentanyl). Infant development was evaluated using Griffiths Mental Developmental Scales (Griffiths, 1996) until 24 months of corrected age by trained psychologists who were not aware of the group allocation. 106/131 infants survived at discharge; 3 died after discharge, 25 were lost to follow-up (12 in the fentanyl and 13 in the placebo group). Seventy-eight patients were evaluated at 2 years of corrected age. Children in the fentanyl group, compared with those in the placebo group, obtained significantly lower Griffiths general developmental quotient (mean [SD]: 89.95 [13.64] vs 97.18 [12.72], P = 0.024) together with the scores on the eye-hand coordination (mean [SD]: 89.09 [12.13] vs 99.19 [13.19], P = 0.002) and performance skills (mean [SD]: 79.71 [15.80] vs 90.09 [15.28], P = 0.009) scales. After adjustment for clinical confounders (gestational age, CRIB score, and sex) only eye-hand co-ordination was associated with fentanyl infusion. This study demonstrates that continuous infusion of fentanyl in very preterm infants, given at 1 mcg·kg·h during mechanical ventilation, is associated with a significant decrease in eye and hand co-ordination skills. Longer follow-up is needed to evaluate the impact on future motor, cognitive, and behavioral functions.

Identification of Unique Metabolites of the Designer Opioid Furanyl Fentanyl.

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Goggin, Melissa M; Nguyen, An; Janis, Gregory C

2017-06-01

The illicit drug market has seen an increase in designer opioids, including fentanyl and methadone analogs, and other structurally unrelated opioid agonists. The designer opioid, furanyl fentanyl, is one of many fentanyl analogs clandestinely synthesized for recreational use and contributing to the fentanyl and opioid crisis. A method has been developed and validated for the analysis of furanyl fentanyl and furanyl norfentanyl in urine specimens from pain management programs. Approximately 10% of samples from a set of 500 presumptive heroin-positive urine specimens were found to contain furanyl fentanyl, with an average concentration of 33.8 ng/mL, and ranging from 0.26 to 390 ng/mL. Little to no furanyl norfentanyl was observed; therefore, the furanyl fentanyl specimens were further analyzed by untargeted high-resolution mass spectrometry to identify other metabolites. Multiple metabolites, including a dihydrodiol metabolite, 4-anilino-N-phenethyl-piperidine (4-ANPP) and a sulfate metabolite were identified. The aim of the presented study was to identify the major metabolite(s) of furanyl fentanyl and estimate their concentrations for the purpose of toxicological monitoring. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Intraoperative "Analgesia Nociception Index"-Guided Fentanyl Administration During Sevoflurane Anesthesia in Lumbar Discectomy and Laminectomy: A Randomized Clinical Trial.

Science.gov (United States)

Upton, Henry D; Ludbrook, Guy L; Wing, Andrew; Sleigh, Jamie W

2017-07-01

The "Analgesia Nociception Index" (ANI; MetroDoloris Medical Systems, Lille, France) is a proposed noninvasive guide to analgesia derived from an electrocardiogram trace. ANI is scaled from 0 to 100; with previous studies suggesting that values ≥50 can indicate adequate analgesia. This clinical trial was designed to investigate the effect of intraoperative ANI-guided fentanyl administration on postoperative pain, under anesthetic conditions optimized for ANI functioning. Fifty patients aged 18 to 75 years undergoing lumbar discectomy or laminectomy were studied. Participants were randomly allocated to receive intraoperative fentanyl guided either by the anesthesiologist's standard clinical practice (control group) or by maintaining ANI ≥50 with boluses of fentanyl at 5-minute intervals (ANI group). A standardized anesthetic regimen (sevoflurane, rocuronium, and nonopioid analgesia) was utilized for both groups. The primary outcome was Numerical Rating Scale pain scores recorded from 0 to 90 minutes of recovery room stay. Secondary outcomes included those in the recovery room period (total fentanyl administration, nausea, vomiting, shivering, airway obstruction, respiratory depression, sedation, emergence time, and time spent in the recovery room) and in the intraoperative period (total fentanyl administration, intraoperative-predicted fentanyl effect-site concentrations over time [CeFent], the correlation between ANI and predicted CeFent and the incidence of movement). Statistical analysis was performed with 2-tailed Student t tests, χ tests, ordinal logistic generalized estimating equation models, and linear mixed-effects models. Bonferroni corrections for multiple comparisons were made for primary and secondary outcomes. Over the recovery room period (0-90 minutes) Numerical Rating Scale pain scores were on average 1.3 units lower in ANI group compared to the control group (95% confidence interval [CI], -0.4 to 2.4; P= .01). Patients in the ANI group

Evaluation of the Coat-A-Count 125I fentanyl RIA: Comparison of 125I RIA and GC/MS-SIM for quantification of fentanyl in case urine specimens

International Nuclear Information System (INIS)

Watts, V.W.; Caplan, Y.H.

1990-01-01

The Coat-A-Count solid phase 125 I Fentanyl Radioimmunoassay was evaluated with respect to linearity and precision using equine urine fortified with fentanyl and then compared with a gas chromatographic/mass spectrometric method for quantification of fentanyl in urine. The RIA assay was found to be linear over the urine fentanyl concentration range of 0.25 to 7.5 ng/mL and precise with coefficients of variation (CV) ranging from 9.6 to 19.3%. The RIA calibrators, ranging in fentanyl concentrations from 0.25 to 7.5 ng/mL, and controls, at mean fentanyl concentrations of 0.46 and 1.32 ng/mL, were compared by both the RIA and GC/MS methods. The cross-reactivity with the 125 I RIA test was determined for the fentanyl metabolites, norfentanyl and hydroxyfentanyl, and found to be 5% and 35%, respectively. The illicit fentanyl analogs were found to show significant cross-reactivity, ranging from 20 to 100%. The 125 I RIA was compared to GC/MS quantifications of fentanyl in 35 positive and 20 negative case urine specimens

Postoperative analgesia in children when using clonidine in addition to fentanyl with bupivacaine given caudally.

Science.gov (United States)

Jarraya, Anouar; Elleuch, Sahar; Zouari, Jawhar; Smaoui, Mohamed; Laabidi, Sofiene; Kolsi, Kamel

2016-01-01

The aim of the study was to evaluate the efficacy of clonidine in association with fentanyl as an additive to bupivacaine 0.25% given via single shot caudal epidural in pediatric patients for postoperative pain relief. In the present prospective randomized double blind study, 40 children of ASA-I-II aged 1-5 years scheduled for infraumblical surgical procedures were randomly allocated to two groups to receive either bupivacaine 0.25% (1 ml/kg) with fentanyl 1 μg/kg and clonidine 1μg/kg (group I) or bupivacaine 0.25% (1 ml/kg) with fentanyl 1 μg/kg (group II). Caudal block was performed after the induction of general anesthesia. Postoperatively patients were observed for analgesia, sedation, hemodynamic parameters, and side effects or complications. Both the groups were similar with respect to patient and various block characteristics. Heart rate and blood pressure were not different in 2 groups. Significantly prolonged duration of post-operative analgesia was observed in group I (Pbupivacaine in single shot caudal epidural in children may provide better and longer analgesia after infraumblical surgical procedures.

Fatal Fentanyl: One Pill Can Kill.

Science.gov (United States)

Sutter, Mark E; Gerona, Roy R; Davis, M Thais; Roche, Bailey M; Colby, Daniel K; Chenoweth, James A; Adams, Axel J; Owen, Kelly P; Ford, Jonathan B; Black, Hugh B; Albertson, Timothy E

2017-01-01

The current national opioid epidemic is a public health emergency. We have identified an outbreak of exaggerated opioid toxicity caused by fentanyl adulterated tablets purchased on the street as hydrocodone/acetaminophen. Over an 8-day period in late March 2016, a total of 18 patients presented to our institution with exaggerated opioid toxicity. The patients provided a similar history: ingesting their "normal dose" of hydrocodone/acetaminophen tablets but with more pronounced symptoms. Toxicology testing and analysis was performed on serum, urine, and surrendered pills. One of the 18 patients died in hospital. Five patients underwent cardiopulmonary resuscitation, one required extracorporeal life support, three required intubation, and two received bag-valve-mask ventilation. One patient had recurrence of toxicity after 8 hours after naloxone discontinuation. Seventeen of 18 patients required boluses of naloxone, and four required prolonged naloxone infusions (26-39 hours). All 18 patients tested positive for fentanyl in the serum. Quantitative assays conducted in 13 of the sera revealed fentanyl concentrations of 7.9 to 162 ng/mL (mean = 52.9 ng/mL). Pill analysis revealed fentanyl amounts of 600-6,900 μg/pill. The pills are virtually indistinguishable from authentic hydrocodone/acetaminophen tablets and are similar in weight. To date, our county has reported 56 cases of fentanyl opioid toxicity, with 15 fatalities. In our institution, the outbreak has stressed the capabilities and resources of the emergency department and intensive care units. A serious outbreak of exaggerated opioid toxicity caused by fentanyl-adulterated tablets purchased on the street as hydrocodone/acetaminophen is under way in California. These patients required higher dosing and prolonged infusions of naloxone. Additionally, observation periods off naloxone were extended due to delayed, recurrent toxicity. The outbreak has serious ramifications for public health and safety, law

Combination effect of low dose fentanyl and propofol on emergence agitation in children following sevoflurane anesthesia

International Nuclear Information System (INIS)

Bakhamees, Hassan S; Mercan, Arzu; ElHalafawy, Yasser M

2009-01-01

To investigate the combination effect of low dose fentanyl and subhypnotic dose of propofol on emergence agitation in children receiving sevoflurane for adenotonsillectomy procedure.After ethical approval, a prospective, randomized, clinical study was performed in Saad Specialist Hospital, Al-Khobar, Kingdom of Saudi Arabia in 2007-2008. One hundred and twenty children in physical status of I according to the American Society of Anesthesiologists, aged 2-6 years, scheduled for adentonsillectomy under general anesthesia were allocated into 3 groups randomly. Anesthesia was induced and maintained by sevoflurane in all groups. Children received 0.1 ml.kg-1 normal saline at the end of surgery in group C (n=40), 1.5 mcg.kg-1 fentanyl during induction, and 0.1 ml.kg-1 normal saline at the end of surgery in group F (n=40), and 1.5 mcg.kg-1 fentanyl during induction and 1 mg.kg-1 propofol at the end of surgery in group FP (n=40). Postoperative agitation was recorded, if any, for the first postoperative hour.Three groups were comparable with regard to demographic data. Twenty-one patients (53%) in the control group, 14 patients (35%) in group F and 7 (18%) patients in group FP experienced postoperative agitation.The combination of low dose fentanyl before surgery and propofol at the end of surgery decreases the incidence and level of emergence agitation in children after adenotonsillectomy procedure under sevoflurane anesthesia. (author)

Comparison of Postoperative Analgesic Effects of Thoracic Epidural Morphine and Fentanyl

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Gönül Sağıroğlu

2011-11-01

Full Text Available Objective: In our study, we aimed to compare epidural morphine and fentanyl analgesia and the side effects in post-thoracotomy pain management. Material and Methods: Forty patients, planned for elective thoracotomy were included. Bupivacain- morphine was administered through an epidural catheter to the patients in Group-M while bupivacain-fentanyl was given in Group-F. Pain assessment was carried out with the Visual Analogue Scale (VAS and VAS-I and VAS-II were assessed in 0, 4, 16 and 24th hour in the postoperative unit. Adverse effects were recorded after the 24th hour. Statistical analyses were performed by using Two-sample independent-t test, Mann Whitney-U test, Wilcoxon-signed ranks test and Pearson chi-squared tests. Results: Although, the VAS-I and VAS-II scores were lower in Group-M than Group-F, the difference was not significant statistically (p>0.05. When other hours were compared with initial states, beginning from the 4th hour, in both groups there was a statistically significant drop in VAS-I and VAS-II scores at all times (p<0.001. Comparing the complications between the groups, in Group-M nausea-vomiting (p<0.015 and bradycardia (p<0.012 were found significantly more frequently than in Group-F. Conclusion: We concluded that, in pain management after thoracic surgery, either morphine or fentanyl may be chosen in thoracal epidural analgesia but, especially in the early postoperative hours, close follow-up is necessary due to the risk of bradycardia development.

The effect of small dose bupivacaine-fentanyl in spinal anesthesia on hemodynamic nausea and vomiting in cesarean section

International Nuclear Information System (INIS)

Seyedhejazi, M.; Madarek, E.

2007-01-01

To compare the hemodynamic, nausea and vomiting with small dose bupivacaine-fentanyl spinal anesthetic versus a conventional dose of spinal bupivacaine in parturients undergoing cesarean section. Forty patients aged 17-35 years old which underwent cesarean section were randomized into two groups. Group-A received spinal anesthesia with 8 mg of bupivacaine and 10 microg fentanyl, group B received 12 mg bupivacaine. The mean dose of ephedrine needed was 4mg in group A and 11.75 mg in group B (P=0.006). The mean ratio of lowest systolic pressure to baseline systolic pressure was 0.75 for group A and 0.65 for group B (P=0.04). Nausea and vomiting was observed in 10% of group A versus 20% in group B. Small dose of bupivacaine and fentanyl provides good spinal anesthesia for cesarean section with less hypotension, nausea and vomiting. (author)

Transdermal granisetron.

Science.gov (United States)

Duggan, Sean T; Curran, Monique P

2009-01-01

Granisetron is a highly selective serotonin 5-HT(3) receptor antagonist for the prevention of chemotherapy-induced nausea and vomiting. The transdermal granisetron system delivers continuous granisetron (3.1 mg/day) into the systemic circulation (via passive diffusion) for up to 7 days. In a large phase III trial in cancer patients receiving multi-day (3-5 days) moderately or highly emetogenic chemotherapy, transdermal granisetron applied 24-48 hours prior to chemotherapy and remaining in place for 7 days was noninferior to oral granisetron 2 mg once daily administered for 3-5 days 1 hour prior to chemotherapy. Efficacy was assessed according to the proportion of patients achieving complete response (no vomiting and/or retching, no more than mild nausea, no rescue medication) from the first day, until 24 hours after the start of the last day, of administration of the chemotherapy regimen. In a phase II trial in patients with cancer receiving single-day, moderately-emetogenic chemotherapy, transdermal granisetron applied at least 24 hours prior to chemotherapy and removed after 5 days was as effective as a single oral dose of granisetron 2 mg in achieving total control (no nausea, no vomiting/retching, no use of rescue medication and no study withdrawal) during the delayed (24-120 hours; primary endpoint) period after chemotherapy. Transdermal granisetron was generally well tolerated in clinical trials, with few adverse events being treatment related.

Subcutaneous Fentanyl Administration: A Novel Approach for Pain Management in a Rural and Suburban Prehospital Setting.

Science.gov (United States)

Lebon, Johann; Fournier, Francis; Bégin, François; Hebert, Denise; Fleet, Richard; Foldes-Busque, Guilaume; Tanguay, Alain

2016-01-01

To determine the feasibility, safety, and effectiveness of the subcutaneous route of fentanyl administration by Basic Life Support-Emergency Medical Technicians (BLS-EMT) in a rural and suburban region, with the support of an online pain management medical control center. Retrospective study of patients who received subcutaneous fentanyl and were transported by BLS-EMT to the emergency department (ED) of an academic hospital between July 1, 2013 and January 1, 2014, inclusively. Fentanyl orders were obtained from emergency physicians via an online medical control (OLMC) center. Effectiveness was defined by changes in pain scores 15 minutes, 30 minutes, and 45+ minutes after initial fentanyl administration. Safety was evaluated by measuring vital signs, Ramsay sedation scores, and adverse events subsequent to fentanyl administration. Feasibility was defined as successful fentanyl administration by BLS-EMT. SPSS-20 was used for descriptive statistics, and independent t-tests and Mann-Whitney U tests were used to determine inter- and intra-group differences based on transport time. Two hundred and eighty-eight patients (288; 14 to 93 years old) with pain scores ≥7 were eligible for the study. Of the 284 (98.6%) who successfully received subcutaneous fentanyl, 35 had missing records or data, and 249 (86.5%) were included in analyses. Average pain score pre-fentanyl was 8.9 ± 1.1. Patients fentanyl than those ≥70 years old (1.4 ± 0.3 vs, 0.8 ± 0.2 mcg/kg, p fentanyl administration and the proportion of patients achieving pain relief increased significantly (p 3 (n = 1; 0.4%). Prehospital subcutaneous fentanyl administration by BLS-EMT with the support of an OLMC center is a safe and feasible approach to pain relief in prehospital settings, and is not associated with major adverse events. Effectiveness, subsequent to subcutaneous fentanyl administration is characterized by a decrease in pain over the course of transport to ED. Further studies are needed to

A COMPARATIVE STUDY OF PREEMPTIVE USE OF 0.2% ROPIVACAINE AND 0.125% BUPIVACAINE ALONG WITH FENTANYL AND FENTANYL INCREMENTS TO PROVIDE POSTOPERATIVE EPIDURAL ANALGESIA UP TO 24 HOURS

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Chiranji Lal Khedia

2016-06-01

Full Text Available BACKGROUND AND OBJECTIVES The present study was carried out to compare duration of analgesia, haemodynamic changes (Systolic and Diastolic Blood Pressure, Pulse Rate, Respiratory Rate, total incremental doses of epidural fentanyl required to maintain VAS 3 up to 24 hours in each group and total required incremental fentanyl doses were compared between both the groups. Once the data were collected from all the patients, they were compared using, chi-square test, two sample t-test. The p-value was calculated and P <0.05 was considered statistically significant. RESULTS The duration of analgesia was more with Group BF (245+17.58 min. than Group RF (217.6+22.41 min., thus it is concluded that difference in duration of analgesia was statistically significant between the groups (P<0.05. In this study, it was noticed that patients of Group RF required much more incremental doses of epidural fentanyl (218+31.88 μg to maintain VAS<3 up to 24 hours than group BF (170+32.27 μg, and difference was statistically significant (P<0.05. Haemodynamic parameters like SBP, DBP, HR and RR were comparable in both the groups. Hypotension and bradycardia were noted in two patients of group BF. CONCLUSION Duration of analgesia was longer and comparatively better in group BF and less incremental doses were required to maintain VAS <3 up to 24 hours as compared to group RF, but haemodynamic stability was more in group RF as compared to group BF.

Safety and efficiency of prehospital pain management with fentanyl administered by emergency medical technicians

DEFF Research Database (Denmark)

Nielsen, Niels Dalsgaard; Brogaard, Kjeld; Dahl, Michael

2007-01-01

Introduction: In our region Advanced Emergency Medical Technicians (AEMTs) respond to acutely ill or injured patients in rural areas. The AEMTs have been authorized to administer fentanyl intravenously in doses up to 2 μg/kg to selected groups of patients in pain. Higher doses can be allowed...... by a physician after a teleconference. We examined the effect of intravenous (IV) fentanyl treatment, expressed as pain reduction on a 10-point Numeric Rating Scale (NRS). Moreover we examined the occurrence of negative coincident events to assess whether it was safe to let non-medical staff administer potent...... opioids intravenously.   Methods: Retrospectively we collected the case sheets for all patients treated with IV fentanyl by the AEMTs in 2005 and 2006. We excluded all patients where a physician had been directly involved in the prehospital treatment. We recorded the IV fentanyl dose, NRS-score before...

Transdermal therapeutic system of narcotic analgesics using nonporous membrane (I) : Effect of the ethanol permeability on vinylacetate content of EVA membrane

Energy Technology Data Exchange (ETDEWEB)

Kwon, H.; Song, H.Y. [Chungnam National University, Taejon (Korea); Khang, G.S. [Chonbuk National University, Chonju (Korea); Lee, H.B. [Korea Research Institute of Chemical Technology, Taejon (Korea)

1999-05-01

The fundamental properties of transdermal therapeutic patch as narcotic analgesics agent has been investigated. From the study of drug and ethanol release patterns from the fentanyl base (FB) patches through diffusion cell and hairless mouse skin, it was observed that the FB release patterns were largely affected by the content of vinyl acetate (VA) of ethylene-co-vinyl acetate (EVA) membrane, and volume fraction of ethanolic solution. Additionally, a variety of control membrane as a function of VA content were examined for swelling following equilibration with ethanolic solutions. Generally, ethanol was incorporated into a transdermal therapeutic device to enable the controlled delivery of enhancer and drug to the skin surface. In vitro skin permeation analysis of the control membrane showed that ethanol flux was linearly related to the ethanol volume fraction. This result was shown that drug permeability increased with increasing as the content of VA. But, the FB flux from saturated aqueous ethanol solutions increases until 80% ethanol volume fraction. Over 80% ethanol volume fraction, the FB flux through skin samples is independent of ethanol volume. These results showed that the decrease in skin permeation due to dehydration nis the dominant effect. 26 refs., 8 figs.

Challenges and opportunities in dermal/transdermal delivery

Science.gov (United States)

Paudel, Kalpana S; Milewski, Mikolaj; Swadley, Courtney L; Brogden, Nicole K; Ghosh, Priyanka; Stinchcomb, Audra L

2010-01-01

Transdermal drug delivery is an exciting and challenging area. There are numerous transdermal delivery systems currently available on the market. However, the transdermal market still remains limited to a narrow range of drugs. Further advances in transdermal delivery depend on the ability to overcome the challenges faced regarding the permeation and skin irritation of the drug molecules. Emergence of novel techniques for skin permeation enhancement and development of methods to lessen skin irritation would widen the transdermal market for hydrophilic compounds, macromolecules and conventional drugs for new therapeutic indications. As evident from the ongoing clinical trials of a wide variety of drugs for various clinical conditions, there is a great future for transdermal delivery of drugs. PMID:21132122

Pharmacokinetics and safety of fentanyl sublingual spray and fentanyl citrate intravenous: a single ascending dose study in opioid-naïve healthy volunteers.

Science.gov (United States)

Rauck, Richard; Oh, D Alexander; Parikh, Neha; Koch, Christian; Singla, Neil; Yu, Jin; Nalamachu, Srinivas; Vetticaden, Santosh

2017-11-01

Fentanyl sublingual spray offers rapid pain relief in opioid-tolerant cancer patients, and may be useful in acute or post-operative pain. Both opioid-naïve and non-tolerant patients are likely to receive opioids in these settings. Understanding the relationship between systemic exposure of fentanyl sublingual spray and effects on respiratory function in opioid-naïve or non-tolerant populations is important to ensure patient safety. This study evaluated single-dose fentanyl sublingual spray in opioid-naïve participants. Participants were randomized to receive single-dose fentanyl sublingual spray (100, 200, 400, 600, 800 mcg) or fentanyl citrate IV in one of five cohorts. Dosing occurred following a 10-h fast, with fasting continuing for 4 h post-dose. Dose proportionality was assessed using analysis of variance and linear regression techniques. PK assessments and safety monitoring were performed through 24 h post-dose. Safety assessments, including adverse event (AE) monitoring, occurred from dosing through Day 7. Fifty participants (19-53 years) received fentanyl sublingual spray or fentanyl citrate IV. Mean maximum plasma concentrations were reached between 0.27-0.60 h post-dose for fentanyl sublingual spray. Peak (C max ) and total (AUC 0- t , AUC 0-∞ ) fentanyl exposures increased in a linear, but more than dose-proportional manner, with higher doses. The most common AEs were somnolence, nausea, and vomiting. All AEs were mild or moderate in severity. Doses at 400, 600, and 800 mcg were associated with nausea and vomiting, requiring pharmacologic intervention. Hypoxia episodes requiring nasal cannula oxygenation were observed with 600mcg and 800mcg doses. Overall, single-dose fentanyl sublingual spray (100-800 mcg) was generally well tolerated, with greater incidences of AEs (e.g. nausea, vomiting, hypoxia) at higher doses. Doses up to 200 mcg may be safely administered to healthy opioid-naïve individuals with routine monitoring; doses

Fentanyl bolus induces muscle tremors in sevoflurane-anaesthetized piglets.

Science.gov (United States)

Ringer, S K; Spielmann, N; Weiss, M; Mauch, J Y

2016-08-01

Intravenous fentanyl (10 mcg/kg) or saline (control) was randomly administered to 10 healthy sevoflurane-mono-anaesthetized piglets. Trembling was assessed by two blinded observers using a visual analogue scale (VAS) and a simple ordinal scale at baseline and 5 min (T5) after drug administration. If no trembling was observed at that time point, the opposite treatment was administered and piglets were re-evaluated after another 5 min (T10). Four out of five piglets showed trembling after fentanyl (T5), while none given saline showed any trembling. With fentanyl the VAS scores were significantly higher at T5 compared either with baseline or with the control treatment. Control animals received fentanyl after the 5 min evaluation and all piglets showed clear trembling afterwards. The median time after fentanyl administration until first muscle tremors was 51 (20-840) s. In summary, nine out of 10 sevoflurane-anaesthetized piglets showed muscle tremors after intravenous fentanyl. Tremors subsided over time and no specific treatment was necessary. © The Author(s) 2015.

Myth or Reality-Transdermal Magnesium?

Science.gov (United States)

Gröber, Uwe; Werner, Tanja; Vormann, Jürgen; Kisters, Klaus

2017-07-28

In the following review, we evaluated the current literature and evidence-based data on transdermal magnesium application and show that the propagation of transdermal magnesium is scientifically unsupported. The importance of magnesium and the positive effects of magnesium supplementation are extensively documented in magnesium deficiency, e.g., cardiovascular disease and diabetes mellitus. The effectiveness of oral magnesium supplementation for the treatment of magnesium deficiency has been studied in detail. However, the proven and well-documented oral magnesium supplementation has become questioned in the recent years through intensive marketing for its transdermal application (e.g., magnesium-containing sprays, magnesium flakes, and magnesium salt baths). In both, specialist and lay press as well as on the internet, there are increasing numbers of articles claiming the effectiveness and superiority of transdermal magnesium over an oral application. It is claimed that the transdermal absorption of magnesium in comparison to oral application is more effective due to better absorption and fewer side effects as it bypasses the gastrointestinal tract.

Self-identification of nonpharmaceutical fentanyl exposure following heroin overdose.

Science.gov (United States)

Griswold, Matthew K; Chai, Peter R; Krotulski, Alex J; Friscia, Melissa; Chapman, Brittany; Boyer, Edward W; Logan, Barry K; Babu, Kavita M

2018-01-01

To compare user self-identification of nonpharmaceutical fentanyl exposure with confirmatory urine drug testing in emergency department (ED) patients presenting after heroin overdose. This was a cross-sectional study of adult ED patients who presented after a heroin overdose requiring naloxone administration. Participants provided verbal consent after which they were asked a series of questions regarding their knowledge, attitudes and beliefs toward heroin and nonpharmaceutical fentanyl. Participants also provided urine samples, which were analyzed using liquid chromatography coupled to quadrupole time-of-flight mass spectrometry to identify the presence of fentanyl, heroin metabolites, other clandestine opioids, common pharmaceuticals and drugs of abuse. Thirty participants were enrolled in the study period. Ten participants (33%) had never required naloxone for an overdose in the past, 20 participants (67%) reported recent abstinence, and 12 participants (40%) reported concomitant cocaine use. Naloxone was detected in all urine drug screens. Heroin or its metabolites were detected in almost all samples (93.3%), as were fentanyl (96.7%) and its metabolite, norfentanyl (93.3%). Acetylfentanyl was identified in nine samples (30%) while U-47700 was present in two samples (6.7%). Sixteen participants self-identified fentanyl in their heroin (sensitivity 55%); participants were inconsistent in their qualitative ability to identify fentanyl in heroin. Heroin users presenting to the ED after heroin overdose requiring naloxone are unable to accurately identify the presence of nonpharmaceutical fentanyl in heroin. Additionally, cutting edge drug testing methodologies identified fentanyl exposures in 96.7% of our patients, as well as unexpected clandestine opioids (like acetylfentanyl and U-47700).

Radioreceptor assay for analysis of fentanyl and its analogs in biological samples

Energy Technology Data Exchange (ETDEWEB)

Alburges, M.E.

1988-01-01

The assay is based on the competition of these drugs with ({sup 3}H) fentanyl for opioid receptors in membrane preparations of rat forebrain in vitro. The binding in stereospecific, reversible and saturable. Scatchard plots of saturation suggest the presence of high and low affinity binding sites. Morphine and hydromorphone complete with ({sup 3}H)fentanyl for the opioid receptor, but other morphine-like compounds were relatively weak displacers of ({sup 3}H)fentanyl. Many other commonly abused drugs do not compete with ({sup 3}H)fentanyl for the opioid receptors. Urine samples from animals injected with fentanyl, ({plus minus})-cis-3-methylfentanyl, alpha-methylfentanyl, butyrylfentanyl and benzylfentanyl were analyzed by radioreceptor assay, radioimmunoassay, and gas chromatography/mass spectrometry. Urinary analysis of fentanyl showed a good correlation with these three methods; however, discrepancies were observed in the analysis of fentanyl analogs. This radioreceptor assay is well-suited as an initial assay for the detection of active analogs of fentanyl in urine with good correlation with other techniques in the analysis of fentanyl; however, there is substantial disagreement between techniques in the quantitation of fentanyl analogs. The implications of these discrepancies are discussed.

Radioreceptor assay for analysis of fentanyl and its analogs in biological samples

International Nuclear Information System (INIS)

Alburges, M.E.

1988-01-01

The assay is based on the competition of these drugs with [ 3 H] fentanyl for opioid receptors in membrane preparations of rat forebrain in vitro. The binding in stereospecific, reversible and saturable. Scatchard plots of saturation suggest the presence of high and low affinity binding sites. Morphine and hydromorphone complete with [ 3 H]fentanyl for the opioid receptor, but other morphine-like compounds were relatively weak displacers of [ 3 H]fentanyl. Many other commonly abused drugs do not compete with [ 3 H]fentanyl for the opioid receptors. Urine samples from animals injected with fentanyl, (±)-cis-3-methylfentanyl, alpha-methylfentanyl, butyrylfentanyl and benzylfentanyl were analyzed by radioreceptor assay, radioimmunoassay, and gas chromatography/mass spectrometry. Urinary analysis of fentanyl showed a good correlation with these three methods; however, discrepancies were observed in the analysis of fentanyl analogs. This radioreceptor assay is well-suited as an initial assay for the detection of active analogs of fentanyl in urine with good correlation with other techniques in the analysis of fentanyl; however, there is substantial disagreement between techniques in the quantitation of fentanyl analogs. The implications of these discrepancies are discussed

Fentanyl Sublingual Spray

Science.gov (United States)

... medication, and who are tolerant (used to the effects of the medication) to narcotic pain medications. Fentanyl ... medications for seizures such as carbamazepine (Tegretol, Teril), oxcarbazepine (Trileptal), and phenytoin (Dilantin, Phenytek); modafinil (Provigil); nalbuphine; ...

Fentanyl Nasal Spray

Science.gov (United States)

... medication, and who are tolerant (used to the effects of the medication) to narcotic pain medications. Fentanyl ... Afrin, Neo-Synephrine, Vicks Sinex, others); nevirapine (Viramune); oxcarbazepine (Trileptal); pentazocine (Talwin); phenytoin (Dilantin, Phenytek); pioglitazone (Actos, ...

Comparison of Preanesthetic Sedation after Intranasal Administration of Fentanyle, Ketamin and Midazolam

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F Javaherforoosh

2006-07-01

Full Text Available Introduction & Objective: Induction of anesthesia in children can be a challenge for anesthetist. A stormy induction may increase the personality & behavioral changes. Therefore, it is desirable that they enter the operating room sedated. Many drugs are used for preanesthetic medication and there are many routes for administration. One route of administration is nasal mucous. In this study we compared the effect and side effect of three drugs (midazolam, ketamin and fentanyle after intra nasal administration. Materials & Methods: This is a double blind clinical trial. In this study we selected 60 patients (20 patients for every group A, B or C. We used 3 mg/kg ketamin or 3µg/kg fentanyle or 0.3 mg/kg midazolam by intranasal spray. After administration and in 5, 10 and 15 minutes, we observed the SPO2, PR and RR. After 15 min’s we separated children from parents and brought them to the operating room and controlled the acceptance of separation, depth of sedation with Ramsay score, acceptance of mask and tolerance of IV canulation. The data were then analyzed using K2 and kruskal-wallis test. Results: In our study we found that in SPO2 fentanyle had the highest rate of reduction even though none of the children had SPO2 lower than 90%. There were no differences between drugs in RR. In fentanyle group, we had the lowest rate and in ketamin group the highest rate. Midazolam had the medium rate. The rate of sedation for acceptance of separation from parents had no difference between the groups and all drugs with this dosage were effective for this aim. However, in Ramsay score, acceptance of mask and tolerance of IV canulation, the midazolam was more effective than the others. Conclusion: Intranasal administration of midazolam is a safe route for sedation in children in the pre-anesthetic time.

Comparison of the effects of oxycodone versus fentanyl on airway reflex to tracheal extubation and postoperative pain during anesthesia recovery after laparoscopic cholecystectomy: A double-blind, randomized clinical consort study.

Science.gov (United States)

Choi, Eun Kyung; Kwon, Nyeongkeon; Park, Sang-Jin

2018-03-01

Fentanyl has been suggested to be effective for controlling airway and hemodynamic responses to tracheal extubation. This study was performed to compare the effects of oxycodone and fentanyl on airway and hemodynamic responses and postoperative pain during the recovery period in patients undergoing laparoscopic cholecystectomy. Ninety patients aged 18 to 65 years were randomly allocated to 1 of 3 groups: fentanyl, oxycodone, and control. Coughing responses (incidence and severity), hemodynamic responses during the recovery period, and acute postoperative pain were assessed. The incidence of cough was decreased in the fentanyl and oxycodone groups compared with that in the control group at the points of awareness and extubation, and no significant difference was observed between the 2 treatment groups. Severe cough response was decreased in the fentanyl and oxycodone groups compared with that in the control group at the point of extubation, and no significant change was observed in cough severity between the 2 treatment groups. Postoperative pain scores were lower in the fentanyl and oxycodone groups than those in the control group at 5 and 30 minutes postoperatively, and no significant difference was observed between the 2 treatment groups. Hemodynamic responses did not differ among the 3 groups during the recovery period. Oxycodone treatment before tracheal extubation reduced cough response and was as effective as fentanyl treatment for improving extubation quality. Furthermore, single boluses of fentanyl and oxycodone showed equal effectiveness in attenuating acute postoperative pain in patients undergoing laparoscopic cholecystectomy.

Transdermal patches: history, development and pharmacology

Science.gov (United States)

Pastore, Michael N; Kalia, Yogeshvar N; Horstmann, Michael; Roberts, Michael S

2015-01-01

Transdermal patches are now widely used as cosmetic, topical and transdermal delivery systems. These patches represent a key outcome from the growth in skin science, technology and expertise developed through trial and error, clinical observation and evidence-based studies that date back to the first existing human records. This review begins with the earliest topical therapies and traces topical delivery to the present-day transdermal patches, describing along the way the initial trials, devices and drug delivery systems that underpin current transdermal patches and their actives. This is followed by consideration of the evolution in the various patch designs and their limitations as well as requirements for actives to be used for transdermal delivery. The properties of and issues associated with the use of currently marketed products, such as variability, safety and regulatory aspects, are then described. The review concludes by examining future prospects for transdermal patches and drug delivery systems, such as the combination of active delivery systems with patches, minimally invasive microneedle patches and cutaneous solutions, including metered-dose systems. PMID:25560046

Transdermal drug delivery

OpenAIRE

Prausnitz, Mark R.; Langer, Robert

2008-01-01

Transdermal drug delivery has made an important contribution to medical practice, but has yet to fully achieve its potential as an alternative to oral delivery and hypodermic injections. First-generation transdermal delivery systems have continued their steady increase in clinical use for delivery of small, lipophilic, low-dose drugs. Second-generation delivery systems using chemical enhancers, non-cavitational ultrasound and iontophoresis have also resulted in clinical products; the ability ...

Investigating the Effects of Adding Fentanyl to Bupivacaine in Spinal Anesthesia of Opium-addicted Patients

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H Satari

2014-10-01

Full Text Available Introduction: Spinal anesthesia in opium-addicted patients can be associated with many complications. Hence, this study aimed to investigate sensory and motor block characteristics, duration of postoperative analgesia, hemodynamic and side effects by adding Fentanyl to bupivacaine in spinal Anesthesia of opium-addicted patients. Methods: In a double-blind randomized clinical trial, 60 American society of Anesthesiology (ASA class I and II opium-addicted patients under spinal anesthesia in lower abdominal and lower limb operations were randomly classified into two groups of spinal anesthesia with bupivacaine and bupivacaine-fentanyl. Clinical symptoms, side effects, the duration of sensory and motor block, initiation of analgesia requirement and sensory block were assessed. Results: The study results indicated no significant difference between bupivacaine and bupivacaine-fentanyl groups in regard with demographic, side effects, blood pressure and heart rate, though a significant difference was observed in respiratory rate 5min, 10min, 45min, 75min and 90 min after block. Duration of sensory (100.33 to 138.83 and motor block (93.43 to 107.66 and , initiation of analgesia requirement (165.33 to 187.76 was significantly longer in bupivacaine-fentanyl, though initiation of sensory block (8.83 to 4.93 was significantly longer in bupivacaine. Conclusion: Addition of fentanyl to bupivacaine in spinal anesthesia increases the duration of sensory and motor block and initiation of analgesia requirement in opium-addicted patients and also decreases initiation of sensory block in these patients.

Efficacy of magnesium sulphate and/or fentanyl as adjuvants to intrathecal low-dose bupivacaine in parturients undergoing elective caesarean section

Directory of Open Access Journals (Sweden)

Shelly Rana

2017-01-01

Full Text Available Background and Aim: Recent developments in the field of intrathecal adjuvants have led to accelerated functional recovery with adequate postoperative analgesia following caesarean section. Encouraging results have been obtained with the use of intrathecal magnesium with or without fentanyl in parturients. This study was conceived to evaluate the effects of adding magnesium sulphate and/or fentanyl to low-dose intrathecal bupivacaine in parturients undergoing caesarean section under subarachnoid block (SAB. Materials and Methods: Ninety, American Society of Anesthesiologists I or II, parturients for the elective caesarean section were enrolled in this prospective randomized, double-blind study. The parturients were randomly assigned to three groups. In Group M, parturients received 8.5 mg (1.7 mL hyperbaric bupivacaine 0.5% with 50 mg (0.1 mL magnesium sulphate and 0.4 mL normal saline. Group F received 8.5 mg hyperbaric bupivacaine 0.5% with 20 μg (0.4 mL fentanyl and 0.1 mL of normal saline and Group MF parturients received 8.5 mg hyperbaric bupivacaine 0.5% with 20 μg fentanyl added to 50 mg magnesium sulphate. Results: Parturients in the group MF were pain free for longest period (273.70 ± 49.30 min as compared to group M (252.67 ± 40.76 min and group F (239.80 ± 38.45 mins [gp MF vs F and, gp M vs F (P = 0.00]. The total doses of rescue analgesics were least in group MF (2.43 ± 0.56 and maximum in group F (3.30 ± 0.63, with comparable neonatal outcomes in three groups. Conclusion: Our data supports synergistic action of intrathecal magnesium sulphate to fentanyl, and it is concluded that on addition of intrathecal magnesium sulphate and fentanyl to low-dose bupivacaine as adjuvant in subarachnoid block, results in prolonged duration of postoperative analgesia with lesser pain scores and lesser dose of rescue analgesia with better haemodynamic stability.

Challenges and opportunities in dermal/transdermal delivery

OpenAIRE

Paudel, Kalpana S; Milewski, Mikolaj; Swadley, Courtney L; Brogden, Nicole K; Ghosh, Priyanka; Stinchcomb, Audra L

2010-01-01

Transdermal drug delivery is an exciting and challenging area. There are numerous transdermal delivery systems currently available on the market. However, the transdermal market still remains limited to a narrow range of drugs. Further advances in transdermal delivery depend on the ability to overcome the challenges faced regarding the permeation and skin irritation of the drug molecules. Emergence of novel techniques for skin permeation enhancement and development of methods to lessen skin i...

Spray-on transdermal drug delivery systems.

Science.gov (United States)

Ibrahim, Sarah A

2015-02-01

Transdermal drug delivery possesses superior advantages over other routes of administration, particularly minimizing first-pass metabolism. Transdermal drug delivery is challenged by the barrier nature of skin. Numerous technologies have been developed to overcome the relatively low skin permeability, including spray-on transdermal systems. A transdermal spray-on system (TSS) usually consists of a solution containing the drug, a volatile solvent and in many cases a chemical penetration enhancer. TSS promotes drug delivery via the complex interplay between solvent evaporation and drug-solvent drag into skin. The volatile solvent carries the drug into the upper layers of the stratum corneum, and as the volatile solvent evaporates, an increase in the thermodynamic activity of the drug occurs resulting in an increased drug loading in skin. TSS is easily applied, delivering flexible drug dosage and associated with lower incidence of skin irritation. TSS provides a fast-drying product where the volatile solvent enables uniform drug distribution with minimal vehicle deposition on skin. TSS ensures precise dose administration that is aesthetically appealing and eliminates concerns of residual drug associated with transdermal patches. Furthermore, it provides a better alternative to traditional transdermal products due to ease of product development and manufacturing.

In vitro and in vivo evaluation of a sublingual fentanyl wafer formulation

Science.gov (United States)

Lim, Stephen CB; Paech, Michael J; Sunderland, Bruce; Liu, Yandi

2013-01-01

Background The objective of this study was to prepare a novel fentanyl wafer formulation by a freeze-drying method, and to evaluate its in vitro and in vivo release characteristics, including its bioavailability via the sublingual route. Methods The wafer formulation was prepared by freeze-drying an aqueous dispersion of fentanyl containing sodium carboxymethylcellulose and amylogum as matrix formers. Uniformity of weight, friability, and dissolution testing of the fentanyl wafer was achieved using standard methods, and the residual moisture content was measured. The fentanyl wafer was also examined using scanning electron microscopy and x-ray diffraction. The absolute bioavailability of the fentanyl wafer was evaluated in 11 opioid-naïve adult female patients using a randomized crossover design. Results In vitro release showed that almost 90% of the fentanyl dissolved in one minute. In vivo, the first detectable plasma fentanyl concentration was observed after 3.5 minutes and the peak plasma concentration between 61.5 and 67 minutes. The median absolute bioavailability was 53.0%. Conclusion These results indicate that this wafer has potential as an alternative sublingual fentanyl formulation. PMID:23596347

Transdermal drug delivery

Science.gov (United States)

Prausnitz, Mark R.; Langer, Robert

2009-01-01

Transdermal drug delivery has made an important contribution to medical practice, but has yet to fully achieve its potential as an alternative to oral delivery and hypodermic injections. First-generation transdermal delivery systems have continued their steady increase in clinical use for delivery of small, lipophilic, low-dose drugs. Second-generation delivery systems using chemical enhancers, non-cavitational ultrasound and iontophoresis have also resulted in clinical products; the ability of iontophoresis to control delivery rates in real time provides added functionality. Third-generation delivery systems target their effects to skin’s barrier layer of stratum corneum using microneedles, thermal ablation, microdermabrasion, electroporation and cavitational ultrasound. Microneedles and thermal ablation are currently progressing through clinical trials for delivery of macromolecules and vaccines, such as insulin, parathyroid hormone and influenza vaccine. Using these novel second- and third-generation enhancement strategies, transdermal delivery is poised to significantly increase impact on medicine. PMID:18997767

Efficacy and safety of intravenous fentanyl administered by ambulance personnel

DEFF Research Database (Denmark)

Friesgaard, Kristian Dahl; Nikolajsen, Lone; Giebner, Matthias

2016-01-01

BACKGROUND: Management of pain in the pre-hospital setting is often inadequate. In 2011, ambulance personnel were authorized to administer intravenous fentanyl in the Central Denmark Region. The aim of this study was to evaluate the efficacy and safety of intravenous fentanyl administered...... by ambulance personnel. METHODS: Pre-hospital medical charts from 2348 adults treated with intravenous fentanyl by ambulance personnel during a 6-month period were reviewed. The primary outcome was the change in pain intensity on a numeric rating scale (NRS) from before fentanyl treatment to hospital arrival...... patients (1.3%) and hypotension observed in 71 patients (3.0%). CONCLUSION: Intravenous fentanyl caused clinically meaningful pain reduction in most patients and was safe in the hands of ambulance personnel. Many patients had moderate to severe pain at hospital arrival. As the protocol allowed higher doses...

Comparison of Dexmedetomidine and Fentanyl as an Adjuvant to Ropivacaine for Postoperative Epidural Analgesia in Pediatric Orthopedic Surgery.

Science.gov (United States)

Park, Sang Jun; Shin, Seokyung; Kim, Shin Hyung; Kim, Hyun Woo; Kim, Seung Hyun; Do, Hae Yoon; Choi, Yong Seon

2017-05-01

Opioids are commonly used as an epidural adjuvant to local anesthetics, but are associated with potentially serious side effects, such as respiratory depression. The aim of this study was to compare the efficacy and safety of dexmedetomidine with that of fentanyl as an adjuvant to epidural ropivacaine in pediatric orthopedic surgery. This study enrolled 60 children (3-12 years old) scheduled for orthopedic surgery of the lower extremities and lumbar epidural patient-controlled analgesia (PCA). Children received either dexmedetomidine (1 μg/kg) or fentanyl (1 μg/kg) along with 0.2% ropivacaine (0.2 mL/kg) via an epidural catheter at 30 minutes before the end of surgery. Postoperatively, the children were observed for ropivacaine consumption via epidural PCA, postoperative pain intensity, need for rescue analgesics, emergence agitation, and other adverse effects. The mean dose of bolus epidural ropivacaine was significantly lower within the first 6 h after surgery in the dexmedetomidine group, compared with the fentanyl group (0.029±0.030 mg/kg/h vs. 0.053±0.039 mg/kg/h, p=0.012). The median pain score at postoperative 6 h was also lower in the dexmedetomidine group, compared to the fentanyl group [0 (0-1.0) vs. 1.0 (0-3.0), p=0.039]. However, there was no difference in the need for rescue analgesia throughout the study period between groups. The use of dexmedetomidine as an epidural adjuvant had a significantly greater analgesic and local anesthetic-sparing effect, compared to fentanyl, in the early postoperative period in children undergoing major orthopedic lower extremity surgery. © Copyright: Yonsei University College of Medicine 2017

Topical fentanyl stimulates healing of ischemic wounds in diabetic rats

Science.gov (United States)

FAROOQUI, Mariya; ERICSON, Marna E; GUPTA, Kalpna

2016-01-01

Background Topically applied opioids promote angiogenesis and healing of ischemic wounds in rats. We examined if topical fentanyl stimulates wound healing in diabetic rats by stimulating growth-promoting signaling, angiogenesis, lymphangiogenesis and nerve regeneration. Methods We used Zucker diabetic fatty rats that develop obesity and diabetes on a high fat diet due to a mutation in the Leptin receptor. Fentanyl blended with hydrocream was applied topically on ischemic wounds twice daily, and wound closure was analyzed regularly. Wound histology was analyzed by hematoxylin and eosin staining. Angiogenesis, lymphangiogenesis, nerve fibers and phospho-PDGFR-β were visualized by CD31-, lymphatic vessel endothelium-1, protein gene product 9.5- and anti-phospho PDGFR-β-immunoreactivity, respectively. Nitric oxide synthase (NOS) and PDGFR-β signaling were analyzed using Western immunoblotting. Results Fentanyl significantly promoted wound closure as compared to PBS. Histology scores were significantly higher in fentanyl-treated wounds, indicative of increased granulation tissue formation, reduced edema and inflammation, and increased matrix deposition. Fentanyl treatment resulted in increased wound angiogenesis, lymphatic vasculature, nerve fibers, nitric oxide, NOS and PDGFR-β signaling as compared to PBS. Phospho PDGFR-β co-localized with CD31 co-staining for vasculature. Conclusions Topically applied fentanyl promotes closure of ischemic wounds in diabetic rats. Increased angiogenesis, lymphangiogenesis, peripheral nerve regeneration, NO and PDGFR-β signaling are associated with fentanyl-induced tissue remodeling and wound healing. PMID:25266258

Comparison of intrathecal plain articaine and levobupivacaine with fentanyl for Caesarean section.

Science.gov (United States)

Demircioglu, Rüveyda I; Gozdemir, Muhammet; Usta, Burhanettin; Sert, Hüseyin; Karabayirli, Safinaz; Muslu, Bünyamin; Keskin, Esra A

2016-12-01

Articaine is used as a local anesthetic for outpatient surgery because it offers rapid onset of anesthesia and short duration motor block. Levobupivacaine is often preferred for Caesarean section. We evaluated the anesthetic characteristics of fentanyl-supplemented plain articaine and levobupivacaine for Caesarean section under combine spinal epidural anesthesia. Patients undergoing Caesarean section received in random order plain articaine 40 mg (Group A, n=50) or plain levobupivacaine 10 mg (Group L, n=50) mixed with fentanyl 20 µg intrathecally. The onset and duration of sensory and motor block, first analgesic request, and hemodynamic parameters were recorded. Onset times of maximum motor block were longer in Group L than Group A (P=0,001). Time to two-segment regression of sensory block were 70 min for Group A and 90 min group L (P=0.001). Times to complete regression of motor blockade were significantly longer in group L than group A (P =0,001). To have a faster onset and shorter duration of spinal anesthesia, we recommend the use of plain articaine for Caesarean section.

Evaluation of the Coat-A-Count sup 125 I fentanyl RIA: Comparison of sup 12 5I RIA and GC/MS-SIM for quantification of fentanyl in case urine specimens

Energy Technology Data Exchange (ETDEWEB)

Watts, V.W.; Caplan, Y.H. (Mesa Police Crime Laboratory, AZ (USA))

1990-09-01

The Coat-A-Count solid phase {sup 125}I Fentanyl Radioimmunoassay was evaluated with respect to linearity and precision using equine urine fortified with fentanyl and then compared with a gas chromatographic/mass spectrometric method for quantification of fentanyl in urine. The RIA assay was found to be linear over the urine fentanyl concentration range of 0.25 to 7.5 ng/mL and precise with coefficients of variation (CV) ranging from 9.6 to 19.3%. The RIA calibrators, ranging in fentanyl concentrations from 0.25 to 7.5 ng/mL, and controls, at mean fentanyl concentrations of 0.46 and 1.32 ng/mL, were compared by both the RIA and GC/MS methods. The cross-reactivity with the {sup 125}I RIA test was determined for the fentanyl metabolites, norfentanyl and hydroxyfentanyl, and found to be 5% and 35%, respectively. The illicit fentanyl analogs were found to show significant cross-reactivity, ranging from 20 to 100%. The {sup 125}I RIA was compared to GC/MS quantifications of fentanyl in 35 positive and 20 negative case urine specimens.

Therapeutic serum phenobarbital concentrations obtained using chronic transdermal administration of phenobarbital in healthy cats.

Science.gov (United States)

Delamaide Gasper, Joy A; Barnes Heller, Heidi L; Robertson, Michelle; Trepanier, Lauren A

2015-04-01

Seizures are a common cause of neurologic disease, and phenobarbital (PB) is the most commonly used antiepileptic drug. Chronic oral dosing can be challenging for cat owners, leading to poor compliance. The purpose of this study was to determine if the transdermal administration of PB could achieve serum PB concentrations of between 15 and 45 μg/ml in healthy cats. Nineteen healthy cats were enrolled in three groups. Transdermal PB in pluronic lecithin organogel (PLO) was applied to the pinnae for 14 days at a dosage of 3 mg/kg q12h in group 1 (n = 6 cats) and 9 mg/kg q12h in group 2 (n = 7 cats). Transdermal PB in Lipoderm Activemax was similarly applied at 9 mg/kg q12h for 14 days in group 3 (n = 6 cats). Steady-state serum PB concentrations were measured at trough, and at 2, 4 and 6 h after the morning dose on day 15. In group 1, median concentrations ranged from 6.0-7.5 μg/ml throughout the day (observed range 0-11 μg/ml). Group 2 median concentrations were 26.0 μg/ml (observed range 18.0-37.0 μg/ml). For group 3, median concentrations ranged from 15.0-17.0 μg/ml throughout the day (range 5-29 μg/ml). Side effects were mild. One cat was withdrawn from group 2 owing to ataxia and sedation. These results show therapeutic serum PB concentrations can be achieved in cats following chronic transdermal administration of PB in PLO at a dosage of 9 mg/kg q12h. More individual variation was noted using Lipoderm Activemax. Transdermal administration may be an alternative for cats that are difficult to medicate orally. © ISFM and AAFP 2014.

A comparative study of the effect of clonidine, fentanyl, and the combination of both as adjuvant to intrathecal bupivacaine for postoperative analgesia in total abdominal hysterectomy

Science.gov (United States)

Ahmed, Fareed; Khandelwal, Mamta; Sharma, Anil

2017-01-01

Background and Aims: The aim of this study was to evaluate the level of sensory block, onset and duration of motor block, postoperative analgesia, and adverse effects of combination of clonidine and fentanyl given intrathecally with hyperbaric bupivacaine (HB). Material and Methods: Three hundred and twenty eight patients were randomized into four groups. Group bupivacaine (group B) received 15 mg of HB; group bupivacaine clonidine (group BC) received 15 mg of HB plus 25 μg clonidine; group bupivacaine fentanyl (group BF) received 15 mg of HB plus 25 μg fentanyl and group bupivacaine clonidine fentanyl (group BCF) received 15 mg of HB plus 25 μg clonidine and 25 μg fentanyl intrathecally. All groups were evaluated for level of sensory block, onset and duration of motor block, postoperative analgesia, VAS score, sedation score and adverse effects of study drugs. All the data were analyzed using unpaired t-test. P < 0.05 was considered significant. Results: The level of sensory block, onset, and duration of motor block were comparable in all groups. Total duration of analgesia was 407.3 ± 20 min in group BCF compared to 242.1 ± 2 min and 209.2 ± 16 in groups BC and BF, respectively. Lesser doses of rescue analgesic were required in group BCF. The time interval from intrathecal injection to two-segment regression was statistically significant in study groups. Only 2.4% patients showed mild sedation in BCF group. Conclusion: We found that combination of intrathecal clonidine and fentanyl along with bupivacaine increases the total duration of analgesia without significant side effects. PMID:28413281

Fentanyl inhibits proliferation and invasion of colorectal cancer via β-catenin

Science.gov (United States)

Zhang, Xiu-Lai; Chen, Min-Li; Zhou, Sheng-Li

2015-01-01

Background and aim: Fentanyl is widely used for relieving pain and narcotizing in cancer patients. However, there are few published reports regarding the effects of fentanyl on tumor control and treatment. Here we investigated the effects of fentanyl on tumor growth and cell invasion in the human colorectal carcinoma (HCT116) cells. Methods: Nude mice xenografts of HCT116 cells were established to assess the inhibition effect on tumor growth by fentanyl. MTT and Transwell were employed to determine the cell survival rate and cell invasion, respectively. MicroRNAs and mRNAs expression were quantified by real-time PCR. β-catenin and matrix metalloproteinases (MMP-2 and MMP-9) expression were assayed by western blotting. β-Catenin-specific small interfering RNA (Si-β-catenin) and miR-182 mimics were transfected in cells to investigate the mechanism underlying the effects of fentanyl on the colorectal tumor and HCT116 cells. Results: Treatment with fentanyl inhibited the tumor growth and HCT116 cells invasion. Fentanyl also downregulated the expression of β-catenin and miR-182 in both xenograft tumors and HCT116 cells, and decreased the protein level of MMP-9 in HCT116 cells. Downregulation of β-Catenin resulted in the decrease of miR-182 expression in colorectal cells. In addition, the overexpression of miR-182 reversed the effect of fentanyl on MMP-9 expression and cell invasion of HCT116 cells. Conclusions: The current study demonstrated that the inhibition of tumor growth and cell invasion in colorectal cancer by fentanyl is probably due to downregulation of miR-182 and MMP-9 expression by β-catenin. PMID:25755709

The effect of titrated fentanyl on suppressed cough reflex in healthy adult volunteers.

Science.gov (United States)

Kelly, H E; Shaw, G M; Brett, C N; Greenwood, F M; Huckabee, M L

2016-05-01

Cough suppression is part of the pharmacodynamic profile of opioids. We investigated the impact of clinical doses of fentanyl on suppressing the cough reflex. Thirteen volunteers received 2 μg.kg(-1) of fentanyl in a divided administration protocol. Three minutes after each administration and at 10 min intervals during washout, suppressed cough reflex testing with nebulised citric acid was performed and compared with fentanyl effect-site concentration. Mean (SD) citric acid concentration provoking cough increased from 0.5 (0.28) mol.l(-1) at baseline to 1.2 (0.50) mol.l(-1) after 2 μg.kg(-1) of fentanyl (p = 0.01). Mean (SD) fentanyl effect-site concentration after the final dose of fentanyl was 1.89 (0.05) ng.ml(-1) . A strong positive correlation was found between suppressed cough reflex thresholds and fentanyl effect-site concentrations during both fentanyl administration and washout phases of the study (r(2) = 0.79, p = 0.01). The mean (SD) length of time for return of suppressed cough response was 44.6 (18.8) min. Clinically relevant doses of fentanyl produced cough reflex suppression in healthy volunteers. © 2016 The Association of Anaesthetists of Great Britain and Ireland.

Comparison of topical oxybuprocaine and intravenous fentanyl in pediatric strabismus surgery.

Science.gov (United States)

Yousafzai, Ibrahim; Zahoor, Abdul; Andrey, Butrov; Ahmad, Nauman

2017-01-01

To compare the outcomes such as postoperative nausea/vomiting, analgesic requirements, and hospital stay following the use of topical oxybuprocaine hydrochloride 0.4% or intravenous (IV) fentanyl in children undergoing strabismus surgery. This was a prospective cohort study. Children operated under general anesthesia for strabismus were given topical oxybuprocaine hydrochloride 0.4% (Group T) and IV fentanyl (Group F) before surgery. The episodes of nausea/vomiting, pain score, requirement of additional analgesia during postoperative period, and duration of hospital stay were compared in two groups. There were 47 children in Group T and 59 children in Group F. The median pain score in two groups were 2.38 (25% quartile; 2.0) and 3.00 (25% quartile; 3.00), respectively. The difference was significant (K W P < 0.03). The episodes of nausea/vomiting in two groups were in 2 and 6 children in Group T and Group F, respectively. The median hospital stay of children of Group T and Group F were 242 and 285 min, respectively. The difference was not statistically significant ( P = 0.22). Using intraoperative topical oxybuprocaine drops, one can achieve better analgesic outcomes and reduce risk of nausea and vomiting compared to intravenous opioid analgesics and therefore, the hospital stay could also be marginally reduced.

Encapsulated Curcumin for Transdermal Administration

African Journals Online (AJOL)

Purpose: To develop a proniosomal carrier system of curcumin for transdermal delivery. Methods: Proniosomes of curcumin were prepared by encapsulation of the drug in a mixture of Span 80, cholesterol and diethyl ether by ether injection method, and then investigated as a transdermal drug delivery system (TDDS).

Transdermal delivery of isoniazid and rifampin in guinea pigs by electro-phonophoresis.

Science.gov (United States)

Chen, Suting; Han, Yi; Yu, Daping; Huo, Fengmin; Wang, Fen; Li, Yunxu; Dong, Lingling; Liu, Zhidong; Huang, Hairong

2017-11-01

Electro-phonophoresis (EP) has been used as a drug delivery approach in clinical fields. The objective of the present study is to evaluate the skin permeability of isoniazid and rifampin in guinea pigs by EP to provide reference basis for clinical applications of such transdermal delivery system in the treatment of patients with superficial tuberculosis. Isoniazid and rifampin solutions were delivered transdermally with or without EP in health guinea pigs for 0.5 h. Local skin and blood samples were collected serially at 0, 1/2, 1, 2, 4, 6 and 24 h after dosing. Drug concentrations in local skin and blood were evaluated by high-performance liquid chromatography. Isoniazid concentrations in local skin of guinea pigs receiving isoniazid through EP transdermal delivery were significantly higher than in animals receiving only isoniazid with transdermal patch. However, for rifampin, patches alone group presented almost uniform concentration versus time curve with that of EP group, and both groups had concentrations much higher than the therapeutic concentration of the drug over sustainable time. After EP transdermal delivery, the mean peak concentrations of isoniazid and rifampin in skin were 771.0 ± 163.4 μg/mL and 81.2 ± 17.3 μg/mL respectively. Neither isoniazid nor rifampin concentration in blood could be detected (below the lower detection limit of 1 μg/mL) at any time point. The present study showed that application of EP significantly enhanced INH penetration through skin in guinea pigs, while RIF patch alone obtained therapeutic concentration in local skin. Our work suggests several possible medication approaches for efficient treatment of superficial tuberculosis.

Drug withdrawal symptoms in children after continuous infusions of fentanyl.

Science.gov (United States)

French, J P; Nocera, M

1994-04-01

The purpose of this research was to determine the extent to which critically ill infants exhibited signs and symptoms of narcotic withdrawal after receiving continuous infusions of fentanyl. The convenience sample consisted of 12 pediatric intensive care unit (PICU) patients under 25 months of age who received fentanyl infusions for at least 24 hours. Drug withdrawal symptoms were monitored using the Neonatal Abstinence Score Tool (NAST), which assigns a score to each behavior indicative of withdrawal. A score of 8 or greater indicates Neonatal Abstinence Syndrome (NAS). Scoring began 4 hours after discontinuation of fentanyl and was conducted once per hour for 8 hours. Six subjects had a NAST score exceeding 8; these infants frequently exhibited tremors with or without stimulation, increased muscle tone, insomnia, and increased respiratory rate and effort. There were significant correlations between fentanyl dosage and NAST score (r = .76, p observation protocol and a possible weaning regimen after fentanyl is discontinued.

Fentanyl Suppresses the Survival of CD4+ T Cells Isolated from Human Umbilical Cord Blood through Inhibition of IKKs-mediated NF-κB Activation.

Science.gov (United States)

Ma, K; Ma, P; Lu, H; Liu, S; Cao, Q

2017-05-01

The aim of this study was to investigate the effects and the underlying mechanisms of fentanyl anaesthetic on T lymphocytes isolated from human umbilical cord blood in vitro. The percentages of CD4 + , CD8 + and regulatory T (Treg) cells in human umbilical cord blood mononuclear cells (UBMC) treated with fentanyl in vitro were analysed by flow cytometry. The levels of cytokines IFN-γ, IL-2, IL-4 and IL-17 secreted by activated CD4 + T cells were measured by ELISA assays. Expressions of MAPK and NF-κB signalling pathway proteins were determined by Western blotting. Effects of fentanyl on IKK and p65 expression promoter activities were analysed by luciferase assay. Fentanyl decreased the percentages and amounts of CD4 + , CD8 + and Foxp3 + Treg T lymphocyte subsets in UBMCs in a dose-dependent manner. Fentanyl inhibited the proliferation and induced apoptosis of activated CD4 + T cells dose dependently. Fentanyl could not reverse the increase of cell proliferation in activated groups to be equivalent with those in inactivated group. Secretions of IFN-γ, IL-2 and IL-4 cytokines were significantly decreased by moderate to high dose of fentanyl compared with controls. No significant differences were observed in protein expressions of MAPK pathway. In addition, fentanyl suppressed the IKKs-mediated activation of NF-κB. This study demonstrates that fentanyl exerts immunosuppressive effects on T lymphocytes obtained from UBMCs. Thus, the clinical application of fentanyl would not only relieve pain caused by surgery but regulate immune responses post-operation possibly through inhibition of IKKs-mediated NF-κB activation. © 2017 The Foundation for the Scandinavian Journal of Immunology.

Effects of Fentanyl on Emergence Agitation in Children under Sevoflurane Anesthesia: Meta-Analysis of Randomized Controlled Trials

Science.gov (United States)

Xiong, Wei; Zhou, Qin; Yang, Peng; Huang, Xiongqing

2015-01-01

Background and Objectives The goal of this meta-analysis study was to assess the effects of fentanyl on emergence agitation (EA) under sevoflurane anesthesia in children. Subjects and Methods We searched electronic databases (PubMed, Embase, Web of Science and the Cochrane Central Register of Controlled Trials) for articles published until December 2014. Randomized controlled trials (RCTs) that assessed the effects of fentanyl and placebo on EA under sevoflurane anesthesia in children that the outcome were the incidence of EA, postoperative pain, emergence time or adverse effects were included in this meta-analysis. Results A total of 16 studies, including 1362 patients (737 patients for the fentanyl group and 625 for the placebo group), were evaluated in final analysis. We found that administration of fentanyl decreased the incidences of EA (RR = 0.37, 95% CI 0.27~0.49, Pfentanyl decreases the incidence of EA under sevoflurane anesthesia in children and postoperative pain, but has a higher incidence of PONV. Considering the inherent limitations of the included studies, more RCTs with extensive follow-up should be performed to validate our findings in the future. PMID:26275039

Comparison of clonidine versus fentanyl as an adjuvant to intrathecal ropivacaine for major lower limb surgeries: A randomized double-blind prospective study

Directory of Open Access Journals (Sweden)

Anita R Chhabra

2013-01-01

Full Text Available Background: Ropivacaine is a newer local anesthetic, proven to have a better safety margin than bupivacaine and lignocaine. While maintaining this advantage and improving the intraoperative quality of anesthesia, the use of analgesic adjuvants has been proven to be valuable. Aim: To compare the efficacy of clonidine and fentanyl as adjuvants to intrathecal isobaric ropivacaine for major lower limb surgeries. Settings and Designs: Randomized double-blind control trial. Materials and Methods: Seventy patients were randomly divided in two groups. Ropivacaine-Clonidine group (RC received 60 mcg of clonidine with 15 mg of 0.5% isobaric ropivacaine, Ropivacaine Fentanyl group (RF received 25 mcg of fentanyl with 15 mg of 0.5% isobaric ropivacaine intrathecally. The onset and duration of sensory-motor block were recorded. The total analgesia time, sedation score, hemodynamic parameters, and side-effects were noted. Statistical Analysis: SPSS statistical package was used for statistical analysis. Paired and unpaired t-test, analysis of variance and chi-square test were used for statistical calculation. Result: The duration of sensory block in RC (329.42 ± 33.86, RF (226 ± 46.98, and motor block in RC (248.51 ± 55, RF (212.60 ± 43.52 out lasted the duration of surgery (125.61 + 64.46. In clonidine group, there was significant prolongation of sensory block (P < 0.001, motor block (P < 0.01 and the total analgesia time (P < 0.001. Hypotension and bradycardia occurred in 8.6% patients in clonidine group, whereas pruritus was experienced by 8.6% patients in fentanyl group. Conclusion: Ropivacaine when combined with clonidine or fentanyl provided adequate subarachnoid block for major surgeries, wherein clonidine has advantage over fentanyl as it increased the duration of subarachnoid block and prolonged the postoperative analgesia.

A Cluster of Fentanyl-Laced Heroin Deaths in 2015 in Melbourne, Australia.

Science.gov (United States)

Rodda, Luke N; Pilgrim, Jennifer L; Di Rago, Matthew; Crump, Kerryn; Gerostamoulos, Dimitri; Drummer, Olaf H

2017-05-01

The prevalence of opioid use in therapeutic and recreational settings has steadily increased throughout the western world. The addition of fentanyl into heroin products can produce potentially dangerous consequences, even to opioid tolerant individuals who may be unaware of such additions. Following an observed spike of heroin-fentanyl related deaths in Melbourne, Australia, a study was undertaken to determine the prevalence of these cases. All reportable deaths occurring in Victoria during 2015 and submitted to the toxicology laboratory were analysed using LC-MS-MS to confirm the combination of the heroin marker 6-acetylmorphine and/or morphine, and fentanyl. Over 4,000 coronial cases in 2015 underwent toxicological analysis for these drugs, there were nine cases identified that involved fentanyl-laced heroin. There was no specific mention of fentanyl use in any of these cases. All occurred within 2 months and in two distinct locations. The first four deaths occurred within 3 days of each other, in neighboring suburbs. The ages ranged from 25 to 57 years with an average of 40 and median of 37 years, and consisted of eight males and one female. The average and median femoral blood concentration of fentanyl was 18 and 20 ng/mL (range: fentanyl, which supported the likelihood of fentanyl-laced heroin. This is the first reported case series of fatalities involving heroin and fentanyl outside of North America in published literature. These findings may help inform public health and prevention strategies serving to decrease the potential for such fatalities in the future. © Crown copyright 2017.

In vitro and in vivo evaluation of a sublingual fentanyl wafer formulation

Directory of Open Access Journals (Sweden)

Lim SCB

2013-04-01

Full Text Available Stephen CB Lim,1,3 Michael J Paech,2 Bruce Sunderland,3 Yandi Liu3 1Pharmacy Department, Armadale Health Service, Armadale, 2School of Medicine and Pharmacology, University of Western Australia, and Department of Anaesthesia and Pain Medicine, King Edward Memorial Hospital for Women, Subiaco, 3School of Pharmacy, Curtin Health Innovation Research Institute, Curtin University, Perth, WA, Australia Background: The objective of this study was to prepare a novel fentanyl wafer formulation by a freeze-drying method, and to evaluate its in vitro and in vivo release characteristics, including its bioavailability via the sublingual route. Methods: The wafer formulation was prepared by freeze-drying an aqueous dispersion of fentanyl containing sodium carboxymethylcellulose and amylogum as matrix formers. Uniformity of weight, friability, and dissolution testing of the fentanyl wafer was achieved using standard methods, and the residual moisture content was measured. The fentanyl wafer was also examined using scanning electron microscopy and x-ray diffraction. The absolute bioavailability of the fentanyl wafer was evaluated in 11 opioid-naïve adult female patients using a randomized crossover design. Results: In vitro release showed that almost 90% of the fentanyl dissolved in one minute. In vivo, the first detectable plasma fentanyl concentration was observed after 3.5 minutes and the peak plasma concentration between 61.5 and 67 minutes. The median absolute bioavailability was 53.0%. Conclusion: These results indicate that this wafer has potential as an alternative sublingual fentanyl formulation. Keywords: absolute bioavailability, fentanyl wafer, in vitro dissolution, in vivo study, pharmacokinetics, sublingual

Dose sparing of induction dose of propofol by fentanyl and butorphanol: A comparison based on entropy analysis

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Jasleen Kaur

2013-01-01

Full Text Available Background: The induction dose of propofol is reduced with concomitant use of opioids as a result of a possible synergistic action. Aim and Objectives: The present study compared the effect of fentanyl and two doses of butorphanol pre-treatment on the induction dose of propofol, with specific emphasis on entropy. Methods: Three groups of 40 patients each, of the American Society of Anaesthesiologistsphysical status I and II, were randomized to receive fentanyl 2 μg/kg (Group F, butorphanol 20 μg/kg (Group B 20 or 40 μg/kg (Group B 40 as pre-treatment. Five minutes later, the degree of sedation was assessed by the observer′s assessment of alertness scale (OAA/S. Induction of anesthesia was done with propofol (30 mg/10 s till the loss of response to verbal commands. Thereafter, rocuronium 1 mg/kg was administered and endotracheal intubation was performed 2 min later. OAA/S, propofol induction dose, heart rate, blood pressure, oxygen saturation and entropy (response and state were compared in the three groups. Statistical Analysis: Data was analyzed using ANOVA test with posthoc significance, Kruskal-Wallis test, Chi-square test and Fischer exact test. A P<0.05 was considered as significant. Results: The induction dose of propofol (mg/kg was observed to be 1.1±0.50 in Group F, 1.05±0.35 in Group B 20 and 1.18±0.41 in Group B40. Induction with propofol occurred at higher entropy values on pre-treatment with both fentanyl as well as butorphanol. Hemodynamic variables were comparable in all the three groups. Conclusion: Butorphanol 20 μg/kg and 40 μg/kg reduce the induction requirement of propofol, comparable to that of fentanyl 2 μg/kg, and confer hemodynamic stability at induction and intubation.

Optimal dose of rocuronium bromide undergoing adenotonsillectomy under 5% sevoflurane with fentanyl.

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Huh, Hyub; Park, Jeong Jun; Kim, Ji Yeong; Kim, Tae Hoon; Yoon, Seung Zhoo; Shin, Hye Won; Lee, Hye-Won; Lim, Hye-Ja; Cho, Jang Eun

2017-10-01

Adenotonsillectomy is a short surgical procedure under general anaesthesia in children. An ideal muscle relaxant for adenotonsillectomy would create an intense neuromuscular block while having a quick recovery time without postoperative morbidity. We compared the effect of different doses of rocuronium for the tracheal intubation in children under 5% sevoflurane and fentanyl. 75 children (aged 3-10 years, ASA I) scheduled for adenotonsillectomy were enrolled. Anaesthesia was induced with propofol 2.5 mg/kg, followed by fentanyl 2 μg/kg. After mask ventilation with 5 vol% sevoflurane in 100% oxygen for 2 min, 2 ml of study drug was administered intravenously, i.e., either normal saline (S Group) or one of two doses (0.15 or 0.3 mg/kg) of rocuronium. We assessed conditions during tracheal intubation and also recorded the surgical condition, the time from discontinuation of sevoflurane to extubation and PAED scale, pain scores in PACU. Rocuronium groups (96% and 100%, respectively; P rocuronium (80%) treatment clearly resulted in excellent intubating conditions compared with the 0.15 mg/kg group (44%; p = 0.028). There was no significant difference in the time to extubation and surgical condition, and in the postoperative measures of emergence delirium, pain, and recovery time among the three groups. A dose of 0.3 mg/kg rocuronium may provide optimal intubating conditions without delayed recovery in 5% sevoflurane anaesthesia with fentanyl in children undergoing adenotonsillectomy. NCT02467595. Copyright © 2017 Elsevier B.V. All rights reserved.

Pain Levels Within 24 Hours After UFE: A Comparison of Morphine and Fentanyl Patient-Controlled Analgesia

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Kim, Hyun S.; Czuczman, Gregory J.; Nicholson, Wanda K.; Pham, Luu D.; Richman, Jeffrey M.

2008-01-01

The purpose of this study was to assess the presence and severity of pain levels during 24 h after uterine fibroid embolization (UFE) for symptomatic leiomyomata and compare the effectiveness and adverse effects of morphine patient-controlled analgesia (PCA) versus fentanyl PCA. We carried out a prospective, nonrandomized study of 200 consecutive women who received UFE and morphine or fentanyl PCA after UFE. Pain perception levels were obtained on a 0-10 scale for the 24-h period after UFE. Linear regression methods were used to determine pain trends and differences in pain trends between two groups and the association between pain scores and patient covariates. One hundred eighty-five patients (92.5%) reported greater-than-baseline pain after UFE, and 198 patients (99%) required IV opioid PCA. One hundred thirty-six patients (68.0%) developed nausea during the 24-h period. Seventy-two patients (36%) received morphine PCA and 128 (64%) received fentanyl PCA, without demographic differences. The mean dose of morphine used was 33.8 ± 26.7 mg, while the mean dose of fentanyl was 698.7 ± 537.4 μg. Using this regimen, patients who received morphine PCA had significantly lower pain levels than those who received fentanyl PCA (p < 0.0001). We conclude that patients develop pain requiring IV opioid PCA within 24 h after UFE. Morphine PCA is more effective in reducing post-uterine artery embolization pain than fentanyl PCA. Nausea is a significant adverse effect from opioid PCA.

Hyperbaric bupivacaine 2.5 mg prolongs analgesia compared with plain bupivacaine when added to intrathecal fentanyl 25 microg in advanced labor.

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Teoh, Wendy H L; Sia, Alex T H

2003-09-01

We investigated the effect of sequential administration of intrathecal (IT) hyperbaric bupivacaine (after the initial administration of IT hypobaric fentanyl) on the duration of spinal analgesia. Thirty-seven nulliparous parturients with a cervical dilation >/= 5 cm were randomized to receive either IT fentanyl 25 micro g and plain bupivacaine 2.5 mg (group P; n = 19) or IT fentanyl 25 micro g and hyperbaric (with 8% glucose) bupivacaine 2.5 mg (group H; n = 18). The two components of the IT injectate were administered sequentially (fentanyl 25 micro g diluted in 2 mL of normal saline, immediately followed by 0.5 mL of 0.5% bupivacaine). Patients were then positioned with their torso elevated at 30 degrees for 30 min. Pain scores using 0-100 visual analog scales were collected before combined spinal/epidural analgesia and at 5, 15, and 30 min after the block. Patients in Group H had a longer median duration of analgesia (122 min; range, 80-210 min) than Group P (95 min; range, 75-125 min) (P hyperbaric bupivacaine conferred an increased duration of IT analgesia compared with plain bupivacaine.

Cardiovascular effects, induction and recovery characteristics and alfaxalone dose assessment in alfaxalone versus alfaxalone-fentanyl total intravenous anaesthesia in dogs.

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Dehuisser, Virginie; Bosmans, Tim; Kitshoff, Adriaan; Duchateau, Luc; de Rooster, Hilde; Polis, Ingeborgh

2017-11-01

To compare cardiovascular effects and anaesthetic quality of alfaxalone alone or in combination with a fentanyl constant rate infusion (CRI) when used for total intravenous anaesthesia (TIVA) in dogs. Prospective, blinded, randomized, experimental study. A group of 12 intact female dogs. Following intramuscular dexmedetomidine (10 μg kg -1 ) and methadone (0.1 mg kg -1 ) administration, anaesthesia was induced intravenously with alfaxalone (2 mg kg -1 ) (group AP) or alfaxalone (2 mg kg -1 ) preceded by fentanyl (2 μg kg -1 ) (group AF). Anaesthetic maintenance was obtained with an alfaxalone variable rate infusion (VRI) started at 0.15 mg kg -1 minute -1 (group AP) or an alfaxalone VRI (same starting rate) combined with a CRI of fentanyl (10 μg kg -1 hour -1 ) (group AF). The alfaxalone VRI was adjusted every 5 minutes, based on clinical assessment. Cardiovascular parameters (recorded every 5 minutes) and recovery characteristics (using a numerical rating scale) were compared between groups. A mixed model statistical approach was used to compare the mean VRI alfaxalone dose and cardiovascular parameters between groups; recovery scores were analysed using the Wilcoxon rank-sum test (α = 0.05). The mean CRI alfaxalone dose for anaesthetic maintenance differed significantly between treatments [0.16 ± 0.01 mg kg -1 minute -1 (group AP) versus 0.13 ± 0.01 mg kg -1 minute -1 (group AF)]. Overall heart rate, systolic, mean and diastolic arterial pressures were lower in group AF than in group AP (p < 0.0001, p = 0.0058, p < 0.0001 and p < 0.0001, respectively. Recovery quality scores did not differ significantly and were poor in both groups. In combination with a fentanyl CRI, an alfaxalone TIVA provides a cardiovascular stable anaesthesia in dogs. The addition of fentanyl results in a significant dose reduction. The quality of anaesthetic recovery remains poor. Copyright © 2017 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia

Some Recent Advances in Transdermal Drug Delivery Systems ...

African Journals Online (AJOL)

Some Recent Advances in Transdermal Drug Delivery Systems. ... Advances in Transdermal Drug Delivery Systems. EC Ibezim, B Kabele-Toge, CO Anie, C Njoku. Abstract. Transdermal delivery systems are forms of drug delivery involving the dermis, as distinct from topical, oral or other forms of parenteral dosage forms.

A comparative study of efficacy of esmolol and fentanyl for pressure attenuation during laryngoscopy and endotracheal intubation

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Shobhana Gupta

2011-01-01

Full Text Available Objective: To compare the effectiveness of single bolus dose of esmolol or fentanyl in attenuating the hemodynamic responses during laryngoscopy and endotracheal intubation. Methods: Ninety adult ASA I and ASA II patients were included in the study who underwent elective surgical procedures. Patients were divided into three groups. Group C (control receiving 10 ml normal saline, group E (esmolol receiving bolus dose of esmolol 2 mg/kg and group F (fentanyl receiving bolus dose of fentanyl 2 μg/kg intravenously slowly. Study drug was injected 3 min before induction of anesthesia. Heart rate, systemic arterial pressure and ECG were recorded as baseline and after administration of study drug at intubation and 15 min thereafter. Results: Reading of heart rate, blood pressure and rate pressure product were compared with baseline and among each group. The rise in heart rate was minimal in esmolol group and was highly significant. Also the rate pressure product at the time of intubation was minimal and was statistically significant rate 15 min thereafter in group E. Conclusion: Esmolol 2 mg/kg as a bolus done proved to be effective in attenuating rises in heart rate following laryngoscopy and intubation while the rise in blood pressure was suppressed but not abolished by bolus dose of esmolol.

Effect of fentanyl and lidocaine on the end-tidal sevoflurane concentration preventing motor movement in dogs.

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Suarez, Martin A; Seddighi, Reza; Egger, Christine M; Rohrbach, Barton W; Cox, Sherry K; KuKanich, Butch K; Doherty, Thomas J

2017-01-01

OBJECTIVE To determine effects of fentanyl, lidocaine, and a fentanyl-lidocaine combination on the minimum alveolar concentration of sevoflurane preventing motor movement (MAC NM ) in dogs. ANIMALS 6 adult Beagles. PROCEDURES Dogs were anesthetized with sevoflurane in oxygen 3 times (1-week intervals). Baseline MAC NM (MAC NM-B ) was determined starting 45 minutes after induction of anesthesia. Dogs then received 1 of 3 treatments IV: fentanyl (loading dose, 15 μg/kg; constant rate infusion [CRI], 6 μg/kg/h), lidocaine (loading dose, 2 mg/kg; CRI, 6 mg/kg/h), and the fentanyl-lidocaine combination at the same doses. Determination of treatment MAC NM (MAC NM-T ) was initiated 90 minutes after start of the CRI. Venous blood samples were collected at the time of each treatment MAC NM measurement for determination of plasma concentrations of fentanyl and lidocaine. RESULTS Mean ± SEM overall MAC NM-B for the 3 treatments was 2.70 ± 0.27 vol%. The MAC NM decreased from MAC NM-B to MAC NM-T by 39%, 21%, and 55% for fentanyl, lidocaine, and the fentanyl-lidocaine combination, respectively. This decrease differed significantly among treatments. Plasma fentanyl concentration was 3.25 and 2.94 ng/mL for fentanyl and the fentanyl-lidocaine combination, respectively. Plasma lidocaine concentration was 2,570 and 2,417 ng/mL for lidocaine and the fentanyl-lidocaine combination, respectively. Plasma fentanyl and lidocaine concentrations did not differ significantly between fentanyl and the fentanyl-lidocaine combination or between lidocaine and the fentanyl-lidocaine combination. CONCLUSIONS AND CLINICAL RELEVANCE CRIs of fentanyl, lidocaine, and the fentanyl-lidocaine combination at the doses used were associated with clinically important and significant decreases in the MAC NM of sevoflurane in dogs.

Effect of chronic pain on fentanyl self-administration in mice.

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Carrie L Wade

Full Text Available The development of opioid addiction in subjects with established chronic pain is an area that is poorly understood. It is critically important to clearly understand the neurobiology associated with propensity toward conversion to addiction under conditions of chronic pain. To pose the question whether the presence of chronic pain influences motivation to self-administer opioids for reward, we applied a combination of rodent models of chronic mechanical hyperalgesia and opioid self-administration. We studied fentanyl self-administration in mice under three conditions that induce chronic mechanical hyperalgesia: inflammation, peripheral nerve injury, and repeated chemotherapeutic injections. Responding for fentanyl was compared among these conditions and their respective standard controls (naïve condition, vehicle injection or sham surgery. Acquisition of fentanyl self-administration behavior was reduced or absent in all three conditions of chronic hyperalgesia relative to control mice with normal sensory thresholds. To control for potential impairment in ability to learn the lever-pressing behavior or perform the associated motor tasks, all three groups were evaluated for acquisition of food-maintained responding. In contrast to the opioid, chronic hyperalgesia did not interfere with the reinforcing effect of food. These studies indicate that the establishment of chronic hyperalgesia is associated with reduced or ablated motivation to seek opioid reward in mice.

Permeation enhancer strategies in transdermal drug delivery.

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Marwah, Harneet; Garg, Tarun; Goyal, Amit K; Rath, Goutam

2016-01-01

Today, ∼74% of drugs are taken orally and are not found to be as effective as desired. To improve such characteristics, transdermal drug delivery was brought to existence. This delivery system is capable of transporting the drug or macromolecules painlessly through skin into the blood circulation at fixed rate. Topical administration of therapeutic agents offers many advantages over conventional oral and invasive techniques of drug delivery. Several important advantages of transdermal drug delivery are prevention from hepatic first pass metabolism, enhancement of therapeutic efficiency and maintenance of steady plasma level of the drug. Human skin surface, as a site of drug application for both local and systemic effects, is the most eligible candidate available. New controlled transdermal drug delivery systems (TDDS) technologies (electrically-based, structure-based and velocity-based) have been developed and commercialized for the transdermal delivery of troublesome drugs. This review article covers most of the new active transport technologies involved in enhancing the transdermal permeation via effective drug delivery system.

Comparison of the Effects of Intrathecal Fentanyl and Intrathecal Morphine on Pain in Elective Total Knee Replacement Surgery

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Refika Kılıçkaya

2016-01-01

Full Text Available Objective. Total knee replacement is one of the most painful orthopedic surgical procedures. In this study, our goal was to compare the intraoperative and postoperative hemodynamic effects, the side effects, the effect on the duration of pain start, the 24-hour VAS, and the amount of additional analgesia used, of the fentanyl and morphine we added to the local anesthetic in the spinal anesthesia we administered in cases of elective knee replacement. Materials and Methods. After obtaining the approval of the Erciyes University Medical Faculty Clinical Drug Trials Ethics Committee, as well as the verbal and written consent of the patients, we included 50 patients in our prospective, randomized study. Results. In our study, the morphine group (Group M had lower pain scores in the 2nd, 6th, 12th, and 24th hours compared to the fentanyl group (Group F. When additional analgesic requirements were compared, it was found that in the 2nd, 6th, and 24th hours fewer Group M patients needed more analgesics than did Group F patients. Conclusion. The fentanyl group also had lower first analgesic requirement times than did the morphine group. In terms of nausea and vomiting, there was no statistically significant difference between the two groups.

Fatalities Involving Carfentanil and Furanyl Fentanyl: Two Case Reports.

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Swanson, Dina M; Hair, Laura S; Strauch Rivers, Selly R; Smyth, Brianna C; Brogan, Sara C; Ventoso, Alexis D; Vaccaro, Samantha L; Pearson, Julia M

2017-07-01

Carfentanil is a fentanyl analog frequently used in large animal veterinary medicine. Recently, carfentanil has been discovered in postmortem and antemortem cases throughout the United States in the heroin supply either alone or mixed with heroin and/or other fentanyl analogs. The potency of carfentanil is ~10,000 times greater than morphine and 100 times greater than fentanyl. In two recent cases, carfentanil was identified and ruled to be the cause of death, either alone or in combination with other drugs. Case 1 involved a known heroin user. He was discovered slumped over in a running van blocking the bays of a carwash. Two syringes, a spoon with cotton and residue and a yellow baggie of powder were found in the van. Case 2 involved a man living in a tent in a park with his mother. He was last heard from by a sister via phone who stated he sounded very intoxicated and by his mother who noted him to be "itching all over" and upset over his girlfriend. When the mother returned from work, she discovered him unresponsive with a small baggie of brown powder next to him. Routine drug and volatile screening tests were performed on heart blood using headspace gas chromatography, immunoassay and gas chromatography mass spectrometry methods. Results from initial testing on both cases did not have any significant toxicological findings. However, due to the history, scene photos, toxicological findings in blood and urine and analysis of the drug paraphernalia on one of the cases which identified carfentanil and furanyl fentanyl, fentanyl analogues were suspected. Heart blood was sent to a reference laboratory for carfentanil and furanyl fentanyl analysis. Case 1 had a carfentanil concentration of 1.3 ng/mL and a furanyl fentanyl concentration of 0.34 ng/mL. Case 2 had a carfentanil concentration of 0.12 ng/mL. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The Efficacy and Tolerability of the Clonidine Transdermal Patch in the Treatment for Children with Tic Disorders: A Prospective, Open, Single-Group, Self-Controlled Study.

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Song, Pan-Pan; Jiang, Li; Li, Xiu-Juan; Hong, Si-Qi; Li, Shuang-Zi; Hu, Yue

2017-01-01

To evaluate the efficacy and tolerability of a clonidine transdermal patch in the treatment of children with tic disorders (TD) and to establish a predictive model for patients. Forty-one patients who met the inclusion criteria entered into 12 weeks of prospective, open, single-group, self-controlled treatment with a clonidine transdermal patch. The Yale Global Tic Severity Scale (YGTSS) was employed before therapy (baseline) and at 4, 8, and 12 weeks after therapy. (1) The total effect rates of treatment with a clonidine transdermal patch were 29.27, 53.66, and 63.41% at 4, 8, and 12 weeks, respectively. Compared with the baseline, the differences were significant at three different observation periods. (2) Compared to the level of 25% reduction, there were significant decreases in the score-reducing rate of motor tic and total tic severities at 12 weeks. (3) If the disease course was ≤24 months and the motor tic score was tic score was >16, there was an effective rate of 57.1%. If the disease course was >24 months and the clinical classification was chronic TD, there was an effective rate of 62.5%. If the disease course was >24 months and the clinical classification was Tourette's syndrome, 90% of the patients were invalid. (4) The main adverse events were rash, slight dizziness, and headache. (1) When patients were pretreated with a D2-dopamine receptor antagonist that was ineffective or not tolerated well, switching to a clonidine transdermal patch treatment was effective and safe. (2) A clonidine transdermal patch could be a first-line medication for mild and moderate TD cases that are characterized by motor tics.

Epidural 0.5% levobupivacaine with dexmedetomidine versus fentanyl for vaginal hysterectomy: A prospective study

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Kumkum Gupta

2014-01-01

Full Text Available Background: Epidural adjuvants enhance the quality and duration of surgical anesthesia. The present study was aimed to compare the hemodynamic, sedative, and analgesia potentiating effects of dexmedetomidine versus fentanyl with epidural 0.5% levobupivacaine for vaginal hysterectomy. Patients and Methods: Sixty consented females of ASA physical status I and II aged 35-65 years weighing 55-75 kg, were double blindly randomized into two treatment groups. Patients received epidural 0.5% levobupivacaine 15 ml either with of 25 μg dexmedetomidine (Group LD or 50 μg fentanyl (Group LF and the total volume of study solution was kept 16 ml. Onset of analgesia at T10, sensory and motor block levels and duration of analgesia were observed. Intra-operatively, they were assessed for sedation, hemodynamic changes, respiratory efficiency, and side effects. The data obtained, was compiled systematically and analyzed statistically using Chi-square test and ANOVA. Value of P < 0.05 is considered significant. Result: The demographic profile was comparable between groups. The onset of sensory analgesia at T10 (7.25 ± 2.3 versus 9.27 ± 2.79 min and time to achieve complete motor blockade (19.27 ± 4.7 versus 22.78 ± 5.57 min was significantly earlier in patients of LD Group. The intraoperative hemodynamic changes were comparable between groups. Ramsey Sedation score was better in LD group with statistically significance. Postoperative analgesia was significantly prolonged in LD Group. Incidence of nausea, vomiting, and pruritus was high in LF group. Conclusion: Dexmedetomidine was better than fentanyl as an epidural adjuvant for providing early onset of sensory analgesia, adequate sedation with no respiratory depression and prolonged postoperative analgesia.

A Comparison of Fentanyl and Flurbiprofen Axetil on Serum VEGF-C, TNF-α, and IL-1ß Concentrations in Women Undergoing Surgery for Breast Cancer.

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Wen, Yiyun; Wang, Mingde; Yang, Jinfeng; Wang, Yichun; Sun, Huiping; Zhao, Jianghong; Liu, Weizhen; Zhou, Zhengyu; Deng, Hongwu; Castillo-Pedraza, Catalina; Zhang, Yi; Candiotti, Keith A

2015-07-01

Vascular endothelial growth factor-C (VEGF-C), tumor necrosis factor-α (TNF-α), and interleukin-1ß(IL-1ß) have been shown to be associated with the recurrence and metastasis of breast cancer after surgery. This study tested the hypothesis that patients undergoing surgery for breast cancer, who received postoperative analgesia with flurbiprofen axetil combined with small doses of fentanyl (FA), exhibited reduced levels of VEGF-C, TNF-α, and IL-1ß compared with those patients receiving fentanyl alone (F). Forty-women with primary breast cancer undergoing a modified radical mastectomy were randomized to receive postoperative analgesia with flurbiprofen axetil combined with fentanyl or fentanyl alone. Venous blood was sampled before anesthesia, at the end of surgery, and at 48 hours after surgery, and the serum was analyzed. The primary endpoint was changes in the VEGF-C concentrations in serum. Group FA patients reported similar analgesic effects as group F patients at 2, 24, and 48 hours. At 48 hours, mean postoperative concentrations of VEGF-C in group F patients were higher than in group FA patients, 730.9 versus. 354.1 pg/mL (P = 0.003), respectively. The mean postoperative concentrations of TNF-α in group F patients were also higher compared with group FA patients 27.1 vs. 15.8 pg/mL (P = 0.005). Finally, the mean postoperative concentrations of IL-1ß in group F were also significantly higher than in group FA 497.5 vs. 197.7 pg/mL (P = 0.001). In patients undergoing a mastectomy, postoperative analgesia with flurbiprofen axetil, combined with fentanyl, were associated with decreases in serum concentrations of VEGF-C, TNF-α, and IL-1ß compared with patients receiving doses of only fentanyl. © 2014 World Institute of Pain.

Supraspinally-administered agmatine attenuates the development of oral fentanyl self-administration

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Wade, Carrie L.; Schuster, Daniel J.; Domingo, Kristine M.; Kitto, Kelley F.; Fairbanks, Carolyn A.

2009-01-01

The decarboxylation product of arginine, agmatine, has effectively reduced or prevented opioid-induced tolerance and dependence when given either systemically (intraperitoneally or subcutaneously) or centrally (intrathecally or intracerebroventricularly). Systemically administered agmatine also reduces the escalation phase of intravenous fentanyl self-administration in rats. The present study assessed whether centrally (intracerebroventricular, i.c.v.) delivered agmatine could prevent the development of fentanyl self-administration in mice. Mice were trained to respond under a fixed-ratio 1 (FR1) schedule for either fentanyl (0.7 μg/70 μl, p.o.) or food reinforcement. Agmatine (10 nmol/5 μl), injected i.c.v. 12-14h before the first session and every other evening (12-14h before session) for 2 weeks, completely attenuated oral fentanyl self-administration (but not food-maintained responding) compared to saline-injected controls. When agmatine was administered after fentanyl self-administration had been established (day 8) it had no attenuating effects on bar pressing. This dose of agmatine does not decrease locomotor activity as assessed by rotarod. The present findings significantly extend the previous observation that agmatine prevents opioid-maintained behavior to a chronic model of oral fentanyl self-administration as well as identifying a supraspinal site of action for agmatine inhibition of drug addiction. PMID:18495108

Synthesis and analysis of the opioid analgesic [14C]-fentanyl

International Nuclear Information System (INIS)

Bagley, J.R.; Wilhelm, J.A.

1992-01-01

The synthesis of [ 14 C]-fentanyl, the radiolabelled congener of the potent opioid analgesic chosen for utilization in drug disposition studies, is described. [ 14 C]-Labelling was achieved in the first of two steps, a room temperature reduction of the in situ generated Schiff base from 1-phenylethyl-4-piperidone and [UL- 14 C]-aniline hydrochloride with sodium triacetoxyborohydride. A nearly instantaneous production of fentanyl was accomplished at room temperature with the addition of propionyl chloride. The overall radiochemical yield was 18%. The method described is efficiently adaptable for submicromolar scale while yielding a product of sufficient specific activity for in vivo studies. Our solvent system for thin layer chromatography was superior to the USP system reported for chromatographic analysis of fentanyl. This is the first reported preparation of [ 14 C]-fentanyl with the radiolabel in the aniline benzene ring. (author)

Comparison of different doses of magnesium sulphate and fentanyl as adjuvants to bupivacaine for infraumbilical surgeries under subarachnoid block

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Sarika Katiyar

2015-01-01

Full Text Available Background and Aims: Spinal anaesthesia is used for many years for surgeries below the level of umbilicus. It has certain disadvantages such as limited duration of blockade and post-operative analgesia. This study was undertaken to evaluate the effects of additives fentanyl and magnesium sulphate along with bupivacaine during spinal anaesthesia for prolongation of analgesia and motor blockade. Methods: This randomised study was conducted in 120 patients of either sex of American Society of Anesthesiologists physical status I and II, posted for infraumbilical surgeries. Patients were randomly allocated to four groups and were given the following drugs intrathecally as per group distribution; group A - bupivacaine 15 mg (0.5% heavy with fentanyl 25 μg, group B - bupivacaine 15 mg (0.5% heavy with magnesium 100 mg, group C - bupivacaine 15 mg (0.5% heavy with magnesium 50 mg and group D - bupivacaine 15 mg (0.5% heavy with 0.5 ml normal saline. Parameters monitored were duration of analgesia along with haemodynamic parameters and side effects. Data were analysed using the Student′s t-test for the continuous variables and two-tailed Fisher exact test or Chi-square test for categorical variables. Results: There was significant increase in duration of analgesia in group A (374.37 min and B (328.13 min as compared to group C (274.87 min and D (246.03 min. In group A, all haemodynamic parameters decreased by more than 20%, compared to baseline parameters, which was clinically and statistically significant as compared to other groups. There was also increase in duration of motor blockade in groups A and B. Conclusion: Addition of magnesium sulphate at 100 mg dose or fentanyl 25 μg as adjuvants to intrathecal bupivacaine significantly prolongs the duration of analgesia, though in the given doses, magnesium provides better haemodynamic stability than fentanyl, with fewer side effects.

Perbandingan Efektivitas Kombinasi Fentanyl Patch 12,5 µg/jam dan 25 µg/jam dengan Ketorolak 30 mg Intravena pada Pascabedah Ortopedi Ekstremitas Bawah

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Poppy Novita Rini

2016-08-01

Full Text Available Fentanyl patch is the first injection-free system for post surgery pain management that is a safe, easy to use, and comfortable modality for patient. The aim of this study was to differentiate the effectiveness and side effect of 12.5 µg/hour and 25 µg/hour fentanyl patch combinations with 30 mg intravenous ketorolac after orthopedic surgery of lower extremity under spinal anesthetic. This was a double random clinical trial for 24 patients with physical status American Society of Anesthesiologist (ASA I and II, 18–50 years old of age, who underwent orthopedic extremity surgery in the operating theaters of H. Adam Malik Hospital and other hospitals in October–November 2015. Patients were divided into two groups, i.e. 12 patients received 12.5 µg/hour fentanyl patch (A and 12 patients received 25 µg/hour fentanyl patch (B for ±2 hours before surgery, combined with 30 mg intravenous ketorolac given at the start of incision. The pain was scored using a visual analog scale. Data were then statistically analyzed using chi-square test. The result of the study showed that the use of 25 µg/hour fentanyl patch was significantly more effective than the 12.5 µg/hour fentanyl patch (p<0.05. It is concluded that the clinical VAS scores for the two groups after orthopedic surgery of lower extremity are different.

A COMPARATIVE CLINICAL STUDY BETWEEN IV ESMOLOL AND IV FENTANYL ON ATTENUATION OF HAEMODYNAMIC RESPONSES TO LARYNGOSCOPY AND INTUBATION

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Abu Lais Mustaque

2016-04-01

Full Text Available INTRODUCTION Laryngoscopy and intubation is an integral part for providing general anaesthesia to patients undergoing various types of surgery. It also plays an important role in critical care units viz. for providing mechanical ventilation. It is a very essential tool in the hands of anaesthesiologist in maintaining airway. The present study is undertaken to determine and compare the efficacy of single bolus dose of IV esmolol 1 mg/kg and IV fentanyl 2 mcg/kg in attenuating the haemodynamic responses to laryngoscopy and tracheal intubation and to ascertain the effectiveness of esmolol hydrochloride and fentanyl citrate in suppressing sympathetic responses. MATERIAL & METHODS The study was conducted under the Department of Anaesthesiology and Critical Care, Assam Medical College and Hospital, Dibrugarh, during the period July 2013 to June 2014. For this purpose, 150 patients of either sex between 20-50 years of ASA I & II physical status were selected after obtaining informed and written consent and were divided into two groups namely, Group E receiving IV esmolol (1 mg/kg and Group F receiving IV fentanyl (2 mcg/kg. RESULTS Inj. fentanyl 2 mcg/kg IV administered 5 minutes before laryngoscopy and intubation was able to prevent adverse haemodynamic changes better than Inj. esmolol 1 mg/kg IV administered 3 minutes prior to laryngoscopy and intubation during elective surgeries under general anaesthesia. CONCLUSION Hence, from the findings of this study we can conclude that IV bolus dose of fentanyl 2 mcg/kg administered 5 minutes before laryngoscopy and intubation can attenuate the sympathetic response to laryngoscopy and intubation without any side effects of the drug in healthy patients undergoing elective surgeries under general anaesthesia.

[Studies on transdermal delivery of ferulic acid through rat skin treated by microneedle arrays].

Science.gov (United States)

Yang, Bing; Du, Shou-ying; Bai, Jie; Shang, Ke-xin; Lu, Yang; Li, Peng-yue

2014-12-01

In order to investigate the characteristics of transdermal delivery of ferulic acid under the treated of microneedle arrays and the influence on permeability of rat skin capillaries, improved Franz-cells were used in the transdermal delivery experiment with the rat skin of abdominal wall and the length of microneedle arrays, different insertion forces, retention time were studied in the influence of characteristics of transdermal delivery of FA. The amount of FA was determined by HPLC system. Intravenous injection Evans blue and FA was added after microneedle arrays treated. Established inflammation model was built by daubing dimethylbenzene. The amount of Evans blue in the rat skin was read at 590 nm wavelength with a Multiskan Go microplate reader. Compared with passive diffusion group the skin pretreated with microneedle arrays had a remarkable enhancement of FA transport (P Microneedle arrays with different length had a remarkable enhancement of FA transport, but was not related to the increase of the length. The research of FA on the reduce of permeability of rat skin capillaries indicated that the skin pretreated with microneedle arrays could reduce the content of Evans blue in the skins of rat significantly compared with the untreated group. The permeation rate of ferulic acid transdermal delivery had remarkable increase under the treated of microneedle arrays and the length of microneedle arrays ,the retention time so as to the insertion force were important to the transdermal delivery of ferulic acid.

The influence of a fentanyl and dexmedetomidine combination on external respiratory functions in acute hemorrhage model

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Nikolay G. Vengerovich

2017-01-01

Full Text Available Background. The synthetic opioid analgesic fentanyl is widely used for prophylaxis and therapy of traumatic shock associated with massive bleeding. Its side effects – skeletal muscle rigidity and respiratory center depression – are especially pronounced with repeated administration. It is rational to apply fentanyl in diminished doses in combination with non-opioid analgesics in order to reduce respiratory disturbances risk.Aim. The aim of the work is to justify the influence of opioid analgesic fentanyl and α2 -adrenomimetic dexmedetomidine combination on external respiratory functions in acute hemorrhage model.Materials and methods. Acute loss of 35–40% of circulating blood volume was modeled in experiments on 75 white mongrel male rats. The external respiratory functions (respiratory rate, respiratory volume, breath volume per minute were estimated in animals of 5 groups: 1 – rats without analgesic help (controls; 2–3 – rats receiving a single fentanyl intramuscular injection (ED99 98,96 mcg/kg or fentanyl together with dexme detomidine (ED99 of combination 67,94 mcg/kg 15 min after acute blood loss; 4–5 – rats receiving the same drugs 15 min, 30, 45 and 60 min later.Results. In experimental acute loss of 35–40% of circulating blood volume, 15 min later a secondary acute respiratory failure developed with a drop of respiratory rate, respiratory volume and volume of breath per minute by 30%, 21 and 47% (p < 0,05. The external respiratory functions recoverеd after 4 h mainly due to the increase of respiratory volume. A single intramuscular injection of fentanyl caused respiratory depression 15 min after experimental blood loss which resulted in the decrease of breath volume per minute to 30–61% (p < 0,05 for 90 min. Four intramuscular injections of fentanyl 15 min, 30, 45 and 60 min after hemorrhage caused a severe respiratory dysfunction, accompanied by apnea periods and Biot’s respiration. Respiratory rate was reduced

Pre-emptive oral dexmethorphan reduces fentanyl-induced cough as well as immediate postoperative adrenocortico-tropic hormone and growth hormone level

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Avik Mukherjee

2011-01-01

Full Text Available Background : Fentanyl-induced cough is not always benign and brief and can be remarkably troublesome, spasmodic, and explosive. Dextromethorphan, an opioid derivative with an antitussive action, may be effective in reducing the fentanyl-induced cough. Dextromethorphan, a N-methyl D aspartate receptor antagonist, may have some effect on diminishing the stress response to surgery. This study was undertaken to determine whether preoperative dextromethorphan could effectively attenuate its incidence, severity, and effect on postoperative stress hormone levels. Materials and Methods : Three hundred and twenty patients of American society of anesthesiologists I-II, aged 18-60 years, undergoing elective laparoscopic cholecystectomy or appendicectomy were randomly allocated into two groups (Group C, control; Group D, dextromethorphan consisting of 160 patients each. Patients in Group D received dextromethorphan 40 mg orally and in Group C received placebo tablets 60 minutes before induction of anesthesia. The incidence of cough was recorded for 1 minute after fentanyl injection and graded as none (0, mild (1-2, moderate (3-5, and severe (>5 cough. Blood samples were collected for estimation of stress hormone levels before surgery and again at 1 hour and 24 hours postoperatively and compared. The appearance of adverse reactions was recorded. Results : The incidence of reflex fentanyl cough was lower in dextromethorphan group (3.9% in comparison to placebo (59.8%. Five patients developed mild and one moderate cough in the dextromethorphan group. In the control group, 31 patients developed mild, 29 moderate, and 32 severe cough. The stress hormones were significantly higher at 1 hour and 24 hours postoperatively in both groups in comparison to its preoperative values. However, at 1 hour postoperatively, adrenocorticotropic hormone, epinephrine, and growth hormone values were significantly low in the dextromethorphan group (61.5 ± 21.1 pg/ ml, 142.1 ± 11

Effects of Parecoxib and Fentanyl on nociception-induced cortical activity

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Wang Ying-Wei

2010-01-01

Full Text Available Abstract Background Analgesics, including opioids and non-steroid anti-inflammatory drugs reduce postoperative pain. However, little is known about the quantitative effects of these drugs on cortical activity induced by nociceptive stimulation. The aim of the present study was to determine the neural activity in response to a nociceptive stimulus and to investigate the effects of fentanyl (an opioid agonist and parecoxib (a selective cyclooxygenase-2 inhibitor on this nociception-induced cortical activity evoked by tail pinch. Extracellular recordings (electroencephalogram and multi-unit signals were performed in the area of the anterior cingulate cortex while intracellular recordings were made in the primary somatosensory cortex. The effects of parecoxib and fentanyl on induced cortical activity were compared. Results Peripheral nociceptive stimulation in anesthetized rats produced an immediate electroencephalogram (EEG desynchronization resembling the cortical arousal (low-amplitude, fast-wave activity, while the membrane potential switched into a persistent depolarization state. The induced cortical activity was abolished by fentanyl, and the fentanyl's effect was reversed by the opioid receptor antagonist, naloxone. Parecoxib, on the other hand, did not significantly affect the neural activity. Conclusion Cortical activity was modulated by nociceptive stimulation in anesthetized rats. Fentanyl showed a strong inhibitory effect on the nociceptive-stimulus induced cortical activity while parecoxib had no significant effect.

Hybrid electrospun chitosan-phospholipids nanofibers for transdermal drug delivery

DEFF Research Database (Denmark)

Mendes, Ana Carina Loureiro; Gorzelanny, Christian; Halter, Natalia

2016-01-01

Chitosan (Ch) polysaccharide was mixed with phospholipids (P) to generate electrospun hybrid nanofibers intended to be used as platforms for transdermal drug delivery. Ch/P nanofibers exibithed average diameters ranging from 248 +/- 94 nm to 600 +/- 201 nm, depending on the amount of phospholipids...... used. Fourier Transformed Infra-Red (FTIR) spectroscopy and Dynamic Light Scattering (DLS) data suggested the occurrence of electrostatic interactions between amine groups of chitosan with the phospholipid counterparts. The nanofibers were shown to be stable for at least 7 days in Phosphate Buffer...... culture plate (control). The release of curcumin, diclofenac and vitamin B12, as model drugs, from Ch/P hybrid nanofibers was investigated, demonstrating their potential utilization as a transdermal drug delivery system....

Comparison of the Effects of Fentanyl and Midazolam as a Premedication in Children Undergoing Inguinal Hernial Surgery

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MH Abdollahi

2011-04-01

Full Text Available Introduction: Premedication with midazolam can occasionally result in increased pediatric anxiety. In this study, we compared the effects of intravenous midazolam and fentanyl as pediatric premedication in children posted for inguinal hernia surgery. Methods: In this double blind randomized clinical trial study, sixty pediatric patients were randomly allocated to two study groups. Anesthesia was similar in both groups. Sedation score by Richmond agitation sedation scale was repeatedly measured on arrival to the preoperative part of the operating room, during drug administration, separation of the child from parent for transfer to the operating room, induction of anesthesia, time of transfer to the recovery room and discharge from the recovery room. Post-operative nausea and vomiting was also recorded. The collected data was analyzed with SPSS 15 and P value<0.05 was considered meaningful. Results: Baseline characteristics of the two study groups were similar. Mean RASS at separation of patients from parents; the time between the study drug administrations till separation from parents, induction of anesthesia and end of operation and need for additional drug during separation was significantly lower in the midazolam group. Opioid need in the fentanyl group was higher. Other findings were similar in the two groups. Conclusion: Use of fentanyl instead of midazolam as a premedication is not a priority in children posted for surgery.

Heroin uncertainties: Exploring users' perceptions of fentanyl-adulterated and -substituted 'heroin'.

Science.gov (United States)

Ciccarone, Daniel; Ondocsin, Jeff; Mars, Sarah G

2017-08-01

The US is experiencing an unprecedented opioid overdose epidemic fostered in recent years by regional contamination of the heroin supply with the fentanyl family of synthetic opioids. Since 2011 opioid-related overdose deaths in the East Coast state of Massachusetts have more than tripled, with 75% of the 1374 deaths with an available toxicology positive for fentanyl. Fentanyl is 30-50X more potent than heroin and its presence makes heroin use more unpredictable. A rapid ethnographic assessment was undertaken to understand the perceptions and experiences of people who inject drugs sold as 'heroin' and to observe the drugs and their use. A team of ethnographers conducted research in northeast Massachusetts and Nashua, New Hampshire in June 2016, performing (n=38) qualitative interviews with persons who use heroin. (1) The composition and appearance of heroin changed in the last four years; (2) heroin is cheaper and more widely available than before; and (3) heroin 'types' have proliferated with several products being sold as 'heroin'. These consisted of two types of heroin (alone), fentanyl (alone), and heroin-fentanyl combinations. In the absence of available toxicological information on retail-level heroin, our research noted a hierarchy of fentanyl discernment methods, with embodied effects considered most reliable in determining fentanyl's presence, followed by taste, solution appearance and powder color. This paper presents a new 'heroin' typology based on users' reports. Massachusetts' heroin has new appearances and is widely adulterated by fentanyl. Persons who use heroin are trying to discern the substances sold as heroin and their preferences for each form vary. The heroin typology presented is inexact but can be validated by correlating users' discernment with drug toxicological testing. If validated, this typology would be a valuable harm reduction tool. Further research on adaptations to heroin adulteration could reduce risks of using heroin and

Optimization of the radioimmunoassays for measuring fentanyl and alfentanil in human serum

International Nuclear Information System (INIS)

Schuettler, J.; White, P.F.

1984-01-01

Measurement of serum fentanyl and alfentanil concentrations by radioimmunoassay (RIA) may result in significant errors and high variability when the technique described in the available fentanyl and alfentanil RIA kits is used. The authors found a 29-94% overestimation of measured fentanyl and alfentanil serum levels when 3H-fentanyl or 3H-alfentanil was added lastly to the mixture of antiserum and sample. This finding is related to a reduction in binding sites for the labeled compounds after preincubation of sample and antiserum. If this sequence is used, it becomes necessary to extend the incubation period up to 6 h for fentanyl and up to 10 h for alfentanil in order to achieve equilibration between unlabeled and labeled drug with respect to antiserum binding. However, when antiserum is added lastly to the mixture of sample and labeled drug, measurement accuracy and precision for fentanyl and alfentanil serum concentrations are enhanced markedly. In addition, it is important to perform the calibration curves and sample measurements using the same medium (i.e., serum alone or a serum/buffer dilution). In summary, to optimize the RIA for fentanyl and alfentanil, the authors recommend the following: 1) adding the antiserum lastly to the mixture of sample and labeled drug; 2) performing calibration curves using patient's blank serum when possible; 3) carefully examining and standardizing each step of the RIA procedure to reduce variability, and, finally; 4) comparing results with those of other established RIA laboratories

Optimization of the radioimmunoassays for measuring fentanyl and alfentanil in human serum

Energy Technology Data Exchange (ETDEWEB)

Schuettler, J.; White, P.F.

1984-09-01

Measurement of serum fentanyl and alfentanil concentrations by radioimmunoassay (RIA) may result in significant errors and high variability when the technique described in the available fentanyl and alfentanil RIA kits is used. The authors found a 29-94% overestimation of measured fentanyl and alfentanil serum levels when 3H-fentanyl or 3H-alfentanil was added lastly to the mixture of antiserum and sample. This finding is related to a reduction in binding sites for the labeled compounds after preincubation of sample and antiserum. If this sequence is used, it becomes necessary to extend the incubation period up to 6 h for fentanyl and up to 10 h for alfentanil in order to achieve equilibration between unlabeled and labeled drug with respect to antiserum binding. However, when antiserum is added lastly to the mixture of sample and labeled drug, measurement accuracy and precision for fentanyl and alfentanil serum concentrations are enhanced markedly. In addition, it is important to perform the calibration curves and sample measurements using the same medium (i.e., serum alone or a serum/buffer dilution). In summary, to optimize the RIA for fentanyl and alfentanil, the authors recommend the following: 1) adding the antiserum lastly to the mixture of sample and labeled drug; 2) performing calibration curves using patient's blank serum when possible; 3) carefully examining and standardizing each step of the RIA procedure to reduce variability, and, finally; 4) comparing results with those of other established RIA laboratories.

Analgesia and side effects of the addition of 10 or 20 µg fentanyl to articaine in spinal anesthesia for knee arthroscopy: a randomized and observer-blinded study.

Science.gov (United States)

Stenman, Paula; Salonen, Merja; Tarkkila, Pekka; Rosenberg, Per

2017-06-01

Articaine, a popular and rapidly acting local anesthetic in dentistry, has been also found to be beneficial in ambulatory spinal anesthesia. Analgesia in the intraoperative and immediate postoperative period may be further improved by adding fentanyl to the local anesthetic solution for spinal anesthesia. The aim was to evaluate dose-dependency of analgesia and side effects associated with intrathecal fentanyl additive to articaine for spinal anesthesia in knee arthroscopy patients. In this randomized, observer- and patient-blinded study, 90 adult patients scheduled for elective ambulatory knee arthroscopy under spinal anesthesia were randomized into three groups: plain articaine 60 mg with saline (group AF0), articaine 60 mg with fentanyl 10 µg (group AF10) or 20 µg (group AF20) in a total volume of 1.9 ml. The blinded observer tested the sensory and the motor block, and performed telephone interviews on the first and seventh postoperative days. The median (IQR) duration of sensory block at the dermatomal level of T10 was significantly longer in groups AF10, 69 min (56) and AF20, 69 min (45) than in group AF0, 41 min (35) (p = 0.013). Motor block duration was similar in all groups (median 120 min). Group AF20 patients experienced pruritus significantly more often than patients in the other groups (p = 0.039). No acute or late anesthetic side effects occurred, and satisfaction with the anesthetic technique was the same in all groups (97% satisfied). Fentanyl 10 or 20 µg as additive to articaine for spinal anesthesia prolonged the duration of sensory block significantly and similarly. Fentanyl 20 µg was more often associated with pruritus than fentanyl 10 µg.

Peptide-chaperone-directed transdermal protein delivery requires energy.

Science.gov (United States)

Ruan, Renquan; Jin, Peipei; Zhang, Li; Wang, Changli; Chen, Chuanjun; Ding, Weiping; Wen, Longping

2014-11-03

The biologically inspired transdermal enhanced peptide TD1 has been discovered to specifically facilitate transdermal delivery of biological macromolecules. However, the biological behavior of TD1 has not been fully defined. In this study, we find that energy is required for the TD1-mediated transdermal protein delivery through rat and human skins. Our results show that the permeation activity of TD1-hEGF, a fusion protein composed of human epidermal growth factor (hEGF) and the TD1 sequence connected with a glycine-serine linker (GGGGS), can be inhibited by the energy inhibitor, rotenone or oligomycin. In addition, adenosine triphosphate (ATP), the essential energetic molecule in organic systems, can effectively facilitate the TD1 directed permeation of the protein-based drug into the skin in a dose-dependent fashion. Our results here demonstrate a novel energy-dependent permeation process during the TD1-mediated transdermal protein delivery that could be valuable for the future development of promising new transdermal drugs.

A Transdermal Measurement Platform Based on Microfluidics

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Wen-Ying Huang

2017-01-01

Full Text Available The Franz diffusion cell is one of the most widely used devices to evaluate transdermal drug delivery. However, this static and nonflowing system has some limitations, such as a relatively large solution volume and skin area and the development of gas bubbles during sampling. To overcome these disadvantages, this study provides a proof of concept for miniaturizing models of transdermal delivery by using a microfluidic chip combined with a diffusion cell. The proposed diffusion microchip system requires only 80 μL of sample solution and provides flow circulation. Two model compounds, Coomassie Brilliant Blue G-250 and potassium ferricyanide, were successfully tested for transdermal delivery experiments. The diffusion rate is high for a high sample concentration or a large membrane pore size. The developed diffusion microchip system, which is feasible, can be applied for transdermal measurement in the future.

A Comprehensive Review on: Transdermal drug delivery systems.

OpenAIRE

Kharat, Rekha; Bathe, Ritesh Suresh

2016-01-01

Transdermal drug delivery system was introduced to overcome the difficulties of drug delivery through oral route. Despite their relatively higher costs, transdermal delivery systems have proved advantageous for delivery of selected drugs, such as estrogens, testosterone, clonidine and nitro-glycerine. Transdermal delivery provides a leading edge over injectable and oral routes by increasing patient compliance and avoiding first pass metabolism respectively. Topical  administration  of  therap...

Clonidine versus fentanyl as adjuvants to bupivacaine in peribulbar anesthesia

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Maha M.I. Youssef

2014-07-01

Conclusion: The addition of either clonidine or fentanyl to the local anesthetic during peribulbar block results in a faster onset and longer duration of the block with a longer period of postoperative analgesia. The addition of clonidine was found to prolong the duration of the block more than fentanyl.

Comparison of fentanyl, sufentanil, and alfentanil anesthesia in patients undergoing valvular heart surgery

NARCIS (Netherlands)

Bovill, J. G.; Warren, P. J.; Schuller, J. L.; van Wezel, H. B.; Hoeneveld, M. H.

1984-01-01

The hemodynamic responses to anesthesia and surgery were studied in three groups of 20 patients undergoing valve replacement surgery. Anesthesia was induced with either fentanyl (75 micrograms/kg), sufentanil (15 micrograms/kg), or alfentanil (125 micrograms/kg). Pancuronium (8 mg) was given for

Intravenous lidocaine suppresses fentanyl-induced cough in Children

OpenAIRE

Gecaj-Gashi, Agreta; Nikolova-Todorova, Zorica; Ismaili-Jaha, Vlora; Gashi, Musli

2013-01-01

Objective Fentanyl-induced cough is usually mild and transitory, but it can be undesirable in patients with increased intracranial pressure, open wounds of the eye, dissecting aortic aneurism, pneumothorax, and reactive airway disease. The aim of this study is to evaluate the efficacy of lidocaine in suppressing fentanyl-induced cough in children during induction in general anesthesia. Methods One hundred and eighty-six children of both sexes, aged between 4?10?years, ASA physical status I an...

Increased Hyperalgesia and Proinflammatory Cytokines in the Spinal Cord and Dorsal Root Ganglion After Surgery and/or Fentanyl Administration in Rats.

Science.gov (United States)

Chang, Lu; Ye, Fang; Luo, Quehua; Tao, Yuanxiang; Shu, Haihua

2018-01-01

Perioperative fentanyl has been reported to induce hyperalgesia and increase postoperative pain. In this study, we tried to investigate behavioral hyperalgesia, the expression of proinflammatory cytokines, such as interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), and the activation of microglia in the spinal cord and dorsal root ganglion (DRG) in a rat model of surgical plantar incision with or without perioperative fentanyl. Four groups of rats (n = 32 for each group) were subcutaneously injected with fentanyl at 60 μg/kg or normal saline for 4 times with 15-minute intervals. Plantar incisions were made to rats in 2 groups after the second drug injection. Mechanical and thermal nociceptive thresholds were assessed by the tail pressure test and paw withdrawal test on the day before, at 1, 2, 3, 4 hours, and on the days 1-7 after drug injection. The lumbar spinal cord, bilateral DRG, and cerebrospinal fluid of 4 rats in each group were collected to measure IL-1β, IL-6, and TNF-α on the day before, at the fourth hour, and on the days 1, 3, 5, and 7 after drug injection. The lumbar spinal cord and bilateral DRG were removed to detect the ionized calcium-binding adapter molecule 1 on the day before and on the days 1 and 7 after drug injection. Rats injected with normal saline only demonstrated no significant mechanical or thermal hyperalgesia or any increases of IL-1β, IL-6, and TNF-α in the spinal cord or DRG. However, injection of fentanyl induced analgesia within as early as 4 hours and a significant delayed tail mechanical and bilateral plantar thermal hyperalgesia after injections lasting for 2 days, while surgical plantar incision induced a significant mechanical and thermal hyperalgesia lasting for 1-4 days. The combination of fentanyl and incision further aggravated the hyperalgesia and prolonged the duration of hyperalgesia. The fentanyl or surgical incision upregulated the expression of IL-1β, IL-6, and TNF-α in the

Chemical Penetration Enhancers for Transdermal Drug Delivery ...

African Journals Online (AJOL)

for transdermal administration. The permeation of drug through skin can be enhanced by both chemical penetration enhancement and physical methods. In this review, we have discussed the chemical penetration enhancement technology for transdermal drug delivery as well as the probable mechanisms of action.

Intranasal fentanyl in the treatment of acute pain--a systematic review

DEFF Research Database (Denmark)

Hansen, M S; Mathiesen, O; Trautner, S

2012-01-01

Due to its non-invasive mode of administration, intranasal (IN) application of drugs may be a valuable alternative to non-invasive pain management. With characteristics that appear to be ideal for IN application, IN fentanyl may have a place in the out-of-hospital treatment and the paediatric...... population. The objective of this systematic review was to evaluate the current evidence of IN fentanyl in the treatment of acute pain. Reports of randomized controlled trials (RCTs) of IN fentanyl in treatment of pain were systematically sought using the PubMed database, Embase, Google scholar, Cochrane...... database, and Cumulative Index to Nursing and Allied Health Literature. Reports were considered for inclusion if they were double-blinded randomized controlled trials (RCTs) of IN fentanyl in the treatment of acute pain. Thirty-two RCTs were identified, and 16 were included in the final analysis...

Labour analgesia with intrathecal fentanyl decreases maternal stress.

Science.gov (United States)

Cascio, M; Pygon, B; Bernett, C; Ramanathan, S

1997-06-01

Lumbar epidural analgesia (LEA) decreases maternal stress as measured by maternal circulating plasma catecholamine concentrations. Intrathecal fentanyl (ITF) provides effective labour analgesia but its effect on maternal epinephrine (Epi) and norepinephrine (NE) concentrations is not known. This study assesses whether ITF reduces maternal stress in the same manner as conventional LEA. Twenty-four healthy women in active labour received either 25 micrograms ITF (n = 12) or epidural lidocaine 1.5% (n = 12) for analgesia. Venous blood samples were collected before anaesthesia and at five minute intervals for 30 min following anaesthesia for the measurement of plasma Epi and NE by high performance liquid chromatography. Maternal blood pressure (BP), heart rate (HR), visual analog scores (VAS) to pain and pruritus were recorded at the same time. Both ITF and LEA decreased pain VAS scores, maternal BP, and plasma Epi concentrations with only minimal effects on plasma NE concentrations. Intrathecal fentanyl (ITF) and LEA reduced plasma epi to a similar extent, with ITF reducing the levels slightly faster than LEA. Intrathecal fentanyl(ITF) and LEA reduced plasma Epi concentrations by 52% and 51%, respectively (P value < 0.01). We conclude that ITF is as effective as LEA in producing pain relief in the labouring patient. Intrathecal Fentanyl (ITF) is also capable of reducing maternal plasma epinephrine concentration, thus avoiding the possibly deleterious side effects of excess amounts of this catecholamine during labour.

Butorphanol suppresses fentanyl-induced cough during general anesthesia induction

OpenAIRE

Cheng, Xiao-Yan; Lun, Xiao-Qin; Li, Hong-Bo; Zhang, Zhi-Jie

2016-01-01

Abstract Fentanyl-induced cough (FIC) is unwanted in the patients requiring stable induction of general anesthesia. This study was designed to evaluate the suppressive effects of butorphanol pretreatment on the incidence and severity of FIC during the induction of general anesthesia. A total of 315 patients of American Society of Anesthesiologists physical status I and II, scheduled for elective surgery under general anesthesia were randomized into 3 equally sized groups (n = 0105). Two minut...

A STUDY COMPARING DIFFERENT CONCENTRATIONS OF ROPIVACAINE 0.125% VS. 0.2%, WHEN GIVEN WITH FENTANYL 2 MCG/ML FOR EPIDURAL LABOUR ANALGESIA

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Vindhya K

2017-07-01

Full Text Available BACKGROUND Epidural administration of local anaesthetics, with or without opioids, is commonly used for the relief of pain in labor. Lower concentration of local anesthetics is used for providing labor epidural analgesia. MATERIALS AND METHODS After approval of the Institutional Ethical Committee, this study was conducted at a teaching hospital in GGH, Kakinada on 50 term parturients. 50 parturients of ASA I & II, primi or multi gravida with singleton pregnancy having vertex presentation were taken up for the study. They were randomly divided into 2 groups–Group R1 and Group R2 each comprising of 25 parturients. Study patients (n=50 were randomly assigned to one of two groups of 25 each. They received aliquots of epidural injection using either, 10 ml of ropivacaine 0.125 % with 2 μg/ml fentanyl (group R1 or 10 ml of ropivacaine 0.2% with 2 μg/ml fentanyl (group R2. RESULTS Demographic data, obstetric data, and injection delivery interval were comparable in both groups. Effective labor analgesia with no motor blockade was observed in both groups. Duration of analgesia after initial bolus dose was also significantly longer in group R2 (126.45 ± 12.34 min than in group R1 (73.05±27.4min. Ropivacaine at both concentrations (0.2% vs. 0.125% along with fentanyl 2μg / ml decreased visual analog scale (VAS scores to <3 in all parturients uniformly. Mean VAS scores were significantly less in group R2 than in group R1 at 5,60, and 90 min. Requirement of top-up doses was significantly less in group R2 as compared to group R1. Consumption of ropivacaine was comparable in both the groups (58.23 ± 5.48 mg in group R1 and 65.88 ± 6.29 mg in group R2, but consumption of fentanyl was significantly more in group R1 (94.31 ± 4.93 mg as compared to group R2 (31.58 ± 2.38 mg. There were no significant changes in haemodynamics, nor adverse effects related to neonatal or maternal outcomes in both groups. CONCLUSION We conclude that both the concentrations

Protection against soman and sarin exposure by transdermal physostigmine and scopolamine

Energy Technology Data Exchange (ETDEWEB)

Meshulam, Y.; Davidovici, R.; Levy, A.

1993-05-13

The purpose of this study was to evaluate the prophylactic efficacy of physostigmine (physo), administered via sustained release (SR) methods, with and without scopolamine, against soman and sarin exposure in guinea-pigs. Transdermal physo pad (3 sq cm/kg; 60-80 ug/sq cm), containing a vehicle based on propionic acid, was applied onto the dorsal back of the animals, 24 hours before exposure to the cholinesterase (ChE) inhibitors. At the time of exposure, physo concentrations in brain and plasma were 3.6 ng/g and 4.1 ng/ml respectively. Brain and whole blood ChE activity were inhibited to 70% and 57% of their original activity. Transdermal physo by itself protected up to 70% of the animals exposed to 1.5 LD(50) of soman or sarin (100% mortality was recorded in the control group). Combining transdermal physo with Scopoderm (by Ciba Geigy Inc.) provided full protection against 1.5 LD(50).

Use of intranasal fentanyl in children undergoing myringotomy and tube placement during halothane and sevoflurane anesthesia.

Science.gov (United States)

Galinkin, J L; Fazi, L M; Cuy, R M; Chiavacci, R M; Kurth, C D; Shah, U K; Jacobs, I N; Watcha, M F

2000-12-01

Many children are restless, disoriented, and inconsolable immediately after bilateral myringotomy and tympanosotomy tube placement (BMT). Rapid emergence from sevoflurane anesthesia and postoperative pain may increase emergence agitation. The authors first determined serum fentanyl concentrations in a two-phase study of intranasal fentanyl. The second phase was a prospective, placebo-controlled, double-blind study to determine the efficacy of intranasal fentanyl in reducing emergence agitation after sevoflurane or halothane anesthesia. In phase 1, 26 children with American Society of Anesthesiologists (ASA) physical status I or II who were scheduled for BMT received intranasal fentanyl, 2 microg/kg, during a standardized anesthetic. Serum fentanyl concentrations in blood samples drawn at emergence and at postanesthesia care unit (PACU) discharge were determined by radioimmunoassay. In phase 2, 265 children with ASA physical status I or II were randomized to receive sevoflurane or halothane anesthesia along with either intranasal fentanyl (2 microg/kg) or saline. Postoperative agitation, Children's Hospital of Eastern Ontario Pain Scale (CHEOPS) scores, and satisfaction of PACU nurses and parents with the anesthetic technique were evaluated. In phase 1, the mean fentanyl concentrations at 10 +/- 4 min (mean +/- SD) and 34 +/- 9 min after administering intranasal fentanyl were 0.80 +/- 0.28 and 0.64 +/- 0.25 ng/ml, respectively. In phase 2, the incidence of severe agitation, highest CHEOPS scores, and heart rate in the PACU were decreased with intranasal fentanyl. There were no differences between sevoflurane and halothane in these measures and in times to hospital discharge. The incidence of postoperative vomiting, hypoxemia, and slow respiratory rates were not increased with fentanyl. Serum fentanyl concentrations after intranasal administration exceed the minimum effective steady state concentration for analgesia in adults. The use of intranasal fentanyl during

Two Different Epidural Analgesic Combinations: Morphine vs. Fentanyl/Bupivacaine or Fentanyl/Ropivacaine and Their Post Operative Effects

National Research Council Canada - National Science Library

Pearce, Tori

2001-01-01

.... This study's purpose was to compare one institutions postoperative epidural opioid/local anesthetic protocol, currently fentanyl with bupivacaine or ropivacaine and compare it to the previously used morphine...

Comparative evaluation of dexmedetomidine and fentanyl for epidural analgesia in lower limb orthopedic surgeries

Directory of Open Access Journals (Sweden)

Sukhminder Jit Singh Bajwa

2011-01-01

Full Text Available Background and Aims: Opioids as epidural adjunct to local anesthetics (LA have been in use since long and α-2 agonists are being increasingly used for similar purpose. The present study aims at comparing the hemodynamic, sedative, and analgesia potentiating effects of epidurally administered fentanyl and dexmedetomidine when combined with ropivacaine. Methods: A total of one hundred patients of both gender aged 21-56 years, American Society of Anaesthesiologist (ASA physical status I and II who underwent lower limb orthopedic surgery were enrolled into the present study. Patients were randomly divided into two groups: Ropivacaine + Dexmedetomidine (RD and Ropivacaine + Fentanyl (RF, comprising 50 patie nts each. Inj. Ropivacaine, 15 ml of 0.75%, was administered epidurally in both the groups with addition of 1 μg/kg of dexmedetomidine in RD group and 1 μg/kg of fentanyl in RF group. Besides cardio-respiratory parameters and sedation scores, various block characteristics were also observed which included time to onset of analgesia at T10, maximum sensory analgesic level, time to complete motor blockade, time to two segmental dermatomal regressions, and time to first rescue analgesic. At the end of study, data was compiled systematically and analyzed using ANOVA with post-hoc significance, Chi-square test and Fisher′s exact test. Value of P<0.05 is considered significant and P<0.001 as highly significant. Results: The demographic profile of patients was comparable in both the groups. Onset of sensory analgesia at T10 (7.12±2.44 vs 9.14±2.94 and establishment of complete motor blockade (18.16±4.52 vs 22.98±4.78 was significantly earlier in the RD group. Postoperative analgesia was prolonged significantly in the RD group (366.62±24.42 and consequently low dose consumption of local anaesthetic LA (76.82±14.28 vs 104.35±18.96 during epidural top-ups postoperatively. Sedation scores were much better in the RD group and highly significant on

Inhibition of protein kinase A and GIRK channel reverses fentanyl-induced respiratory depression.

Science.gov (United States)

Liang, Xiaonan; Yong, Zheng; Su, Ruibin

2018-06-11

Opioid-induced respiratory depression is a major obstacle to improving the clinical management of moderate to severe chronic pain. Opioids inhibit neuronal activity via various pathways, including calcium channels, adenylyl cyclase, and potassium channels. Currently, the underlying molecular pathway of opioid-induced respiratory depression is only partially understood. This study aimed to investigate the mechanisms of opioid-induced respiratory depression in vivo by examining the effects of different pharmacological agents on fentanyl-induced respiratory depression. Respiratory parameters were detected using whole body plethysmography in conscious rats. We show that pre-treatment with the protein kinase A (PKA) inhibitor H89 reversed the fentanyl-related effects on respiratory rate, inspiratory time, and expiratory time. Pre-treatment with the G protein-gated inwardly rectifying potassium (GIRK) channel blocker Tertiapin-Q dose-dependently reversed the fentanyl-related effects on respiratory rate and inspiratory time. A phosphodiesterase 4 (PDE4) inhibitor and cyclic adenosine monophosphate (cAMP) analogs did not affect fentanyl-induced respiratory depression. These findings suggest that PKA and GIRK may be involved in fentanyl-induced respiratory depression and could represent useful therapeutic targets for the treatment of fentanyl-induced ventilatory depression. Copyright © 2018 Elsevier B.V. All rights reserved.

Synthesis and analysis of the opioid analgesic [[sup 14]C]-fentanyl

Energy Technology Data Exchange (ETDEWEB)

Bagley, J.R.; Wilhelm, J.A. (Anaquest Inc., Murray Hill, NJ (United States))

1992-11-01

The synthesis of [[sup 14]C]-fentanyl, the radiolabelled congener of the potent opioid analgesic chosen for utilization in drug disposition studies, is described. [[sup 14]C]-Labelling was achieved in the first of two steps, a room temperature reduction of the in situ generated Schiff base from 1-phenylethyl-4-piperidone and [UL-[sup 14]C]-aniline hydrochloride with sodium triacetoxyborohydride. A nearly instantaneous production of fentanyl was accomplished at room temperature with the addition of propionyl chloride. The overall radiochemical yield was 18%. The method described is efficiently adaptable for submicromolar scale while yielding a product of sufficient specific activity for in vivo studies. Our solvent system for thin layer chromatography was superior to the USP system reported for chromatographic analysis of fentanyl. This is the first reported preparation of [[sup 14]C]-fentanyl with the radiolabel in the aniline benzene ring. (author).

A commentary on transdermal drug delivery systems in clinical trials.

Science.gov (United States)

Watkinson, Adam C

2013-09-01

The number of drugs available as marketed transdermal products is limited to those that exhibit the correct physicochemical and pharmacokinetic properties that enable their effective delivery across the skin. In this respect, there are less than 20 drugs that are currently marketed in the US and EU as products that deliver systemic levels of their active ingredients. An analysis of clinical trials conducted in the transdermal sector shows a similar picture with only nine drugs accounting for approximately 80% of all transdermal clinical trials listed on ClinicalTrials.gov. Those drugs for which there are very few transdermal trials listed consist mostly of molecules that are inherently unsuitable for transdermal delivery and serve as a clear warning to drug developers that the science that governs transdermal drug delivery is well reflected by the successes and failures of drugs in development as well as those that make it to the market. Copyright © 2013 Wiley Periodicals, Inc.

[Assessment of the use of racemic ketamine and its S(+) isomer, associated or not with low doses of fentanyl, in balneotherapy for major burn patients].

Science.gov (United States)

Cantinho, Fernando Antônio de Freitas; Silva, Antonio Carlos Pereira da

2009-01-01

The care of the wounds of major burn patients triggers severe painful stimuli. The objective of this study was to assess the safety and efficacy of different drug combinations in anesthesia for balneotherapy. After approval by the Ethics Commission, 200 procedures of balneotherapy in 87 major burn adult patients were evaluated. Midazolam was used in all cases. The vials of ketamine were numbered and, therefore, at the time of the use, one did not know whether racemic or S(+)ketamine was being used. Each morning it was decided by drawing lots whether fentanyl would be used or not in the procedures of that day. Patients were included in one of four groups: ISO/sf (S(+) isomer without fentanyl), ISO/cf (S(+) isomer with fentanyl), RAC/sf (racemic ketamine without fentanyl), and RAC/cf (racemic ketamine with fentanyl). The initial doses proposed were as follows: midazolam, 0.06 mg.kg-1; ketamine, 1.0 to 1.1 mg.kg-1; and fentanyl, 0.8 (1/4)g.kg1-1; additional doses were administered as needed. Only one patient recalled the pain of balneotherapy. In the group that received S(+)ketamine, the use of fentanyl did not bring additional advantages; however, when associated with racemic ketamine, fentanyl reduced the total dose and the number of ketamine boluses. The extension of body surface burned was the main determinant of the severity of post-procedure pain. Reduced pain severity was the main factor considered by patients when grading their satisfaction with the anesthesia. The four different drug combinations proved to be safe and guaranteed the absence of pain during balneotherapy. Characteristics not directly related to the anesthetics proved to be more important in the incidence of post-procedure pain, which was the main factor considered by major burn patient to define their satisfaction with the anesthesia used.

Estradiol Transdermal Patch

Science.gov (United States)

... menopause (change of life; the end of monthly menstrual periods). Transdermal estradiol is also used to prevent ... patch. Ask your pharmacist or doctor for a copy of the manufacturer's information for the patient.

Overdose Deaths Related to Fentanyl and Its Analogs - Ohio, January-February 2017.

Science.gov (United States)

Daniulaityte, Raminta; Juhascik, Matthew P; Strayer, Kraig E; Sizemore, Ioana E; Harshbarger, Kent E; Antonides, Heather M; Carlson, Robert R

2017-09-01

Ohio is experiencing unprecedented loss of life caused by unintentional drug overdoses (1), with illicitly manufactured fentanyl (IMF) emerging as a significant threat to public health (2,3). IMF is structurally similar to pharmaceutical fentanyl, but is produced in clandestine laboratories and includes fentanyl analogs that display wide variability in potency (2); variations in chemical composition of these drugs make detection more difficult. During 2010-2015, unintentional drug overdose deaths in Ohio increased 98%, from 1,544 to 3,050.* In Montgomery County (county seat: Dayton), one of the epicenters of the opioid epidemic in the state, unintentional drug overdose deaths increased 40% in 1 year, from 249 in 2015 to 349 in 2016 (estimated unadjusted mortality rate = 57.7 per 100,000) (4). IMFs have not been part of routine toxicology testing at the coroner's offices and other types of medical and criminal justice settings across the country (2,3). Thus, data on IMF test results in the current outbreak have been limited. The Wright State University and the Montgomery County Coroner's Office/Miami Valley Regional Crime Laboratory (MCCO/MVRCL) collaborated on a National Institutes of Health study of fentanyl analogs and metabolites and other drugs identified in 281 unintentional overdose fatalities in 24 Ohio counties during January-February 2017. Approximately 90% of all decedents tested positive for fentanyl, 48% for acryl fentanyl, 31% for furanyl fentanyl, and 8% for carfentanil. Pharmaceutical opioids were identified in 23% of cases, and heroin in 6%, with higher proportions of heroin-related deaths in Appalachian counties. The majority of decedents tested positive for more than one type of fentanyl. Evidence suggests the growing role of IMFs, and the declining presence of heroin and pharmaceutical opioids in unintentional overdose fatalities, compared with 2014-2016 data from Ohio and other states (3-5). There is a need to include testing for IMFs as part

Detection of illicit online sales of fentanyls via Twitter [version 1; referees: 2 approved

Directory of Open Access Journals (Sweden)

Tim K. Mackey

2017-11-01

Full Text Available A counterfeit fentanyl crisis is currently underway in the United States.  Counterfeit versions of commonly abused prescription drugs laced with fentanyl are being manufactured, distributed, and sold globally, leading to an increase in overdose and death in countries like the United States and Canada.  Despite concerns from the U.S. Drug Enforcement Agency regarding covert and overt sale of fentanyls online, no study has examined the role of the Internet and social media on fentanyl illegal marketing and direct-to-consumer access.  In response, this study collected and analyzed five months of Twitter data (from June-November 2015 filtered for the keyword “fentanyl” using Amazon Web Services.  We then analyzed 28,711 fentanyl-related tweets using text filtering and a machine learning approach called a Biterm Topic Model (BTM to detect underlying latent patterns or “topics” present in the corpus of tweets.  Using this approach we detected a subset of 771 tweets marketing the sale of fentanyls online and then filtered this down to nine unique tweets containing hyperlinks to external websites.  Six hyperlinks were associated with online fentanyl classified ads, 2 with illicit online pharmacies, and 1 could not be classified due to traffic redirection.  Importantly, the one illicit online pharmacy detected was still accessible and offered the sale of fentanyls and other controlled substances direct-to-consumers with no prescription required at the time of publication of this study.   Overall, we detected a relatively small sample of Tweets promoting illegal online sale of fentanyls.  However, the detection of even a few online sellers represents a public health danger and a direct violation of law that demands further study.

Increase in Drug Overdose Deaths Involving Fentanyl-Rhode Island, January 2012-March 2014.

Science.gov (United States)

Mercado, Melissa C; Sumner, Steven A; Spelke, M Bridget; Bohm, Michele K; Sugerman, David E; Stanley, Christina

2018-03-01

This study identified sociodemographic, substance use, and multiple opioid prescriber and dispenser risk factors among drug overdose decedents in Rhode Island, in response to an increase in overdose deaths (ODs) involving fentanyl. This cross-sectional investigation comprised all ODs reviewed by Rhode Island's Office of the State Medical Examiners (OSME) during January 2012 to March 2014. Data for 536 decedents were abstracted from OSME's charts, death certificates, toxicology reports, and Prescription Monitoring Program (PMP) databases. Decedents whose cause of death involved illicit fentanyl (N = 69) were compared with decedents whose causes of death did not involve fentanyl (other drug decedents; N = 467). Illicit-fentanyl decedents were younger than other drug decedents (P = 0.005). While more other-drug decedents than illicit fentanyl decedents had postmortem toxicological evidence of consuming heroin (31.9% vs 19.8%, P < 0.001) and various pharmaceutical substances (P = 0.002-0.027), third party reports indicated more recent heroin use among illicit fentanyl decedents (62.3% vs 45.6%, P = 0.002). Approximately 35% of decedents filled an opioid prescription within 90 days of death; of these, one-third had a mean daily dosage greater than 100 morphine milligram equivalents (MME/day). Most decedents' opioid prescriptions were filled at one to two dispensers (83.9%) and written by one to two prescribers (75.8%). Notably, 29.2% of illicit fentanyl and 10.5% of other drug decedents filled prescriptions for buprenorphine, which is used to treat opioid use disorders. Illicit-fentanyl deaths frequently involved other illicit drugs (e.g., cocaine, heroin). The proportion of all decedents acquiring greater than 100 MME/day prescription dosages written and/or filled by few prescribers and dispensers is concerning. To protect patients, prescribers and dispensers should review PMP records and substance abuse history prior to providing opioids.

Fentanyl Enhances Hepatotoxicity of Paclitaxel via Inhibition of CYP3A4 and ABCB1 Transport Activity in Mice

Science.gov (United States)

Pan, Jia-Hao; Bi, Bing-Tian; Feng, Kun-Yao; Huang, Wan; Zeng, Wei-An

2015-01-01

Fentanyl, a potent opioid analgesic that is used to treat cancer pain, is commonly administered with paclitaxel in advanced tumors. However, the effect of fentanyl on the hepatotoxicity of paclitaxel and its potential mechanism of action is not well studied. The purpose of this study was to investigate the effect of fentanyl on the hepatotoxicity of paclitaxel and its potential mechanisms of action. Pharmacokinetic parameters of paclitaxel were tested using reversed phase high-performance liquid chromatography (RP-HPLC). Aspartate transaminase (AST), alanine aminotransferase (ALT), and mouse liver histopathology were examined. Moreover, the cytotoxicity of anti-carcinogens was examined using 1-(4, 5-dimethylthiazol-2-yl)-3,5-diphenylformazan (MTT), and the intracellular accumulation of doxorubicin and rhodamine 123 was detected by flow cytometry. Furthermore, the expression of ABCB1 and the activity of ABCB1 ATPase and CYP3A4 were also examined. In this study, the co-administration of fentanyl and paclitaxel prolonged the half-life (t1/2) of paclitaxel from 1.455 hours to 2.344 hours and decreased the clearance (CL) from 10.997 ml/h to 7.014 ml/h in mice. Fentanyl significantly increased the levels of ALT in mice to 88.2 U/L, which is more than 2-fold higher than the level detected in the control group, and it increased the histological damage in mouse livers. Furthermore, fentanyl enhanced the cytotoxicity of anti-carcinogens that are ABCB1 substrates and increased the accumulation of doxorubicin and rhodamine 123. Additionally, fentanyl stimulated ABCB1 ATPase activity and inhibited CYP3A4 activity in the liver microsomes of mice. Our study indicates that the obvious hepatotoxicity during this co-administration was due to the inhibition of CYP3A4 activity and ABCB1 transport activity. These findings suggested that the accumulation-induced hepatotoxicity of paclitaxel when it is combined with fentanyl should be avoided. PMID:26633878

76 FR 19997 - Determination That FENTORA (Fentanyl Citrate) Buccal Tablet, 300 Micrograms, Was Not Withdrawn...

Science.gov (United States)

2011-04-11

...] Determination That FENTORA (Fentanyl Citrate) Buccal Tablet, 300 Micrograms, Was Not Withdrawn From Sale for... Food and Drug Administration (FDA) has determined that FENTORA (fentanyl citrate) buccal tablet, 300... allow FDA to approve abbreviated new drug applications (ANDAs) for fentanyl citrate buccal tablet, 300...

Synthesis of conjugated chitosan and its effect on drug permeation from transdermal patches.

Science.gov (United States)

Satheeshababu, B K; Shivakumar, K L

2013-03-01

The aim of this study was to synthesis the conjugated chitosan by covalent attachment of thiol moieties to the cationic polymer, mediated by a carbodiimide to improve permeation properties of chitosan. Thioglycolic acid was covalently attached to chitosan by the formation of amide bonds between the primary amino groups of the polymer and the carboxylic acid groups of thioglycolic acid. Hence, these polymers are called as thiomers or thiolated polymers. Conjugation of chitosan was confirmed by Fourier transform-infrared and differential scanning calorimetric analysis. Matrix type transdermal patches of carvedilol were prepared using the different proportions of chitosan and chitosan-thioglycolic acid conjugates (2:0, 1.7:0.3, 1.4:0.6, 1:1, 0.6:1.4 and 0.3:1.7) by solvent casting technique. Prepared matrix type patches were evaluated for their physicochemical characterization followed by in vitro evaluation. Selected formulations were subjected for their ex vivo studies on Wistar albino rat skin and human cadaver skin using the modified Franz diffusion cell. As the proportion of conjugated chitosan increased, the transdermal patches showed increased drug permeation. The mechanism of drug release was found to be nonFickian profiles. The present study concludes that the transdermal patches of carvedilol using conjugated chitosan with different proportions of chitosan were successfully developed to provide improved drug permeation. The transdermal patches can be a good approach to improve drug bioavailability by bypassing the extensive hepatic first-pass metabolism of the drug.

The interaction of fentanyl on the Cp50 of propofol for loss of consciousness and skin incision.

Science.gov (United States)

Smith, C; McEwan, A I; Jhaveri, R; Wilkinson, M; Goodman, D; Smith, L R; Canada, A T; Glass, P S

1994-10-01

We have previously demonstrated that the minimum alveolar concentration of isoflurane at 1 atm that is required to prevent movement in 50% of patients or animals exposed to a maximal noxious stimulus is markedly reduced by increasing fentanyl concentrations. Total intravenous anesthesia with propofol is increasing in popularity, yet the propofol concentrations required for total intravenous anesthesia or the interaction between propofol and fentanyl have not yet been defined. Propofol and fentanyl were administered via computer-assisted continuous infusion to provide pseudo-steady-state concentrations and allow equilibration between plasma-blood concentration and their biophase concentration. For the induction of anesthesia patients were randomly allocated to receive propofol only or propofol plus fentanyl 0.2, 0.8, 1.5, 3.0, and 4.5 ng/ml. In each group patients were randomized to target propofol concentrations of 1.5-10 micrograms/ml. At 7 and 10 min arterial blood samples were taken for subsequent measurement of propofol and fentanyl concentrations. At 10 min loss of consciousness was assessed by the patients' ability to respond to a simple verbal command. Thereafter a new target concentration of propofol was entered to ensure loss of consciousness, and succinylcholine was administered to facilitate tracheal intubation. Patients were rerandomized to a new target concentration of propofol (1-19 micrograms/ml) until skin incision. Before skin incision and 1 min after skin incision, arterial blood samples were again obtained for subsequent measurement of fentanyl and propofol concentrations. At skin incision and for 1 min the patient was observed for purposeful movement. Only samples in which the pre- and poststimulus drug concentrations were within 35% of each other were included. The propofol blood concentration at which 50% or 95% of patients did not respond to verbal command (Cp50s and Cp95s, respectively) and to skin incision (Cp50i and Cp95i, respectively

A comparative study of low concentration of levobupivacaine versus ropivacaine with fentanyl for patient-controlled epidural labour analgesia

Directory of Open Access Journals (Sweden)

Priyanka Chuttani

2018-01-01

Full Text Available >Background and Aims: Lumbar epidural analgesia is considered the modality of choice for labour analgesia. Despite its super analgesia and improved safety profile, it has been associated with maternal adverse effects like higher incidence of instrumental assisted vaginal delivery (AVD and motor block leading to decreased ambulation. This study was designed to evaluate the efficacy of low concentrations of local anaesthetics (0.1% ropivacaine and 0.1% levobupivacaine with 2 μg/ml fentanyl as a patient controlled epidural analgesia (PCEA technique on the incidence of instrumental AVD along with evaluation of obstetric, maternal, and foetal outcomes.Materials and Methods: In this prospective study, 60 labouring parturients were randomly allocated into two equal groups to receive either 0.1% ropivacaine with 2 μg/ml fentanyl or 0.1% levobupivacaine with 2 μg/ml fentanyl as epidural solutions via PCEA pump infusions (4 ml/h after 15 ml loading dose of the respective solutions. The incidence of instrumental AVD was noted as the primary outcome along with demographic data, maternal and foetal vital parameters, maternal VAS scores, degree of motor blockade and total epidural drug consumption.Results: The incidence of instrumental AVD was found to be 43.3% in the levobupivacaine group and 30% in the ropivacaine group. This difference was not statistically significant. Both the groups were comparable in terms of demographic data, maternal VAS scores, total epidural drug consumption and foetal APGAR scores.Conclusion: The use of newer local anaesthetics (levobupivacaine and ropivacaine in low concentrations with opioids (fentanyl as a PCEA technique may offer high maternal satisfaction in terms of quality of pain relief with fewer adverse events like instrumental AVD and adverse foetal outcomes.

Subeffective doses of dexketoprofen trometamol enhance the potency and duration of fentanyl antinociception

Science.gov (United States)

Gaitán, Gema; Herrero, Juan F

2002-01-01

The combination of classic non-steroidal antiinflammatory drugs (NSAIDs) with opiates induces more analgesia than the summed effect of each drug given separately. No studies have been performed using new generation NSAIDs and fentanyl nor on the duration of this effect. We have studied the analgesic effect of fentanyl alone and after the administration of subeffective doses of dexketoprofen trometamol in rat nociceptive responses. The responses were evoked by noxious mechanical stimulation and were recorded as single motor units in male Wistar rats anaesthetized with α-chloralose. The effective dose 50 (ED50) observed with fentanyl was 22.4±1.5 μg kg−1 and full recovery was apparent 20 min later. The administration of a total dose of 40 μg kg−1 of dexketoprofen trometamol did not induce any significant effect on the nociceptive responses. In the presence of dexketoprofen trometamol, the ED50 for fentanyl was 5 fold lower than before: 3.8±1.1 μg kg−1 and no significant recovery was observed 45 min later. The opioid antagonist naloxone (200 μg kg−1) did not reverse the effect, although in control experiments the same dose was able to prevent any action of fentanyl given alone. We conclude that the combination of fentanyl and subeffective doses of dexketoprofen trometamol induces a more potent and longer lasting analgesic effect than that observed with fentanyl alone, and that this is not an opioid mediated action. PMID:11815374

Randomized Controlled Feasibility Trial of Intranasal Ketamine Compared to Intranasal Fentanyl for Analgesia in Children with Suspected Extremity Fractures.

Science.gov (United States)

Reynolds, Stacy L; Bryant, Kathleen K; Studnek, Jonathan R; Hogg, Melanie; Dunn, Connell; Templin, Megan A; Moore, Charity G; Young, James R; Walker, Katherine Rivera; Runyon, Michael S

2017-12-01

We compared the tolerability and efficacy of intranasal subdissociative ketamine to intranasal fentanyl for analgesia of children with acute traumatic pain and investigated the feasibility of a larger noninferiority trial that could investigate the potential opioid-sparing effects of intranasal ketamine. This randomized controlled trial compared 1 mg/kg intranasal ketamine to 1.5 μg/kg intranasal fentanyl in children 4 to 17 years old with acute pain from suspected isolated extremity fractures presenting to an urban Level II pediatric trauma center from December 2015 to November 2016. Patients, parents, treating physicians, and outcome assessors were blinded to group allocation. The primary outcome, a tolerability measure, was the frequency of cumulative side effects and adverse events within 60 minutes of drug administration. The secondary outcomes included the difference in mean pain score reduction at 20 minutes, the proportion of patients achieving a clinically significant reduction in pain in 20 minutes, total dose of opioid pain medication in morphine equivalents/kg/hour (excluding study drug) required during the emergency department (ED) stay, and the feasibility of enrolling children presenting to the ED in acute pain into a randomized trial conducted under U.S. regulations. All patients were monitored until 6 hours after their last dose of study drug or until admission to the hospital ward or operating room. Of 629 patients screened, 87 received the study drug and 82 had complete data for the primary outcome (41 patients in each group). The median (interquartile range) age was 8 (6-11) years and 62% were male. Baseline pain scores were similar among patients randomized to receive ketamine (73 ± 26) and fentanyl (69 ± 26; mean difference [95% CI] = 4 [-7 to 15]). The cumulative number of side effects was 2.2 times higher in the ketamine group, but there were no serious adverse events and no patients in either group required intervention. The most

[Understanding Oral and Nasal Mucosal Absorption of Fentanyl, and Rectal Absorption of Buprenorphine].

Science.gov (United States)

Shimoyama, Naohito; Shimoyama, Megumi; Kubota, Yukino; Kato, Yoko

2015-11-01

One of the key issues in the treatment of pain is to choose the appropriate route and dosage form of analgesics for each individual patient in pain. New drug forms of fentanyl absorbed by oral or nasal mucosa, and buprenorphine absorbed by rectal mucosa are described in this chapter. Only lipophilic opioids such as fentanyl and buprenorphine can be absorbed via the mucosa of oral or nasal cavity of the human body. The T max of rapid onset opioids (ROO) such as fentanyl buccal or sublingual tablets is the fastest among various dosage forms of opioid analgesics. However, such rapid increase in plasma concentration of fentanyl by ROO formulations may cause the risk of respiratory depression. Safe ways to use ROO analgesics are described.

A physiologically-based recirculatory meta-model for nasal fentanyl in man

DEFF Research Database (Denmark)

Upton, RN; Foster, DJR; Christrup, Lona Louring

2012-01-01

Pharmacokinetic (PK) and pharmacodynamic (PD) data were available from a study of a nasal delivery system for the opioid analgesic fentanyl, together with data on the kinetics of fentanyl in arterial blood in man, and in the lung and brain of sheep. Our aim was to reconcile these data using a phy...

Two placebo-controlled, randomized withdrawal studies to evaluate the fentanyl 1 day patch in opioid-naïve patients with chronic pain.

Science.gov (United States)

Arai, Tsutomu; Kashimoto, Yuji; Ukyo, Yoshifumi; Tominaga, Yushin; Imanaka, Keiichiro

2015-12-01

To evaluate the efficacy and safety of fentanyl 1 day patch in opioid-naïve patients with non-cancer chronic pain insufficiently relieved by non-opioid analgesics. Two phase III placebo-controlled, double-blind, group-comparison, randomized withdrawal studies were conducted in patients with osteoarthritis and/or low back pain (N01 study) and post-herpetic neuralgia, complex regional pain syndrome, or chronic postoperative pain (N02) in Japan. Both studies consisted of period I (10-29 days of titration, fentanyl 12.5-50.0 µg/h) and period II (12 weeks double-blind). N01, NCT01008618; N02, NCT01008553 MAIN OUTCOME MEASURES: The primary endpoint was the number of days until study discontinuation due to insufficient pain relief in period II, and secondary endpoints included pain scored on visual analog scale (VAS), subject's overall assessment, the number of rescue dose, brief pain inventory short form score, score on short-form 36-item health survey version 2.0, physician's overall assessment, and assessment of adverse events. Of the 218 (N01) and 258 (N02) subjects who entered period I, 150 and 163 subjects entered period II, respectively. In the N01 study, the between-group difference was significant in the VAS score (95% CI: 7.3 [1.1, 13.5] mm, P = 0.0215) but not in the primary endpoint (P = 0.0846, log-rank test). In the N02 study, both primary efficacy (P = 0.0003) and VAS (8.7 [2.4, 15.0] mm, P = 0.0071) results showed that fentanyl was more effective than placebo. The major adverse events were nervous system and gastrointestinal disorders typically associated with opioid analgesic use. The incidence of adverse events in the fentanyl group was 68.5% to 85.7%. Although the primary efficacy results showed significant effects of fentanyl in the N02 but not the N01 study, overall results showed that fentanyl 1 day patch is effective and well tolerated.

Association between UGT2B7 gene polymorphisms and fentanyl sensitivity in patients undergoing painful orthognathic surgery

Science.gov (United States)

Muraoka, Wataru; Nishizawa, Daisuke; Fukuda, Kenichi; Kasai, Shinya; Hasegawa, Junko; Wajima, Koichi; Nakagawa, Taneaki

2016-01-01

Background Fentanyl is often used instead of morphine for the treatment of pain because it has fewer side effects. The metabolism of morphine by glucuronidation is known to be influenced by polymorphisms of the UGT2B7 gene. Some metabolic products of fentanyl are reportedly metabolized by glucuronate conjugation. The genes that are involved in the metabolic pathway of fentanyl may also influence fentanyl sensitivity. We analyzed associations between fentanyl sensitivity and polymorphisms of the UGT2B7 gene to clarify the hereditary determinants of individual differences in fentanyl sensitivity. Results This study examined whether single-nucleotide polymorphisms (SNPs) of the UGT2B7 gene affect cold pain sensitivity and the analgesic effects of fentanyl, evaluated by a standardized pain test and fentanyl requirements in healthy Japanese subjects who underwent uniform surgical procedures. The rs7439366 SNP of UGT2B7 is reportedly associated with the metabolism and analgesic effects of morphine. We found that this SNP is also associated with the analgesic effects of fentanyl in the cold pressor-induced pain test. It suggested that the C allele of the rs7439366 SNP may enhance analgesic efficacy. Two SNPs of UGT2B7, rs4587017 and rs1002849, were also found to be novel SNPs that may influence the analgesic effects of fentanyl in the cold pressor-induced pain test. Conclusions Fentanyl sensitivity for cold pressor-induced pain was associated with the rs7439366, rs4587017, and rs1002849 SNPs of the UGT2B7 gene. Our findings may provide valuable information for achieving satisfactory pain control and open to new avenues for personalized pain treatment. PMID:28256933

Analysis of fentanyl in urine by DLLME-GC-MS.

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Gardner, Michael A; Sampsel, Sheena; Jenkins, Werner W; Owens, Janel E

2015-03-01

Fentanyl is a synthetic narcotic anesthetic ∼80-100 times more potent than morphine. Owing to the potential for its abuse, the drug may be included in a forensic toxicology work-up, which requires fast, precise and accurate measurements. Here, the stability of fentanyl was assessed when stored at three different temperatures (-20, 4 and 25°C) in synthetic urine. Stability at those three temperatures was demonstrated over 12 weeks upon analysis by gas chromatography-mass spectrometry with a deuterated internal standard (fentanyl-D5) utilizing three different extraction techniques: liquid-liquid extraction (LLE), solid-phase extraction and dispersed liquid-liquid microextraction (DLLME). The DLLME method was then optimized before use in the analysis of fentanyl in urine samples obtained from autopsy cases at the El Paso County Coroner's Office. Accuracy of the DLLME method was assessed by completing spike and recovery studies at three different fortification levels (10, 100 and 250 ng/mL) with excellent recovery (89.9-102.6%). The excellent comparability between DLLME and LLE is demonstrated (Bland-Altman difference plot with a mean difference of 4.9 ng/mL) and the use of this methodology in the analysis of forensically relevant samples is discussed. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Minidose Bupivacaine – Fentanyl Spinal Anesthesia for Cesarean Section In Preeclamptic Parturients

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N. Fatholahzadeh

2006-07-01

Full Text Available Background:Spinal anesthesia for cesarean section is associated with a high incidence of hypotension. The synergism between intrathecal opioids and local anesthetics may make it possible to achieve reliable spinal anesthesia with minimal hypotension using a minidose of local anesthetic. Methods: Forty-four preeclamptic parturients undergoing cesarean section were randomized in two groups of 22 patients. Group A received a spinal anesthetic of bupivacaine 6 mg plus fentanyl 20 µg , and group B received 12 mg bupivacaine. Hypotension was defined as a 30% decrease in systolic and diastolic pressure from baseline. Hypotension was treated with intravenous ephedrine boluses 2.5-5 mg up to maximum 50 mg. Results: All patients had satisfactory anesthesia. Five of 22 patients in group A required ephedrine, a single dose of 5 mg. Seventeen of 22 patients in group B required vasopressor support of blood pressure.The lowest recorded systolic,diastolic and mean blood pressures as fractions of the baseline pressures were 71.2%, 64.5% and 70.3% versus 59.9%, 53.5% and 60.2% respectively for group A versus group B. Conclusion: A “minidose” of 6 mg bupivacaine in combination with 20 µg fentanyl may provide satisfactory spinal anesthesia for cesarean section in the preeclamptic patient. The minidose combination caused dramatically less hypotension than 12 mg bupivacaine and nearly eliminated the need for vasopressor support of blood pressure. 

Safety and efficiency of prehospital pain management with fentanyl administered by emergency medical technicians

DEFF Research Database (Denmark)

Nielsen, Niels Dalsgaard; Brogaard, Kjeld; Dahl, Michael

2007-01-01

minor, and were not treated with naloxone.   Conclusions: Our results suggest that non-medical personnel safely can administer IV fentanyl to selected groups of patients with a satisfactory result in terms of a considerable reduction in pain score and an acceptable rate of negative coincident events....

Multiscale modeling of transdermal drug delivery

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Rim, Jee Eun

2006-04-01

This study addresses the modeling of transdermal diffusion of drugs, to better understand the permeation of molecules through the skin, and especially the stratum corneum, which forms the main permeation barrier of the skin. In transdermal delivery of systemic drugs, the drugs diffuse from a patch placed on the skin through the epidermis to the underlying blood vessels. The epidermis is the outermost layer of the skin and can be further divided into the stratum corneum (SC) and the viable epidermis layers. The SC consists of keratinous cells (corneocytes) embedded in the lipid multi-bilayers of the intercellular space. It is widely accepted that the barrier properties of the skin mostly arises from the ordered structure of the lipid bilayers. The diffusion path, at least for lipophilic molecules, seems to be mainly through the lipid bilayers. Despite the advantages of transdermal drug delivery compared to other drug delivery routes such as oral dosing and injections, the low percutaneous permeability of most compounds is a major difficulty in the wide application of transdermal drug delivery. In fact, many transdermal drug formulations include one or more permeation enhancers that increase the permeation of the drug significantly. During the last two decades, many researchers have studied percutaneous absorption of drugs both experimentally and theoretically. However, many are based on pharmacokinetic compartmental models, in which steady or pseudo-steady state conditions are assumed, with constant diffusivity and partitioning for single component systems. This study presents a framework for studying the multi-component diffusion of drugs coupled with enhancers through the skin by considering the microstructure of the stratum corneum (SC). A multiscale framework of modeling the transdermal diffusion of molecules is presented, by first calculating the microscopic diffusion coefficient in the lipid bilayers of the SC using molecular dynamics (MD). Then a

Effects of fentanyl on isoflurane minimum alveolar concentration in New Zealand White rabbits (Oryctolagus cuniculus).

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Barter, Linda S; Hawkins, Michelle G; Pypendop, Bruno H

2015-02-01

To determine effects of increasing plasma fentanyl concentrations on the minimum alveolar concentration (MAC) of isoflurane in rabbits. 6 adult female New Zealand White rabbits (Oryctolagus cuniculus). Rabbits were anesthetized with isoflurane in oxygen; ventilation was controlled and body temperature maintained between 38.5° and 39.5°C. Fentanyl was administered IV by use of a computer-controlled infusion system to achieve 6 target plasma concentrations. Isoflurane MAC was determined in duplicate by use of the bracketing technique with a supramaximal electrical stimulus. Blood samples were collected for measurement of plasma fentanyl concentration at each MAC determination. The MAC values were analyzed with a repeated-measures ANOVA followed by Holm-Sidak pairwise comparisons. Mean ± SD plasma fentanyl concentrations were 0 ± 0 ng/mL (baseline), 1.2 ± 0.1 ng/mL, 2.2 ± 0.3 ng/mL, 4.4 ± 0.4 ng/mL, 9.2 ± 0.4 ng/mL, 17.5 ± 2.6 ng/mL, and 36.8 ± 2.4 ng/mL. Corresponding mean values for isoflurane MAC were 1.92 ± 0.16%, 1.80 ± 0.16%, 1.60 ± 0.23%, 1.46 ± 0.22%, 1.12 ± 0.19%, 0.89 ± 0.14%, and 0.70 ± 0.15%, respectively. Isoflurane MAC for plasma fentanyl concentrations ≥ 2.2 ng/mL differed significantly from the baseline value. In 3 rabbits, excessive spontaneous movement prevented MAC determination at the highest plasma fentanyl concentration. Fentanyl reduced isoflurane MAC by approximately 60% in New Zealand White rabbits. Further studies will be needed to investigate the cardiorespiratory effects of isoflurane and fentanyl combinations in rabbits; however, fentanyl may prove to be a useful adjunct to inhalation anesthesia in this species.

Qualitative Identification of Fentanyl Analogs and Other Opioids in Postmortem Cases by UHPLC-Ion Trap-MSn.

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Shoff, Elisa N; Zaney, M Elizabeth; Kahl, Joseph H; Hime, George W; Boland, Diane M

2017-07-01

Since 2013, the Miami-Dade County Medical Examiner Department has experienced an increase in the number of opioid-related deaths. The majority of cases coincided with the introduction of fentanyl into the local heroin supply. From 2014 to 2015, Miami-Dade County experienced a near 600% increase in fentanyl-related deaths, followed by an additional 200% increase in 2016. In 2015, two novel fentanyl analogs were identified in medical examiner cases: beta-hydroxythiofentanyl and acetyl fentanyl. In 2016, four additional fentanyl analogs emerged: para-fluoroisobutyryl fentanyl, butyryl fentanyl, furanyl fentanyl and carfentanil, as well as the synthetic opioid U-47700. In order to address this epidemic, a method was developed and validated to identify 44 opioid-related and analgesic compounds in postmortem samples using ultra high performance liquid chromatography ion trap mass spectrometry with MSn capabilities. The limit of detection for all compounds ranged from 0.1 to 5 ng/mL, with a majority having MS3 spectral fragmentation. Blood, urine, liver or brain specimens from ~500 postmortem cases were submitted for analysis based on case history and/or initial screening results. Of those cases, 375 were positive for illicit fentanyl and/or one or more fentanyl analogs. Due to the potency of these compounds, they were almost always included in the cause of death. Worth emphasizing and extremely alarming is the detection of carfentanil in 134 cases, 104 of which were initially missed by gas chromatography mass spectrometry. By incorporating this sensitive, highly specific, and evolving screening procedure into the workflow, the toxicology laboratory continues to effectively assist the medical examiners in determining the cause and manner of death of decedents in Miami-Dade County. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

TRANSDERMAL DRUG DELIVERY AND METHODS TO ENHANCE IT

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E. G. Kuznetsova

2016-01-01

Full Text Available The paper presents the common methods employed in recent years for enhancing transdermal delivery of drug substances when applying transdermal therapeutic delivery systems. The chemical, physical and mechanical methods to enhance the transport of macromolecular compounds through the skin are considered in details. 

3D printing applications for transdermal drug delivery.

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Economidou, Sophia N; Lamprou, Dimitrios A; Douroumis, Dennis

2018-06-15

The role of two and three-dimensional printing as a fabrication technology for sophisticated transdermal drug delivery systems is explored in literature. 3D printing encompasses a family of distinct technologies that employ a virtual model to produce a physical object through numerically controlled apparatuses. The applicability of several printing technologies has been researched for the direct or indirect printing of microneedle arrays or for the modification of their surface through drug-containing coatings. The findings of the respective studies are presented. The range of printable materials that are currently used or potentially can be employed for 3D printing of transdermal drug delivery (TDD) systems is also reviewed. Moreover, the expected impact and challenges of the adoption of 3D printing as a manufacturing technique for transdermal drug delivery systems, are assessed. Finally, this paper outlines the current regulatory framework associated with 3D printed transdermal drug delivery systems. Copyright © 2018 Elsevier B.V. All rights reserved.

Exposure to fentanyl-contaminated heroin and overdose risk among illicit opioid users in Rhode Island: A mixed methods study.

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Carroll, Jennifer J; Marshall, Brandon D L; Rich, Josiah D; Green, Traci C

2017-08-01

Illicit fentanyl use has become wide spread in the US, causing high rates of overdose deaths among people who use drugs. This study describes patterns and perceptions of fentanyl exposure among opioid users in Rhode Island. A mixed methods study was conducted via questionnaire with a convenience sample of 149 individuals using illicit opioids or misusing prescription opioids in Rhode Island between January and November 2016. Of these, 121 knew of fentanyl and reported known or suspected exposure to fentanyl in the past year. Semi-structured interviews were conducted with the first 47 participants. Study participants were predominantly male (64%) and white (61%). Demographic variables were similar across sample strata. Heroin was the most frequently reported drug of choice (72%). Self-reported exposure to illicit fentanyl in the past year was common (50.4%, n=61). In multivariate models, regular (at least weekly) heroin use was independently associated with known or suspected fentanyl exposure in the past year (adjusted prevalence ratio (APR)=4.07, 95% CI: 1.24-13.3, p=0.020). In interviews, users described fentanyl as unpleasant, potentially deadly, and to be avoided. Participants reporting fentanyl exposure routinely experienced or encountered non-fatal overdose. Heroin users reported limited ability to identify fentanyl in their drugs. Harm reduction strategies used to protect themselves from fentanyl exposure and overdose, included test hits, seeking prescription opioids in lieu of heroin, and seeking treatment with combination buprenorphine/naloxone. Participants were often unsuccessful in accessing structured treatment programs. Among illicit opioid users in Rhode Island, known or suspected fentanyl exposure is common, yet demand for fentanyl is low. Fentanyl-contaminated drugs are generating user interest in effective risk mitigation strategies, including treatment. Responses to the fentanyl epidemic should be informed by the perceptions and experiences of

[Comparative study on transdermal osmosis in vitro of Aconitum brachypodium liniment, gel and patcher].

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Lin, Ya-ping; Zhao, Ying; Zhang, Yong-ping; Liang, Guang-yi

2007-02-01

To study the transdermal osmosis process of Aconitum brachypodum's liniment, gel and patcher to provide basis for selecting dosage form and controlling the quality. Taking the cumulate rate of transdermal as index, a imitated Fick's diffusion device was used for the investigating the transdermal osmosis course of the three preparations. The best transdermal mathematics models are obtained and the relations between the transdermal course and the release course are analysed. The three preparations have different characteristics of transdermal osmosis course. The liniment meets dynamics 0 order process, the gel and the patcher meet dynamic 0 order process of non-corroded drug system. And the relation is good cubic equation between their transdermal course and release course. The transdermal osmosis experiment in vitro for three preparations can provide basis for selecting dosage form and the quality control in future studies.

Efficacy of tramadol versus fentanyl for postoperative analgesia in neonates.

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Alencar, Ana Julia Couto; Sanudo, Adriana; Sampaio, Virginia Maria Ramos; Góis, Rôsicler Pereira; Benevides, Fernando Antônio Barbosa; Guinsburg, Ruth

2012-01-01

To assess, in newborn infants submitted to surgical procedures, the efficacy of two opioids-fentanyl and tramadol-regarding time to extubate, time to achieve 100 ml/kg of enteral feeding and pain in the first 72 h after surgery. Controlled, blind, randomised clinical trial. Neonatal intensive care unit. 160 newborn infants up to 28 days of life requiring major or minor surgeries. Patients were randomised to receive analgesia with fentanyl (1-2 μg/kg/h intravenously) or tramadol (0.1-0.2 mg/kg/h intravenously) in the first 72 h of the postoperative period, stratified by surgical size and by patient's gender. Pain assessed by validated neonatal scales (Crying, Requires oxygen, Increased vital signs, Expression and Sleepless Scale and the Neonatal Facial Coding System), time until extubation and time to reach 100 ml/kg enteral feeding. Statistical analysis included repeated measures analysis of variance adjusted for confounding variables and Kaplan-Meier curve adjusted by a Cox model of proportional risks. Neonatal characteristics were (mean±SD) birth weight of 2924±702 g, gestational age of 37.6±2.2 weeks and age at surgery of 199±63 h. The main indication of surgery was gastrointestinal malformation (85 newborns; 53%). Neonates who received fentanyl or tramadol were similar regarding time until extubation, time to reach 100 ml/kg of enteral feeding and pain scores in the first 72 h after surgery. Tramadol was as effective as fentanyl for postoperative pain relief in neonates but does not appear to offer advantages over fentanyl regarding the duration of mechanical ventilation and time to reach full enteral feeding. Trial registration NCT00713726.

Cardiopulmonary and analgesics effects of epidural morphine, fentanyl or tramadol in female dog undergoing a ovariohysterectomy

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Odete Duarte de Oliveira Neta

2014-09-01

Full Text Available ABSTRACT. Oliveira Neta O.D., Caires L.P., Clark R.M.O, Ferreira M.L., Said R.A., Munhoz A.D. & Tarazi R. [Cardiopulmonary and analgesics effects of epidural morphine, fentanyl or tramadol in female dog undergoing a ovariohysterectomy.] Efeitos cardiorrespiratórios e analgésicos da morfina, fentanil ou tramadol pela via epidural em cadelas submetidas à ovariosalpingohisterectomia. Revista Brasileira de Medicina Veterinária, 36(3:281-288, 2014. Departamento de Ciências Agrárias e Ambientais, Universidade Estadual de Santa Cruz, Rodovia Jorge Amado, Km 16, Salobrinho, Ilhéus, BA 45662-900, Brasil. E-mail: rosanaclark@gmail.com The objective was to evaluate the cardiorespiratory and analgesic effects provided by epidural morphine, tramadol and fentanyl in female dog submitted to ovariohysterectomy. Eighteen healthy female dogs, aged 3.4±2.2 years old, weithing 31.0±8.0Kg, were premedicated with chlorpromazine (0,5mg/kg, with subsequent propofol (5mg/Kg anesthetic induction by intravenous route and maintenance with isoflurane anesthesia. The animals were distributed in three groups and received: 1,25mg/kg of lignocaine 2% diluted in 0,26ml/kg of saline solution with0,1 mg/kg of morphine (GM group, 5μg/kg of fentanyl (GF group or 2mg/kg of tramadol (GT group epidurally.. Heart rate, arterial blood pressure, respiratory rate, end-tidal carbon dioxide (ETCO2 , oxyhemoglobin saturation (SpO2 and body temperature were evaluated before premedication (M0, 15 minutes after premedication (M1, 10 minutes after epidural opioids administration during maintenance and during postoperative period. Postoperative analgesia was evaluated using the by University of Melbourne pain scale (UMPS and a simple descriptive scale every hour during six hours (M3 – M8. In M2 time, the arterial blood pressure was significantly lower for all treatments and ETCO2 was higher in GM e GT when compared to GF. Pain scores were lower in GM with a UMPS. In the last three

Fentanyl versus magnesium sulphate as adjuvant to peribulbar anesthesia in cataract surgery

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Mohamed M. Abu Elyazed

2017-04-01

Conclusions: Addition of fentanyl (2 μg/ml or magnesium sulphate (50 mg to peribulbar block in patients undergoing cataract surgery equally prolongs the duration of postoperative analgesia. In addition to this effect, fentanyl fastens the onset lid and globe akinesia and provides better akinesia score.

Rotigotine transdermal patch for the treatment of Parkinson's Disease.

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Perez-Lloret, Santiago; Rey, María Verónica; Ratti, Pietro Lucca; Rascol, Olivier

2013-02-01

Rotigotine, a non-ergot dopamine agonist, has been developed as a novel transdermal formulation. The rotigotine transdermal patch has received EMEA marketing authorization for the treatment of adult patients with early or advanced Parkinson's disease (PD) or with moderate to severe restless legs syndrome (RLS). FDA originally granted a marketing authorization for early PD, which was later suspended, and is now studying the authorization for RLS. The aim of this review is to review the pharmacokinetics, pharmacodynamics as well as the clinical efficacy and tolerability of the rotigotine transdermal patch in PD. Source material was identified using a PubMed search for the term 'rotigotine' and PD. Articles published up to January 2011 or abstract submitted to most relevant international neurology congresses were reviewed. The rotigotine transdermal patch is efficacious for the treatment of PD. Tolerability profile appears to be well within the range of that observed with other non-ergot dopamine agonists in PD. Application-site reactions were the most frequent adverse event, and they were considered mild to moderate in the majority of cases. The rotigotine transdermal patch offers a safe and efficacious alternative for the treatment of PD. Further studies should focus on the possibility that continuous dopamine stimulation by means of the transdermal patch has any influence on levodopa-related motor complications. © 2012 The Authors Fundamental and Clinical Pharmacology © 2012 Société Française de Pharmacologie et de Thérapeutique.

A New Combination of Testosterone and Nestorone Transdermal Gels for Male Hormonal Contraception

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Ilani, Niloufar; Roth, Mara Y.; Amory, John K.; Swerdloff, Ronald S.; Dart, Clint; Page, Stephanie T.; Bremner, William J.; Sitruk-Ware, Regine; Kumar, Narender; Blithe, Diana L.

2012-01-01

Context: Combinations of testosterone (T) and nestorone (NES; a nonandrogenic progestin) transdermal gels may suppress spermatogenesis and prove appealing to men for contraception. Objective: The objective of the study was to determine the effectiveness of T gel alone or combined with NES gel in suppressing spermatogenesis. Design and Setting: This was a randomized, double-blind, comparator clinical trial conducted at two academic medical centers. Participants: Ninety-nine healthy male volunteers participated in the study. Interventions: Volunteers were randomized to one of three treatment groups applying daily transdermal gels (group 1: T gel 10 g + NES 0 mg/placebo gel; group 2: T gel 10 g + NES gel 8 mg; group 3: T gel 10 g + NES gel 12 mg). Main Outcome Variable: The main outcome variable of the study was the percentage of men whose sperm concentration was suppressed to 1 million/ml or less by 20–24 wk of treatment. Results: Efficacy data analyses were performed on 56 subjects who adhered to the protocol and completed at least 20 wk of treatment. The percentage of men whose sperm concentration was 1 million/ml or less was significantly higher for T + NES 8 mg (89%, P male range throughout the treatment period. Adverse effects were minimal in all groups. Conclusion: A combination of daily NES + T gels suppressed sperm concentration to 1 million/ml or less in 88.5% of men, with minimal adverse effects, and may be further studied as a male transdermal hormonal contraceptive. PMID:22791756

Pragmatic pharmacology: population pharmacokinetic analysis of fentanyl using remnant samples from children after cardiac surgery

Science.gov (United States)

Van Driest, Sara L.; Marshall, Matthew D.; Hachey, Brian; Beck, Cole; Crum, Kim; Owen, Jill; Smith, Andrew H.; Kannankeril, Prince J.; Woodworth, Alison; Caprioli, Richard M.

2016-01-01

Aims One barrier contributing to the lack of pharmacokinetic (PK) data in paediatric populations is the need for serial sampling. Analysis of clinically obtained specimens and data may overcome this barrier. To add evidence for the feasibility of this approach, we sought to determine PK parameters for fentanyl in children after cardiac surgery using specimens and data generated in the course of clinical care, without collecting additional blood samples. Methods We measured fentanyl concentrations in plasma from leftover clinically‐obtained specimens in 130 paediatric cardiac surgery patients and successfully generated a PK dataset using drug dosing data extracted from electronic medical records. Using a population PK approach, we estimated PK parameters for this population, assessed model goodness‐of‐fit and internal model validation, and performed subset data analyses. Through simulation studies, we compared predicted fentanyl concentrations using model‐driven weight‐adjusted per kg vs. fixed per kg fentanyl dosing. Results Fentanyl clearance for a 6.4 kg child, the median weight in our cohort, is 5.7 l h–1 (2.2–9.2 l h–1), similar to values found in prior formal PK studies. Model assessment and subset analyses indicated the model adequately fit the data. Of the covariates studied, only weight significantly impacted fentanyl kinetics, but substantial inter‐individual variability remained. In simulation studies, model‐driven weight‐adjusted per kg fentanyl dosing led to more consistent therapeutic fentanyl concentrations than fixed per kg dosing. Conclusions We show here that population PK modelling using sparse remnant samples and electronic medical records data provides a powerful tool for assessment of drug kinetics and generation of individualized dosing regimens. PMID:26861166

Budget impact analysis of the fentanyl buccal tablet for treatment of breakthrough cancer pain

Directory of Open Access Journals (Sweden)

Darbà J

2013-12-01

Full Text Available Josep Darbà,1 Lisette Kaskens,2 Rainel Sánchez-de la Rosa31University of Barcelona, Barcelona, 2BCN Health Economics and Outcomes Research SL, Barcelona, 3Medical and HEOR Department, TEVA Pharmaceutical Industries Ltd, Madrid, SpainBackground: The purpose of this study was to assess the economic impact of the fentanyl buccal tablet for the management of breakthrough cancer pain (BTcP in Spain.Methods: A 4-year budget impact model was developed for the period 2012–2015 for patients with BTcP from the perspective of the Spanish National Health System. BTcP products included in this model were rapid-onset opioids containing fentanyl (buccal, sublingual, or nasal transmucosal. Prevalence data on cancer, BTcP, opioid use, and number of BTcP episodes were obtained from the literature. Input data on health care resources associated with opioid use and opioid-induced side effects were obtained by consulting experts in oncology from different Spanish hospitals. Resources used included drugs, medical and emergency visits, other nonpharmacologic treatments, and treatment of opioid-induced side effects. Unit costs were obtained from the literature, and a 3% discount rate was applied to costs. Based on the unit costs for drugs and health care resources, the annual BTcP treatment costs per patient associated with each fentanyl product were determined to estimate the overall budget impact based on the total treatment population and the percentage of drug utilization associated with each product. One-way sensitivity analyses were conducted to test the robustness of the model.Results: Patients treated with oral opioids for BTcP were estimated at 23,291 in 2012, with an increase up to 23,413 in 2015. The average annual budget savings, with an increase of fentanyl buccal tablets, fentanyl sublingual tablets, and intranasal fentanyl spray, and a decrease in oral transmucosal fentanyl citrate, was estimated at €2.6 million, which represents a 0.5% decrease in

Epidural Neostigmine versus Fentanyl to Decrease Bupivacaine Use in Patient-controlled Epidural Analgesia during Labor: A Randomized, Double-blind, Controlled Study.

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Booth, Jessica L; Ross, Vernon H; Nelson, Kenneth E; Harris, Lynnette; Eisenach, James C; Pan, Peter H

2017-07-01

The addition of opioids to epidural local anesthetic reduces local anesthetic consumption by 20% but at the expense of side effects and time spent for regulatory compliance paperwork. Epidural neostigmine also reduces local anesthetic use. The authors hypothesized that epidural bupivacaine with neostigmine would decrease total hourly bupivacaine use compared with epidural bupivacaine with fentanyl for patient-controlled epidural analgesia. A total of 215 American Society of Anesthesiologists physical status II, laboring parturients requesting labor epidural analgesia consented to the study and were randomized to receive 0.125% bupivacaine with the addition of either fentanyl (2 μg/ml) or neostigmine (2, 4, or 8 μg/ml). The primary outcome was total hourly local anesthetic consumption, defined as total patient-controlled epidural analgesia use and top-ups (expressed as milliliters of 0.125% bupivacaine) divided by the infusion duration. A priori analysis determined a group size of 35 was needed to have 80% power at α = 0.05 to detect a 20% difference in the primary outcome. Of 215 subjects consented, 151 patients were evaluable. Demographics, maternal and fetal outcomes, and labor characteristics were similar among groups. Total hourly local anesthetic consumption did not differ among groups (P = 0.55). The total median hourly bupivacaine consumption in the fentanyl group was 16.0 ml/h compared with 15.3, 14.6, and 16.2 ml/h in the 2, 4, and 8 μg/ml neostigmine groups, respectively (P = 0.55). The data do not support any difference in bupivacaine requirements for labor patient-controlled epidural analgesia whether patients receive epidural bupivacaine with 2 to 8 μg/ml neostigmine or epidural bupivacaine with 2 μg/ml fentanyl.

Use of Fentanyl in Adolescents with Clinically Severe Obesity Undergoing Bariatric Surgery: A Pilot Study.

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Vaughns, Janelle D; Ziesenitz, Victoria C; Williams, Elaine F; Mushtaq, Alvina; Bachmann, Ricarda; Skopp, Gisela; Weiss, Johanna; Mikus, Gerd; van den Anker, Johannes N

2017-06-01

The number of obese pediatric patients requiring anesthesia is rapidly increasing. Although fentanyl is a commonly used narcotic during surgery, there are no pharmacokinetic (PK) data available for optimal dosing of fentanyl in adolescents with clinically severe obesity. An institutional review board-approved exploratory pilot study was conducted in six adolescents aged 14-19 years undergoing bariatric surgery. Mean total body weight (TBW) and mean BMI were 137.4 ± 14.3 kg and 49.6 ± 6.4 kg/m 2 (99.5th BMI percentile), respectively. Fentanyl was administered intravenously for intraoperative analgesia based on ideal body weight per standard of care. PK blood samples were drawn over a 24-h post-dose period. Fentanyl PK parameters were calculated by non-compartmental analysis. Mean fentanyl AUC 0-∞ was 1.5 ± 0.5 h·ng/mL. Systemic clearance of fentanyl was 1522 ± 310 mL/min and 11.2 ± 2.6 mL/min·kg TBW. Volume of distribution was 635 ± 282 L and 4.7 ± 2.1 L/kg TBW. While absolute clearance was increased, absolute volume of distribution was comparable to previously established adult values. These results suggest that fentanyl clearance is enhanced in adolescents with clinically severe obesity while volume of distribution is comparable to previously published studies. NCT01955993 (clinicaltrials.gov).

Fentanyl Utility Function: A Risk-Benefit Composite of Pain Relief and Breathing Responses

NARCIS (Netherlands)

van der Boom, M.; Olofsen, E.; Neukirchen, M.; Fussen, R.; Hay, J.; Groeneveld, G.J.; Aarts, L.; Sarton, E.; Dahan, A.

2013-01-01

INTRODUCTION:: Integrating opioid risk and benefit into a single function may give a useful single measure of the opioid's positive and negative effects. An explorative study on the effects of fentanyl on antinociception and respiratory depression was performed to construct fentanyl risk-benefit

Increases in self-reported fentanyl use among a population entering drug treatment: The need for systematic surveillance of illicitly manufactured opioids.

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Cicero, Theodore J; Ellis, Matthew S; Kasper, Zachary A

2017-08-01

Recent reports indicate a sharp increase in fentanyl-related overdose deaths across the United States, much of which is likely related to the introduction of cheap, illicitly manufactured fentanyl derivatives. In this study, we sought to estimate the magnitude of illicit fentanyl use from 2012 to 2016 using a national opioid abuse surveillance system. The study program surveyed 10,900 individuals entering substance abuse treatment for opioid use disorder, with participants asked to endorse past month 'use to get high' of fentanyl drugs, stratified by identifiable (i.e., branded) fentanyl formulations or a 'type unknown' drug alleged to contain fentanyl. Total past-month fentanyl-use rose modestly from 2012 to 2016. While use of known fentanyl products remained relatively stable (mean=10.9%; P=0.25), endorsements of 'unknown' fentanyl products nearly doubled from 9% in 2013 to 15.1% by 2016 (Pfentanyl use shows that recent increases in fentanyl use seem to be due almost entirely to 'unknown' fentanyl presumed to be illicitly manufactured. Given that it is difficult to assess the extent to which fentanyl may have been substituted for another drug (i.e., oxycodone, alprazolam, etc.) or was used as a heroin admixture, our data likely represent an underestimation of the full magnitude of illicit fentanyl abuse. As such, this growing public health problem requires immediate attention and more systematic efforts to identify and track its abuse. Copyright © 2017. Published by Elsevier B.V.

Continuous paravertebral infusion of ropivacaine with or without fentanyl for pain relief in unilateral multiple fractured ribs

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Medha Mohta

2013-01-01

Full Text Available Background: Continuous thoracic paravertebral block (TPVB provides effective analgesia for unilateral multiple fractured ribs (MFR. However, prolonged infusion of local anaesthetic (LA in high doses can predispose to risk of LA toxicity, which may be reduced by using safer drugs or drug combinations. This study was conducted to assess efficacy and safety of paravertebral infusion of ropivacaine and adrenaline with or without fentanyl to provide analgesia to patients with unilateral MFR. Methods: Thirty adults, having ≥3 unilateral MFR, with no significant trauma outside chest wall, were studied. All received bolus of 0.5% ropivacaine 0.3 ml/kg through paravertebral catheter, followed by either 0.1-0.2 ml/kg/hr infusion of ropivacaine 0.375% with adrenaline 5 μg/ml in group RA or ropivacaine 0.2% with adrenaline 5 μg/ml and fentanyl 2 μg/ml in group RAF. Rescue analgesia was provided by IV morphine. Results: Statistical analysis was performed using unpaired Student t-test, Chi-square test and repeated measures ANOVA. After TPVB, VAS scores, respiratory rate and PEFR improved in both groups with no significant inter-group differences. Duration of ropivacaine infusion, morphine requirements, length of ICU and hospital stay, incidence of pulmonary complications and opioid-related side-effects were similar in both groups. Ropivacaine requirement was higher in group RA than group RAF. No patient showed signs of LA toxicity. Conclusion: Continuous paravertebral infusion of ropivacaine 0.375% with adrenaline 5 μg/ml at 0.1-0.2 ml/kg/hr provided effective and safe analgesia to patients with unilateral MFR. Addition of fentanyl 2 μg/ml allowed reduction of ropivacaine concentration to 0.2% without decreasing efficacy or increasing opioid-related side-effects.

Functionally Selective Signaling for Morphine and Fentanyl Antinociception and Tolerance Mediated by the Rat Periaqueductal Gray

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Morgan, Michael M.; Reid, Rachel A.; Saville, Kimber A.

2014-01-01

Functionally selective signaling appears to contribute to the variability in mechanisms that underlie tolerance to the antinociceptive effects of opioids. The present study tested this hypothesis by examining the contribution of G protein-coupled receptor kinase (GRK)/Protein kinase C (PKC) and C-Jun N-terminal kinase (JNK) activation on both the expression and development of tolerance to morphine and fentanyl microinjected into the ventrolateral periaqueductal gray of the rat. Microinjection of morphine or fentanyl into the periaqueductal gray produced a dose-dependent increase in hot plate latency. Microinjection of the non-specific GRK/PKC inhibitor Ro 32-0432 into the periaqueductal gray to block mu-opioid receptor phosphorylation enhanced the antinociceptive effect of morphine but had no effect on fentanyl antinociception. Microinjection of the JNK inhibitor SP600125 had no effect on morphine or fentanyl antinociception, but blocked the expression of tolerance to repeated morphine microinjections. In contrast, a microinjection of Ro 32-0432 blocked the expression of fentanyl, but not morphine tolerance. Repeated microinjections of Ro 32-0432 blocked the development of morphine tolerance and inhibited fentanyl antinociception whether rats were tolerant or not. Repeated microinjections of SP600125 into the periaqueductal gray blocked the development of tolerance to both morphine and fentanyl microinjections. These data demonstrate that the signaling molecules that contribute to tolerance vary depending on the opioid and methodology used to assess tolerance (expression vs. development of tolerance). This signaling difference is especially clear for the expression of tolerance in which JNK contributes to morphine tolerance and GRK/PKC contributes to fentanyl tolerance. PMID:25503060

COMPARISON OF DEXMEDETOMIDINE, BUPRENORPHINE AND FENTANYL AS AN ADJUVANT TO BUPIVACAINE DURING SPINAL ANAESTHESIA FOR HEMIARTHROPLASTY

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Pradeep R

2016-10-01

Full Text Available BACKGROUND Opioids such as fentanyl or buprenorphine are being added as adjuvant to local anaesthetic for spinal anaesthesia. Dexmedetomidine, a new α2 agonist is being tried as an adjuvant in the recent times. MATERIALS AND METHODS The patients were randomised into three Groups (n=30 each by closed envelope technique. Patients in Group 1 received 10 µg fentanyl with 15 mg of 0.5% hyperbaric bupivacaine, Group 2 received 15 mg of 0.5% hyperbaric bupivacaine supplemented with 30 µg of buprenorphine and Group 3 received 15 mg of 0.5% hyperbaric bupivacaine plus 5 µg dexmedetomidine intrathecally. The time to reach maximum sensory and motor level, the regression time of the same, any adverse effects were recorded. Data were analysed using chi-square test or Fisher’s exact test for categorical data and analysis of variance for continuous data. A value of P<0.05 was accepted as statistically significant. Settings and Design- The study was conducted in a prospective, randomised and double-blind manner. It included ninety American Society of Anaesthesiologists class I and II patients undergoing hemiarthroplasty under spinal anaesthesia. RESULTS In this study, the patients in dexmedetomidine group showed significantly longer duration of motor block (240±20 mins. and sensory blockade (180±22.2 mins. compared to other groups, which is statistically significant (P=0.0001 and P=0.006, respectively. The time to first request of analgesic postoperatively was also longer (260±30.2 in dexmedetomidine group when compared with other groups (P=0.0001. Haemodynamic parameters were stable and there were no complications in any group. CONCLUSIONS We concluded that intrathecal dexmedetomidine (5 µg with bupivacaine provides significantly longer duration of sensory and motor blockade and longer duration for first request of analgesia in the recovery than intrathecal buprenorphine (30 µg or fentanyl (10 µg with bupivacaine for spinal anaesthesia for

Future of the transdermal drug delivery market--have we barely touched the surface?

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Watkinson, Adam C; Kearney, Mary-Carmel; Quinn, Helen L; Courtenay, Aaron J; Donnelly, Ryan F

2016-01-01

Transdermal drug delivery is the movement of drugs across the skin for absorption into the systemic circulation. Transfer of the drug can occur via passive or active means; passive transdermal products do not disrupt the stratum corneum to facilitate delivery whereas active technologies do. Due to the very specific physicochemical properties necessary for successful passive transdermal drug delivery, this sector of the pharmaceutical industry is relatively small. There are many well-documented benefits of this delivery route however, and as a result there is great interest in increasing the number of therapeutic substances that can be delivered transdermally. This review discusses the various transdermal products that are currently/have been marketed, and the paths that led to their success, or lack of. Both passive and active transdermal technologies are considered with the advantages and limitations of each highlighted. In addition to marketed products, technologies that are in the investigative stages by various pharmaceutical companies are reviewed. Passive transdermal drug delivery has made limited progress in recent years, however with the ongoing intense research into active technologies, there is great potential for growth within the transdermal delivery market. A number of active technologies have already been translated into marketed products, with other platforms including microneedles, rapidly progressing towards commercialisation.

The synthesis and pharmacological evaluation of (±-2,3-seco-fentanyl analogues

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LJ. DOSEN-MICOVIC

2004-11-01

Full Text Available An efficient, five-step synthetic approach to various acyclic 1,3-diamines has been developed and applied to the preparation of a novel class of open-chained fentanyl analogues. The acyclic derivatives 5.1–5.5 (all new compounds were synthesized with the aim of estimating the significance of the piperidine ring for the opioid analgesic activity of anilido-piperidines. The starting b-keto-amide 1.1, prepared by the aminolysis of methyl acetoacetate with methylphenethylamine, (93 % yield, was successively reacted with NaH and BuLi, to form the highly reactive a,g-dienolate anion 1.1a. Regio and chemoselective g-alkylation of the dienolate with various primary and secondary alkyl halides furnished the b-keto-amides 1.2–1.5 (76–91 %. Reductive amination of the keto-amides 1.1–1.5 with aniline and Zn powder in acetic acid, via the enamine intermediates 2.1–2.5, afforded the b-anilino amides 3.1–3.5 (74–85 %. After reductive deoxygenation of the tertiary amide group, using in situ generated diborane, the corresponding 1,3-diamines 4.1–4.5 were obtained (87–97 %. The synthesis of (±-2,3-seco-fentanyls 5.1–5.5 was completed by N-acylation of the diamines 4.1–4.5 with propionyl chloride, followed by precipitation of the monooxalate salts (86–95 %. The parent compound, 2,3-seco-fentanyl 5.1, was found to be a 40 times less potent narcotic analgesic than fentanyl but still 5–6 times more active than morphine in rats, while i-Pr derivative 5.3 was inactive. Apart from the pharmacological significance, the general procedure described herein may afford various functionalized, 1,3-diamines as potential complexing agents and building blocks for the synthesis of aza-crown ethers.

Pharmacokinetic characteristics of formulated alendronate transdermal delivery systems in rats and humans.

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Choi, Ahyoung; Gang, Hyesil; Whang, Jiae; Gwak, Hyesun

2010-05-01

The objective of this study was to examine the absorption of alendronate from formulated transdermal delivery systems in rats and humans. When alendronate was applied to rats by transdermal delivery systems (7.2 mg) and oral administration (30 mg/kg), a statistically significant difference was found in the amount remaining to be excreted at time t (Ae(t)) and the amount remaining to be excreted at time 0 (Ae(infinity)) (p transdermal delivery systems. There was a linear relationship (r(2) = 0.9854) between the drug loading dose and Ae(infinity). The Ae(infinity) values from the transdermal delivery system containing 6% caprylic acid (53.8 mg as alendronate) and an oral product (Fosamax), 70 mg as alendronate) in humans were 127.0 +/- 34.2 microg and 237.2 +/- 56.3 microg, respectively. The dose-adjusted relative Ae(infinity) ratio of the transdermal delivery system to oral product was calculated to be 69.7%. The long half-life of alendronate in the transdermal delivery system (50.6 +/- 6.4 h), compared to that of the oral product (3.5 +/- 1.1 h) could allow less-frequent dosing. In conclusion, this study showed that a transdermal delivery system containing 6% caprylic acid in PG could be a favorable alternative for alendronate administration.

Transdermal delivery and cutaneous targeting of antivirals using a penetration enhancer and lysolipid prodrugs.

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Diblíková, Denisa; Kopečná, Monika; Školová, Barbora; Krečmerová, Marcela; Roh, Jaroslav; Hrabálek, Alexandr; Vávrová, Kateřina

2014-04-01

In this work, we investigate prodrug and enhancer approaches for transdermal and topical delivery of antiviral drugs belonging to the 2,6-diaminopurine acyclic nucleoside phosphonate (ANP) group. Our question was whether we can differentiate between transdermal and topical delivery, i.e., to control the delivery of a given drug towards either systemic absorption or retention in the skin. The in vitro transdermal delivery and skin concentrations of seven antivirals, including (R)- and (S)-9-[2-(phosphonomethoxy)propyl]-2,6-diaminopurine (PMPDAP), (S)-9-[3-hydroxy-2-(phosphonomethoxy)propyl]-2,6-diaminopurine ((S)-HPMPDAP), its 8-aza analog, and their cyclic and hexadecyloxypropyl (HDP) prodrugs, was investigated with and without the penetration enhancer dodecyl-6-(dimethylamino)hexanoate (DDAK) using human skin. The ability of ANPs to cross the human skin barrier was very low (0.5-1.4 nmol/cm(2)/h), and the majority of the compounds were found in the stratum corneum, the uppermost skin layer. The combination of antivirals and the penetration enhancer DDAK proved to be a viable approach for transdermal delivery, especially in case of (R)-PMPDAP, an anti-HIV effective drug (30.2 ± 2.3 nmol/cm(2)/h). On the other hand, lysophospholipid-like HDP prodrugs, e.g., HDP-(S)-HPMPDAP, reached high concentrations in viable epidermis without significant systemic absorption. By using penetration enhancers or lysolipid prodrugs, it is possible to effectively target systemic diseases by the transdermal route or to target cutaneous pathologies by topical delivery.

EFFECTS OF PREANESTHETIC SINGLE DOSE INTRAVENOUS DEXMEDETOMIDINE VERSUS FENTANYL ON HEMODYNAMIC RESPONSE TO ENDOTRACHEAL INTUBATION-A CLINICAL COMPARATIVE STUDY

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Chandita

2015-12-01

Full Text Available INTRODUCTION Many pharmacological agents have been evaluated in regards to their efficacy of blunting the adverse cardiovascular response to laryngoscopy and tracheal intubation. The aim of this study was to evaluate the efficacy of dexmedetomidine compared to fentanyl in blunting the haemodynamic response to laryngoscopy and intubation. METHOD Sixty patients were randomly allocated into two groups (30 patients in each group. The group D received intravenously 1 µgm/kg dexmedetomidine infusion and group F received 2µgm/kg fentanyl infusion. The study drugs were prepared in an identical looking container and were infused fifteen minutes prior to induction of anaesthesia. The study drugs were infused over a period of ten minutes and all the patients underwent a similar anaesthetics technique. Heart rate (HR and blood pressure (systolic, diastolic and mean blood pressure were noted at baseline, at the end of infusion of the study drugs, after induction of anaesthesia, immediately after laryngoscopy and intubation and at 1, 3, 5, 7 and 10 minutes after laryngoscopy and intubation. RESULTS HR significantly decreased in the group D when compared to group F immediately after study drug infusion and there was statistically significant reduction in heart rate for up to 5 min after intubation in both the groups. Although HR increased after intubation in both the groups, the magnitude was lower in the group D. In both the groups, laryngoscopy and intubation led to an increase in systolic, diastolic and mean arterial pressure; the magnitude was lower in the group D. CONCLUSION Dexmeditomidine (1µ/kg attenuates these untoward responses of laryngoscopy and intubation more effectively than fentanyl (2 µ/kg when administered as bolus dose in the pre-induction period of general anaesthesia.

Differential effect of intravenous S-ketamine and fentanyl on atypical odontalgia and capsaicin-evoked pain

DEFF Research Database (Denmark)

Baad-Hansen, Lene; Juhl, Gitte Irene; Jensen, Troels Staehelin

2007-01-01

temporal summation were compared between groups and sides. Both drugs failed to produce an analgesic effect on spontaneous AO pain, but fentanyl effectively reduced capsaicin-evoked pain. AO patients showed increased sensitivity to capsaicin and heat pain, but no significant differences in cold......Atypical odontalgia (AO) is an intraoral pain condition of currently unknown mechanisms. In 10 AO patients and 10 matched healthy controls, we examined the effect of intravenous infusion of an N-methyl-D-aspartate (NMDA) receptor antagonist S-ketamine and a mu-opioid agonist fentanyl on spontaneous...... AO pain and on an acute intraoral nociceptive input evoked by topical application of capsaicin. The drugs were administered in a randomized, placebo-controlled, cross-over manner. Furthermore, measures of intraoral sensitivity to mechanical and thermal quantitative sensory testing (QST) including...

Transdermal drug delivery: feasibility for treatment of superficial bone stress fractures.

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Aghazadeh-Habashi, Ali; Yang, Yang; Tang, Kathy; Lőbenberg, Raimar; Doschak, Michael R

2015-12-01

Transdermal drug delivery offers the promise of effective drug therapy at selective sites of pathology whilst reducing systemic exposure to the pharmaceutical agents in off-target organs and tissues. However, that strategy is often limited to cells comprising superficial tissues of the body (rarely to deeper bony structures) and mostly indicated with small hydrophobic pharmacological agents, such as steroid hormones and anti-inflammatory gels to skin, muscle, and joints. Nonetheless, advances in transdermal liposomal formulation have rendered the ability to readily incorporate pharmacologically active hydrophilic drug molecules and small peptide biologics into transdermal dosage forms to impart the effective delivery of those bioactive agents across the skin barrier to underlying superficial tissue structures including bone, often enhanced by some form of electrical, chemical, and mechanical facilitation. In the following review, we evaluate transdermal drug delivery systems, with a particular focus on delivering therapeutic agents to treat superficial bone pain, notably stress fractures. We further introduce and discuss several small peptide hormones active in bone (such as calcitonins and parathyroid hormone) that have shown potential for transdermal delivery, often under the added augmentation of transdermal drug delivery systems that employ lipo/hydrophilicity, electric charge, and/or microprojection facilitation across the skin barrier.

Transdermal testosterone replacement therapy in men

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Ullah MI

2014-01-01

Full Text Available M Iftekhar Ullah,1 Daniel M Riche,1,2 Christian A Koch1,31Department of Medicine, University of Mississippi Medical Center, 2Department of Pharmacy Practice, The University of Mississippi, 3GV (Sonny Montgomery VA Medical Center, Jackson, MS, USAAbstract: Androgen deficiency syndrome in men is a frequently diagnosed condition associated with clinical symptoms including fatigue, decreased libido, erectile dysfunction, and metabolic syndrome. Serum testosterone concentrations decline steadily with age. The prevalence of androgen deficiency syndrome in men varies depending on the age group, known and unknown comorbidities, and the respective study group. Reported prevalence rates may be underestimated, as not every man with symptoms of androgen deficiency seeks treatment. Additionally, men reporting symptoms of androgen deficiency may not be correctly diagnosed due to the vagueness of the symptom quality. The treatment of androgen deficiency syndrome or male hypogonadism may sometimes be difficult due to various reasons. There is no consensus as to when to start treating a respective man or with regards to the best treatment option for an individual patient. There is also lack of familiarity with treatment options among general practitioners. The formulations currently available on the market are generally expensive and dose adjustment protocols for each differ. All these factors add to the complexity of testosterone replacement therapy. In this article we will discuss the general indications of transdermal testosterone replacement therapy, available formulations, dosage, application sites, and recommended titration schedule.Keywords: hypogonadism, transdermal, testosterone, sexual function, testosterone replacement therapy, estradiol

Transdermal deferoxamine prevents pressure-induced diabetic ulcers.

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Duscher, Dominik; Neofytou, Evgenios; Wong, Victor W; Maan, Zeshaan N; Rennert, Robert C; Inayathullah, Mohammed; Januszyk, Michael; Rodrigues, Melanie; Malkovskiy, Andrey V; Whitmore, Arnetha J; Walmsley, Graham G; Galvez, Michael G; Whittam, Alexander J; Brownlee, Michael; Rajadas, Jayakumar; Gurtner, Geoffrey C

2015-01-06

There is a high mortality in patients with diabetes and severe pressure ulcers. For example, chronic pressure sores of the heels often lead to limb loss in diabetic patients. A major factor underlying this is reduced neovascularization caused by impaired activity of the transcription factor hypoxia inducible factor-1 alpha (HIF-1α). In diabetes, HIF-1α function is compromised by a high glucose-induced and reactive oxygen species-mediated modification of its coactivator p300, leading to impaired HIF-1α transactivation. We examined whether local enhancement of HIF-1α activity would improve diabetic wound healing and minimize the severity of diabetic ulcers. To improve HIF-1α activity we designed a transdermal drug delivery system (TDDS) containing the FDA-approved small molecule deferoxamine (DFO), an iron chelator that increases HIF-1α transactivation in diabetes by preventing iron-catalyzed reactive oxygen stress. Applying this TDDS to a pressure-induced ulcer model in diabetic mice, we found that transdermal delivery of DFO significantly improved wound healing. Unexpectedly, prophylactic application of this transdermal delivery system also prevented diabetic ulcer formation. DFO-treated wounds demonstrated increased collagen density, improved neovascularization, and reduction of free radical formation, leading to decreased cell death. These findings suggest that transdermal delivery of DFO provides a targeted means to both prevent ulcer formation and accelerate diabetic wound healing with the potential for rapid clinical translation.

Physiologically-based pharmacokinetic model for Fentanyl in support of the development of Provisional Advisory Levels

Energy Technology Data Exchange (ETDEWEB)

Shankaran, Harish, E-mail: harish.shankaran@pnnl.gov [Computational Biology and Bioinformatics Group, Pacific Northwest National Laboratory, Richland, WA 99352 (United States); Adeshina, Femi [National Homeland Security Research Center, United States Environmental Protection Agency, Washington, DC 20460 (United States); Teeguarden, Justin G. [Systems Toxicology Group, Pacific Northwest National Laboratory, Richland, WA 99352 (United States)

2013-12-15

Provisional Advisory Levels (PALs) are tiered exposure limits for toxic chemicals in air and drinking water that are developed to assist in emergency responses. Physiologically-based pharmacokinetic (PBPK) modeling can support this process by enabling extrapolations across doses, and exposure routes, thereby addressing gaps in the available toxicity data. Here, we describe the development of a PBPK model for Fentanyl – a synthetic opioid used clinically for pain management – to support the establishment of PALs. Starting from an existing model for intravenous Fentanyl, we first optimized distribution and clearance parameters using several additional IV datasets. We then calibrated the model using pharmacokinetic data for various formulations, and determined the absorbed fraction, F, and time taken for the absorbed amount to reach 90% of its final value, t90. For aerosolized pulmonary Fentanyl, F = 1 and t90 < 1 min indicating complete and rapid absorption. The F value ranged from 0.35 to 0.74 for oral and various transmucosal routes. Oral Fentanyl was absorbed the slowest (t90 ∼ 300 min); the absorption of intranasal Fentanyl was relatively rapid (t90 ∼ 20–40 min); and the various oral transmucosal routes had intermediate absorption rates (t90 ∼ 160–300 min). Based on these results, for inhalation exposures, we assumed that all of the Fentanyl inhaled from the air during each breath directly, and instantaneously enters the arterial circulation. We present model predictions of Fentanyl blood concentrations in oral and inhalation scenarios relevant for PAL development, and provide an analytical expression that can be used to extrapolate between oral and inhalation routes for the derivation of PALs. - Highlights: • We develop a Fentanyl PBPK model for relating external dose to internal levels. • We calibrate the model to oral and inhalation exposures using > 50 human datasets. • Model predictions are in good agreement with the available

Limited evidence for intranasal fentanyl in the emergency department and the prehospital setting--a systematic review

DEFF Research Database (Denmark)

Hansen, Morten Sejer; Dahl, Jørgen Berg

2013-01-01

The intranasal (IN) mode of application may be a valuable asset in non-invasive pain management. Fentanyl demonstrates pharmacokinetic and pharmacodynamic properties that are desirable in the management of acute pain, and IN fentanyl may be of value in the prehospital setting. The aim...... of this systematic review was to evaluate the current evidence for the use of IN fentanyl in the emergency department (ED) and prehospital setting....

Stress, Predictability, and Oral Fentanyl Self-Administration in Female and Male Rats

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1995-03-09

naloxone. When dissolved in water, fentanyl hydrochloride (Hel) is less bitter-tasting than morphine and it is readily self- administered by rats...and for assessment of the biochemical effects of the stressor. Drugs Fentanyl- hydrochloride (HCI) (NIDA, Baltimore, MD), in a concentration of 50...responses despite lower opioid SA, treatment for men might focus on pharmacologic replacement therapies, such as methadone maintenance programs. The

Comparison of IV dexketoprofen trometamol, fentanyl, and paracetamol in the treatment of renal colic in the ED: A randomized controlled trial.

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Al, Behcet; Sunar, Mehmet Mustafa; Zengin, Suat; Sabak, Mustafa; Bogan, Mustafa; Can, Basri; Kul, Seval; Murat Oktay, M; Eren, Sevki Hakan

2018-04-01

In this study, we aimed to compare the analgesic efficacy of intravenous dexketoprofen trometamol, fentanyl, and paracetamol in patients presenting to the emergency department with renal colic. Data obtained from the emergency departments of Gaziantep University's Hospital for Research and Practice along with two other state hospitals in Gaziantep, Turkey between January 2016 and January 2017 was used for this study. A total of three hundred patients (n=300), who presented to the ER with complaints most common to renal colic whose diagnoses were subsequently confirmed with Computerized Tomography were included in the study. Patients' pain scores were recorded using the Visual Analogue Scale, at admission (immediately before drug administration), then at the 15th, and 30th minutes. SPSS 22.0 software package was used for analysis. pdexketoprofen trometamol was statistically more effective than paracetamol and fentanyl. There was no statistically significant difference between fentanyl and paracetamol. The need for additional analgesia in the group receiving dexketoprofen trometamol was found to be lower. Dexketoprofen trometamol was statistically superior to the other two agents in achieving full analgesia at the end of the thirty-minute period. Fentanyl was found to be statistically significant in achieving moderate analgesia. As a Non-steroidal antiinflammatory drug dexketoprofen trometamol is superior to paracetamol and fentanyl in achieving analgesia and reducing the need for additional drugs for the treatment of renal colic. Copyright © 2017 Elsevier Inc. All rights reserved.

Recent trends in challenges and opportunities of Transdermal drug delivery system

OpenAIRE

P.M.Patil; P.D.Chaudhari; Jalpa K.Patel; K.A.Kedar; P.P.Katolkar

2012-01-01

Drug delivery system relates to the production of a drug, its delivery medium, and the way of administration. Drug delivery systems are even used for administering nitroglycerin. Transdermal drug delivery system is the system in which the delivery of the active ingredients of the drug occurs by the means of skin. Various types of transdermal patches are used. There are various methods to enhance the transdermal drug delivery system. But using microfabricated microneedles drugs are delivered v...

Current advances in the fabrication of microneedles for transdermal delivery

NARCIS (Netherlands)

Indermun, S.; Luttge, R.; Choonara, Y.E.; Kumar, Pradeep; Toit, Du L.C.; Modi, G.; Pillay, V.

2014-01-01

The transdermal route is an excellent site for drug delivery due to the avoidance of gastric degradation and hepatic metabolism, in addition to easy accessibility. Although offering numerous attractive advantages, many available transdermal systems are not able to deliver drugs and other compounds

Fentanyl and Other Synthetic Opioids Drug Overdose Deaths

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... Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Over-the-Counter Medicines Prescription Medicines Steroids (Anabolic) Synthetic Cannabinoids (K2/Spice) Synthetic Cathinones (Bath Salts) Tobacco/ ...

Evaluation of Fentanyl Disposition and Effects in Newborn Piglets as an Experimental Model for Human Neonates

Science.gov (United States)

Valls-i-Soler, Adolfo; Encinas, Esther; Lukas, John C.; Vozmediano, Valvanera; Suárez, Elena

2014-01-01

Background Fentanyl is widely used off-label in NICU. Our aim was to investigate its cerebral, cardiovascular and pulmonary effects as well as pharmacokinetics in an experimental model for neonates. Methods Fentanyl (5 µg/kg bolus immediately followed by a 90 minute infusion of 3 µg/kg/h) was administered to six mechanically ventilated newborn piglets. Cardiovascular, ventilation, pulmonary and oxygenation indexes as well as brain activity were monitored from T = 0 up to the end of experiments (T = 225–300 min). Also plasma samples for quantification of fentanyl were drawn. Results A “reliable degree of sedation” was observed up to T = 210–240 min, consistent with the selected dosing regimen and the observed fentanyl plasma levels. Unlike cardiovascular parameters, which were unmodified except for an increasing trend in heart rate, some of the ventilation and oxygenation indexes as well as brain activity were significantly altered. The pulmonary and brain effects of fentanyl were mostly recovered from T = 210 min to the end of experiment. Conclusion The newborn piglet was shown to be a suitable experimental model for studying fentanyl disposition as well as respiratory and cardiovascular effects in human neonates. Therefore, it could be extremely useful for further investigating the drug behaviour under pathophysiological conditions. PMID:24595018

Evaluation of fentanyl disposition and effects in newborn piglets as an experimental model for human neonates.

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Carmen Rey-Santano

Full Text Available BACKGROUND: Fentanyl is widely used off-label in NICU. Our aim was to investigate its cerebral, cardiovascular and pulmonary effects as well as pharmacokinetics in an experimental model for neonates. METHODS: Fentanyl (5 µg/kg bolus immediately followed by a 90 minute infusion of 3 µg/kg/h was administered to six mechanically ventilated newborn piglets. Cardiovascular, ventilation, pulmonary and oxygenation indexes as well as brain activity were monitored from T = 0 up to the end of experiments (T = 225-300 min. Also plasma samples for quantification of fentanyl were drawn. RESULTS: A "reliable degree of sedation" was observed up to T = 210-240 min, consistent with the selected dosing regimen and the observed fentanyl plasma levels. Unlike cardiovascular parameters, which were unmodified except for an increasing trend in heart rate, some of the ventilation and oxygenation indexes as well as brain activity were significantly altered. The pulmonary and brain effects of fentanyl were mostly recovered from T = 210 min to the end of experiment. CONCLUSION: The newborn piglet was shown to be a suitable experimental model for studying fentanyl disposition as well as respiratory and cardiovascular effects in human neonates. Therefore, it could be extremely useful for further investigating the drug behaviour under pathophysiological conditions.

How can lipid nanocarriers improve transdermal delivery of olanzapine?

Science.gov (United States)

Iqbal, Nimra; Vitorino, Carla; Taylor, Kevin M G

2017-06-01

The development of a transdermal nanocarrier drug delivery system with potential for the treatment of psychiatric disorders, such as schizophrenia and bipolar disorder, is described. Lipid nanocarriers (LN), encompassing various solid:liquid lipid compositions were formulated and assessed as potential nanosystems for transdermal delivery of olanzapine. A previously optimized method of hot high pressure homogenization (HPH) was adopted for the production of the LN, which comprised solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC) and nanoemulsions (NE). Precirol  ® was selected as the solid lipid for progression of studies. SLN exhibited the best performance for transdermal delivery of olanzapine, based on in vitro release and permeation studies, coupled with results from physicochemical characterization of several solid:liquid lipid formulations. Stability tests, performed to give an indication of long-term storage behavior of the formulations, were in good agreement with previous studies for the best choice of solid:liquid lipid ratio. Overall, these findings highlight the SLN-based formulation as promising for the further inclusion in and production of transdermal patches, representing an innovative therapeutic approach.

Transdermal and Topical Drug Administration in the Treatment of Pain

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Wojciech Leppert

2018-03-01

Full Text Available The comprehensive treatment of pain is multidimodal, with pharmacotherapy playing a key role. An effective therapy for pain depends on the intensity and type of pain, the patients’ age, comorbidities, and appropriate choice of analgesic, its dose and route of administration. This review is aimed at presenting current knowledge on analgesics administered by transdermal and topical routes for physicians, nurses, pharmacists, and other health care professionals dealing with patients suffering from pain. Analgesics administered transdermally or topically act through different mechanisms. Opioids administered transdermally are absorbed into vessels located in subcutaneous tissue and, subsequently, are conveyed in the blood to opioid receptors localized in the central and peripheral nervous system. Non–steroidal anti–inflammatory drugs (NSAIDs applied topically render analgesia mainly through a high concentration in the structures of the joint and a provision of local anti–inflammatory effects. Topically administered drugs such as lidocaine and capsaicin in patches, capsaicin in cream, EMLA cream, and creams containing antidepressants (i.e., doxepin, amitriptyline act mainly locally in tissues through receptors and/or ion channels. Transdermal and topical routes offer some advantages over systemic analgesic administration. Analgesics administered topically have a much better profile for adverse effects as they relieve local pain with minimal systemic effects. The transdermal route apart from the above-mentioned advantages and provision of long period of analgesia may be more convenient, especially for patients who are unable to take drugs orally. Topically and transdermally administered opioids are characterised by a lower risk of addiction compared to oral and parenteral routes.

Nebulized fentanyl vs intravenous morphine for ED patients with acute abdominal pain: a randomized double-blinded, placebo-controlled clinical trial.

Science.gov (United States)

Deaton, Travis; Auten, Jonathan D; Darracq, Michael A

2015-06-01

Patients with acute abdominal pain commonly present to emergency departments. The safe and effective relief of discomfort is a concern to patients and physicians. Intravenous opioids are the traditional method used to provide pain relief in this setting, but intravenous access is time consuming and not always achievable. Alternative methods of pain control may therefore be necessary for the acute management of painful conditions without adding to the overall physical or psychological discomfort. The purpose of this study was to evaluate the feasibility of nebulized fentanyl (NF) in the alleviation of acute and undifferentiated abdominal pain. We also sought to compare NF with intravenous morphine (IVM) and to assess patient and provider satisfaction with NF. Nebulized fentanyl (2 μg/kg) was compared to IVM (0.1 mg/kg) at 10, 20, 30, and 40 minutes; and patient and physician satisfaction was recorded. The NF group experienced more rapid pain relief and more sustained and clinically significant pain relief over the 40-minute study interval. There were no adverse effects noted in the NF group. Both patient and physician satisfaction scores were higher in the NF group. Fentanyl citrate at a dose of 2 μg/kg through a breath-actuated nebulizer appears to be a feasible and safe alternative to IVM (0.1 mg/kg) in the treatment of acute abdominal pain. Copyright © 2015 Elsevier Inc. All rights reserved.

COMBINED SPINAL EPIDURAL ANALGESIA IN LABOUR: COMPARISON OF BUPIVACAINE 1.25 MG WITH FENTANYL AND ROPIVACAINE 2.5 MG WITH FENTANYL INTRATHECAL

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Prakash T. S. N

2016-10-01

with ASA I and ASA II in established labour with cervical dilatation less than 5 cm was selected and randomly allocated into two groups using closed envelope method. Informed written consent was taken from all participants. They were divided into 2 groups of 20 each. Group I received intrathecal Inj. Bupivacaine 1.25 mg and Inj. Fentanyl 20 µg. Group II received intrathecal Inj. Ropivacaine 2.5 mg and Inj. Fentanyl 20 µg for combined spinal epidural. IV line was secured with 18G cannula. Patient was preloaded with 500 mL of Hartmann’s solution. Basal vital parameter like pulse rate, blood pressure, respiration, O2 saturation were recorded. The patient was positioned in a sitting position with the help of an assistant. Under aseptic conditions, the back was prepared with 5% povidone-iodine solution, spirit and area was draped. L3-L4 interspace was identified. Skin was infiltrated with 2 mL of 1% Xylocaine. After infiltration of local anaesthetic by using needle through needle technique 18-gauge Tuohy needle, epidural space was identified with loss of resistance to air technique. Then, a 15 mm (27 G long ‘Whitacre’ spinal needle was introduced through the epidural needle and the correct position of the tip in the intrathecal space was confirmed by observation of free flow of CSF. Patients were allocated randomly to receive intrathecal injection of bupivacaine 1.25 mg (0.5% bupivacaine 0.25 mL with fentanyl 20 µg (Group I n=30 or ropivacaine 2.5 mg/0.2% ropivacaine 1.25 mL with fentanyl 20 µg (Group II, n=30 both made up to total volume of 2 mL with saline. Injection of intrathecal drug was completed in 10 secs., then 20G epidural catheter was threaded through the epidural needle into the epidural space in cephalad direction. The epidural needle was slowly pulled out without disturbing the catheter. About 3 to 5 cm of catheter was left in epidural space. The catheter was well secured with plaster. Patients vitals was recorded every 5, 10, 15, 30, 45, 60, 75, 90

Transdermal deferoxamine prevents pressure-induced diabetic ulcers

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Duscher, Dominik; Neofytou, Evgenios; Wong, Victor W.; Maan, Zeshaan N.; Rennert, Robert C.; Januszyk, Michael; Rodrigues, Melanie; Malkovskiy, Andrey V.; Whitmore, Arnetha J.; Galvez, Michael G.; Whittam, Alexander J.; Brownlee, Michael; Rajadas, Jayakumar; Gurtner, Geoffrey C.

2015-01-01

There is a high mortality in patients with diabetes and severe pressure ulcers. For example, chronic pressure sores of the heels often lead to limb loss in diabetic patients. A major factor underlying this is reduced neovascularization caused by impaired activity of the transcription factor hypoxia inducible factor-1 alpha (HIF-1α). In diabetes, HIF-1α function is compromised by a high glucose-induced and reactive oxygen species-mediated modification of its coactivator p300, leading to impaired HIF-1α transactivation. We examined whether local enhancement of HIF-1α activity would improve diabetic wound healing and minimize the severity of diabetic ulcers. To improve HIF-1α activity we designed a transdermal drug delivery system (TDDS) containing the FDA-approved small molecule deferoxamine (DFO), an iron chelator that increases HIF-1α transactivation in diabetes by preventing iron-catalyzed reactive oxygen stress. Applying this TDDS to a pressure-induced ulcer model in diabetic mice, we found that transdermal delivery of DFO significantly improved wound healing. Unexpectedly, prophylactic application of this transdermal delivery system also prevented diabetic ulcer formation. DFO-treated wounds demonstrated increased collagen density, improved neovascularization, and reduction of free radical formation, leading to decreased cell death. These findings suggest that transdermal delivery of DFO provides a targeted means to both prevent ulcer formation and accelerate diabetic wound healing with the potential for rapid clinical translation. PMID:25535360

A prospective randomized comparative study of the effects of intranasal and transdermal 17 β-estradiol on postmenopausal symptoms and vaginal cytology

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Odabasi A

2007-01-01

Full Text Available Context: Investigating the adverse effects of oral hormone replacement therapy (HRT, the clinical effectiveness of alternative combinations and route of administrations. Aim: To compare the effects of intranasal and transdermal 17β-estradiol combined with vaginal progesterone on vasomotor symptoms and vaginal cytology. Settings and Design: A 12-week, prospective, randomized comparative study was conducted between July 2005 and September 2006. Materials and Methods: Eighty postmenopausal women aged between 42-57 years, who had scores of ≥1.7 on the menopause rating scale-I (MRS-I items "1-6", were randomly assigned to receive intranasal (300 µg/day, n =40 or transdermal (50 µg/day, n =40 17β-estradiol continuously. All patients also received a vaginal progesterone gel twice weekly. Vasomotor symptoms were evaluated at weeks 0, 4, 8 and 12. Vaginal maturation index (VMI was evaluated at weeks 0 and 12 of the study. Statistical Analyses: The Mann-Whitney U and the Wilcoxon tests were used. P < 0.05 was regarded as significant. Results: Thirty-two women in the intranasal and 29 women in the transdermal group completed the study. The total score of the MRS, the sum-scores of Factor 1 "HOT FLUSHES" and Factor 2 "PSYCHE" significantly decreased in both groups at week 4. Factor 3 "ATROPHY" scores significantly decreased only in the transdermal group at week 12. The VMI showed no changes within and between the two groups at the end of the study. Conclusion: Intranasal and transdermal 17β-estradiol combined with vaginal progesterone gel as a continuous HRT caused a similar decrease in vasomotor symptoms but did not have any significant effect on VMI after 12 weeks of treatment in this study population.

[Matrix transdermal systems for caffeine delivery based on polymer and emulsion compounds].

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Kuznetsova, E G; Kuryleva, O M; Salomatina, L A; Sevast'ianov, V I

2008-01-01

The goal of this work was to develop and test transdermal therapeutic systems for caffeine delivery. In vitro experiments showed that the rate of caffeine diffusion through untreated rabbit skin from a transdermal therapeutic systems based on polymer compound containing 50 mg medicine was 67.2 (9.1 microg/cm2h; for a system based on emulsion compound it was 173 (19 microg/cm2h. Methods for studying the caffeine release rate and quantitative measurement of caffeine content in the emulsion-based transdermal therapeutic system were developed. These methods are required to obtain data for standard drug documentation. The results of in vivo experiments in rabbits showed the absence of irritating effect of the emulsion-based transdermal therapeutic system. The obtained data on the specific efficiency of the transdermal therapeutic systems for caffeine delivery (50 mg) in healthy volunteers showed that this medicine could be used as a nonnarcotic psychoactivator for improving mental and physical activities and attention concentration.

A randomized controlled trial to compare fentanyl-propofol and ketamine-propofol combination for procedural sedation and analgesia in laparoscopic tubal ligation

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Ranju Singh

2013-01-01

Full Text Available Background: Procedural sedation and analgesia is widely being used for female laparoscopic sterilization using combinations of different drugs at varying doses. This study compared the combination of fentanyl and propofol, and ketamine and propofol in patients undergoing outpatient laparoscopic tubal ligation, with respect to their hemodynamic effects, postoperative recovery characteristics, duration of hospital stay, adverse effects, and patient comfort and acceptability. Settings and Design: Randomized, double blind. Methods: Patients were assigned to receive premixed injection of either fentanyl 1.5 μg/kg + propofol 2 mg/kg (Group PF, n0=50 or ketamine 0.5 mg/kg + propofol 2 mg/kg (Group PK, n=50. Hemodynamic data, peripheral oxygen saturation, and respiratory rate were recorded perioperatively. Recovery time, time to discharge, and comfort score were noted. Statistical Analysis: Chi-square (χ2 test was used for categorical data. Student′s t-test was used for quantitative variables for comparison between the two groups. For intragroup comparison, paired t-test was used. SPSS 14.0 was used for analysis. Results: Although the heart rate was comparable, blood pressures were consistently higher in group PK. Postoperative nausea and vomiting and delay in voiding were more frequent in group PK ( P<0.05. The time to reach Aldrete score ≥8 was significantly longer in group PK (11.14±3.29 min in group PF vs. 17.3±6.32 min in group PK, P<0.01. The time to discharge was significantly longer in group PK (105.8±13.07 min in group PF vs.138.18±13.20 min in group PK, P<0.01. Patient comfort and acceptability was better in group PF, P<0.01. Conclusion: As compared to ketamine-propofol, fentanyl-propofol combination is associated with faster recovery, earlier discharge, and better patient acceptability.

Comparison of Effect of Intrathecal Sufentanil-Bupivacaine and Fentanyl-Bupivacaine Combination on Postoperative Analgesia

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Ishwar Singh

2008-01-01

Full Text Available Fifty ASA grade I/II patients scheduled for elective lower abdominal, lower limb and urological procedures were divided into two groups of 25 each .The first group (Group S received 2.5 ml of heavy bupivacaine with 0.2. ml sufentanil made up to 3 ml with saline. The second group (Group F received 2.5 ml of heavy bupivacaine with 0.5 ml of fentanyl. From our study it can be concluded that bupivacaine sufentanil combination although had shorter onset of action, but had more side effects especially nausea, vomiting and headache. The time for rescue analgesia in both groups was however similar.

Withdrawal syndrome associated with cessation of fentanyl and midazolam in pediatrics

OpenAIRE

Bicudo, J.n. [UNIFESP; Souza, N. de [UNIFESP; Mângia, C.m.f. [UNIFESP; Carvalho, Werther Brunow de [UNIFESP

1999-01-01

PURPOSE: To determine the incidence of abstinence syndrome in children interned in the Pediatric Intensive Care Unit (PICU) in fentanyl use and midazolam METHODS: Evaluation of 36 children interned in PICU of the Hospital São Paulo - Federal University of São Paulo, in the period from March to September 1997, with age varying from 5 days to 22 months (22 masc: 14 fem) who used fentanyl use and midazolam for more than 24 hours. Used the Escore Neonatal of Abstinence adapted by Finnegan determi...

Intravenous Dexmedetomidine Infusion Compared with that of Fentanyl in Patients Undergoing Arthroscopic Shoulder Surgery under General Anesthesia.

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Abdel Hamid, Mona Hossam Eldin

2017-01-01

Anesthesia for arthroscopic shoulder surgery is challenging due to the need for oligaemic surgical field as well as a good postoperative recovery profile. The present study was prospective, randomized to evaluate the efficacy of dexmdetomidine infusion compared to that of fentanyl in patients undergoing arthroscopic shoulder surgery under general anesthesia. A total of 60 patients aged from thirty to fifty years, American Society of Anesthesiologists Class I/II of either sex for arthroscopic shoulder surgery, were included. The patients were divided into two groups of 30 patients each. Group I received dexmedetomidine loading 1 μg/kg over 10 min followed by maintenance 0.5 μg/kg/h and Group II Fentanyl loading 1 μg/kg followed by maintenance 0.5 μg/kg/h. Hemodynamic readings (Heart rate HR, and mean arterial blood pressure MAP) were recorded after the start of the study drug infusion (T1), after intubation (T2), then every 15 minutes till the end of surgery (T15, T30, T45, T60, T75, T90). In the PACU, MAP, and HR were recorded on arrival, after 30 min, 1 hr, and 2 hrs (R0, R30, R1 hr, R2 hr) Postoperative analgesia was assessed by visual analogue scale (VAS), Modified Observers's Assessment of Alertness and Sedation OAA/S was recorded on arrival to PACU. This study showed that in the dexmedatomidine group there was statistically significant decrease of MAP and HR after drug infusion up to two hours in the recovery period, more sedation, better control of pain and surgeon satisfaction. Iv infusion of dexamedatomidine may be an attractive option during arthroscopic shoulder surgery as it provided a better hypotensive anesthesia by lowering MAP and HR which leads to better surgical field and surgeon satisfaction than iv infusion fentanyl along with a better postoperative VAS.

A review of factors explaining variability in fentanyl pharmacokinetics; focus on implications for cancer patients

NARCIS (Netherlands)

Kuip, E.J.M.; Zandvliet, M.L.; Koolen, S.L.; Mathijssen, R.H.; Rijt, C.C. van der

2017-01-01

Fentanyl is a strong opioid that is available for various administration routes, and which is widely used to treat cancer-related pain. Many factors influence the fentanyl pharmacokinetics leading to a wide inter- and intrapatient variability. This systematic review summarizes multiple studied

Engineering approaches to transdermal drug delivery: a tribute to contributions of prof. Robert Langer.

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Mitragotri, S

2013-01-01

Transdermal drug delivery continues to provide an advantageous route of drug administration over injections. While the number of drugs delivered by passive transdermal patches has increased over the years, no macromolecule is currently delivered by the transdermal route. Substantial research efforts have been dedicated by a large number of researchers representing varied disciplines including biology, chemistry, pharmaceutics and engineering to understand, model and overcome the skin's barrier properties. This article focuses on engineering contributions to the field of transdermal drug delivery. The article pays tribute to Prof. Robert Langer, who pioneered the engineering approach towards transdermal drug delivery. Over a period spanning nearly 25 years since his first publication in the field of transdermal drug delivery, Bob Langer has deeply impacted the field by quantitative analysis and innovative engineering. At the same time, he has inspired several generations of engineers by collaborations and mentorship. His scientific insights, innovative technologies, translational efforts and dedicated mentorship have transformed the field. © 2013 S. Karger AG, Basel.

Intravenous patient-controlled fentanyl with and without transversus abdominis plane block in cirrhotic patients post liver resection

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Serag Eldin M

2014-05-01

Full Text Available Manar Serag Eldin,1 Fatma Mahmoud,1 Rabab El Hassan,2 Mohamed Abdel Raouf,1 Mohamed H Afifi,2 Khaled Yassen,1 Wesam Morad31Department of Anaesthesia, Liver Institute, 2Department of Anaesthesia, Faculty of Medicine, 3Department of Community Medicine and Public Health, Liver Institute, Menoufiya University, Shebin El-Kom, EgyptBackground: Coagulation changes can complicate liver resection, particularly in patients with cirrhosis. The aim of this prospective hospital-based comparative study was to compare the postoperative analgesic efficacy of intravenous fentanyl patient-controlled analgesia (IVPCA with and without transversus abdominis plane (TAP block.Methods: Fifty patients with Child’s A cirrhosis undergoing liver resection were randomly divided into two groups for postoperative analgesia, ie, an IVPCA group receiving a 10 µg/mL fentanyl bolus of 15 µg with a 10-minute lockout and a maximum hourly dose of 90 µg, and an IVPCA + TAP group that additionally received TAP block (15 mL of 0.375% bupivacaine on both sides via a posterior approach with ultrasound guidance before skin incision. Postoperatively, bolus injections of bupivacaine 0.375% were given every 8 hours through a TAP catheter inserted by the surgeon in the open space during closure of the inverted L-shaped right subcostal with midline extension (subcostal approach guided by the visual analog scale score (<3, 5 mL; 3 to <6, 10 mL; 6–10, 15–20 mL according to weight (maximum 2 mg/kg. The top-up dosage of local anesthetic could be omitted if the patient was not in pain. Coagulation was monitored using standard coagulation tests.Results: Age, weight, and sex were comparable between the groups (P<0.05. The visual analog scale score was significantly lower at 12, 18, 24, 48, and 72 hours (P<0.01 in IVPCA + TAP group. The Ramsay sedation score was lower only after 72 hours in the IVPCA + TAP group when compared with the IVPCA group (1.57±0.74 versus 2.2±0.41, respectively, P

An epidemic of illicit fentanyl deaths in Cook County, Illinois: September 2005 through April 2007.

Science.gov (United States)

Denton, J Scott; Donoghue, Edmund R; McReynolds, Jennifer; Kalelkar, Mitra B

2008-03-01

Between September 2005 and April 2007, 350 fentanyl intoxication deaths were investigated and certified by the Cook County Medical Examiners Office. Investigations revealed that the majority of these fatalities were by intravenous injection of a white powder followed by a rapid collapse. The fentanyl was clandestinely produced in a lab in Toluca, Mexico and sold by the Mickey Cobra street gang. The term "Drop Dead" was coined for this "tainted heroin." Postmortem samples were screened by ELISA and confirmed by standard GC-MS methods. Fentanyl fatalities peaked at 47 per month in May and June 2006. Fifty-two percent were single fentanyl intoxications, with the remainder accompanied by either cocaine, morphine from heroin, or alcohol. This epidemic stressed the limited resources of the toxicology laboratory and autopsy service of the Medical Examiners Office. The clandestine lab was terminated, distributing gang members and leaders arrested, and the epidemic ceased in April 2007.

Intrathecal tramadol versus intrathecal fentanyl for visceral pain ...

African Journals Online (AJOL)

2013-10-29

Oct 29, 2013 ... Nigerian Journal of Clinical Practice • May-Jun 2014 • Vol 17 • Issue 3. Original ... intrathecal fentanyl and a normal saline placebo‑controlled protocol for ..... pain experienced by pregnant women during Caesarean section.

Isoflurane minimum alveolar concentration sparing effects of fentanyl in the dog.

Science.gov (United States)

Williamson, Allan J; Soares, Joao H N; Pavlisko, Noah D; McAlister Council-Troche, Robert; Henao-Guerrero, Natalia

2017-07-01

To characterize the isoflurane-sparing effects of a high and a low dose of fentanyl in dogs, and its effects on mean arterial pressure (MAP) and heart rate (HR). Prospective, randomized crossover trial. Eight healthy male Beagle dogs weighing 12.1 ± 1.6 kg [mean ± standard deviation (SD)] and approximate age 1 year. Dogs were anesthetized using isoflurane and minimum alveolar concentration (MAC) was determined in duplicate by the bracketing method using an electrical stimulus on the tarsus. Animals were administered fentanyl: low dose (33 μg kg -1 loading dose, 0.2 μg kg -1  minute -1 ) or high dose (102 μg kg -1 loading dose, 0.8 μg kg -1  minute -1 ) and MAC was re-determined (MAC ISO-F ). Blood was collected for analysis of plasma fentanyl concentrations before administration and after MAC ISO-F determination. All values are presented as mean ± SD. Isoflurane MAC (MAC ISO ) was 1.30 ± 0.23% in the low dose treatment, which significantly decreased to 0.75 ± 0.22% (average MAC reduction 42.3 ± 9.4%). MAC ISO was 1.30 ± 0.18% in the high dose treatment, which significantly decreased to 0.30 ± 0.11% (average MAC reduction 76.9 ± 7.4%). Mean fentanyl plasma concentrations were 6.2 and 29.5 ng mL -1 for low and high dose treatments, respectively. MAP increased significantly only in the high dose treatment (from 81 ± 8 to 92 ± 9 mmHg). HR decreased significantly in both treatments from 108 ± 25 to 61 ± 14 beats minute -1 with the low dose and from 95 ± 14 to 42 ± 4 beats minute -1 with the high dose. Fentanyl administration resulted in a dose-dependent isoflurane MAC-sparing effect with bradycardia at both doses and an increase in MAP only at high dose. Further evaluation is needed to determine the effects of fentanyl on the overall cardiovascular function. Copyright © 2017 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All

Efficacy of a single dose of a transdermal diclofenac patch as pre ...

African Journals Online (AJOL)

2012-01-25

Jan 25, 2012 ... When the side-effects were compared between the groups using a test of proportions, it was not significant. Discussion. The results of our study suggest that when applied at the beginning of surgery, a transdermal patch of diclofenac is as effective as intramuscular diclofenac in prolonging the requirement ...

Synergism between fentanyl and tramadol in tonic inflammatory pain: the orofacial formalin test.

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Miranda, Hugo F; Noriega, Viviana; Zepeda, Ramiro J; Sierralta, Fernando; Prieto, Juan C

2012-06-01

Opioids have been used for long time to management of pain, the coadministration of two opioids may induce synergism. The present study was conducted to determine the antinociceptive interaction between the dual mechanism of action of tramadol compared to the main of fentanyl antinociception in the orofacial formalin which represents a model of persistent cutaneous nociception in the region innervated by the trigeminal nerve. The i.p. administration of tramadol and fentanyl induced a dose-dependent antinociception with an ED(50) of 2.97 ± 0.32 mg/kg for phase I and 1.79 ± 0.30 mg/kg for phase II and 0.062 ± 0.0040 mg/kg in phase I and 0.041 ± 0.0039 mg/kg in phase II, respectively. The coadministration of fentanyl with tramadol induced synergism in both phases of the test with an interaction index of 0.343 and 0.163 for phase I and phase II, respectively. This finding could be explained by the more complex pharmacology of tramadol compared to fentanyl.

Hybrid electrospun chitosan-phospholipids nanofibers for transdermal drug delivery.

Science.gov (United States)

Mendes, Ana C; Gorzelanny, Christian; Halter, Natalia; Schneider, Stefan W; Chronakis, Ioannis S

2016-08-20

Chitosan (Ch) polysaccharide was mixed with phospholipids (P) to generate electrospun hybrid nanofibers intended to be used as platforms for transdermal drug delivery. Ch/P nanofibers exibithed average diameters ranging from 248±94nm to 600±201nm, depending on the amount of phospholipids used. Fourier Transformed Infra-Red (FTIR) spectroscopy and Dynamic Light Scattering (DLS) data suggested the occurrence of electrostatic interactions between amine groups of chitosan with the phospholipid counterparts. The nanofibers were shown to be stable for at least 7days in Phosphate Buffer Saline (PBS) solution. Cytotoxicity studies (WST-1 and LDH assays) demonstrated that the hybrid nanofibers have suitable biocompatibility. Fluorescence microscopy, also suggested that L929 cells seeded on top of the CH/P hybrid have similar metabolic activity comparatively to the cells seeded on tissue culture plate (control). The release of curcumin, diclofenac and vitamin B12, as model drugs, from Ch/P hybrid nanofibers was investigated, demonstrating their potential utilization as a transdermal drug delivery system. Copyright © 2016 Elsevier B.V. All rights reserved.

Pretreatment with remifentanil, fentanyl, or lidocaine to prevent withdrawal after rocuronium using venous occlusion technique in children and adolescents: a prospective randomized placebo-controlled double-blind study.

Science.gov (United States)

Abu-Halaweh, S A; Aloweidi, A K; Qudaisat, I Y; Al-Hussami, M O; Al Zaben, K R; Abu-Halaweh, A S

2014-12-01

Pain caused by intravenous injection of the muscle relaxant rocuronium bromide is common in children and adolescents. The cause of this unwanted effect is still unclear, and different pretreatment drugs have been administered in attempts to alleviate this side effect, with varying degrees of success. This study used a 60-s venous occlusion technique to evaluate the effectiveness of pretreatment with lidocaine, fentanyl, or remifentanil in preventing pain-induced withdrawal caused by intravenous injection of rocuronium bromide during the induction of general anesthesia. One hundred and one child and adolescent patients, ASA Ι-II, requiring various surgical procedures under general anesthesia with muscle relaxation and mechanical ventilation, were enrolled. Patients were allocated randomly using computer-generated randomization into one of four pretreatment groups: a remifentanil group (1 µg/kg, n = 25), fentanyl group (1 µg/kg, n = 26), lidocaine 1% group (0.5 mg/kg, n = 25), and normal saline group (n = 25). Drug doses were prepared in normal saline to a total volume of 5 ml. Venous occlusion was applied 10 cm above the venous access site. Pretreatment drugs were injected and retained for 60 s at the site of injection by an anesthetist blinded to group allocation. After release of the tourniquet, rocuronium (0.5 mg/kg) was then injected over 5 s, and withdrawal was recorded by another anesthetist blinded to group allocation. Descriptive statistics, analysis of variance, and a chi-squared test were used to statistically analyze the results as appropriate. Compared to normal saline, all other pretreatment groups scored a significantly lower mean of withdrawal response (P rocuronium injection. Remifentanil was superior to fentanyl in suppressing the withdrawal response caused by rocuronium injection (P rocuronium injection in children and adolescents. Lidocaine was superior to remifentanil which, in turn, was more effective than fentanyl.

Inhibitory effect of fentanyl citrate on the release of endothlin-1 induced by bradykinin in melanoma cells.

Science.gov (United States)

Andoh, Tsugunobu; Shinohara, Akira; Kuraishi, Yasushi

2017-02-01

Our previous study showed that the μ-opioid receptor agonist fentanyl citrate inhibits endothelin-1-and bradykinin-mediated pain responses in mice orthotopically inoculated with melanoma cells. We also demonstrated that bradykinin induces endothelin-1 secretion in melanoma cells. However, the analgesic mechanisms of fentanyl citrate remain unclear. Thus, the present study was conducted to determine whether fentanyl citrate affects bradykinin-induced endothelin-1 secretion in B16-BL6 melanoma cells. The amount of endothelin-1 in the culture medium was measured using an enzyme immunoassay. The expression of endothelin-1, kinin B 2 receptors, and μ-opioid receptors in B16-BL/6 melanoma cells was determined using immunocytochemistry. Fentanyl citrate inhibited bradykinin-induced endothelin-1 secretion. The inhibitory effect of fentanyl citrate on the secretion of endothelin-1 was attenuated by the μ-opioid receptor antagonist naloxone methiodide. The immunoreactivities of endothelin-1, kinin B 2 receptors, and μ-opioid receptors in B16-BL6 melanoma cells were observed. These results suggest that fentanyl citrate regulates bradykinin-induced endothelin-1 secretion through μ-opioid receptors in melanoma cells. Copyright © 2016 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Systemic delivery of β-blockers via transdermal route for hypertension

Science.gov (United States)

Ahad, Abdul; Al-Jenoobi, Fahad I.; Al-Mohizea, Abdullah M.; Akhtar, Naseem; Raish, Mohammad; Aqil, Mohd.

2014-01-01

Hypertension is the most common cardiovascular disease worldwide. Moreover, management of hypertension requires long-term treatment that may result in poor patient compliance with conventional dosage forms due to greater frequency of drug administration. Although there is availability of a plethora of therapeutically effective antihypertensive molecules, inadequate patient welfare is observed; this arguably presents an opportunity to deliver antihypertensive agents through a different route. Ever since the transdermal drug delivery came into existence, it has offered great advantages including non-invasiveness, prolonged therapeutic effect, reduced side effects, improved bioavailability, better patient compliance and easy termination of drug therapy. Attempts were made to develop the transdermal therapeutic system for various antihypertensive agents, including β-blockers, an important antihypertensive class. β-blockers are potent, highly effective in the management of hypertension and other heart ailments by blocking the effects of normal amounts of adrenaline in the heart and blood vessels. The shortcomings associated with β-blockers such as more frequent dose administration, extensive first pass metabolism and variable bioavailability, make them an ideal candidate for transdermal therapeutic systems. The present article gives a brief view of different β-blockers formulated as transdermal therapeutic system in detail to enhance the bioavailability as well as to improve patient compliance. Constant improvement in this field holds promise for the long-term success in technologically advanced transdermal dosage forms being commercialized sooner rather than later. PMID:26702253

Transdermal microneedles for drug delivery applications

International Nuclear Information System (INIS)

Teo, Ai Ling; Shearwood, Christopher; Ng, Kian Chye; Lu Jia; Moochhala, Shabbir

2006-01-01

Transdermal drug delivery (TDD) has many advantages, the main one being the ability to maintain the prolonged release of drugs to attain optimal blood concentrations. Unfortunately, nature has provided a very effective protective barrier, the stratum corneum (sc), which limits TDD to certain types of drugs with specific properties. In order to enhance TDD, the idea of using microneedles to painlessly penetrate the sc barrier has previously been proposed. In this paper, we will review the different microneedles that are currently being developed as well as our own efforts in this area. Based on our experiences, we will offer our view on the key parameters for effective transdermal microneedle design as well as future directions in this area

Transdermal microneedles for drug delivery applications

Energy Technology Data Exchange (ETDEWEB)

Teo, Ai Ling [Defence Medical and Environmental Research Institute, DSO National Laboratories (Kent Ridge), 27 Medical Drive, 12-00, Singapore 117510 (Singapore); Shearwood, Christopher [School of Mechanical and Aerospace Engineering, 50 Nanyang Avenue, Singapore 639798 (Singapore); Ng, Kian Chye [Defence Medical and Environmental Research Institute, DSO National Laboratories (Kent Ridge), 27 Medical Drive, 12-00, Singapore 117510 (Singapore); Lu Jia [Defence Medical and Environmental Research Institute, DSO National Laboratories (Kent Ridge), 27 Medical Drive, 12-00, Singapore 117510 (Singapore); Moochhala, Shabbir [Defence Medical and Environmental Research Institute, DSO National Laboratories (Kent Ridge), 27 Medical Drive, 12-00, Singapore 117510 (Singapore)]. E-mail: mshabbir@dso.org.sg

2006-07-25

Transdermal drug delivery (TDD) has many advantages, the main one being the ability to maintain the prolonged release of drugs to attain optimal blood concentrations. Unfortunately, nature has provided a very effective protective barrier, the stratum corneum (sc), which limits TDD to certain types of drugs with specific properties. In order to enhance TDD, the idea of using microneedles to painlessly penetrate the sc barrier has previously been proposed. In this paper, we will review the different microneedles that are currently being developed as well as our own efforts in this area. Based on our experiences, we will offer our view on the key parameters for effective transdermal microneedle design as well as future directions in this area.

Minimization of CYP2D6 Polymorphic Differences and Improved Bioavailability via Transdermal Administration: Latrepirdine Example.

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Chew, Marci L; Mordenti, Joyce; Yeoh, Thean; Ranade, Gautam; Qiu, Ruolun; Fang, Juanzhi; Liang, Yali; Corrigan, Brian

2016-08-01

Transdermal delivery has the potential to offer improved bioavailability by circumventing first-pass gut and hepatic metabolism. This study evaluated the pharmacokinetics of oral immediate release and transdermal latrepirdine in extensive and poor CYP2D6 metabolizers (EM/PM). Latrepirdine transdermal solution was prepared extemporaneously. The solution was applied with occlusive dressing to upper or middle back for 24 h. Each subject received a single dose of 8.14 mg oral, 5 mg transdermal, and 10 mg transdermal (EMs only) latrepirdine free base in a fixed sequence. Twelve EMs and 7 PMs (50-79 years) enrolled and completed the study. Latrepirdine was well tolerated following both routes of administration. Dose-normalized latrepirdine total exposures were approximately 11-fold and 1.5-fold higher in EMs and PMs, respectively following administration of transdermal relative to oral. Differences between EM and PM latrepirdine exposures were decreased, with PMs having 1.9- and 2.7-fold higher peak and total exposures, respectively, following transdermal administration compared to 11- and 20-fold higher exposures, respectively, following oral administration. Transdermal delivery can potentially mitigate the large intersubject differences observed with compounds metabolized primarily by CYP2D6. Transdermal delivery was readily accomplished in the clinic using an extemporaneously prepared solution [NCT00990613].

A COMPARATIVE STUDY OF DEXMEDETOMIDINE AND FENTANYL COMBINED WITH ROPIVACAINE FOR EPIDURAL ANAESTHESIA IN LOWER LIMB ORTHOPAEDIC SURGERIES

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Ravi Vasupalli

2016-09-01

Full Text Available BACKGROUND Intrathecal anaesthesia and epidural anaesthesia are the most popular regional anaesthesia techniques used for lower limb surgeries. Intrathecal anaesthesia also called as subarachnoid block. It has few limitations like short duration of anaesthesia, extension of anaesthesia cannot be made for prolonged surgeries, rapid onset of sympathetic blockade, shorter duration of postoperative analgesia and troublesome complication of Post-Dural Puncture Headache (PDPH. Hence, epidural anaesthesia is the most preferred anaesthetic technique for lower limb surgeries these days. METHODS TIME FRAME The study was conducted during period spanning December 2013 to November 2014. STUDY POPULATION Patients who met all inclusion criteria were randomly selected. No distinction is made between males and females. STUDY DESIGN A prospective, randomised, double blind, case control, observational, interventional comparative study is designed after getting the informed written consent was obtained from the patient. RANDOMISATION Randomisation was done using a computer generated random number table. One hundred patients scheduled for various elective lower limb surgical procedures belonging to ASA class I and II were included in the study. 1. Group RD (n=50 15 mL of 0.75% ropivacaine + 0.6 µg/kg of dexmedetomidine (Inj. DEXTOMID-1 mL=100 mcg, 1 mL ampoule; 2. Group RF (n=50 15 mL of 0.75% ropivacaine (ropivacaine 0.75% preservative free-ROPIN 0.75%, 20 mL ampoules-Neon Laboratories, India, fentanyl 1 µg/kg Inj. FENTANYL-1 mL=50 mcg, 2 mL ampoule. The patients were premedicated with tablet alprazolam 0.5 mg and tablet ranitidine 150 mg orally at bedtime on the previous night before surgery. They were kept nil orally 10 p.m. onwards on the previous night. On the day of surgery, patient’s basal pulse rate and blood pressure were recorded. A peripheral intravenous line with 18 gauge cannula after local anaesthesia was secured in one of the upper limbs. All the

Plasma concentrations of fentanyl with subcutaneous infusion in palliative care patients.

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Miller, R S; Peterson, G M; Abbott, F; Maddocks, I; Parker, D; McLean, S

1995-01-01

1. Plasma concentrations of fentanyl were measured by g.c. in 20 patients (median age: 75 years and range: 54-86 years; eight females) in palliative care receiving the drug by continuous s.c. infusion (median rate: 1200 micrograms day-1 and range: 100-5000 micrograms day-1). 2. The infusion rate was significantly related to the duration of therapy (Spearman rho = 0.56, P < 0.05). The total steady-state plasma concentrations of fentanyl ranged between 0.1 and 9 ng ml-1, with a median of 1 ng m...

Comparison of estrus synchronization by controlled internal drug release device (CIDR) and adhesive transdermal progestin patch in postpartum beef cows.

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Kajaysri, Jatuporn; Chumchoung, Chaiwat; Wutthiwitthayaphong, Supphathat; Suthikrai, Wanvipa; Sangkamanee, Praphai

2017-09-15

Estrous synchronization with progesterone based protocols has been essentially used in cattle industry. Although intravaginal devices have been commonly used, this technique may induce vaginitis. This study aimed at examining the efficiency of novel transdermal progestin patch on follicle development and comparing the progestin patch versus CIDR device on estrous synchronization, complication at treated site and pregnancy in beef cattle. In experiment 1, seven beef cows were treated with an adhesive transdermal progestin patch on the ventral surface of the proximal part of the tail for 7 days. The cows were daily examined the follicular development using ultrasonography starting on Day 0 till 3 days after hormone removal. Experiment 2, forty beef cows were divided into two equal groups (20 cows per group). The cows randomly allocated to received either vaginal insertion of CIDR (n = 20) or treated with an adhesive transdermal progestin patch (n = 20). The levels of plasma progesterone during the experiment and the numbers of standing estrous cows were recorded. Timed artificial inseminated (TAI) was performed at 60 h after CIDR or patch termination. Pregnancy rates were determined at 60 days after TAI. Experiment 1 revealed that the novel transdermal progestin patch could efficiently control follicular growth. All the seven treated cows had dominant follicle upon dermal patch removal indicating the effectiveness of the progestin patch. In experiment 2, the percentages of cows exhibited standing estrus were similar between transdermal patch (72.22%) and CIDR (70.00%). The levels of plasma progesterone during CIDR treatment were significantly higher (4.06 ± 1.65 ng/mL on Day 1 and 3.62 ± 1.60 ng/mL on Day 7) compared with transdermal patch (2.60 ± 1.43 ng/mL on Day 1 and 1.81 ± 1.57 ng/mL on Day 7). Three cows treated with CIDR (15%) developed vaginitis while none of cows had physically dermal reaction at adhesive site. Cows synchronized with

Heat: A Highly Efficient Skin Enhancer for Transdermal Drug Delivery.

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Szunerits, Sabine; Boukherroub, Rabah

2018-01-01

Advances in materials science and bionanotechnology have allowed the refinements of current drug delivery systems, expected to facilitate the development of personalized medicine. While dermatological topical pharmaceutical formulations such as foams, creams, lotions, gels, etc., have been proposed for decades, these systems target mainly skin-based diseases. To treat systemic medical conditions as well as localized problems such as joint or muscle concerns, transdermal delivery systems (TDDSs), which use the skin as the main route of drug delivery, are very appealing. Over the years, these systems have shown to offer important advantages over oral as well as intravenous drug delivery routes. Besides being non-invasive and painless, TDDSs are able to deliver drugs with a short-half-life time more easily and are well adapted to eliminate frequent administrations to maintain constant drug delivery. The possibility of self-administration of a predetermined drug dose at defined time intervals makes it also the most convenient personalized point-of-care approach. The transdermal market still remains limited to a narrow range of drugs. While small and lipophilic drugs have been successfully delivered using TDDSs, this approach fails to deliver therapeutic macromolecules due to size-limited transport across the stratum corneum , the outermost layer of the epidermis. The low permeability of the stratum corneum to water-soluble drugs as well as macromolecules poses important challenges to transdermal administration. To widen the scope of drugs for transdermal delivery, new procedures to enhance skin permeation to hydrophilic drugs and macromolecules are under development. Next to iontophoresis and microneedle-based concepts, thermal-based approaches have shown great promise to enhance transdermal drug delivery of different therapeutics. In this inaugural article for the section "Frontiers in Bioengineering and Biotechnology," the advances in this field and the handful of

Intravenous Fentanyl for Dyspnea at the End of Life: Lessons for Future Research in Dyspnea.

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Pang, G S; Qu, L M; Tan, Y Y; Yee, A C P

2016-04-01

To determine the efficacy of intravenous (IV) Fentanyl in dyspnoeic patients with advanced cancer. Dyspnoeic patients with advanced cancer satisfying the selection criteria received (IV) Fentanyl and were evaluated for response 24 hours post-administration in a prospective observational study. Altogether 36 patients were enrolled into the study. However, data from only 16 patients could be analysed as 20 patients had died or were too sick to self-report scores. Seven out of 16 patients responded to IV Fentanyl although the result was not statistically significant (non-responders versus responders: 56.3% vs 43.8%, p = 0.33). The strongest correlations for variables predictive of responder status were the absence of anxiety and lung metastases. This exploratory study shows that IV Fentanyl can alleviate dyspnea in some patients but is an example of the difficulties conducting dyspnea research. Future studies would benefit from novel developments in the areas of measuring dyspnea in dying patients and statistical analysis of small sample sizes. © The Author(s) 2014.

Population pharmacokinetic model of transdermal nicotine delivered from a matrix-type patch.

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Linakis, Matthew W; Rower, Joseph E; Roberts, Jessica K; Miller, Eleanor I; Wilkins, Diana G; Sherwin, Catherine M T

2017-12-01

Nicotine addiction is an issue faced by millions of individuals worldwide. As a result, nicotine replacement therapies, such as transdermal nicotine patches, have become widely distributed and used. While the pharmacokinetics of transdermal nicotine have been extensively described using noncompartmental methods, there are few data available describing the between-subject variability in transdermal nicotine pharmacokinetics. The aim of this investigation was to use population pharmacokinetic techniques to describe this variability, particularly as it pertains to the absorption of nicotine from the transdermal patch. A population pharmacokinetic parent-metabolite model was developed using plasma concentrations from 25 participants treated with transdermal nicotine. Covariates tested in this model included: body weight, body mass index, body surface area (calculated using the Mosteller equation) and sex. Nicotine pharmacokinetics were best described with a one-compartment model with absorption based on a Weibull distribution and first-order elimination and a single compartment for the major metabolite, cotinine. Body weight was a significant covariate on apparent volume of distribution of nicotine (exponential scaling factor 1.42). After the inclusion of body weight in the model, no other covariates were significant. This is the first population pharmacokinetic model to describe the absorption and disposition of transdermal nicotine and its metabolism to cotinine and the pharmacokinetic variability between individuals who were administered the patch. © 2017 The British Pharmacological Society.

An evaluation of total disintegration time for three different doses of sublingual fentanyl tablets in patients with breakthrough pain.

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Nalamachu, Srinivas

2013-12-01

Breakthrough pain is common among patients with cancer and presents challenges to effective pain management. Breakthrough pain is characterized by rapid onset, severe intensity, and duration typically lasting disintegration time of three different doses of sublingual fentanyl tablets in opioid-tolerant patients. This was a single-center, non-randomized, open-label study. Opioid-tolerant adult patients (N = 30) with chronic pain were assigned to one of three dose groups and self-administered a single 100, 200, or 300 μg sublingual fentanyl tablet (Abstral(®), Galena Biopharma, Portland, OR, USA). Time to complete disintegration was measured by each patient with a stopwatch and independently verified by study personnel. Disintegration time (mean ± SD) for sublingual fentanyl tablets (all doses) was 88.2 ± 55.1 s. Mean disintegration times tended to be slightly longer for the 200 μg (96.7 ± 57.9 s) and 300 μg doses (98.6 ± 64.8 s) compared to the 100 μg dose (69.5 ± 40.5 s). Differences were not statistically significant. Disintegration time was not significantly different between men and women and was not affected by age. Sublingual fentanyl tablets dissolved rapidly (average time <2 min) in all patients, with the higher doses taking slightly more time to dissolve.

Fentanyl induces autophagy via activation of the ROS/MAPK pathway and reduces the sensitivity of cisplatin in lung cancer cells.

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Yao, Jiaqi; Ma, Chi; Gao, Wei; Liang, Jinxiao; Liu, Chang; Yang, Hongfang; Yan, Qiu; Wen, Qingping

2016-12-01

Cancer pain is the most common complication of lung carcinoma. Opioid agonist fentanyl is widely used for relieving pain in cancer patients, and cisplatin (DDP)‑based chemotherapy is commonly used for the treatment of advanced lung cancer; these two drugs are always used together in lung carcinoma patients. However, the mechanisms and related biological pathways by which fentanyl influences cisplatin sensitivity are relatively poorly reported. Here, we found that fentanyl reduces the sensitivity of cisplatin in human lung cancer cells and induces autophagy. Fentanyl induced reactive oxygen species (ROS) generation and JNK activation. N-acetyl‑L‑cysteine is a ROS scavenger and antioxidant, and the inhibition of JNK with SP600125 prevented fentanyl‑induced autophagy. We also found that 3-methyladenine (3-MA; an autophagy inhibitor) increased the sensitivity of DDP and weakened the inhibition of fentanyl. In conclusion, fentanyl reduces the sensitivity of cisplatin in lung cancer cells through the ROS-JNK-autophagy pathway, whereas the autophagy inhibitor 3-MA may weaken this effect.

Fentanyl and heroin contained in seized illicit drugs and overdose-related deaths in British Columbia, Canada: An observational analysis.

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Baldwin, Nicholas; Gray, Roger; Goel, Anirudh; Wood, Evan; Buxton, Jane A; Rieb, Launette Marie

2018-04-01

Due to the alarming rise in opioid-related overdose deaths, a public health emergency was declared in British Columbia (BC). In this study, we examined the relationship between illicit fentanyl and heroin found in seized drugs and illicit overdose deaths in BC. An observational cross-sectional survey was conducted using BC data from Health Canada's Drug Analysis Service, which analyzes drug samples seized by law enforcement agencies, and non-intentional illicit overdoses from the BC Coroner's Service, from 2000 to 2016. Initial scatter plots and subsequent multivariate regression analysis were performed to describe the potential relationship between seized illicit fentanyl samples and overdose deaths and to determine if this differed from seized heroin and overdose deaths. Fentanyl samples were analyzed for other drug content. Fentanyl is increasingly being found combined with other opioid and non-opioid illicit drugs. Strong positive relationships were found between the number of seized fentanyl samples and total overdose deaths (R2 = 0.97) as well as between seized fentanyl and fentanyl-detected overdose deaths (R2 = 0.99). A positive association was found between the number of seized heroin samples and total overdose deaths (R2 = 0.78). This research contributes to the expanding body of evidence implicating illicit fentanyl use (often combined with heroin or other substances) in overdose deaths in BC. Policy makers and healthcare providers are urged to implement drug treatment and harm reduction strategies for people at risk of overdose associated with current trends in illicit opioid use. Copyright © 2018 Elsevier B.V. All rights reserved.

Transdermal rivastigmine for HIV-associated cognitive impairment: A randomized pilot study.

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Jose A Muñoz-Moreno

Full Text Available To assess the efficacy and safety of transdermal rivastigmine for the treatment of HIV-associated cognitive impairment.We recruited HIV-infected patients with cognitive impairment on stable antiretroviral therapy in a randomized controlled pilot trial with a 48-week follow-up. An additional assessment was held at 12 weeks. Participants received transdermal rivastigmine (9.5 mg daily, lithium (400 mg twice daily, titrated progressively, or remained in a control group (no new medication. The primary efficacy endpoint was change in a global cognitive score (NPZ-7. Secondary endpoints included change in specific cognitive measures, domains, and functional parameters. Safety covered the frequency of adverse events and changes in laboratory results.Seventy-six subjects were screened, and 29 were finally enrolled. Better cognitive outcomes were observed in all groups, although there were no significant differences between the arms (mean NPZ-7 change [SD]: rivastigmine, 0.35 (0.14; lithium, 0.25 (0.40; control, 0.20 (0.44 (p = 0.78. The rivastigmine group showed the highest positive trend (mean NPZ-7 [SD], baseline vs week 48: rivastigmine, -0.47 (0.22 vs -0.11 (0.29, p = 0.06; lithium, -0.50 (0.40 vs -0.26 (0.21, p = 0.22; control, -0.52 (0.34 vs -0.32 (0.52, p = 0.44. The cognitive domains with the highest positive trends were information processing speed at week 12 and executive function at week 48 (rivastigmine vs control: information processing speed, 0.35 (0.64 vs -0.13 (0.25, p = 0.17, d = 0.96; and executive functioning, 0.73 (0.33 vs 0.03 (0.74, p = 0.09, d = 1.18. No relevant changes were observed regarding functional outcomes. A total of 12 (41% individuals dropped out of the study: 2 (20% were due to medication-related effects in the rivastigmine group and 4 (36% in the lithium group. No severe adverse events were reported.The results from this small randomized trial indicate that transdermal rivastigmine did not provide significant

Poly(lactic-co-glycolic) acid drug delivery systems through transdermal pathway: an overview.

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Naves, Lucas; Dhand, Chetna; Almeida, Luis; Rajamani, Lakshminarayanan; Ramakrishna, Seeram; Soares, Graça

2017-05-01

In past few decades, scientists have made tremendous advancement in the field of drug delivery systems (DDS), through transdermal pathway, as the skin represents a ready and large surface area for delivering drugs. Efforts are in progress to design efficient transdermal DDS that support sustained drug release at the targeted area for longer duration in the recommended therapeutic window without producing side-effects. Poly(lactic-co-glycolic acid) (PLGA) is one of the most promising Food and Drug Administration approved synthetic polymers in designing versatile drug delivery carriers for different drug administration routes, including transdermal drug delivery. The present review provides a brief introduction over the transdermal drug delivery and PLGA as a material in context to its role in designing drug delivery vehicles. Attempts are made to compile literatures over PLGA-based drug delivery vehicles, including microneedles, nanoparticles, and nanofibers and their role in transdermal drug delivery of different therapeutic agents. Different nanostructure evaluation techniques with their working principles are briefly explained.

Effect of components (polymer, plasticizer and solvent as a variable in fabrication of diclofenac transdermal patch

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Chetna Modi

2012-01-01

Full Text Available Transdermal drug delivery influence consumer acceptance and marked increase in bioavailability of some drugs which undergoes hepatic first-pass metabolism. Fabrication of transdermal patch requires lots of attention regarding the amount of components used for it. Because of varied nature of polymer and plasticizer, transdermal patches have different properties and different drug release. This study is on the basis to evaluate the amount to be needed for fabrication of diclofenac transdermal patch. Study shows that Hydroxy Propyl Methyl Cellulose has great influence on transdermal patch, if it is used alone in combination with glycerin or PEG-4000 plasticizer.

Assessment of simvastatin niosomes for pediatric transdermal drug delivery.

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Zidan, Ahmed S; Hosny, Khaled M; Ahmed, Osama A A; Fahmy, Usama A

2016-06-01

The prevalence of childhood dyslipidemia increases and is considered as an important risk factor for the incidence of cardiovascular disease in the adulthood. To improve dosing accuracy and facilitate the determination of dosing regimens in function of the body weight, the proposed study aims at preparing transdermal niosomal gels of simvastatin as possible transdermal drug delivery system for pediatric applications. Twelve formulations were prepared to screen the influence of formulation and processing variables on critical niosomal characteristics. Nano-sized niosomes with 0.31 μm number-weighted size displayed highest simvastatin release rate with 8.5% entrapment capacity. The niosomal surface coverage by negative charges was calculated according to Langmuir isotherm with n = 0.42 to suggest that the surface association was site-independent, probably producing surface rearrangements. Hypolipidemic activities after transdermal administration of niosomal gels to rats showed significant reduction in cholesterol and triglyceride levels while increasing plasma high-density lipoproteins concentration. Bioavailability estimation in rats revealed an augmentation in simvastatin bioavailability by 3.35 and 2.9 folds from formulation F3 and F10, respectively, compared with oral drug suspension. Hence, this transdermal simvastatin niosomes not only exhibited remarkable potential to enhance its bioavailability and hypolipidemic activity but also considered a promising pediatric antihyperlipidemic formulation.

Schedules of Controlled Substances: Temporary Placement of 4-Fluoroisobutyryl Fentanyl into Schedule I. Temporary scheduling order.

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2017-05-03

The Administrator of the Drug Enforcement Administration is issuing this temporary scheduling order to schedule the synthetic opioid, N-(4-fluorophenyl)-N-(1-phenethylpiperidin-4-yl)isobutyramide (4-fluoroisobutyryl fentanyl or para-fluoroisobutyryl fentanyl), and its isomers, esters, ethers, salts and salts of isomers, esters, and ethers, into schedule I pursuant to the temporary scheduling provisions of the Controlled Substances Act. This action is based on a finding by the Administrator that the placement of 4-fluoroisobutyryl fentanyl into schedule I of the Controlled Substances Act is necessary to avoid an imminent hazard to the public safety. As a result of this order, the regulatory controls and administrative, civil, and criminal sanctions applicable to schedule I controlled substances will be imposed on persons who handle (manufacture, distribute, reverse distribute, import, export, engage in research, conduct instructional activities or chemical analysis, or possess), or propose to handle, 4-fluoroisobutyryl fentanyl.

Efficient Transdermal Delivery of Benfotiamine in an Animal Model

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Varadi, Gyula; Zhu, Zhen; G. Carter, Stephen

2015-01-01

We designed a transdermal system to serve as a delivery platform for benfotiamine utilizing the attributes of passive penetration enhancing molecules to penetrate through the outer layers of skin combined with the advance of incorporating various peripherally-acting vasodilators to enhance drug uptake.  Benfotiamine, incorporated into this transdermal formulation, was applied to skin in an animal model in order to determine the ability to deliver this thiamine pro-drug effectively to the sub-...

Plasma concentrations of fentanyl with subcutaneous infusion in palliative care patients.

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Miller, R S; Peterson, G M; Abbott, F; Maddocks, I; Parker, D; McLean, S

1995-12-01

1. Plasma concentrations of fentanyl were measured by g.c. in 20 patients (median age: 75 years and range: 54-86 years; eight females) in palliative care receiving the drug by continuous s.c. infusion (median rate: 1200 micrograms day-1 and range: 100-5000 micrograms day-1). 2. The infusion rate was significantly related to the duration of therapy (Spearman rho = 0.56, P Infusion rates and both total and unbound plasma concentrations of fentanyl were correlated (Spearman rho = 0.92, P infusion in the palliative care setting, which necessitates careful titration of dosage according to individual clinical response.

Use of electroporation and reverse iontophoresis for extraction of transdermal multibiomarkers

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Ching CTS

2012-02-01

Full Text Available Congo Tak-Shing Ching1,2, Lin-Shien Fu3-5, Tai-Ping Sun1, Tzu-Hsiang Hsu1, Kang-Ming Chang21Department of Electrical Engineering, National Chi Nan University, Puli, Nantou County, 2Department of Photonics and Communication Engineering, Asia University, Wufeng, Taichung, 3Department of Pediatrics, National Yang Ming University, Taipei, 4Institute of Technology, National Chi Nan University, Puli, 5Department of Pediatrics, Taichung Veterans General Hospital, Taichung City, TaiwanBackground: Monitoring of biomarkers, like urea, prostate-specific antigen (PSA, and osteopontin, is very important because they are related to kidney disease, prostate cancer, and ovarian cancer, respectively. It is well known that reverse iontophoresis can enhance transdermal extraction of small molecules, and even large molecules if reverse iontophoresis is used together with electroporation. Electroporation is the use of a high-voltage electrical pulse to create nanochannels within the stratum corneum, temporarily and reversibly. Reverse iontophoresis is the use of a small current to facilitate both charged and uncharged molecule transportation across the skin. The objectives of this in vitro study were to determine whether PSA and osteopontin are extractable transdermally and noninvasively and whether urea, PSA, and osteopontin can be extracted simultaneously by electroporation and reverse iontophoresis.Methods: All in vitro experiments were conducted using a diffusion cell assembled with the stratum corneum of porcine skin. Three different symmetrical biphasic direct currents (SBdc, five various electroporations, and a combination of the two techniques were applied to the diffusion cell via Ag/AgCl electrodes. The three different SBdc had the same current density of 0.3 mA/cm2, but different phase durations of 0 (ie, no current, control group, 30, and 180 seconds. The five different electroporations had the same pulse width of 1 msec and number of pulses per second

The efficacy and safety of a novel lipophilic formulation of methimazole for the once daily transdermal treatment of cats with hyperthyroidism.

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Hill, K E; Gieseg, M A; Kingsbury, D; Lopez-Villalobos, N; Bridges, J; Chambers, P

2011-01-01

Previous studies on transdermal methimazole have used pluronic lecithin organogel as the vehicle. This might not be the most suitable vehicle for a lipophilic drug, such as methimazole. Once daily transdermal administration of a novel lipophilic formulation of methimazole is as safe and effective as oral carbimazole in treating hyperthyroidism in cats. Forty-five client-owned cats diagnosed with hyperthyroidism. Prospective study. Cats with newly diagnosed, untreated hyperthyroidism were treated with carbimazole (5 mg p.o., q12h) or methimazole (10 mg) applied to the inner pinnae q24h. Cats were examined after 0, 1, 4, 8, and 12 weeks of treatment. Clinical signs, body weight, systolic blood pressure, hematologic, serum biochemical and urine parameters, total serum thyroxine concentrations (TT4), and serum methimazole concentrations were recorded. No significant differences between groups were detected at day 0. Both formulations were effective in treating hyperthyroidism. No significant differences were detected in thyroxine concentrations, body weight, blood pressure, heart rate, alkaline phosphatase, alanine aminotransferase, creatinine, urea, and urine specific gravity (USG) between groups. The serum methimazole concentrations correlated poorly with TT4-concentrations in both groups. In this 12-week trial, once daily application of a novel formulation of transdermal methimazole applied to the pinnae was as effective and safe as twice daily oral carbimazole in the treatment of cats with hyperthyroidism. This novel formulation and transdermal application could have practical advantages to some pet owners. Copyright © 2011 by the American College of Veterinary Internal Medicine.

Syndrome surveillance of fentanyl-laced heroin outbreaks: Utilization of EMS, Medical Examiner and Poison Center databases.

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Moore, P Quincy; Weber, Joseph; Cina, Steven; Aks, Steven

2017-11-01

Describe surveillance data from three existing surveillance systems during an unexpected fentanyl outbreak in a large metropolitan area. We performed a retrospective analysis of three data sets: Chicago Fire Department EMS, Cook County Medical Examiner, and Illinois Poison Center. Each included data from January 1, 2015 through December 31, 2015. EMS data included all EMS responses in Chicago, Illinois, for suspected opioid overdose in which naloxone was administered and EMS personnel documented other criteria indicative of opioid overdose. Medical Examiner data included all deaths in Cook County, Illinois, related to heroin, fentanyl or both. Illinois Poison Center data included all calls in Chicago, Illinois, related to fentanyl, heroin, and other prescription opioids. Descriptive statistics using Microsoft Excel® were used to analyze the data and create figures. We identified a spike in opioid-related EMS responses during an 11-day period from September 30-October 10, 2015. Medical Examiner data showed an increase in both fentanyl and mixed fentanyl/heroin related deaths during the months of September and October, 2015 (375% and 550% above the median, respectively.) Illinois Poison Center data showed no significant increase in heroin, fentanyl, or other opioid-related calls during September and October 2015. Our data suggests that EMS data is an effective real-time surveillance mechanism for changes in the rate of opioid overdoses. Medical Examiner's data was found to be valuable for confirmation of EMS surveillance data and identification of specific intoxicants. Poison Center data did not correlate with EMS or Medical Examiner data. Copyright © 2017 Elsevier Inc. All rights reserved.

Development, characterization & invivo evaluation of proniosomal based transdermal delivery system of Atenolol

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S. Ramkanth

2018-06-01

Full Text Available The potential of proniosomes as a transdermal drug delivery system for Atenolol was investigated by encapsulating the drug in various formulations of proniosomal gel composed of various ratios of sorbitan fatty acid esters, cholesterol, lecithin prepared by Coacervation-phase separation method. The objectives of the present study were to define effects on the antihypertension activity and pharmacokinetics of a novel transdermal Proniosomal gel incorporating Atenolol. The formulated systems were characterized in vitro for size, drug entrapment, In vitro and in vivo drug permeation profiles and vesicular stability at different storage conditions. The optimized Atenolol proniosomes (AT8 showed nanometric vesicle size, high entrapment efficiency and marked enhancement in transdermal permeation. The prepared Proniosomal gel showed the relative bioavailability of 365.38 fold increased for AT8 than oral. The maximal concentrations (Cmax, of drug were significantly reduced while the areas under the plasma concentration–time curve (AUC, and mean residence times (MRT, t1/2 were evidently increased and extended, respectively. The results suggest that proniosomes can act as promising carrier which offers an alternative approach for transdermal delivery of Atenolol. Keywords: Proniosomes, Atenolol, Niosomes, Pharmacokinetic study, Transdermal delivery

Recent Advances in Skin Penetration Enhancers for Transdermal Gene and Drug Delivery.

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Amjadi, Morteza; Mostaghaci, Babak; Sitti, Metin

2017-01-01

There is a growing interest in transdermal delivery systems because of their noninvasive, targeted, and on-demand delivery of gene and drugs. However, efficient penetration of therapeutic compounds into the skin is still challenging largely due to the impermeability of the outermost layer of the skin, known as stratum corneum. Recently, there have been major research activities to enhance the skin penetration depth of pharmacological agents. This article reviews recent advances in the development of various strategies for skin penetration enhancement. We show that approaches such as ultrasound waves, laser, and microneedle patches have successfully been employed to physically disrupt the stratum corneum structure for enhanced transdermal delivery. Rather than physical approaches, several non-physical route have also been utilized for efficient transdermal delivery across the skin barrier. Finally, we discuss some clinical applications of transdermal delivery systems for gene and drug delivery. This paper shows that transdermal delivery devices can potentially function for diverse healthcare and medical applications while further investigations are still necessary for more efficient skin penetration of gene and drugs. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Efficacy of intrathecal midazolam versus fentanyl for endoscopic

African Journals Online (AJOL)

intrathecal midazolam versus fentanyl as an adjunct to bupivacaine for endoscopic urology surgery. Methods: Sixty adult ASA grade I–II patients undergoing transurethral resection of prostate or bladder tumor under spinal block. Postoperative analgesia was provided with intravenous diclofenac. The onset and duration of ...

Transdermal carbamate poisoning – a case of misuse

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Lalit Kumar Rajbanshi

2017-01-01

Full Text Available Acute pesticide poisoning is a common mode of intentional self harm. Oral ingestion is the usual mode of poisoning. However, inhalation, accidental or occupational transdermal exposure leading to acute or chronic poisoning can be the other route of poisoning. It has been seen that the purpose of poising is suicidal intensity in most of the cases. We report an unusual case where the victim had acute pesticide poisoning through transdermal route that was intended for non suicidal purpose. The patient was managed successfully with immediate decontamination and adequate antidote.

REMIFENTANIL VS FENTANYL DURING DAY CASE DENTAL SURGERY IN PEOPLE WITH SPECIAL NEEDS: A COMPARATIVE, PILOT STUDY OF THEIR EFFECT ON STRESS RESPONSE AND POSTOPERATIVE PAIN.

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Sklika, Eirini; Kalimeris, Konstantinos; Perrea, Despina; Stavropoulos, Nikolaos; Kostopanagiotou, Georgia; Matsota, Paraskevi

2016-06-01

People with special needs undergoing dental surgery frequently require general anesthesia. We investigated the effect of remifentanil vs fentanyl on stress response and postoperative pain in people with special needs undergoing day-case dental surgery. Forty-six adult patients with cognitive impairment undergoing day-case dental surgery under general anesthesia were allocated to receive intraoperatively either fentanyl 50 μg iv bolus (group F, n = 23) or continuous infusion of remifentanil 0.5-1 μg/kg/min (group R, n = 23). Iintraoperative hemodynamic parameters were recorded and serum inflammatory mediators [tumor necrosis factor-α, substance-P], stress hormons (melatonin, cortisol) and β-endorphin were measured. Postoperative pain was assessed during the first postoperative 12 hours with the Wong-Baker faces pain-rating scale. Demographics were similar in two groups. The two groups did not differ regarding their effects on inflammatory mediators, stress hormons and postoperative pain scores. However, the use of remifentanil prevented intraoperative increases of arterial blood pressure and heart rate. Remifentanil and fentanyl did not affect differently stress and inflammatory hormones during day-case dental surgery, although remifentanil may render intraoperative management of hemodynamic responses easier. Both opioids are equally efficient for postoperative pain management following dental surgery in people with special needs.

[Effects of Frankincense and Myrrh essential oil on transdermal absorption in vitro of Chuanxiong and penetration mechanism of skin blood flow].

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Zhu, Xiao-Fang; Luo, Jing; Guan, Yong-Mei; Yu, Ya-Ting; Jin, Chen; Zhu, Wei-Feng; Liu, Hong-Ning

2017-02-01

The aim of this paper was to explore the effects of Frankincense and Myrrh essential oil on transdermal absorption in vitro of Chuanxiong, and to investigate the possible penetration mechanism of their essential oil from the perspective of skin blood perfusion changes. Transdermal tests were performed in vitro with excised mice skin by improved Franz diffusion cells. The cumulative penetration amounts of ferulic acid in Chuanxiong were determined by HPLC to investigate the effects of Frankincense and Myrrh essential oil on transdermal permeation properties of Chuanxiong. Simultaneously, the skin blood flows were determined by laser flow doppler. The results showed that the cumulative penetration amount of ferulic acid in Chuanxiong was (8.13±0.76) μg•cm⁻² in 24 h, and was (48.91±4.87), (57.80±2.86), (63.34±4.56), (54.17±4.40), (62.52±7.79) μg•cm⁻² respectively in Azone group, Frankincense essential oil group, Myrrh essential oil, frankincense and myrrh singly extracted essential oil mixture group, and frankincense and myrrh mixed extraction essential oil group. The enhancement ratios of each essential oil groups were 7.68, 8.26, 7.26, 8.28, which were slightly greater than 6.55 in Azone group. In addition, as compared with the conditions before treatment, there were significant differences and obvious increasing trend in blood flow of rats in Frankincense essential oil group, Myrrh essential oil group, frankincense and myrrh singly extracted essential oil mixture group, and frankincense and myrrh mixed extraction essential oil group when were dosed at 10, 20, 30, 10 min respectively, indicating that the skin blood flows were increased under the effects of Frankincense and Myrrh essential oil to a certain extent. Thus, Frankincense and Myrrh essential oil had certain effect on promoting permeability of Chuanxiong both before and after drug combination, and may promote the elimination of drugs from epidermis to dermal capillaries through increase of

Is general anesthesia a risk for myocardium? Effect of anesthesia on myocardial function as assessed by cardiac troponin-i in two different groups (isofluran+N2O inhalation and propofol+fentanyl iv anesthesia

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Demet Dogan Erol

2007-11-01

Full Text Available Demet Dogan Erol1, Ibrahim Ozen21Department of Anaesthesiology and Reanimation, School of Medicine, Kocatepe University, Afyonkarahisar, Turkey; 2Department of Anaesthesiology and Reanimation, Karadeniz Technical University Faculty of Medicine, Trabzon, TurkeyBackground and objectives: Peroperative myocardial infarction (MI is the most common cause of morbidity and mortality. What is the role of general anesthesia in this process? Is general anesthesia a risk for myocardial infarction? The present study was designed to determine whether the measurement of serum levels of cardiac troponin I (cTnI, a highly sensitive and specific marker for cardiac injury, would help establish the diagnosis of myocardial infarction in two different types of anesthesia.Method: Elective abdominal hysterectomy was planned with the permission of the ethic committee in 40 patients who were 20–45 years range, in ASA-I group, and have a Goldman Cardiac Risk Index-0. The patients were divided into two groups. Isoflurane + N2O was administrated to first group, and Propofol + Fentanyl to second group. cTnI levels were determined before anesthesia, after induction before surgery and 9 hours after the second period respectively.Results: There was no significant difference between the groups by the means of demographic properties, hemodynamic parameters and cTnI levels, and the cTnI levels were determined under the basal levels in all samples.Conclusion: General anesthesia is not a risk for myocardial infarction to state eliminating risk factors and protection hemodynamia cardiac.Keywords: cardiac troponin-I, myocardial infarction, isofluran + N2O inhalation anesthesia, propofol + fentanyl intravenous anesthesia.

Preparation and the Biopharmaceutical Evaluation for the Metered Dose Transdermal Spray of Dexketoprofen

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Luo, Huafei; Zhu, Zhuangzhi; Wu, Yubo; Luo, Jing; Wang, Hao

2014-01-01

The objective of the present work was to develop a metered dose transdermal spray (MDTS) formulation for transdermal delivery of dexketoprofen (DE). DE release from a series of formulations was assessed in vitro. Various qualitative and quantitative parameters like spray pattern, pump seal efficiency test, average weight per metered dose, and dose uniformity were evaluated. The optimized formulation with good skin permeation and an appropriate drug concentration and permeation enhancer (PE) content was developed incorporating 7% (w/w, %) DE, 7% (v/v, %) isopropyl myristate (IPM), and 93% (v/v, %) ethanol. In vivo pharmacokinetic study indicated that the optimized formulation showed a more sustainable plasma-concentration profile compared with the Fenli group. The antiinflammatory effect of DE MDTS was evaluated by experiments involving egg-albumin-induced paw edema in rats and xylene-induced ear swelling in mice. Acetic acid-induced abdominal constriction was used to evaluate the anti-nociceptive actions of DE MDTS. Pharmacodynamic studies indicated that the DE MDTS has good anti-inflammatory and anti-nociceptive activities. Besides, skin irritation studies were performed using rat as an animal model. The results obtained show that the MDTS can be a promising and innovative therapeutic system used in transdermal drug delivery for DE. PMID:24660066

Preparation and the Biopharmaceutical Evaluation for the Metered Dose Transdermal Spray of Dexketoprofen

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Wangding Lu

2014-01-01

Full Text Available The objective of the present work was to develop a metered dose transdermal spray (MDTS formulation for transdermal delivery of dexketoprofen (DE. DE release from a series of formulations was assessed in vitro. Various qualitative and quantitative parameters like spray pattern, pump seal efficiency test, average weight per metered dose, and dose uniformity were evaluated. The optimized formulation with good skin permeation and an appropriate drug concentration and permeation enhancer (PE content was developed incorporating 7% (w/w, % DE, 7% (v/v, % isopropyl myristate (IPM, and 93% (v/v, % ethanol. In vivo pharmacokinetic study indicated that the optimized formulation showed a more sustainable plasma-concentration profile compared with the Fenli group. The antiinflammatory effect of DE MDTS was evaluated by experiments involving egg-albumin-induced paw edema in rats and xylene-induced ear swelling in mice. Acetic acid-induced abdominal constriction was used to evaluate the anti-nociceptive actions of DE MDTS. Pharmacodynamic studies indicated that the DE MDTS has good anti-inflammatory and anti-nociceptive activities. Besides, skin irritation studies were performed using rat as an animal model. The results obtained show that the MDTS can be a promising and innovative therapeutic system used in transdermal drug delivery for DE.

COMPARISON BETWEEN FENTANYL 2 μG/mL VERSUS DEXMEDETOMIDINE 1.5 μG/mL AS ADJUVANTS WITH ISOBARIC BUPIVACAINE 0.0625% IN EPIDURAL LABOUR ANALGESIA

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Karuna Harsoor

2016-11-01

Full Text Available BACKGROUND Low-dose bupivacaine with opioids like fentanyl have been used traditionally as an adjunct for epidural labour analgesia, but has side effects like pruritus, urinary retention, nausea, vomiting, etc. Dexmedetomidine, an α-2 adrenergic agonist with a high placental retention, decreased sympathetic outflow and norepinephrine release thereby causing sedation, anxiolysis, analgesia, sympatholysis and maternal haemodynamic stability. Hence, this study was carried out to compare dexmedetomidine and fentanyl as adjuvants in epidural labour analgesia. MATERIALS AND METHODS A prospective randomised, double-blind study was conducted in 60 term parturients in active labour of ASA I and II physical status. They were randomised into 2 groups with 30 parturients in each and received 15 mL of 0.0625% Inj. Bupivacaine plus either 1.5 μg/mL Inj. Dexmedetomidine (BD group or 2 μg/mL Inj. Fentanyl (BF group. VAS, sedation scores, modified four grade Bromage scale, haemodynamics, peripheral oxygen saturation were recorded at baseline and regular intervals. When VAS was ≥4, subsequent doses of 5 mL of the respective group drug was administered. Parturients were ambulated when Bromage scale was 0 with no postural hypotension. Duration of analgesia, labour outcome, neonatal Apgar scores and side effects were noted. RESULTS Demography and haemodynamic stability were similar and comparable. Duration of analgesia was significantly longer in BD group (131.83±45.760 than BF group (85.33±22.512 (p<0.0001. More no. of top-ups was needed in BF group (1.80±1.518 than BD group (0.17±0.461 (p<0.0001. Significantly reduced VAS scores was observed in BD group than BF group. Mean sedation scores (p<0.05 and maximum Bromage scores (p=0.004 were significantly higher in BD group than BF group. Ambulation was less in BD group (3 parturients than BF group (26 parturients. Side effects were significantly more in BF group than BD group (p=0.007. The labour outcomes

The Influence of Low Salivary Flow Rates on the Absorption of a Sublingual Fentanyl Citrate Formulation for Breakthrough Cancer Pain.

Science.gov (United States)

Davies, Andrew; Mundin, Gill; Vriens, Joanna; Webber, Kath; Buchanan, Alison; Waghorn, Melanie

2016-03-01

Salivary gland hypofunction may affect the absorption of drugs through the oral mucosa, which in turn may affect their clinical efficacy (e.g., onset of action). The aim of this study was to assess the pharmacokinetics of a sublingual fentanyl orally disintegrating tablet (Abstral, Prostrakan Inc.) in a group of cancer patients with salivary gland hypofunction. Nine cancer patients with salivary gland hypofunction underwent a series of three pharmacokinetic studies with the sublingual fentanyl orally disintegrating tablet. In the first phase, the patients received no pretreatment; in the second phase, the patients were allowed to moisten the oral cavity before dosing; in the third phase, the patients were given pilocarpine hydrochloride (saliva stimulant) before dosing. Fentanyl concentrations were measured using a method of high-performance liquid chromatography with validated tandem mass spectrometric detection. The Tmax was longer, the Cmax was lower, the AUC0-30 lower, and the AUClast lower in the phase involving no pretreatment; the Tmax/Cmax/AUC0-30/AUClast were similar in the phase involving moistening of the oral cavity and the phase involving giving pilocarpine hydrochloride. The pharmacokinetics of the sublingual fentanyl orally disintegrating tablet appear to be negatively affected by the presence of salivary gland hypofunction, although the moistening of the oral cavity before dosing results in a pharmacokinetic profile similar to that seen with the giving of pilocarpine hydrochloride. Copyright © 2016 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

Differential development of antinociceptive tolerance to morphine and fentanyl is not linked to efficacy in the ventrolateral periaqueductal gray of the rat

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Bobeck, Erin N.; Haseman, Rachel A.; Hong, Dana; Ingram, Susan L.; Morgan, Michael M.

2012-01-01

Systemic administration of morphine typically produces greater tolerance than higher efficacy mu-opioid receptor (MOPr) agonists, such as fentanyl. The objective of the present study was to test this relationship by measuring antinociceptive efficacy and tolerance to morphine and fentanyl microinjected into the ventrolateral periaqueductal gray (vlPAG). MOPr agonist efficacy was evaluated by microinjecting the irreversible opioid receptor antagonist β-funaltrexamine hydrochloride (β-FNA) into the vlPAG prior to a dose-response analysis of morphine and fentanyl antinociception. In contrast to systemic administration of morphine and fentanyl, microinjection of these drugs into the vlPAG had similar efficacy as measured by similar reductions in maximal antinociception following β-FNA administration. Analysis of tolerance revealed a rightward shift in the dose-response curve to a single pretreatment with morphine, but not fentanyl. Moreover, the magnitude of tolerance to morphine was comparable following one, four, or eight pretreatments. Tolerance to fentanyl also was evident following four or eight microinjections. These data are surprising in that antinociceptive efficacy appears to vary depending on the site of administration. Moreover, the similar efficacy following microinjection of morphine and fentanyl into the vlPAG was associated with comparable tolerance, with the one exception of no tolerance to acute administration of fentanyl. Perspective These data reveal that antinociceptive tolerance following vlPAG administration of opioids develops rapidly, is evident with both morphine and fentanyl, and the magnitude is relatively consistent regardless of the number of pretreatments. PMID:22766006

Transdermal Delivery of Drugs with Microneedles—Potential and Challenges

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Kevin Ita

2015-06-01

Full Text Available Transdermal drug delivery offers a number of advantages including improved patient compliance, sustained release, avoidance of gastric irritation, as well as elimination of pre-systemic first-pass effect. However, only few medications can be delivered through the transdermal route in therapeutic amounts. Microneedles can be used to enhance transdermal drug delivery. In this review, different types of microneedles are described and their methods of fabrication highlighted. Microneedles can be fabricated in different forms: hollow, solid, and dissolving. There are also hydrogel-forming microneedles. A special attention is paid to hydrogel-forming microneedles. These are innovative microneedles which do not contain drugs but imbibe interstitial fluid to form continuous conduits between dermal microcirculation and an attached patch-type reservoir. Several microneedles approved by regulatory authorities for clinical use are also examined. The last part of this review discusses concerns and challenges regarding microneedle use.

Microneedle-based drug delivery systems for transdermal route.

Science.gov (United States)

Pierre, Maria Bernadete Riemma; Rossetti, Fabia Cristina

2014-03-01

Transdermal delivery offers an attractive, noninvasive administration route but it is limited by the skin's barrier to penetration. Minimally invasive techniques, such as the use of microneedles (MNs), bypass the stratum corneum (SC) barrier to permit the drug's direct access to the viable epidermis. These novel micro devices have been developed to puncture the skin for the transdermal delivery of hydrophilic drugs and macromolecules, including peptides, DNA and other molecules, that would otherwise have difficulty passing the outermost layer of the skin, the SC. Using the tools of the microelectronics industry, MNs have been fabricated with a range of sizes, shapes and materials. MNs have been shown to be robust enough to penetrate the skin and dramatically increase the skin permeability of several drugs. Moreover, MNs have reduced needle insertion pain and tissue trauma and provided controlled delivery across the skin. This review focuses on the current state of the art in the transdermal delivery of drugs using various types of MNs and developments in the field of microscale devices, as well as examples of their uses and clinical safety.

Development and evaluation of transdermal organogels containing nicorandil.

Science.gov (United States)

Madan, J R; Sagar, Banode; Chellappan, Dinesh K; Dua, Kamal

2013-01-01

The objective of the study was to formulate a transdermal product containing Nicorandil as a model drug, because it has been first drug of choice to treat angina and hypertension. A further objective was to reduce its side effects. The transdermal product was prepared using various synthetic and natural gelling agents such as Carbopol 934p, Carbopol 974p, HPMC K15M and HPMC K100M. Various penetration enhancers were incorporated to enhance the diffusion across the rat skin. A further objective was to formulate organogels and minimize the concentration of penetration enhancer to 50% of the concentration used in gels and yet to achieve the maximum drug release. The prepared formulations were evaluated for their physical appearance, viscosity, spreadability, drug content and freeze thaw cycle. Based on in vitro studies across rat skin and human cadaver skin it was concluded that Nicrorandil transdermal organogel formulation using HPMC K100M with 2% w/w Transcutol-P shows increase in cumulative diffusion of Nicorandil amongst all other formulations.

Transdermal Spray in Hormone Delivery

African Journals Online (AJOL)

market for the delivery system and ongoing development of transdermal sprays for hormone ... (DOAJ), African Journal Online, Bioline International, Open-J-Gate and Pharmacy Abstracts ... patches and gels have been very popular owing ... This product was developed for ... In a safety announcement, the US Food and.

Heat: A Highly Efficient Skin Enhancer for Transdermal Drug Delivery

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Sabine Szunerits

2018-02-01

Full Text Available Advances in materials science and bionanotechnology have allowed the refinements of current drug delivery systems, expected to facilitate the development of personalized medicine. While dermatological topical pharmaceutical formulations such as foams, creams, lotions, gels, etc., have been proposed for decades, these systems target mainly skin-based diseases. To treat systemic medical conditions as well as localized problems such as joint or muscle concerns, transdermal delivery systems (TDDSs, which use the skin as the main route of drug delivery, are very appealing. Over the years, these systems have shown to offer important advantages over oral as well as intravenous drug delivery routes. Besides being non-invasive and painless, TDDSs are able to deliver drugs with a short-half-life time more easily and are well adapted to eliminate frequent administrations to maintain constant drug delivery. The possibility of self-administration of a predetermined drug dose at defined time intervals makes it also the most convenient personalized point-of-care approach. The transdermal market still remains limited to a narrow range of drugs. While small and lipophilic drugs have been successfully delivered using TDDSs, this approach fails to deliver therapeutic macromolecules due to size-limited transport across the stratum corneum, the outermost layer of the epidermis. The low permeability of the stratum corneum to water-soluble drugs as well as macromolecules poses important challenges to transdermal administration. To widen the scope of drugs for transdermal delivery, new procedures to enhance skin permeation to hydrophilic drugs and macromolecules are under development. Next to iontophoresis and microneedle-based concepts, thermal-based approaches have shown great promise to enhance transdermal drug delivery of different therapeutics. In this inaugural article for the section “Frontiers in Bioengineering and Biotechnology,” the advances in this field

Heat: A Highly Efficient Skin Enhancer for Transdermal Drug Delivery

Science.gov (United States)

Szunerits, Sabine; Boukherroub, Rabah

2018-01-01

Advances in materials science and bionanotechnology have allowed the refinements of current drug delivery systems, expected to facilitate the development of personalized medicine. While dermatological topical pharmaceutical formulations such as foams, creams, lotions, gels, etc., have been proposed for decades, these systems target mainly skin-based diseases. To treat systemic medical conditions as well as localized problems such as joint or muscle concerns, transdermal delivery systems (TDDSs), which use the skin as the main route of drug delivery, are very appealing. Over the years, these systems have shown to offer important advantages over oral as well as intravenous drug delivery routes. Besides being non-invasive and painless, TDDSs are able to deliver drugs with a short-half-life time more easily and are well adapted to eliminate frequent administrations to maintain constant drug delivery. The possibility of self-administration of a predetermined drug dose at defined time intervals makes it also the most convenient personalized point-of-care approach. The transdermal market still remains limited to a narrow range of drugs. While small and lipophilic drugs have been successfully delivered using TDDSs, this approach fails to deliver therapeutic macromolecules due to size-limited transport across the stratum corneum, the outermost layer of the epidermis. The low permeability of the stratum corneum to water-soluble drugs as well as macromolecules poses important challenges to transdermal administration. To widen the scope of drugs for transdermal delivery, new procedures to enhance skin permeation to hydrophilic drugs and macromolecules are under development. Next to iontophoresis and microneedle-based concepts, thermal-based approaches have shown great promise to enhance transdermal drug delivery of different therapeutics. In this inaugural article for the section “Frontiers in Bioengineering and Biotechnology,” the advances in this field and the handful of

The effect of ketamine versus fentanyl on the incidence of emergence agitation after sevoflurane anesthesia in pediatric patients undergoing tonsillectomy with or without adenoidectomy

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Ashraf Arafat Abdelhalim

2013-01-01

Full Text Available Background: Emergence agitation (EA has been documented as a common side-effect of sevoflurane anesthesia. This prospective, randomized, double-blind, placebo-controlled study was designed to compare the effects of ketamine versus fentanyl, administered 10 min before the end of surgery on the development of EA. Methods: A total of 120 children aged 3-7 years of American Society of Anesthesiologists I-II physical status were randomly assigned to one of three equal groups receiving either ketamine 0.5 mg/kg (Group K, fentanyl 1 μg/kg (Group F or saline (Group C at 10 min before the end of surgery. Post-operative EA was assessed with Aono′′s four point scale. Recovery times, the post-operative pain and adverse reactions were assessed. Results: There was no significant difference between the three groups regarding recovery and discharge times from post-anesthesia care unit. The incidence of EA was significantly low in Group K and Group F (15% and 17.5%, respectively compared to the control group (42.5%, with no significant difference between Group K and Group F. There were no significant differences in Children′s Hospital of Eastern Ontario Pain Scale between the three groups. The incidence of nausea or vomiting was significantly more in Group F compared to that in other two groups. However, no complications such as somnolence, oxygen desaturation or respiratory depression occurred during the study period and there were no episodes of hallucinations or bad dreams in the ketamine group. Conclusion: The intravenous administration of either ketamine 0.5 mg/kg or fentanyl 1 μg/kg before the end of surgery in sevoflurane-anesthetized children undergoing tonsillectomy with or without adenoidectomy reduces the incidence of post-operative agitation without delaying emergence.

Intrathecal nalbuphine versus intrathecal fentanyl as adjuvant to 0.5% hyperbaric bupivacaine for orthopedic surgery of lower limbs under subarachnoid block: A comparative evaluation

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Kumkum Gupta

2016-01-01

Full Text Available Background: Subarachnoid block (SAB possesses many benefits with a drawback of short duration of anesthetic action. Intrathecal opioids have been used to enhance the clinical efficiency and duration of action of local anesthetic drugs. The present study was aimed to compare the clinical efficiency of intrathecal fentanyl with nalbuphine as adjuvant to 0.5% hyperbaric bupivacaine for orthopedic surgery of lower limbs. Patients and Methods: Sixty-eight adult patients of American Society of Anesthesiologist physical status I and II of both gender aged 25-65 years were randomized into two groups of 34 each to receive either fentanyl 25 μg (Group I or nalbuphine 2 mg (Group II with 3.5 mL 0.5% hyperbaric bupivacaine, making intrathecal drug volume to 4 mL in each group. Sensory and motor block characteristics and time to first rescue analgesic (intravenous tramadol 100 mg were recorded as the primary end points. Drug-related side effects of pruritus, nausea/vomiting, and respiratory depression were recorded as the secondary outcomes. Results: Both groups were comparable regarding the onset and cephalic extension of block. The time to two dermatome regressions and time for complete motor recovery were significantly prolonged in patients of Group II with statistical significant difference (P < 0.05. Duration of analgesia was also extended in patients of Group II (378.0 ± 35.72 min as compared to Group I (234.0 ± 24.10 min with highly significant difference (P < 0.001. No drug-related side effects were observed in either group. Conclusion: Intrathecal nalbuphine 2 mg as adjuvant to 0.5% bupivacaine was clinically more efficient than fentanyl for enhancing the postoperative analgesia.

To evaluate the efficacy of intrathecal magnesium sulphate for hysterectomy under subarachnoid block with bupivacaine and fentanyl: A prospective randomized double blind clinical trial

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Mridu Paban Nath

2012-01-01

Full Text Available Background: Intrathecal magnesium has been found to prolong the duration of analgesia in various surgical procedures like lower limb surgeries and as adjuncts to general anesthesia for pain management. The present study was designed to examine whether addition of intrathecal magnesium sulfate would enhance the analgesic efficacy of intrathecal bupivacaine and fentanyl in patients undergoing total abdominal hysterectomy. Methods: After taking informed consent, 60 patients were randomised into two groups with 30 patients. Group "S" received 2.5 mL (12.5 mg of hyperbaric bupivacaine + 0.5 mL (25 mcg of fentanyl + 0.5 mL of normal saline and Group "M" received 2.5 mL (12.5 mg of hyperbaric bupivacaine + 0.5 mL (25 mcg of fentanyl + 0.5 mL (100 mg of magnesium sulfate. Onset of sensory, motor block and duration of analgesia was noted. Results: Demographic profile and duration of surgery were comparable (P>0.5. Time of onset of sensory and motor blockade was delayed in Group M compared with Group S, and this was statistically significant. A statistically significant longer duration of analgesia was observed in Group M compared with the control Group S. However, the recovery of motor blockade was found to be statistically insignificant in both the groups. The hemodynamic parameters were comparable in the perioperative period (P>0.05. The incidence of side-effects in both the groups were also comparable (P>0.05. Conclusion: The addition of 100 mg intrathecal magnesium led to prolonged duration of analgesia significantly without increasing the incidence of side-effects. Also, there was a significant delay in the onset of both sensory and motor blockade.

The use of peridural catheter in the treatment of chronic malignant pain in the abdomen: Case report (peridural catheter in the treatment chronic pain

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Palibrk Ivan

2017-01-01

Full Text Available Introduction: Chronic pain in the abdomen occurs as a consequence of malignancy in these parts of the body, surgical, of radiological and chemotherapy treatments. It may also be as a result of relapse of the basic process. Non-invasive therapy of oral and transdermal analgesic was successful for some time, where necessary applies and epidural catheter. Case Report: The patient had a diagnosis of chronic postoperative pain malignant etiology. He is already used transdermal fentanyl and Nonsteroidal Anti-Inflammatory Drugs, but without success (VAS score 8-10. We increased doses of analgesics, but without success. In order of pain therapy, peridural catheter placed in the level L3 - L4. 5 ml of a solution of 8 ml of 0.25% bupivacaine, 2 ml (100 micrograms of fentanyl and 10 ml of saline was administered every 6 hours through epidural catheter. The former chronic non-invasive treatment of pain did not stop. The first three to five days of pain relief was quite satisfactory in this way. Then the pain intensified but the peridural catheter had to be removed due to local infection. New peridural catheter was placed in the level L2 -L3. Then, 5 ml of the solution: of 8 ml 0,25% bupivacaine, 2 ml (100 micrograms of fentanyl and 10 ml of saline is administered through peridural catheter. Peridural catheter was total used for 45 days. We had a need for more and more frequently administering analgesics through a catheter during use. The patient was using transdermal fentanyl and Nonsteroidal Anti-Inflammatory Drugs, all the time. The patient soon died due to progression of the underlying disease. Conclusion: After long-term administration of opioids, it is necessary to change the type and route of administration of the drug to achieve the success of the therapy. In this case it was the use of analgesics and local anesthetics through the peridural catheter.

Synthesis and evaluation of fluorinated derivatives of fentanyl as candidates for opiate receptor studies using positron emission tomography

Energy Technology Data Exchange (ETDEWEB)

Hwang, Dahren; Feliu, A L; Wolf, A P; MacGregor, R R; Fowler, J S; Arnett, C D

1986-03-01

Three fluorinated derivatives of fentanyl, fluorofentanyl (3), keto-fluorofentanyl (5), and fluorofentanol (6), were synthesized and their abilities to compete with /sup 3/diprenorphine for binding sites in guinea pig brain membranes were determined. The relative potencies were fentanyl > 3 approx.= 6 >> 5. On the basis of its apparent affinity for opiate receptors and its relative ease of synthesis, 6 was selected for further study. Fentanyl was slightly better than 6 in its ability to compete with (/sup 3/H)naltrexone for binding sites in rat brain membranes. Both fentayl and 6 exhibited a similar high ''sodium ratio'' (quotient of the IC/sub 50/'s against (/sup 3/H)naltrexone in the presence and absence of sodium chloride) generally characteristic of opiate agonists. The analgesic potencies of fentanyl and 6 were determined in rats by measuring suppression of locomotion and vocalization responses to footshock. 6 appeared slightly less potent than fentanyl, but produced a similar analgesia and catalepsy which was entirely blocked by pretreatment of rats with naloxone, an opiate antagonist. A rapid synthesis of (/sup 18/F)-6 was developed and the tissue distribution of (/sup 18/F)-6 in mice was determined 5, 60, and 120 minutes after intravenous injection. The use of this general route to /sup 18/F-labeled derivatives of fentanyl for studies of the opiate receptor using positron emission tomography is planned.

Synthesis and evaluation of fluorinated derivatives of fentanyl as candidates for opiate receptor studies using positron emission tomography

International Nuclear Information System (INIS)

Dahren Hwang; Feliu, A.L.; Wolf, A.P.; MacGregor, R.R.; Fowler, J.S.; Arnett, C.D.

1986-01-01

Three fluorinated derivatives of fentanyl, fluorofentanyl (3), keto-fluorofentanyl (5), and fluorofentanol (6), were synthesized and their abilities to compete with 3 diprenorphine for binding sites in guinea pig brain membranes were determined. The relative potencies were fentanyl > 3 approx.= 6 >> 5. On the basis of its apparent affinity for opiate receptors and its relative ease of synthesis, 6 was selected for further study. Fentanyl was slightly better than 6 in its ability to compete with [ 3 H]naltrexone for binding sites in rat brain membranes. Both fentayl and 6 exhibited a similar high ''sodium ratio'' (quotient of the IC 50 's against [ 3 H]naltrexone in the presence and absence of sodium chloride) generally characteristic of opiate agonists. The analgesic potencies of fentanyl and 6 were determined in rats by measuring suppression of locomotion and vocalization responses to footshock. 6 appeared slightly less potent than fentanyl, but produced a similar analgesia and catalepsy which was entirely blocked by pretreatment of rats with naloxone, an opiate antagonist. A rapid synthesis of [ 18 F]-6 was developed and the tissue distribution of [ 18 F]-6 in mice was determined 5, 60, and 120 minutes after intravenous injection. The use of this general route to 18 F-labeled derivatives of fentanyl for studies of the opiate receptor using positron emission tomography is planned. (author)

Perioperative analgesia with a buprenorphine transdermal patch for hallux valgus surgery: a prospective, randomized, controlled study

Directory of Open Access Journals (Sweden)

Xu C

2018-04-01

Full Text Available Can Xu, Mingqing Li, Chenggong Wang, Hui Li, Hua Liu Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, Hunan Province, People’s Republic of China Purpose: Hallux valgus surgery often results in significant postoperative pain. Adequate control of pain is essential for patient satisfaction and improves the outcome of the procedure. This study aimed to investigate the perioperative analgesic effect of a buprenorphine transdermal patch in patients who underwent hallux valgus surgery.Patients and methods: A total of 90 patients were randomly divided into the following three groups based on the perioperative analgesic method: flurbiprofen axetil intravenous injection (Group F, oral celecoxib (Group C, and buprenorphine transdermal delivery system (BTDS (Group BTDS. The pain status, degree of satisfaction, adverse effects, and administration of tramadol hydrochloride for uncontrolled pain were recorded on the night before surgery, postoperative day 1, postoperative day 2, and postoperative day 3.Results: The BTDS could effectively control perioperative pain for patients undergoing ­hallux valgus surgery. The analgesic effect of the BTDS was better than that of oral celecoxib. In addition, statistically significant differences were not observed in the visual analog scale (VAS scores, adverse effects, and rescue analgesia between the patients who received the BTDS and the patients who received the flurbiprofen axetil intravenous injection. However, the degree of patient satisfaction of the BTDS group was significantly higher (P<0.05 than that of the other two groups.Conclusion: The BTDS (a preemptive analgesia regimen could exert an analgesic effect during the perioperative period for patients who had received hallux valgus surgery, and this effect is beneficial for sustaining postoperative physiological and psychological states and promoting functional rehabilitation. Keywords: hallux valgus, buprenorphine transdermal

Dissolving polymeric microneedle arrays for electrically assisted transdermal drug delivery.

Science.gov (United States)

Garland, Martin J; Caffarel-Salvador, Ester; Migalska, Katarzyna; Woolfson, A David; Donnelly, Ryan F

2012-04-10

It has recently been proposed that the combination of skin barrier impairment using microneedles (MNs) coupled with iontophoresis (ITP) may broaden the range of drugs suitable for transdermal delivery, as well as enabling the rate of delivery to be achieved with precise electronic control. However, no reports exist on the combination of ITP with in situ drug loaded polymeric MN delivery systems. Furthermore, although a number of studies have highlighted the importance of MN design for transdermal drug delivery enhancement, to date, there has been no systematic investigation of the influence of MN geometry on the performance of polymeric MN arrays which are designed to remain in contact with the skin during the period of drug delivery. As such, for the first time, this study reports on the effect of MN heigth and MN density upon the transdermal delivery of small hydrophilic compounds (theophylline, methylene blue, and fluorescein sodium) across neonatal porcine skin in vitro, with the optimised MN array design evaluated for its potential in the electrically faciliatated delivery of peptide (bovine insulin) and protein (fluorescein isothiocyanate-labelled bovine serum albumin (FTIC-BSA)) macromolecules. The results of the in vitro drug release investigations revealed that the extent of transdermal delivery was dependent upon the design of the MN array employed, whereby an increase in MN height and an increase in MN density led to an increase in the extent of transdermal drug delivery achieved 6h after MN application. Overall, the in vitro permeation studies revealed that the MN design containing 361 MNs/cm(2) of 600 μm height resulted in the greatest extent of transdermal drug delivery. As such, this design was evaluated for its potential in the MN mediated iontophoretic transdermal delivery. Whilst the combination of MN and ITP did not further enhance the extent of small molecular weight solute delivery, the extent of peptide/protein release was significantly

Conductive polymer nanotube patch for fast and controlled ex vivo transdermal drug delivery.

Science.gov (United States)

Nguyen, Thao M; Lee, Sebin; Lee, Sang Bok

2014-10-01

To uptake and release hydrophilic model drugs and insulin in a novel conductive polymer (CP) nanotube transdermal patch. The externally controlled transdermal delivery of model drugs and insulin were tested ex vivo and results were compared with CP films. The unique intrinsic properties of CPs provide electrostatic interaction between the model drugs and polymer backbone. When a pulsed potential was applied, the drug delivery release profile mimics that of injection delivery. With a constant potential applied, the release rate constants of the patch system were up to three-times faster than the control (0 V) and released approximately 80% more drug molecules over 24 h. The CP nanotube transdermal patch represents a new and promising drug method, specifically for hydrophilic molecules, which have been a large obstacle for conventional transdermal drug delivery systems.

Identification of Chemical Attribution Signatures of Fentanyl Syntheses Using Multivariate Statistical Analysis of Orthogonal Analytical Data

Energy Technology Data Exchange (ETDEWEB)

Mayer, B. P. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Mew, D. A. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); DeHope, A. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Spackman, P. E. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Williams, A. M. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

2015-09-24

Attribution of the origin of an illicit drug relies on identification of compounds indicative of its clandestine production and is a key component of many modern forensic investigations. The results of these studies can yield detailed information on method of manufacture, starting material source, and final product - all critical forensic evidence. In the present work, chemical attribution signatures (CAS) associated with the synthesis of the analgesic fentanyl, N-(1-phenylethylpiperidin-4-yl)-N-phenylpropanamide, were investigated. Six synthesis methods, all previously published fentanyl synthetic routes or hybrid versions thereof, were studied in an effort to identify and classify route-specific signatures. 160 distinct compounds and inorganic species were identified using gas and liquid chromatographies combined with mass spectrometric methods (GC-MS and LCMS/ MS-TOF) in conjunction with inductively coupled plasma mass spectrometry (ICPMS). The complexity of the resultant data matrix urged the use of multivariate statistical analysis. Using partial least squares discriminant analysis (PLS-DA), 87 route-specific CAS were classified and a statistical model capable of predicting the method of fentanyl synthesis was validated and tested against CAS profiles from crude fentanyl products deposited and later extracted from two operationally relevant surfaces: stainless steel and vinyl tile. This work provides the most detailed fentanyl CAS investigation to date by using orthogonal mass spectral data to identify CAS of forensic significance for illicit drug detection, profiling, and attribution.

Discomfort during bronchoscopy performed after endobronchial intubation with fentanyl and midazolam: a prospective study.

Science.gov (United States)

Minami, Daisuke; Takigawa, Nagio; Kano, Hirohisa; Ninomiya, Takashi; Kubo, Toshio; Ichihara, Eiki; Ohashi, Kadoaki; Sato, Akiko; Hotta, Katsuyuki; Tabata, Masahiro; Tanimoto, Mitsune; Kiura, Katsuyuki

2017-05-01

Although endobronchial intubation during a bronchoscopic examination is useful for invasive procedures, it is not routine practice in Japan. The present study evaluated discomfort due to endobronchial intubation using fentanyl and midazolam sedation during bronchoscopy. Thirty-nine patients were enrolled prospectively from November 2014 to September 2015 at Okayama University Hospital. Fentanyl (20 µg) was administered to the patients just before endobronchial intubation, and fentanyl (10 µg) and midazolam (1 mg) were added as needed during the procedure. A questionnaire survey was administered 2 h after the examination. In the questionnaire, patient satisfaction was scored using a visual analog scale as follows: excellent (1 point), good (2 points), normal (3 points), uncomfortable (4 points) and very uncomfortable (5 points). An additional question ('Do you remember the bronchoscopic examination?') was also asked. Predefined parameters (blood pressure, heart rate, oxygen saturation and complications) were recorded. The enrolled patients included 22 males and 17 females; their median age was 70 (range: 28-88) years. The patients received a mean dose of 47.9 µg of fentanyl (range: 30-90 µg) and 2.79 mg of midazolam (range: 1-7 mg). In total, 28 patients (71.7%) agreed to undergo a second bronchoscopic examination; the mean levels of discomfort and for the re-examination were 2.07 points each. About 41% of the patients remembered the bronchoscopic examination. No severe complications were reported. Endobronchial intubation using fentanyl and midazolam sedation during an invasive bronchoscopic procedure might be recommended. UMIN000015578 in the UMIN Clinical Trials Registry. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Efficacy of a single dose of a transdermal diclofenac patch as pre ...

African Journals Online (AJOL)

Background: We compared the analgesic efficacy of a transdermal diclofenac patch 100 mg (NuPatch® 100, Zydus Cadila, Ahmedabad, India) and intramuscular diclofenac sodium 75 mg (Voveran®, Novartis, India) for postoperative analgesia, and the associated side-effects of the transdermal diclofenac patch. Method: ...

Generic patches containing fentanyl: In vitro equivalence and abuse deterrent evaluation according to EMA and FDA guidelines.

Science.gov (United States)

Padula, Cristina; Pescina, Silvia; Nicoli, Sara; Santi, Patrizia

2018-02-15

The aim of this work was to characterize in vitro and ex vivo the performances of Durogesic and of two bioequivalent generic products, by evaluating: (a) fentanyl release; (b) fentanyl permeation across porcine skin and (c) fentanyl ease of extraction. Additional characteristics studied are the effect of temperature and skin integrity, applied individually or combined, to check a possible synergism. The two generic patches resulted equivalent to the originator according to the new Guideline. Nevertheless, the same data reported in a different way, i.e. considering the total amount of drug permeated from the whole patch over the application time, highlight differences among the patches. The additional tests performed showed that skin integrity does not represent a barrier for fentanyl permeation across the skin, regardless of the type and complexity of the patch. The effect of temperature resulted critical for two out of three patches, probably due to the different composition and to the different structure. The combination of skin damage and elevated temperature did not produce a synergistic effect. Fentanyl extraction was different for the different products and variable according to the conditions used. The results reported in the present work underline the influence of patch composition and complexity on fentanyl extraction, release and skin permeation, in particular in conditions that can be critical, such as elevated temperature. In particular, the effect of critical variables, such as skin integrity and temperature, should be addressed to in the development of a new or new generic patch and new discriminant tests should be developed. Copyright © 2017 Elsevier B.V. All rights reserved.

Supply-side response to declining heroin purity: fentanyl overdose episode in New Jersey.

Science.gov (United States)

Hempstead, Katherine; Yildirim, Emel O

2014-06-01

The inelastic price demand observations characteristic of illegal drug markets have led to the conclusion that the burden of a negative supply shock would be completely reflected to consumers. This paper argues that the increasing availability of prescription opioids may threaten heroin sellers' profit margin and force them to find alternative methods to compensate buyers in the event of a supply shock. We investigate the 2006 fentanyl overdose episode in New Jersey and argue that the introduction of non-pharmaceutical fentanyl, its spatial distribution, and the timing of overdose deaths may have been related to trends in heroin purity. Using medical examiner data, as well as data from the Drug Enforcement Administration, Office of Diversion Control on retail sales of prescription opioids in a negative binomial specification, we show that month-to-month fluctuations in heroin purity have a significant effect on fentanyl-related overdoses, particularly in those areas where prescription opioids are highly available. Copyright © 2013 John Wiley & Sons, Ltd.

Evaluation of the effect of transdermal nitroglycerine patch on intrathecal dexmedetomidine as additive, on postoperative analgesia after abdominal hysterectomy

Directory of Open Access Journals (Sweden)

Rama Chatterji

2017-01-01

Full Text Available Aim: The aim of this study is to evaluate the effect of transdermal nitroglycerin on intrathecal dexmedetomidine as additive, on postoperative analgesia after abdominal hysterectomy. Materials and Methods: Totally 140 patients of the American Society of Anesthesiologists Grade I or II, posted for abdominal hysterectomy under spinal anesthesia, were randomized to four groups using computer-generated random number list. Group B received 3 ml of 0.5% hyperbaric bupivacaine with 0.5 ml normal saline and placebo patch, Group BN received 3 ml of 0.5% hyperbaric bupivacaine with 0.5 ml NS and transdermal nitroglycerin (t-NTG, Group BD received 3 ml of 0.5% hyperbaric bupivacaine with 5 mcg (0.5 ml dexmedetomidine and placebo patch and Group BDN received 3 ml of 0.5% hyperbaric bupivacaine with 5 μg (0.5 ml dexmedetomidine and t-NTG patch. Outcomes measured include the total duration of analgesia, onset, and duration of sensory and motor block and any adverse effects. Results: The total duration of analgesia was longest in Group BDN (349.9 ± 40.6 min. It was significantly longer than Group BD (252.3 ± 34.0 min and Group B and BN (130.5 ± 18.8, 138.3 ± 19.2 min. Time taken for two segment regression was comparable in Group B (79.9 ± 14.4 min and Group BN (87.1 ± 22.6 min, but it was significantly longer in Group BD (122.5 ± 17.2 min and Group BDN (136.4 ± 25.5 min. There was no significant difference in other variables between the groups. Conclusion: Transdermal nitroglycerine itself does not exhibit any analgesic potential of its own but, it enhances the analgesic potential of intrathecal dexmedetomidine.

Fentanyl increases dopamine release in rat nucleus accumbens: involvement of mesolimbic mu- and delta-2-opioid receptors

NARCIS (Netherlands)

Yoshida, Y.; Koide, S.; Hirose, N.; Takada, K.; Tomiyama, K; Koshikawa, N.; Cools, A.R.

1999-01-01

The effects of the u-receptor agonist fentanyl on extracellular levels of dopamine in rat nucleus accumbens were studied in awake animals by in vivo brain microdialysis. Fentanyl dosedependently increased the levels of dopamine when given intravenously (ug/kg) or via a microdialysis probe placed

Transferosomes - A vesicular transdermal delivery system for enhanced drug permeation

Directory of Open Access Journals (Sweden)

Reshmy Rajan

2011-01-01

Full Text Available Transdermal administration of drugs is generally limited by the barrier function of the skin. Vesicular systems are one of the most controversial methods for transdermal delivery of active substances. The interest in designing transdermal delivery systems was relaunched after the discovery of elastic vesicles like transferosomes, ethosomes, cubosomes, phytosomes, etc. This paper presents the composition, mechanisms of penetration, manufacturing and characterization methods of transferosomes as transdermal delivery systems of active substances. For a drug to be absorbed and distributed into organs and tissues and eliminated from the body, it must pass through one or more biological membranes/barriers at various locations. Such a movement of drug across the membrane is called as drug transport. For the drugs to be delivered to the body, they should cross the membranous barrier. The concept of these delivery systems was designed in an attempt to concentrate the drug in the tissues of interest, while reducing the amount of drug in the remaining tissues. Hence, surrounding tissues are not affected by the drug. In addition, loss of drug does not happen due to localization of drug, leading to get maximum efficacy of the medication. Therefore, the phospholipid based carrier systems are of considerable interest in this era.

Det legale opioidforbrug i Danmark

DEFF Research Database (Denmark)

Jarlbaek, Lene; Kehlet, Henrik; Sjøgren, Per

2010-01-01

To identify users and use of opioids in Denmark three databases were combined. The latest fifteen years an increase in users has been noted, and the costs of opioids have increased from 175 million DKK (1994) to 540 million DKK (2008). Oxycodone and transdermal fentanyl constitute 60% of the total...

Det legale opioidforbrug i Danmark

DEFF Research Database (Denmark)

Jarlbaek, Lene; Kehlet, Henrik; Sjøgren, Per

2010-01-01

To identify users and use of opioids in Denmark three databases were combined. The latest fifteen years an increase in users has been noted, and the costs of opioids have increased from 175 million DKK (1994) to 540 million DKK (2008). Oxycodone and transdermal fentanyl constitute 60% of the tota...

Synthesis and evaluation of fluorinated derivatives of fentanyl as candidates for opiate receptor studies using positron emission tomography

Energy Technology Data Exchange (ETDEWEB)

Dahren Hwang; Feliu, A.L.; Wolf, A.P.; MacGregor, R.R.; Fowler, J.S.; Arnett, C.D.

1986-03-01

Three fluorinated derivatives of fentanyl, fluorofentanyl (3), keto-fluorofentanyl (5), and fluorofentanol (6), were synthesized and their abilities to compete with /sup 3/diprenorphine for binding sites in guinea pig brain membranes were determined. The relative potencies were fentanyl > 3 approx.= 6 >> 5. On the basis of its apparent affinity for opiate receptors and its relative ease of synthesis, 6 was selected for further study. Fentanyl was slightly better than 6 in its ability to compete with (/sup 3/H)naltrexone for binding sites in rat brain membranes. Both fentayl and 6 exhibited a similar high ''sodium ratio'' (quotient of the IC/sub 50/'s against (/sup 3/H)naltrexone in the presence and absence of sodium chloride) generally characteristic of opiate agonists. The analgesic potencies of fentanyl and 6 were determined in rats by measuring suppression of locomotion and vocalization responses to footshock. 6 appeared slightly less potent than fentanyl, but produced a similar analgesia and catalepsy which was entirely blocked by pretreatment of rats with naloxone, an opiate antagonist. A rapid synthesis of (/sup 18/F)-6 was developed and the tissue distribution of (/sup 18/F)-6 in mice was determined 5, 60, and 120 minutes after intravenous injection. The use of this general route to /sup 18/F-labeled derivatives of fentanyl for studies of the opiate receptor using positron emission tomography is planned.

Efficacy and safety of fentanyl buccal for cancer pain management by administration through a soluble film: an update

Directory of Open Access Journals (Sweden)

Marvin Omar Delgado-Guay

2010-11-01

Full Text Available Marvin Omar Delgado-GuayDivision of Geriatrics and Palliative Medicine, The University of Texas, Medical School at Houston, Houston, TX, USAAbstract: More than half of patients receiving prescription medicine for cancer pain have been reported to experience inadequate pain relief or breakthrough pain. Buccal administration can deliver lipophilic opioids rapidly to the systemic circulation through the buccal mucosa, limiting gastrointestinal motility and first-pass metabolism. This review updates the safety and efficacy of fentanyl buccal soluble film (FBSF in patients with cancer pain. Literature was identified through searches of Medline (PubMed. Search terms included combinations of the following: cancer pain, fentanyl, fentanyl buccal soluble film, pharmacology, kinetics, safety, efficacy and toxicity. FBSF is an oral transmucosal form of fentanyl citrate developed as a treatment of breakthrough pain in opioid-tolerant patients with cancer. Studies have shown that it is well tolerated in the oral cavity, with adequate bioavailability and safety in cancer patients. Further studies are warranted to evaluate, in comparison with other short-acting opioids, its efficacy in the management of breakthrough cancer pain, its addictive potential and its economic impact in cancer patients.Keywords: fentanyl buccal soluble film, cancer pain

Effect of fentanyl on the induction dose and minimum infusion rate of propofol preventing movement in dogs.

Science.gov (United States)

Davis, Carrie A; Seddighi, Reza; Cox, Sherry K; Sun, Xiaocun; Egger, Christine M; Doherty, Thomas J

2017-07-01

To determine the effect of fentanyl on the induction dose of propofol and minimum infusion rate required to prevent movement in response to noxious stimulation (MIR NM ) in dogs. Crossover experimental design. Six healthy, adult intact male Beagle dogs, mean±standard deviation 12.6±0.4 kg. Dogs were administered 0.9% saline (treatment P), fentanyl (5 μg kg -1 ) (treatment PLDF) or fentanyl (10 μg kg -1 ) (treatment PHDF) intravenously over 5 minutes. Five minutes later, anesthesia was induced with propofol (2 mg kg -1 , followed by 1 mg kg -1 every 15 seconds to achieve intubation) and maintained for 90 minutes by constant rate infusions (CRIs) of propofol alone or with fentanyl: P, propofol (0.5 mg kg -1  minute -1 ); PLDF, propofol (0.35 mg kg -1  minute -1 ) and fentanyl (0.1 μg kg -1  minute -1 ); PHDF, propofol (0.3 mg kg -1  minute -1 ) and fentanyl (0.2 μg kg -1  minute -1 ). Propofol CRI was increased or decreased based on the response to stimulation (50 V, 50 Hz, 10 mA), with 20 minutes between adjustments. Data were analyzed using a mixed-model anova and presented as mean±standard error. ropofol induction doses were 6.16±0.31, 3.67±0.21 and 3.33±0.42 mg kg -1 for P, PLDF and PHDF, respectively. Doses for PLDF and PHDF were significantly decreased from P (pFentanyl, at the doses studied, caused statistically significant and clinically important decreases in the propofol induction dose and MIR NM . Copyright © 2017 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.

Transdermal hormone therapy in postmenopausal women: A review of metabolic effects and drug delivery technologies

Directory of Open Access Journals (Sweden)

Nathan W Kopper

2008-10-01

Full Text Available Nathan W Kopper, Jennifer Gudeman, Daniel J ThompsonKV Pharmaceutical, St. Louis, MO, USAAbstract: Vasomotor symptoms (VMS associated with menopause can cause significant discomfort and decrease the quality of life for women in the peri-menopausal and post-menopausal stages of life. Hormone therapy (HT is the mainstay of treatment for menopausal symptoms and is currently the only therapy proven effective for VMS. Numerous HT options are available to treat VMS, including estrogen-only and estrogen-progestogen combination products to meet the needs of both hysterectomized and nonhysterectomized women. In addition to selecting an appropriate estrogen or estrogen-progestogen combination, consideration should be given to the route of administration to best suit the needs of the patient. Delivery systems for hormone therapy include oral tablets, transdermal patches, transdermal topical (nonpatch products, and intravaginal preparations. Oral is currently the most commonly utilized route of administration in the United States. However, evidence suggests that oral delivery may lead to some undesirable physiologic effects caused by significant gut and hepatic metabolism. Transdermal drug delivery may mitigate some of these effects by avoiding gut and hepatic first-pass metabolism. Advantages of transdermal delivery include the ability to administer unmetabolized estradiol directly to the blood stream, administration of lower doses compared to oral products, and minimal stimulation of hepatic protein production. Several estradiol transdermal delivery technologies are available, including various types of patches, topical gels, and a transdermal spray.Keywords: estradiol, hormone therapy, menopause, transdermal drug delivery, vasomotor symptoms

Fentanyl-related compounds and derivatives: current status and future prospects for pharmaceutical applications

Science.gov (United States)

Vardanyan, Ruben S; Hruby, Victor J

2014-01-01

Fentanyl and its analogs have been mainstays for the treatment of severe to moderate pain for many years. In this review, we outline the structural and corresponding synthetic strategies that have been used to understand the structure–biological activity relationship in fentanyl-related compounds and derivatives and their biological activity profiles. We discuss how changes in the scaffold structure can change biological and pharmacological activities. Finally, recent efforts to design and synthesize novel multivalent ligands that act as mu and delta opioid receptors and NK-1 receptors are discussed. PMID:24635521

Role of central and peripheral opiate receptors in the effects of fentanyl on analgesia, ventilation and arterial blood-gas chemistry in conscious rats

Science.gov (United States)

Henderson, Fraser; May, Walter J.; Gruber, Ryan B.; Discala, Joseph F.; Puscovic, Veljko; Young, Alex P.; Baby, Santhosh M.; Lewis, Stephen J.

2015-01-01

This study determined the effects of the peripherally restricted µ-opiate receptor (µ-OR) antagonist, naloxone methiodide (NLXmi) on fentanyl (25 µg/kg, i.v.)-induced changes in (1) analgesia, (2) arterial blood gas chemistry (ABG) and alveolar-arterial gradient (A-a gradient), and (3) ventilatory parameters, in conscious rats. The fentanyl-induced increase in analgesia was minimally affected by a 1.5 mg/kg of NLXmi but was attenuated by a 5.0 mg/kg dose. Fentanyl decreased arterial blood pH, pO2 and sO2 and increased pCO2 and A-a gradient. These responses were markedly diminished in NLXmi (1.5 mg/kg)-pretreated rats. Fentanyl caused ventilatory depression (e.g., decreases in tidal volume and peak inspiratory flow). Pretreatment with NLXmi (1.5 mg/kg, i.v.) antagonized the fentanyl decrease in tidal volume but minimally affected the other responses. These findings suggest that (1) the analgesia and ventilatory depression caused by fentanyl involve peripheral µ-ORs and (2) NLXmi prevents the fentanyl effects on ABG by blocking the negative actions of the opioid on tidal volume and A-a gradient. PMID:24284037

Transdermal granisetron: a guide to its use in preventing nausea and vomiting induced by chemotherapy.

Science.gov (United States)

Keating, Gillian M; Duggan, Sean T; Curran, Monique P

2012-09-01

Transdermal granisetron (Sancuso®) is effective in the prevention of nausea and vomiting in patients with cancer who are receiving moderately or highly emetogenic chemotherapy for 3-5 days. Transdermal granisetron is noninferior to oral granisetron in this indication, and is generally well tolerated in this indication. Thus, transdermal granisetron provides a convenient option for the prevention of chemotherapy-induced nausea and vomiting, with the potential to improve patient compliance.

Stability of Fentanyl Citrate, Hydromorphone Hydrochloride, Ketamine Hydrochloride, Midazolam, Morphine Sulfate, and Pentobarbital Sodium in Polypropylene Syringes

OpenAIRE

Anderson, Collin; MacKay, Mark

2015-01-01

Purpose: Determine the stability of fentanyl 10 mcg/mL in 0.9% sodium chloride, fentanyl 10 mcg/mL in 5% dextrose, fentanyl 50 mcg/mL, hydromorphone 100 mcg/mL in 0.9% sodium chloride, ketamine 10 mg/mL, midazolam 0.4 mg/mL in 5% dextrose, midazolam 5 mg/mL, morphine 1 mg/mL in 0.9% sodium chloride, morphine 1 mg/mL in 5% dextrose, and pentobarbital 50 mg/mL when stored as single drug entities at room temperature in polypropylene syringes. Methods: Four 5 mL samples of each drug and concentra...

Transdermal optogenetic peripheral nerve stimulation

Science.gov (United States)

Maimon, Benjamin E.; Zorzos, Anthony N.; Bendell, Rhys; Harding, Alexander; Fahmi, Mina; Srinivasan, Shriya; Calvaresi, Peter; Herr, Hugh M.

2017-06-01

Objective: A fundamental limitation in both the scientific utility and clinical translation of peripheral nerve optogenetic technologies is the optical inaccessibility of the target nerve due to the significant scattering and absorption of light in biological tissues. To date, illuminating deep nerve targets has required implantable optical sources, including fiber-optic and LED-based systems, both of which have significant drawbacks. Approach: Here we report an alternative approach involving transdermal illumination. Utilizing an intramuscular injection of ultra-high concentration AAV6-hSyn-ChR2-EYFP in rats. Main results: We demonstrate transdermal stimulation of motor nerves at 4.4 mm and 1.9 mm depth with an incident laser power of 160 mW and 10 mW, respectively. Furthermore, we employ this technique to accurately control ankle position by modulating laser power or position on the skin surface. Significance: These results have the potential to enable future scientific optogenetic studies of pathologies implicated in the peripheral nervous system for awake, freely-moving animals, as well as a basis for future clinical studies.

Comparative enhancing effects of electret with chemical enhancers on transdermal delivery of meloxicam in vitro

International Nuclear Information System (INIS)

Cui, L L; Hou, X M; Li, G D; Jiang, J; Liang, Y Y; Xin, X

2008-01-01

Electret offers enhancing effect in transdermal drug delivery for altering of the arrangement of lipid molecules in the stratum corneum, forming many transient permeable apertures and enhancing the transdermal drug delivery. In this paper, meloxicam patch formulations were developed to make the comparative study of transdermal drug delivery between electret and chemical enhancers. Patches were made into control, electret, chemical enhancer and electret with chemical enhancer ones, according to the preparation procedure. The electret combined with chemical enhancer patch was designed to probe the incorporation between electret and chemical enhancer in transdermal drug delivery. The meloxicam release from the patch was found to increase in order of blank, chemical enhancer, electret and electret with chemical enhancer patch, in general.

MICRONEEDLES AS A WAY TO INCREASE THE TRANSDERMAL INSULIN DELIVERY

Directory of Open Access Journals (Sweden)

E. G. Kuznetsova

2016-01-01

Full Text Available Aim: to prove the possibility of increasing the diffusion of insulin through the skin in vitro with pre-applying microneedles.Materials and methods. Microemulsion for transdermal therapeutic system of insulin has been used in vitro studies. Genetically engineered human insulin has been used in this research. Applicators with silicon microneedles (40 and 150 microns long have been used to enhance the diffusion fl ux of drug substance. The dynamics of insulin release from the transdermal therapeutic systems through the rabbit skin has been studied in glass Franz diffusion cells in analyzer diffusion of drugs HDT 1000 (Copley Scientifi c Ltd., UK. Insulin has been labeled with fl uorescein isothiocyanate to separate the insulin absorption spectrum from the spectra of native skin proteins at spectrophotometer measurements.Results. The amounts of insulin delivered through the skin in vitro after previous application of microneedles of 40 and 150 microns are 282.5 ± 61.1 and 372.3 ± 7.0 microgram, respectively. This is 1.4 and 1.9 times more than in the transdermal system without microneedles.Conclusion. The conditions for increasing the diffusion of insulin through the skin in a model transdermal therapeutic system with microneedles (length – 150 microns, duration of pre-application – 1 hour have been found.

Rationales behind the choice of administration form with fentanyl

DEFF Research Database (Denmark)

Jacobsen, Ramune; Møldrup, Claus; Christrup, Lona

2010-01-01

BACKGROUND AND AIM: The aim of this study was to describe the rationale behind the choice of fentanyl administration forms among Danish general practitioners (GPs). METHODS: Thirty-eight Danish GPs were contacted via an Internet survey system to perform a Delphi survey. In the brainstorming phase...

Effects of oral and transdermal estrogen on IGF1, IGFBP3, IGFBP1, serum lipids, and glucose in patients with hypopituitarism during GH treatment: a randomized study.

Science.gov (United States)

Isotton, Ana Lúcia; Wender, Maria Celeste Osorio; Casagrande, Alessandra; Rollin, Guilherme; Czepielewski, Mauro Antônio

2012-02-01

To evaluate the effects of oral estradiol and transdermal 17β-estradiol on serum concentrations of IGF1 and its binding proteins in women with hypopituitarism. Prospective, comparative study. Eleven patients with hypopituitarism were randomly allocated to receive 2 mg oral estradiol (n=6) or 50 μg/day of transdermal 17β-estradiol (n=5) for 3 months. The oral estrogen group showed a significant reduction in IGF1 levels (mean: 42.7%±41.4, P=0.046); no difference was observed in the transdermal estrogen group. There was a significant increase in IGFBP1 levels (mean: 170.2%±230.9, P=0.028) in the oral group, but not in the transdermal group. There was no significant difference within either group in terms of median IGFBP3 levels. In relation to lipid profiles, there was a significant increase in mean high-density lipoprotein cholesterol levels in the oral group after 3 months of treatment, (27.8±9.3, P=0.003). We found no differences in the anthropometric measurements, blood pressure, heart rate, glucose, insulin, C-peptide, or the homeostasis model assessment index after treatment. Our preliminary data indicate that different estrogen administration routes can influence IGF1 and IGFBP1 levels. These findings in patients with hypopituitarism have an impact on their response to treatment with GH, since patients receiving oral estrogen require increased GH dosage. These results suggest that oral estrogens may reduce the beneficial effects of GH replacement on fat and protein metabolism, body composition, and quality of life.

Comparison of efficacy of meperidine and fentanyl in terms of pain management and quality of life in patients with cervical cancer receiving intracavitary brachytherapy: a double-blind, randomized controlled trial.

Science.gov (United States)

Thanthong, Saengrawee; Rojthamarat, Sirikorn; Worasawate, Wipra; Vichitvejpaisal, Phongthara; Nantajit, Danupon; Ieumwananontachai, Nantakarn

2017-08-01

The aim of this study was to compare the effectiveness of two sedative regimens, a benzodiazepine with either meperidine or fentanyl, in relieving pain in patients with cervical cancer undergoing intracavitary brachytherapy in terms of pain score and quality of life. Forty unselected outpatients undergoing brachytherapy (160 fractions) were enrolled with informed consent and randomized to receive a benzodiazepine with either meperidine or fentanyl. The perceived pain score according to a standard 10-item numeric rating scale was collected every 15 min during the procedure, and the perceived quality of life was determined at the end of each procedure using the EuroQol five-dimension questionnaire. The patients and medical staff members directly involved with the procedure were blinded to the medication used. The patients' pain levels were mild in both analgesic groups. Meperidine appeared to be slightly more effective than fentanyl, although the differences in the average pain score and quality of life were not statistically significant. Both meperidine and fentanyl in combination with benzodiazepine were effective in relieving pain and discomfort in patients undergoing brachytherapy. NCT02684942, ClinicalTrials.gov.

A series of forensic toxicology and drug seizure cases involving illicit fentanyl alone and in combination with heroin, cocaine or heroin and cocaine.

Science.gov (United States)

Marinetti, Laureen J; Ehlers, Brooke J

2014-10-01

The Montgomery County Coroner's Office Toxicology Section and the Miami Valley Regional Crime Lab (MVRCL) Drug Chemistry Section have been receiving case work in drug seizures, death cases and human performance cases involving products marketed as heroin or as illicit fentanyl. Upon analysis by the Drug Chemistry Section, these products were found to contain various drug(s) including illicit fentanyl only, illicit fentanyl and heroin, illicit fentanyl and cocaine and illicit fentanyl, heroin and cocaine. Both the Chemistry and Toxicology Sections began seeing these combinations starting in late October 2013. The percentage of the combinations encountered by the MVRCL as well as the physical appearance of the product, and the results of presumptive screening tests will be discussed. The demographics of the users and the results of toxicology and autopsy findings on the decedents will also be discussed. According to regional drug task force undercover agents, there is evidence that some of the products are being sold as illicit fentanyl and not just as a heroin product. Also, there is no evidence to support that the fentanyl source is being diverted from pharmaceutical grade fentanyl. The chemistry section currently has over 109 confirmed cases, and the toxicology section currently has 81 confirmed drug deaths, 8 driving under the influence of drugs and 1 suicidal hanging. Both sections are continuing to see these cases at the present time. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Influence of endotoxin-induced sepsis on the requirements of propofol-fentanyl infusion rate in pigs

DEFF Research Database (Denmark)

Bollen, Peter; Nielsen, Bjørn J; Toft, Palle

2007-01-01

Endotoxin-induced sepsis in pigs is a recognized experimental model for the study of human septic shock. Generally, pigs are brought into general anaesthesia before sepsis is induced. It is our experience that drug dosages of propofol and fentanyl need to be reduced during endotoxin-induced sepsis......, in order to prevent respiratory and cardiovascular depression, but the scientific evidence for this observation is lacking. Therefore, we measured the consumption of propofol and fentanyl at equal level of anaesthesia in pigs with (n = 5) and without (n = 5) endotoxin-induced sepsis, using the cerebral...... state index (CSI) as measure of anaesthetic depth. Infusion rates of propofol (P endotoxin-induced sepsis had an infusion rate of 2.2 mg/kg/hr (S.D. 0.5) for propofol and 12 microg/kg/hr (S.D. 2) for fentanyl, whereas...

Formulation, in vitro and in vivo evaluation of transdermal patches containing risperidone.

Science.gov (United States)

Aggarwal, Geeta; Dhawan, Sanju; Hari Kumar, S L

2013-01-01

The efficacy of oral risperidone treatment in prevention of schizophrenia is well known. However, oral side effects and patient compliance is always a problem for schizophrenics. In this study, risperidone was formulated into matrix transdermal patches to overcome these problems. The formulation factors for such patches, including eudragit RL 100 and eudragit RS 100 as matrix forming polymers, olive oil, groundnut oil and jojoba oil in different concentrations as enhancers and amount of drug loaded were investigated. The transdermal patches containing risperidone were prepared by solvent casting method and characterized for physicochemical and in vitro permeation studies through excised rat skin. Among the tested preparations, formulations with 20% risperidone, 3:2 ERL 100 and ERS 100 as polymers, mixture of olive oil and jojoba oil as enhancer, exhibited greatest cumulative amount of drug permeated (1.87 ± 0.09 mg/cm(2)) in 72 h, so batch ROJ was concluded as optimized formulation and assessed for pharmacokinetic, pharmacodynamic and skin irritation potential. The pharmacokinetic characteristics of the optimized risperidone patch were determined using rabbits, while orally administered risperidone in solution was used for comparison. The calculated relative bioavailability of risperidone transdermal patch was 115.20% with prolonged release of drug. Neuroleptic efficacy of transdermal formulation was assessed by rota-rod and grip test in comparison with control and marketed oral formulations with no skin irritation. This suggests the transdermal application of risperidone holds promise for improved bioavailability and better management of schizophrenia in long-term basis.

A quality improvement project to reduce the intraoperative use of single-dose fentanyl vials across multiple patients in a pediatric institution.

Science.gov (United States)

Buck, David; Subramanyam, Rajeev; Varughese, Anna

2016-01-01

The use of a single-dose vial across multiple patients presents a risk to sterility and is against CDC guidelines. We initiated a quality improvement (QI) project to reduce the intraoperative use of single-dose vials of fentanyl across multiple patients at Cincinnati Children's Hospital Medical Center (CCHMC). The initial step of the improvement project was the development of a Key Driver Diagram. The diagram has the SMART aim of the project, key drivers inherent to the process we are trying to improve, and specific interventions targeting the key drivers. The number of patients each week receiving an IV dose of fentanyl, from a vial previously accessed for another patient was tracked in a high turnover operating room (OR). The improvement model used was based on the concept of building Plan-Do-Study-Act (PDSA) cycles. Tests of change included provider education, provision of an increased number of fentanyl vials, alternate wasting processes, and provision of single-use fentanyl syringes by the pharmacy. Prior to initiation of this project, it was common for a single fentanyl vial to be accessed for multiple patients. Our data showed an average percentage of failures of just over 50%. During the end of the project, after 7 months, the mean percentage failures had dropped to 5%. Preparation of 20 mcg single-use fentanyl syringes by pharmacy, combined with education of providers on appropriate use, was successful in reducing failures to below our goal of 25%. Appropriately sized fentanyl syringes prepared by pharmacy, education on correct use of single-dose vials, and reminders in the OR, reduced the percentage of patients receiving a dose of fentanyl from a vial previously accessed for another patient in a high-volume otolaryngology room. © 2015 John Wiley & Sons Ltd.

Status of surfactants as penetration enhancers in transdermal drug delivery

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Iti Som

2012-01-01

Full Text Available Surfactants are found in many existing therapeutic, cosmetic, and agro-chemical preparations. In recent years, surfactants have been employed to enhance the permeation rates of several drugs via transdermal route. The application of transdermal route to a wider range of drugs is limited due to significant barrier to penetration across the skin which is associated with the outermost stratum corneum layer. Surfactants have effects on the permeability characteristics of several biological membranes including skin. They have the potential to solubilize lipids within the stratum corneum. The penetration of the surfactant molecule into the lipid lamellae of the stratum corneum is strongly dependent on the partitioning behavior and solubility of surfactant. Surfactants ranging from hydrophobic agents such as oleic acid to hydrophilic sodium lauryl sulfate have been tested as permeation enhancer to improve drug delivery. This article reviews the status of surfactants as permeation enhancer in transdermal drug delivery of various drugs.

Efficacy and safety of fentanyl buccal for cancer pain management by administration through a soluble film: an update

International Nuclear Information System (INIS)

Delgado-Guay, Marvin Omar

2010-01-01

More than half of patients receiving prescription medicine for cancer pain have been reported to experience inadequate pain relief or breakthrough pain. Buccal administration can deliver lipophilic opioids rapidly to the systemic circulation through the buccal mucosa, limiting gastrointestinal motility and first-pass metabolism. This review updates the safety and efficacy of fentanyl buccal soluble film (FBSF) in patients with cancer pain. Literature was identified through searches of Medline (PubMed). Search terms included combinations of the following: cancer pain, fentanyl, fentanyl buccal soluble film, pharmacology, kinetics, safety, efficacy and toxicity. FBSF is an oral transmucosal form of fentanyl citrate developed as a treatment of breakthrough pain in opioid-tolerant patients with cancer. Studies have shown that it is well tolerated in the oral cavity, with adequate bioavailability and safety in cancer patients. Further studies are warranted to evaluate, in comparison with other short-acting opioids, its efficacy in the management of breakthrough cancer pain, its addictive potential and its economic impact in cancer patients

Preparation and the in vitro evaluation of nanoemulsion system for the transdermal delivery of granisetron hydrochloride.

Science.gov (United States)

Zheng, Wen-wu; Zhao, Ling; Wei, Yu-meng; Ye, Yun; Xiao, Shun-han

2010-08-01

The objective of this study was to develop and evaluate nanoemulsion system for transdermal delivery of granisetron hydrochloride. Pseudo-ternary phase diagram was constructed to ascertain the concentration range of components of nanoemulsion composed of isopropyl myristate (IPM) as an oil phase, tween 85 as surfactant, ethanol as cosurfactant, water as aqueous phase. The effects of the content of IPM as an oil phase and n-methyl pyrrolidone (NMP) as transdermal enhancer on rat skin permeation of granisetron hydrochloride nanoemulsion were studied in vitro. The results showed that the mean particle size of nanoemulsion ranged from 50.4+/-1.5 to 82.4+/-0.9 nm with homogeneous size distribution. The resulted optimum formulation composed of 2.5% granisetron hydrochloride, 4% IPM, 40% tween 85/ethanol (1 : 1) and 10% NMP showed that the skin permeation rate was the highest (85.39+/-2.90 microg/cm(2)/h) and enhancement of drug permeability was 4.1-fold for transdermal delivery of granisetron hydrochloridein comparison with the control group (20% of tween 85 and 20% of ethanol micelle solution containing 2.5% of granisetron hydrochloride without IPM), and cumulative permeation amount was the highest (891.8+/-2.86 microg/cm(2)) with the shortest lag time (0.11+/-0.02 h) and was stable for at least 12 months. Therefore, the nanoemulsion system developed in this study offers a promising vehicle for the transdermal delivery system of granisetron hydrochloride, which may be as effective as oral or intravenous dosage forms and avoid some difficulties associated with these dosage forms.

Use of granisetron transdermal system in the prevention of chemotherapy-induced nausea and vomiting: a review

International Nuclear Information System (INIS)

Tuca, Albert

2009-01-01

Until now only intravenous and oral formulations of 5HT 3 receptor antagonists have been available. Recently a new formulation of a 5HT 3 receptor antagonist, transdermal granisetron, has been developed, and approved by the FDA. Three phase I studies to evaluate its pharmacokinetic profile have shown that granisetron administered by a transdermal delivery system is absorbed by passive diffusion and maximal concentration is reached 48 hours after patch application. The patch of 52 cm 2 , which contains 34.3 mg of granisetron, releases 3.3 mg of the drug every day and maintains a stable average plasma concentration of 2.2 ng/mL over 6 days, similar to levels obtained with 2 mg of oral granisetron, administered every day during the same period of time. Two randomized as yet unpublished clinical trials (phase II/III) have been conducted to evaluate the antiemetic efficacy of transdermal granisetron in chemotherapy-induced nausea and vomiting, in patients receiving moderately and highly emetogenic chemotherapy, compared with 2 mg of oral granisetron. More than 800 cancer patients were included in the trials. The rate of complete control of acute emesis was 49% for the phase II trial and 60% for the phase III trial. Neither trial showed a statistically significant difference between transdermal and oral granisetron. The control of delayed emesis was observed in 46% of patients, and there were no statistically significant differences between transdermal and oral granisetron. The most common adverse effects in both trials were constipation (<7%) and headache (<1%); there were no statistically significant differences between transdermal and oral granisetron. These data show that transdermal granisetron is effective and safe in controlling acute emesis induced by chemotherapy with both moderate and high emetogenic potential. Efficacy and safety of transdermal granisetron are fully comparable with that of oral granisetron. More clinical trials using regimens of 2 or 3 drugs

A COMPARISON OF SPINAL ANAESTHESIA WITH LEVOBUPIVACAINE AND HYPERBARIC BUPIVACAINE COMBINED WITH FENTANYL IN CAESAREAN SECTION

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Kurmanadh Kalepalli

2016-10-01

LF (n = 30 – Received 1.8 ml (9 mg Levobupivacaine 0.5% + Fentanyl 10 mcg (0.2 ml. GROUP BF (n = 30 – Received 1.8 ml (9 mg hyperbaric Bupivacaine 0.5% + Fentanyl 10 mcg (0.2 ml. The parameters measured in the two groups included haemodynamic measurements (Pulse rate, systolic blood pressure, diastolic blood pressure, respiratory parameters (Respiratory rate, oxygen saturation characteristics of sensory block, characteristics of motor block, intra operative and post-operative complications like nausea, vomiting, shivering, visceral pain, sedation. In the neonate, Apgar score was measured to assess any effects of drugs the neonate. RESULTS Hypotension and bradycardia was more in hyperbaric Bupivacaine group (BF. Time for Onset of sensory block and maximum dermatome level reached were similar in both groups. Time for maximum sensory level reached, two segment regression time, T12 regression time and time for first analgesic requirement were early in LF group. Onset of motor block was delayed in LF group. Maximum degree of motor block was same in both groups (Bromage 3. Complete regression of motor block was significantly lower in Levobupivacaine group (LF. Intra operative incidence of nausea and vomiting were comparatively lower in LF group. Complications like respiratory depression, headache, back ache, and pruritus were not seen in both groups. Neonatal Apgar score was similar in all neonates. We recorded APGAR scores of 7 - 10 at 1 and 5 minutes in both groups. No significant postoperative complications were seen both the groups. CONCLUSIONS From present study findings and correlating it to the previous studies and literature plain Levobupivacaine 0.5% which is pure s - enantiomer of Bupivacaine is a good alternative for caesarean section in spinal anesthesia as it is less CVS and CNS toxic, early recovery of motor blockade leading to early mobilization of the mother, analgesia almost similar to racemic hyperbaric Bupivacaine. Addition of low dose Fentanyl 10

Effects of Fentanyl-lidocaine-propofol and Dexmedetomidine-lidocaine-propofol on Tracheal Intubation Without Use of Muscle Relaxants

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Volkan Hancı

2010-05-01

Full Text Available The aim of this study was to compare the effects of fentanyl or dexmedetomidine when used in combination with propofol and lidocaine for tracheal intubation without using muscle relaxants. Sixty patients with American Society of Anesthesiologists stage I risk were randomized to receive 1 mg/kg dexmedetomidine (Group D, n = 30 or 2 mg/kg fentanyl (Group F, n = 30, both in combination with 1.5 mg/kg lidocaine and 3 mg/kg propofol. The requirement for intubation was determined based on mask ventilation capability, jaw motility, position of the vocal cords and the patient's response to intubation and inflation of the endotracheal tube cuff. Systolic arterial pressure, mean arterial pressure, heart rate and peripheral oxygen saturation values were also recorded. Rate pressure products were calculated. Jaw relaxation, position of the vocal cords and patient's response to intubation and inflation of the endotracheal tube cuff were significantly better in Group D than in Group F (p < 0.05. The intubation conditions were significantly more satisfactory in Group D than in Group F (p = 0.01. Heart rate was significantly lower in Group D than in Group F after the administration of the study drugs and intubation (p < 0.05. Mean arterial pressure was significantly lower in Group F than in Group D after propofol injection and at 3 and 5 minutes after intubation (p < 0.05. After intubation, the rate pressure product values were significantly lower in Group D than in Group F (p < 0.05. We conclude that endotracheal intubation was better with the dexmedetomidine–lidocaine–propofol combination than with the fentanyl–lidocaine–propofol combination. However, side effects such as bradycardia should be considered when using dexmedetomidine.

Effect of buprenorphine transdermal patch combined with patientcontrolled intravenous analgesia on the serum pain-related biochemical indexes in elderly patients with intertrochanteric fracture

Directory of Open Access Journals (Sweden)

Lei Xu

2017-09-01

Full Text Available Objective: To study the effect of buprenorphine transdermal patch combined with patientcontrolled intravenous analgesia on the serum pain-related biochemical indexes in elderly patients with intertrochanteric fracture. Methods: A total of 92 elderly patients with intertrochanteric fracture who received surgical treatment in the hospital between August 2014 and January 2017 were collected and divided into control group (n=46 and observation group (n=46 according to the random number table method. The control group received patient-controlled intravenous analgesia, and the observation group received buprenorphine transdermal patch combined with patient-controlled intravenous analgesia. Differences in serum levels of inflammatory factors, oxidative stress indexes and pain mediators of two groups of patients were measured before and 24h after surgery. Results: Differences in serum levels of inflammatory factors, oxidative stress indexes and pain mediators were not statistically significant between the two groups before surgery; 24 h after surgery, serum IL- 1β, IL-6, IL-8, TNF-α, MDA, SP, PGE2, 5-HT, HA and NPY levels of both groups of patients increased significantly while SOD, TAC and CAT levels decreased significantly, and serum IL-1β, IL-6, IL-8, TNF-α, MDA, SP, PGE2, 5-HT, HA and NPY levels of observation group were lower than those of control group while SOD, TAC and CAT levels were higher than those of control group. Conclusion: Buprenorphine transdermal patch combined with patient-controlled intravenous analgesia can effectively inhibit the expression of pain-related indexes and relieve early postoperative pain intensity in elderly patients with intertrochanteric fracture.

Safety of a Brief Emergency Department Observation Protocol for Patients With Presumed Fentanyl Overdose.

Science.gov (United States)

Scheuermeyer, Frank X; DeWitt, Christopher; Christenson, Jim; Grunau, Brian; Kestler, Andrew; Grafstein, Eric; Buxton, Jane; Barbic, David; Milanovic, Stefan; Torkjari, Reza; Sahota, Indy; Innes, Grant

2018-03-09

Fentanyl overdoses are increasing and few data guide emergency department (ED) management. We evaluate the safety of an ED protocol for patients with presumed fentanyl overdose. At an urban ED, we used administrative data and explicit chart review to identify and describe consecutive patients with uncomplicated presumed fentanyl overdose (no concurrent acute medical issues) from September to December 2016. We linked regional ED and provincial vital statistics databases to ascertain admissions, revisits, and mortality. Primary outcome was a composite of admission and death within 24 hours. Other outcomes included treatment with additional ED naloxone, development of a new medical issue while in the ED, and length of stay. A prespecified subgroup analysis assessed low-risk patients with normal triage vital signs. There were 1,009 uncomplicated presumed fentanyl overdose, mainly by injection. Median age was 34 years, 85% were men, and 82% received out-of-hospital naloxone. One patient was hospitalized and one discharged patient died within 24 hours (combined outcome 0.2%; 95% confidence interval [CI] 0.04% to 0.8%). Sixteen patients received additional ED naloxone (1.6%; 95% CI 1.0% to 2.6%), none developed a new medical issue (0%; 95% CI 0% to 0.5%), and median length of stay was 173 minutes (interquartile range 101 to 267). For 752 low-risk patients, no patients were admitted or developed a new issue, and one died postdischarge; 3 (0.4%; 95% CI 0.01% to 1.3%) received ED naloxone. In our cohort of ED patients with uncomplicated presumed fentanyl overdose-typically after injection-deterioration, admission, mortality, and postdischarge complications appear low; the majority can be discharged after brief observation. Patients with normal triage vital signs are unlikely to require ED naloxone. Copyright © 2018 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.

Topical and transdermal drug delivery: principles and practice

National Research Council Canada - National Science Library

Benson, Heather A. E; Watkinson, Adam C

2012-01-01

.... Providing an overview of the current science in drug and cosmetic application to and through the skin, Topical and Transdermal Drug Delivery includes treatment of skin conditions, skin permeation...

Enhanced Transdermal Permeability via Constructing the Porous Structure of Poloxamer-Based Hydrogel

Directory of Open Access Journals (Sweden)

Wen-Yi Wang

2016-11-01

Full Text Available A major concern for transdermal drug delivery systems is the low bioavailability of targeted drugs primarily caused by the skin’s barrier function. The resistance to the carrier matrix for the diffusion and transport of drugs, however, is routinely ignored. This study reports a promising and attractive approach to reducing the resistance to drug transport in the carrier matrix, to enhance drug permeability and bioavailability via enhanced concentration-gradient of the driving force for transdermal purposes. This approach simply optimizes and reconstructs the porous channel structure of the carrier matrix, namely, poloxamer 407 (P407-based hydrogel matrix blended with carboxymethyl cellulose sodium (CMCs. Addition of CMCs was found to distinctly improve the porous structure of the P407 matrix. The pore size approximated to normal distribution as CMCs were added and the fraction of pore number was increased by over tenfold. Transdermal studies showed that P407/CMCs saw a significant increase in drug permeability across the skin. This suggests that P407/CMC with improved porous structure exhibits a feasible and promising way for the development of transdermal therapy with high permeability and bioavailability, thereby avoiding or reducing use of any chemical enhancers.

Impact of various progestins with or without transdermal testosterone on gonadotropin levels for non-invasive hormonal male contraception: a randomized clinical trial.

Science.gov (United States)

Zitzmann, M; Rohayem, J; Raidt, J; Kliesch, S; Kumar, N; Sitruk-Ware, R; Nieschlag, E

2017-05-01

Although several progestins have been tested for hormonal male contraception, the effects of dosage and nature of various progestins on gonadotropin suppression combined with and without additional testosterone has not been performed in a comparative trial. The aim of this study was to evaluate the differential impact of four oral or transdermal progestins on the suppression of gonadotropins in healthy men: oral: cyproterone acetate (CPA), levonorgestrel (LNG), norethisterone acetate (NETA), and transdermal: Nestorone ® (NES), all in combination with transdermal testosterone (T). Randomized clinical trial testing was performed with four progestins at two doses each. After a 2-week progestin-only treatment, transdermal T was added for further 4 weeks and was followed by a 3-week recovery period. Progestin-dose per day: CPA 10 mg/20 mg, NES 2 mg/3 mg/dose e.g. 200/300 μg/day absorbed, NETA 5 mg/10 mg, LNG 120 μg/240 μg. From an andrology outpatient clinic, 56 healthy men aged 18-50 years, with body mass index ≤33 kg × m -2 were included in the study. Serum concentrations of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were studied. Secondary outcome measure included were serum testosterone concentrations, sperm concentrations, and safety parameters. Intergroup comparisons demonstrated that CPA and LNG had the strongest effect on LH/FSH suppression. Nevertheless, every substance showed significant inhibitory effects on gonadotropin secretion, especially in combination with transdermal T. A decrease in hematocrit and insulin sensitivity as well as cholesterol subfractions and triglycerides was uniformly seen for every group. The combination of oral or transdermal progestins with a transdermal testosterone preparation is able to suppress gonadotropins. Further dose titration studies with sperm suppression as an end-point should be conducted to determine the lowest effective dose for hormonal male contraception. © 2017 American

Transdermal rivastigmine: management of cutaneous adverse events and review of the literature.

Science.gov (United States)

Greenspoon, Jill; Herrmann, Nathan; Adam, David N

2011-07-01

Alzheimer's disease is a chronic neurodegenerative disorder resulting in part from the degeneration of cholinergic neurons in the brain. Rivastigmine, a cholinesterase inhibitor, is commonly used as a treatment for dementia due to its ability to moderate cholinergic neurotransmission; however, treatment with oral rivastigmine can lead to gastrointestinal adverse effects such as nausea and vomiting. Transdermal administration of rivastigmine can minimize these adverse effects by providing continuous delivery of the medication, while maintaining the effectiveness of the oral treatment. While the transdermal form of rivastigmine has been found to have fewer systemic adverse effects compared with the oral form, cutaneous reactions, such as contact dermatitis, can lead to discontinuation of the drug in its transdermal form. Lack of patient compliance with regard to applying the patch to the designated site, applying the patch for the correct length of time or rotating patch application sites increases the risk of cutaneous adverse reactions. This article outlines the diagnosis and management of irritant contact dermatitis and allergic contact dermatitis secondary to transdermal rivastigmine. The large majority of reactions to transdermal patches are of an irritant type, which can be diagnosed clinically by the presence of a pruritic, erythematous, eczematous plaque strictly confined to the borders of the patch. In contrast, an allergic reaction can be differentiated by the presence of vesicles and/or oedema, erythema beyond the boundaries of the transdermal patch and lack of improvement of the lesion 48 hours after removal of the offending treatment. By encouraging the patient to follow a regular rotation schedule for the patch, and using lipid-based emollients for irritant dermatitis and pre- and post-treatment topical corticosteroids for allergic dermatitis, cutaneous reactions can often be alleviated and patients can continue with their medication regimen. Other

Synthesis and characterization of modified starch/polybutadiene as novel transdermal drug delivery system.

Science.gov (United States)

Saboktakin, Mohammad Reza; Akhyari, Shahab; Nasirov, Fizuli A

2014-08-01

Transdermal drug delivery systems are topically administered medicaments in the form of patches that deliver drugs for systemic effects at a predetermined and controlled rate. It works very simply in which drug is applied inside the patch and it is worn on skin for long period of time. Polymer matrix, drug, permeation enhancers are the main components of transdermal drug delivery systems. The objective of the present study was to develop the modified starch and 1,4-cis polybutadiene nanoparticles as novel polymer matrix system. We have been studied the properties of a novel transdermal drug delivery system with clonidine as drug model. Copyright © 2014 Elsevier B.V. All rights reserved.

Optimization of Biopolymer Based Transdermal Films of Metoclopramide as an Alternative Delivery Approach

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Betül Aktar

2014-05-01

Full Text Available The objectives of this study were to develop and to characterize sodium alginate based matrix-type transdermal films of metoclopramide hydrochloride (MTC in order to improve patient compliance to treatment. The suitability of sodium alginate was shown to be a natural film former in terms of the physicochemical, mechanical, and bioadhesive features of the MTC loaded transdermal films. Terpinolene provided the highest drug release among the different terpenes (nerolidol, eucalyptol, dl-limonene, or terpinolene assessed as enhancer. Attenuated Total Reflectance Infrared (ATR-FTIR spectroscopy analysis performed to evaluate the effect of the transdermal films on skin barrier confirmed enhancer induced lipid bilayer disruption in stratum corneum, indicating its permeation enhancement effect.

An experimental trial exploring the impact of continuous transdermal alcohol monitoring upon alcohol consumption in a cohort of male students.

Science.gov (United States)

Neville, Fergus G; Williams, Damien J; Goodall, Christine A; Murer, Jeffrey S; Donnelly, Peter D

2013-01-01

To examine the impact of continuous transdermal alcohol monitoring upon alcohol consumption in male students at a Scottish university. Using a within-subject mixed-methods design, 60 male university students were randomly allocated into three experimental conditions using AUDIT score stratified sampling. Participants in Conditions A and B were asked not to consume alcohol for a 14-day period, with those in Condition A additionally being required to wear a continuous transdermal alcohol monitoring anklet. Condition C participants wore an anklet and were asked to continue consuming alcohol as normal. Alcohol consumption was measured through alcohol timeline follow-back, and using data collected from the anklets where available. Diaries and focus groups explored participants' experiences of the trial. Alcohol consumption during the 14-day trial decreased significantly for participants in Conditions A and B, but not in C. There was no significant relative difference in units of alcohol consumed between Conditions A and B, but significantly fewer participants in Condition A drank alcohol than in Condition B. Possible reasons for this difference identified from the focus groups and diaries included the anklet acting as a reminder of commitment to the study (and the agreement to sobriety), participants feeling under surveillance, and the use of the anklet as a tool to resist social pressure to consume alcohol. The study provided experience in using continuous transdermal alcohol monitors in an experimental context, and demonstrated ways in which the technology may be supportive in facilitating sobriety. Results from the study have been used to design a research project using continuous transdermal alcohol monitors with ex-offenders who recognise a link between their alcohol consumption and offending behaviour.

Recent trends in the transdermal delivery of therapeutic agents used for the management of neurodegenerative diseases.

Science.gov (United States)

Ita, Kevin

2017-06-01

With the increasing proportion of the global geriatric population, it becomes obvious that neurodegenerative diseases will become more widespread. From an epidemiological standpoint, it is necessary to develop new therapeutic agents for the management of Alzheimer's disease, Parkinson's disease, multiple sclerosis and other neurodegenerative disorders. An important approach in this regard involves the use of the transdermal route. With transdermal drug delivery systems (TDDS), it is possible to modulate the pharmacokinetic profiles of these medications and improve patient compliance. Transdermal drug delivery has also been shown to be useful for drugs with short half-life and low or unpredictable bioavailability. In this review, several transdermal drug delivery enhancement technologies are being discussed in relation to the delivery of medications used for the management of neurodegenerative disorders.

Use of granisetron transdermal system in the prevention of chemotherapy-induced nausea and vomiting: a review

Directory of Open Access Journals (Sweden)

Albert Tuca

2009-12-01

Full Text Available Albert TucaPalliative Care Hospital Team, Palliative Care Department, Institut Català d’Oncologia, L’Hospitalet de Llobregat, Barcelona, SpainAbstract: Until now only intravenous and oral formulations of 5HT3 receptor antagonists have been available. Recently a new formulation of a 5HT3 receptor antagonist, transdermal granisetron, has been developed, and approved by the FDA. Three phase I studies to evaluate its pharmacokinetic profile have shown that granisetron administered by a transdermal delivery system is absorbed by passive diffusion and maximal concentration is reached 48 hours after patch application. The patch of 52 cm2, which contains 34.3 mg of granisetron, releases 3.3 mg of the drug every day and maintains a stable average plasma concentration of 2.2 ng/mL over 6 days, similar to levels obtained with 2 mg of oral granisetron, administered every day during the same period of time. Two randomized as yet unpublished clinical trials (phase II/III have been conducted to evaluate the antiemetic efficacy of transdermal granisetron in chemotherapy-induced nausea and vomiting, in patients receiving moderately and highly emetogenic chemotherapy, compared with 2 mg of oral granisetron. More than 800 cancer patients were included in the trials. The rate of complete control of acute emesis was 49% for the phase II trial and 60% for the phase III trial. Neither trial showed a statistically significant difference between transdermal and oral granisetron. The control of delayed emesis was observed in 46% of patients, and there were no statistically significant differences between transdermal and oral granisetron. The most common adverse effects in both trials were constipation (<7% and headache (<1%; there were no statistically significant differences between transdermal and oral granisetron. These data show that transdermal granisetron is effective and safe in controlling acute emesis induced by chemotherapy with both moderate and high

Turning theory into practice: the development of modern transdermal drug delivery systems and future trends.

Science.gov (United States)

Perumal, O; Murthy, S N; Kalia, Y N

2013-01-01

Despite its remarkable barrier function, the skin remains an attractive site for systemic drug delivery given its easy accessibility, large surface area and the possibility to bypass the gastrointestinal tract and the liver and so modify drug absorption kinetics. The pioneering work of Scheuplein, Higuchi and others in the 1960s helped to explain the processes involved in passive percutaneous absorption and led to the development of mathematical models to describe transdermal drug delivery. The intervening years have seen these theories turned to practice and a significant number of transdermal systems are now available including some that employ active drug delivery. This review briefly discusses the evolution of transdermal therapeutic systems over the years and the potential of newer transdermal technologies to deliver hydrophilic drugs and macromolecules through the skin. © 2013 S. Karger AG, Basel.

Transport efficiency in transdermal drug delivery: What is the role of fluid microstructure?

Science.gov (United States)

Liuzzi, Roberta; Carciati, Antonio; Guido, Stefano; Caserta, Sergio

2016-03-01

Interaction of microstructured fluids with skin is ubiquitous in everyday life, from the use of cosmetics, lotions, and drugs, to personal care with detergents or soaps. The formulation of microstructured fluids is crucial for the control of the transdermal transport. In biomedical applications transdermal delivery is an efficient approach, alternative to traditional routes like oral and parenteral administration, for local release of drugs. Poor skin permeability, mainly due to its outer layer, which acts as the first barrier against the entry of external compounds, greatly limits the applicability of transdermal delivery. In this review, we focus on recent studies on the improvement of skin transport efficiency by using microemulsions (ME). Quantitative techniques, which are able to investigate both skin morphology and penetration processes, are also reviewed. ME are increasingly used as transdermal systems due to their low preparation cost, stability and high bioavailability. ME may act as penetration enhancers for many active principles, but ME microstructure should be chosen appropriately considering several factors such as ratio and type of ingredients and physic-chemical properties of the active components. ME microstructure is strongly affected by the flow conditions applied during processing, or during spreading and rubbing onto skin. Although the role played by ME microstructure has been generally recognized, the skin transport mechanisms associated with different ME microstructures are still to be elucidated and further investigations are required to fully exploit the potential of ME in transdermal delivery. Copyright © 2015 Elsevier B.V. All rights reserved.

Contribution of Central μ-Receptors to Switching Pulmonary C-Fibers-Mediated Rapid Shallow Breathing into An Apnea by Fentanyl in Anesthetized Rats

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Zhang, Zhenxiong; Zhang, Cancan; Zhuang, Jianguo; Xu, Fadi

2012-01-01

Our previous study has shown that activating peripheral μ-receptors is necessary for switching the bronchopulmonary C-fibers (PCFs)-mediated rapid shallow breathing (RSB) into an apnea by systemic administration of fentanyl. The brainstem nuclei, such as the medial nucleus tractus solitarius (mNTS) and the Pre-Botzinger Complex (PBC), are required for completing the PCF-mediated respiratory reflexes. Moreover, these areas contain abundant μ-receptors and their activation prolongs expiratory duration (TE). Thus, we asked if central μ-receptors, especially those in the mNTS and PBC, are involved in fully expressing this RSB-apnea switch by fentanyl. In anesthetized rats, the cardiorespiratory responses to right atrial injection of phenylbiguanide (PBG, 3–6 μg/kg) were repeated after: 1) fentanyl (iv), a μ-receptor agonist, alone (8 μg/kg, iv); 2) fentanyl following microinjection of naloxone methiodide (NXM, an opioid receptor antagonist) into the cisterna magna (10 μg/4 μl); 3) the bilateral mNTS (10 mM, 20 nl); or 4) PBC (10 mM, 20 nl). Our results showed that PBG shortened TE by 37 ± 6 % (RSB, from 0.41 ± 0.05 to 0.26 ± 0.03 s, P fentanyl (iv). Pretreatment with NXM injected into the cisterna magna or the PBC, but not the mNTS, prevented the fentanyl-induced switch. This study, along with our previous results mentioned above, suggests that although peripheral μ-receptors are essential for triggering the fentanyl-induced switch, central μ-receptors, especially those in the PBC, are required to fully exhibit such switch. PMID:22759907

Effect of fentanyl target-controlled infusions on isoflurane minimum anaesthetic concentration and cardiovascular function in red-tailed hawks (Buteo jamaicensis).

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Pavez, Juan C; Hawkins, Michelle G; Pascoe, Peter J; Knych, Heather K DiMaio; Kass, Philip H

2011-07-01

To determine the impact of three different target plasma concentrations of fentanyl on the minimum anaesthetic concentration (MAC) for isoflurane in the red-tailed hawk and the effects on the haemodynamic profile. Experimental study. Six healthy adult red-tailed hawks (Buteo jamaicensis) of unknown sex with body weights (mean ± SD) of 1.21 ± 0.15 kg. This study was undertaken in two phases. In the first phase anaesthesia was induced with isoflurane in oxygen via facemask and maintained with isoflurane delivered in oxygen via a Bain circuit. Following instrumentation baseline determination of the MAC for isoflurane was made for each animal using the bracketing method and a supramaximal electrical stimulus. End-tidal isoflurane concentration (E'Iso) was then set at 0.75 × MAC and after an appropriate equilibration period a bolus of fentanyl (20 μg kg(-1)) was administered intravenously (IV) in order to determine the pharmacokinetics of fentanyl in the isoflurane-anaesthetized red-tailed hawk. During the second phase anaesthesia was induced in a similar manner and E'Iso was set at 0.75 × MAC for each individual. Fentanyl was infused IV to achieve target plasma concentrations between 8 and 32 ng mL(-1). At each fentanyl plasma concentration, the MAC for isoflurane and cardiovascular variables were determined. Data were analyzed by use of repeated-measures anova. Mean ± SD fentanyl plasma concentrations and isoflurane MACs were 0 ± 0, 8.51 ± 4, 14.85 ± 4.82 and 29.25 ± 11.52 ng mL(-1), and 2.05 ± 0.45%, 1.42 ± 0.53%, 1.14 ± 0.31% and 0.93 ± 0.32% for the target concentrations of 0, 8, 16 and 32 ng mL(-1), respectively. At these concentrations fentanyl significantly (p = 0.0016) decreased isoflurane MAC by 31%, 44% and 55%, respectively. Dose had no significant effect on heart rate, systolic, diastolic or mean arterial blood pressure. Fentanyl produced a dose-related decrease of isoflurane MAC with minimal effects on measured cardiovascular parameters in

Safety of Intranasal Fentanyl in the Out-of-Hospital Setting

DEFF Research Database (Denmark)

Karlsen, Anders P H; Pedersen, Danny M B; Trautner, Sven

2014-01-01

: In this prospective observational study, we administered intranasal fentanyl in the out-of-hospital setting to adults and children older than 8 years with severe pain resulting from orthopedic conditions, abdominal pain, or acute coronary syndrome refractory to nitroglycerin spray. Patients received 1 to 3 doses...

Promotion of the transdermal delivery of protein drugs by N-trimethyl chitosan nanoparticles combined with polypropylene electret.

Science.gov (United States)

Tu, Ye; Wang, Xinxia; Lu, Ying; Zhang, He; Yu, Yuan; Chen, Yan; Liu, Junjie; Sun, Zhiguo; Cui, Lili; Gao, Jing; Zhong, Yanqiang

We recently reported that electret, which was prepared by a corona charging system with polypropylene film, could enhance the transdermal delivery of several drugs of low molecular weight. The aim of this study was to investigate whether electret could enhance the transdermal delivery of protein drugs by N -trimethyl chitosan nanoparticles (TMC NPs) prepared by an ionic gelation method. A series of experiments were performed, including in vitro skin permeation assays and anti-inflammatory effects, to evaluate the transdermal delivery of protein drugs by TMC NPs in the presence of electret. The results showed that in the presence of electret, the transdermal delivery of protein drugs in TMC NPs was significantly enhanced, as demonstrated by in vitro permeation studies and confocal laser scanning microscopy. Notably, superoxide dismutase-loaded TMC NPs combined with electret exhibited the best inhibitory effect on the edema of the mouse ear. TMC NPs combined with electret represent a novel platform for the transdermal delivery of protein drugs.

Exposure to time varying magnetic fields associated with magnetic resonance imaging reduces fentanyl-induced analgesia in mice

Energy Technology Data Exchange (ETDEWEB)

Teskey, G.C.; Prato, F.S.; Ossenkopp, K.P.; Kavaliers, M.

1988-01-01

The effects of exposure to clinical magnetic resonance imaging (MRI) on analgesia induced by the mu opiate agonist, fentanyl, was examined in mice. During the dark period, adult male mice were exposed for 23.2 min to the time-varying (0.6 T/sec) magnetic field (TVMF) component of the MRI procedure. Following this exposure, the analgesic potency of fentanyl citrate (0.1 mg/kg) was determined at 5, 10, 15, and 30 min post-injection, using a thermal test stimulus (hot-plate 50 degrees C). Exposure to the magnetic-field gradients attenuated the fentanyl-induced analgesia in a manner comparable to that previously observed with morphine. These results indicate that the time-varying magnetic fields associated with MRI have significant inhibitory effects on the analgesic effects of specific mu-opiate-directed ligands.

[11C]diclofenac sodium: synthesis and PET assessment of transdermal penetration

International Nuclear Information System (INIS)

Petroni, Debora; Menichetti, Luca; Sorace, Oreste; Poli, Michela; Vanasia, Massimo; Salvadori, Piero A.

2011-01-01

The aim of this work was to study the feasibility of using Positron Emission Tomography (PET) imaging as a new tool to detect transdermal penetration of topical drugs in human subjects. The compound used in the study is sodium 2-[(2,6-dichlorophenyl)amino]phenyl]acetate, better known as diclofenac sodium. This molecule belongs to the family of non-steroidal anti-inflammatory drugs and is considered one of the first choices among non-steroidal anti-inflammatory drugs for the treatment of inflammatory diseases; it is widely used and commercially present in a large number of pharmaceutical forms and formulations. 11 C-labeled diclofenac has been synthesized and coformulated, as an internal indicator, with a proprietary preparation based on the use of a sprayer. The radiolabeled preparation was topically administered to healthy volunteers, and PET imaging was used to evaluate transdermal penetration. Results obtained have demonstrated the efficacy of PET and radiolabeled tracers for the evaluation of transdermal penetration of active pharmaceutical ingredients as topical formulations.

Functionalization of Cotton Fabrics with Polycaprolactone Nanoparticles for Transdermal Release of Melatonin

Directory of Open Access Journals (Sweden)

Daniele Massella

2017-12-01

Full Text Available Drug delivery by means of transdermal patches raised great interest as a non-invasive and sustained therapy. The present research aimed to design a patch for transdermal delivery of melatonin, which was encapsulated in polycaprolactone (PCL nanoparticles (NPs by employing flash nanoprecipitation (FNP technique. Melatonin-loaded PCL nanoparticles were successfully prepared with precise control of the particle size by effectively tuning process parameters. The effect of process parameters on the particle size was assessed by dynamic light scattering for producing particles with suitable size for transdermal applications. Quantification of encapsulated melatonin was performed by mean of UV spectrophotometry, obtaining the estimation of encapsulation efficiency (EE% and loading capacity (LC%. An EE% higher than 80% was obtained. Differential scanning calorimetry (DSC analysis of NPs was performed to confirm effective encapsulation in the solid phase. Cotton fabrics, functionalized by imbibition with the nano-suspension, were analyzed by scanning electron microscopy to check morphology, adhesion and distribution of the NPs on the surface; melatonin transdermal release from the functionalized fabric was performed via Franz’s cells by using a synthetic membrane. NPs were uniformly distributed on cotton fibres, as confirmed by SEM observations; the release test showed a continuous and controlled release whose kinetics were satisfactorily described by Baker–Lonsdale model.

Modular reservoir concept for MEMS-based transdermal drug delivery systems

International Nuclear Information System (INIS)

Cantwell, Cara T; Wei, Pinghung; Ziaie, Babak; Rao, Masaru P

2014-01-01

While MEMS-based transdermal drug delivery device development efforts have typically focused on tightly-integrated solutions, we propose an alternate conception based upon a novel, modular drug reservoir approach. By decoupling the drug storage functionality from the rest of the delivery system, this approach seeks to minimize cold chain storage volume, enhance compatibility with conventional pharmaceutical practices, and allow independent optimization of reservoir device design, materials, and fabrication. Herein, we report the design, fabrication, and preliminary characterization of modular reservoirs that demonstrate the virtue of this approach within the application context of transdermal insulin administration for diabetes management. (technical note)

Modular reservoir concept for MEMS-based transdermal drug delivery systems

Science.gov (United States)

Cantwell, Cara T.; Wei, Pinghung; Ziaie, Babak; Rao, Masaru P.

2014-11-01

While MEMS-based transdermal drug delivery device development efforts have typically focused on tightly-integrated solutions, we propose an alternate conception based upon a novel, modular drug reservoir approach. By decoupling the drug storage functionality from the rest of the delivery system, this approach seeks to minimize cold chain storage volume, enhance compatibility with conventional pharmaceutical practices, and allow independent optimization of reservoir device design, materials, and fabrication. Herein, we report the design, fabrication, and preliminary characterization of modular reservoirs that demonstrate the virtue of this approach within the application context of transdermal insulin administration for diabetes management.

Biomaterials as novel penetration enhancers for transdermal and dermal drug delivery systems.

Science.gov (United States)

Chen, Yang; Wang, Manli; Fang, Liang

2013-01-01

The highly organized structure of the stratum corneum provides an effective barrier to the drug delivery into or across the skin. To overcome this barrier function, penetration enhancers are always used in the transdermal and dermal drug delivery systems. However, the conventional chemical enhancers are often limited by their inability to delivery large and hydrophilic molecules, and few to date have been routinely incorporated into the transdermal formulations due to their incompatibility and local irritation issues. Therefore, there has been a search for the compounds that exhibit broad enhancing activity for more drugs without producing much irritation. More recently, the use of biomaterials has emerged as a novel method to increase the skin permeability. In this paper, we present an overview of the investigations on the feasibility and application of biomaterials as penetration enhancers for transdermal or dermal drug delivery systems.

Transdermal administration of radiolabelled [14C]rotigotine by a patch formulation: A mass balance trial

NARCIS (Netherlands)

Cawello, W.; Wolff, H.M.; Meuling, W.J.A.; Horstmann, R.; Braun, M.

2007-01-01

Background and objective: The dopamine agonist rotigotine has been formulated in a silicone-based transdermal system for once-daily administration. The objective of the present study was to characterise the mass balance of rotigotine in humans after administration of a single transdermal patch

Penetration Enhancement Effect of Turpentine Oil on Transdermal ...

African Journals Online (AJOL)

inflammation drastically affect the quality of life after SCI. ... inhibitors may reduce spinal cord ischemic injury. [11]. Various .... Healthy male Wistar rats (200-250 g) were used ..... Guy RH. Transdermal science and technology an update.

Genome-wide association study identifies polymorphisms associated with the analgesic effect of fentanyl in the preoperative cold pressor-induced pain test

Directory of Open Access Journals (Sweden)

Kaori Takahashi

2018-03-01

Full Text Available Opioid analgesics are widely used for the treatment of moderate to severe pain. The analgesic effects of opioids are well known to vary among individuals. The present study focused on the genetic factors that are associated with interindividual differences in pain and opioid sensitivity. We conducted a multistage genome-wide association study in subjects who were scheduled to undergo mandibular sagittal split ramus osteotomy and were not medicated until they received fentanyl for the induction of anesthesia. We preoperatively conducted the cold pressor-induced pain test before and after fentanyl administration. The rs13093031 and rs12633508 single-nucleotide polymorphisms (SNPs near the LOC728432 gene region and rs6961071 SNP in the tcag7.1213 gene region were significantly associated with the analgesic effect of fentanyl, based on differences in pain perception latency before and after fentanyl administration. The associations of these three SNPs that were identified in our exploratory study have not been previously reported. The two polymorphic loci (rs13093031 and rs12633508 were shown to be in strong linkage disequilibrium. Subjects with the G/G genotype of the rs13093031 and rs6961071 SNPs presented lower fentanyl-induced analgesia. Our findings provide a basis for investigating genetics-based analgesic sensitivity and personalized pain control. Keywords: Opioid sensitivity, Analgesia, Fentanyl, Polymorphism, GWAS

Anti-cancer vaccination by transdermal delivery of antigen peptide-loaded nanogels via iontophoresis.

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Toyoda, Mao; Hama, Susumu; Ikeda, Yutaka; Nagasaki, Yukio; Kogure, Kentaro

2015-04-10

Transdermal vaccination with cancer antigens is expected to become a useful anti-cancer therapy. However, it is difficult to accumulate enough antigen in the epidermis for effective exposure to Langerhans cells because of diffusion into the skin and muscle. Carriers, such as liposomes and nanoparticles, may be useful for the prevention of antigen diffusion. Iontophoresis, via application of a small electric current, is a noninvasive and efficient technology for transdermal drug delivery. Previously, we succeeded in the iontophoretic transdermal delivery of liposomes encapsulating insulin, and accumulation of polymer-based nanoparticle nanogels in the stratum corneum of the skin. Therefore, in the present study, we examined the use of iontophoresis with cancer antigen gp-100 peptide KVPRNQDWL-loaded nanogels for anti-cancer vaccination. Iontophoresis resulted in the accumulation of gp-100 peptide and nanogels in the epidermis, and subsequent increase in the number of Langerhans cells in the epidermis. Moreover, tumor growth was significantly suppressed by iontophoresis of the antigen peptide-loaded nanogels. Thus, iontophoresis of the antigen peptide-loaded nanogels may serve as an effective transdermal delivery system for anti-cancer vaccination. Copyright © 2015 Elsevier B.V. All rights reserved.

Microneedles array with biodegradable tips for transdermal drug delivery

Science.gov (United States)

Iliescu, Ciprian; Chen, Bangtao; Wei, Jiashen; Tay, Francis E. H.

2008-12-01

The paper presented an enhancement solution for transdermal drug delivery using microneedles array with biodegradable tips. The microneedles array was fabricated by using deep reactive ion etching (DRIE) and the biodegradable tips were made to be porous by electrochemical etching process. The porous silicon microneedle tips can greatly enhance the transdermal drug delivery in a minimum invasion, painless, and convenient manner, at the same time; they are breakable and biodegradable. Basically, the main problem of the silicon microneedles consists of broken microneedles tips during the insertion. The solution proposed is to fabricate the microneedle tip from a biodegradable material - porous silicon. The silicon microneedles are fabricated using DRIE notching effect of reflected charges on mask. The process overcomes the difficulty in the undercut control of the tips during the classical isotropic silicon etching process. When the silicon tips were formed, the porous tips were then generated using a classical electrochemical anodization process in MeCN/HF/H2O solution. The paper presents the experimental results of in vitro release of calcein and BSA with animal skins using a microneedle array with biodegradable tips. Compared to the transdermal drug delivery without any enhancer, the microneedle array had presented significant enhancement of drug release.