Sorajja, Dan; Munger, Thomas M.; Shen, Win-Kuang
Abstract Electrical storm, defined as 3 or more separate episodes of ventricular tachycardia or ventricular fibrillation within 24 hours, carries significant morbidity and mortality. These unstable ventricular arrhythmias have been described with a variety of conditions including ischemic heart disease, structural heart disease, and genetic conditions. While implantable cardioverter defibrillator implantation and ablation may be indicated and required, antiarrhythmic medication remains an imp...
Fauchier, L; Zannad, N; Clementy, N; Pierre, B; Cosnay, P; Babuty, D
In atrial fibrillation (AF), the absence of a clear benefit of a rhythm-control strategy over a rate-control strategy seen in recent trials may be due to the fact that many of the usual antiarrhythmic strategy have significant weaknesses. Besides research efforts to improve the efficacy and safety of conventional antiarrhythmic agents, therapies directed 'upstream'of the electrical aspects of AF, towards the underlying anatomical substrate and atrial remodelling, have been proposed as new pharmacological therapeutic approaches. Potential upstream therapies for AF comprise a variety of agents such as angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB), statins, N-3 polyunsaturated fatty acids and steroids. On the basis of experimental data, clinical studies have provided information on the potential of upstream therapy for the prevention of AF across a broad spectrum of cardiovascular patient groups. In patients with heart failure or hypertension, data are sufficient to support the use of ACEI or ARB as treatment that may decrease the risk of AF beyond their other beneficial effects. Similarly, it is highly possible that the use of statin in patients with a recognized indication may be associated with a benefit against AF. However, in most clinical settings, the evidence appears to be insufficient to drive changes in therapy management per se, and large-scale, randomized controlled trials with adequately defined endpoints are still needed. The results from these trials may help to understand the complex mechanisms that lead to AF, and may clarify the benefit-to-risk ratio of these new therapeutic approaches. PMID:21211623
Hon-Chi Lee; Kristin TL Huang; Win-Kuang Shen
Human aging is a global issue with important implications for current and future incidence and prevalence of health conditions and disability.Cardiac arrhythmias,including atrial fibrillation,sudden cardiac death,and bradycardia requiring pacemaker placement,all increase exponentially after the age of 60.It is important to distinguish between the normal,physiological consequences of aging on cardiacelectrophysiology and the abnormal,pathological alterations.The age-related cardiac changes include ventricular hypertrophy,senileamyloidosis,cardiac valvular degenerative changes and annular calcification,fibrous infiltration of the conduction system,and loss of naturalpacemaker cells and these changes could have a profound effect on the development of arrhythmias.The age-related cardiac electrophysiological changes include up- and down-regulation of specific ion channel expression and intracellular Ca2+ overload which promote the development of cardiac an-hythmias.As ion channels are the substrates of antiarrhythmic drugs,it follows that the pharmacoldnetics and pharmacodynamics of these drugs will also change with age.Aging alters the absorption,distribution,metabolism,and elimination of antiarrhythmic drugs,so liver and kidney function must be monitored to avoid potential adverse drug effects,and antiarrhythmic dosing may need to be adjusted for age.Elderly patients are also more susceptible to the side effects of many antiarrhythmics,including bradycardia,orthostatic hypotension,urinary retention,and falls.Moreover,the choice of antiarrhythmic drugs in the elderly patient is frequently complicated by the presence of co-morbid conditions and by polyphanmacy,and the astute physician must pay careful attention to potential drug-drug interactions.Finally,it is important to remember that the use of antiarrhythmic drugs in elderly patients must be individualized and tailored to each patient's physiology,disease processes,and medication regimen.
Mark D McCAULEY; Xander H T WEHRENS
Antiarrhythmic drugs are a group of pharmaceuticals that suppress or prevent abnormal heart rhythms, which are often associated with substantial morbidity and mortality. Current antiarrhythmic drugs that typically target plasma membrane ion channels have limited clinical success and in some cases have been described as being pro-arrhythmic. However, recent studies suggest that pathological release of calcium (Ca2+) from the sarcoplasmic reticulum via cardiac ryanodine receptors (RyR2) could represent a promising target for antiarrhythmic therapy. Diastolic SR Ca2+ release has been linked to arrhythmogenesis in both the inherited arrhythmia synSeveral classes of pharmaceuticals have been shown to reduce abnormal RyR2 activity and may confer protection against triggered arrhythmias through reduction of SR Ca2+ leak. In this review, we will evaluate the current pharmacological methods for stabilizing RyR2 and suggest treatment modalities based on current evidence of molecular mechanisms.
Převorovská, Světlana; Maršík, František
Plzeň : Západočeská univerita, 2007, s. 1-2. ISBN 978-80-7043-607-3. [IMACS 2007. Plzeň (CZ), 10.09.2007-13.09.2007] R&D Projects: GA ČR(CZ) GA106/03/0958; GA ČR GA106/03/1073 Institutional research plan: CEZ:AV0Z20760514 Keywords : cardiac energetics * antiarrhythmic drugs * numerical simulation Subject RIV: BK - Fluid Dynamics
Dorian, P; Newman, D
Most patients with a history of sustained ventricular tachycardia (VT) or ventricular fibrillation (VF) are at high risk of recurrence. Implanted defibrillators (ICDs) are highly effective in sensing and converting VT or VF to a perfusing rhythm. "Conventional" antiarrhythmic agents, which primarily block cardiac sodium channels, are relatively ineffective in preventing arrhythmia recurrence; amiodarone and sotalol appear to be effective in reducing recurrence and mortality rates, although the extent of benefit is not well understood. Despite the apparent advantage of ICDs, they have short- and long-term complications, are costly, and their benefit in prolonging the quantity or quality of life remains unproven. Randomized clinical trials which compare the effect of ICDs with that of antiarrhythmic drugs on mortality, cost, and quality of life will be necessary to understand how patients with malignant arrhythmias ought to be treated. If an ICD is implanted, adjunctive therapies need to be considered to treat the underlying heart disease and to derive optimum benefit from the device. Drugs may have beneficial or adverse interactions with devices, and the full understanding of these interactions requires further study. PMID:8269662
Claudio Tondo; Corrado Carbucicchio; Antonio Dello Russo; Benedetta Majocchi; Martina Zucchetti; Francesca Pizzamiglio; Fabrizio Bologna; Fabio Cattaneo; Daniele Colombo; Eleonora Russo; Michela Casella
Full Text Available Introduction Ventricular tachycardia or frequent premature ventricular contractions (PVCs can occur in the absence of any detectable structural heart disease. In this clinical setting, these arrhythmias are termed idiopathic. Usually, they carry a benign prognosis and any potential ablative intervention is carried out if patients are highly symptomatic or, more importantly, if frequent ventricular arrhythmias can lead to ventricular dysfunction. Methods In this paper, different forms of idiopathic ventricular tachycardia are reviewed. Outflow tract ventricular tachycardia from the right ventricle is the most frequent form of the so-called idiopathic ventricular tachycardia. Other forms of idiopathic ventricular arrhythmias include ventricular tachycardia/PVCs arising from tricuspid annulus, from the mitral annulus, inter-fascicular ventricular tachycardia and papillary muscle ventricular tachycardia. When interventional treatment is deemed necessary, detailed mapping ( earliest activation during VT/PVC, pace mapping is crucial as to identify the successful ablation site. Catheter ablation more than antiarrhythmic drug treatment is usually highly effective in eliminating idiopathic ventricular arrhythmias and providing prevention of recurrence. Conclusion Idiopathic VTs are not considered life-threatening arrhythmias and, prevention of recurrences is often achieved by means of catheter ablation that provides an improvement of quality of life. The overall acute success rate of catheter ablation is about 85-90% with a long–term prevention of arrhythmia recurrence of about 75-80%. It is advisable that the procedure is carried out by electrophysiologists with expertise in VT catheter ablation and extensive knowledge of cardiac anatomy as to ensure a high success rate and reduce the likelihood of major complications.
Rusinova, Radda; Koeppe, Roger E; Andersen, Olaf S
Amiodarone is a widely prescribed antiarrhythmic drug used to treat the most prevalent type of arrhythmia, atrial fibrillation (AF). At therapeutic concentrations, amiodarone alters the function of many diverse membrane proteins, which results in complex therapeutic and toxicity profiles. Other antiarrhythmics, such as dronedarone, similarly alter the function of multiple membrane proteins, suggesting that a multipronged mechanism may be beneficial for treating AF, but raising questions about how these antiarrhythmics regulate a diverse range of membrane proteins at similar concentrations. One possible mechanism is that these molecules regulate membrane protein function by altering the common environment provided by the host lipid bilayer. We took advantage of the gramicidin (gA) channels' sensitivity to changes in bilayer properties to determine whether commonly used antiarrhythmics--amiodarone, dronedarone, propranolol, and pindolol, whose pharmacological modes of action range from multi-target to specific--perturb lipid bilayer properties at therapeutic concentrations. Using a gA-based fluorescence assay, we found that amiodarone and dronedarone are potent bilayer modifiers at therapeutic concentrations; propranolol alters bilayer properties only at supratherapeutic concentration, and pindolol has little effect. Using single-channel electrophysiology, we found that amiodarone and dronedarone, but not propranolol or pindolol, increase bilayer elasticity. The overlap between therapeutic and bilayer-altering concentrations, which is observed also using plasma membrane-like lipid mixtures, underscores the need to explore the role of the bilayer in therapeutic as well as toxic effects of antiarrhythmic agents. PMID:26573624
B. Jáuregui-Garrido; Jáuregui-Lobera, I
Objective: A drug interaction is defined as any alteration, pharmacokinetics and/or pharmacodynamics, produced by different substances, other drug treatments, dietary factors and habits such as drinking and smoking. These interactions can affect the antiarrhythmic drugs, altering their therapeutic efficacy and adverse effects. The aim of this study was to conduct a review of available data about interactions between antiarrhythmic drugs and food. Methods: The purpose of this review was to rep...
Yasuda, M.; Nakazato, Y.; Yamashita, H.; Sekita, G; Kawano, Y.; Mineda, Y; Nakazato, K.; Tokano, T; Sumiyoshi, M; Nakata, Y.
Electrocardiographic changes were evaluated retrospectively in five patients without previous episodes of syncope or ventricular fibrillation who developed abnormal ST segment elevation mimicking the Brugada syndrome in leads V1-V3 after the administration of class Ic antiarrhythmic drugs. Pilsicainide (four patients) or flecainide (one patient) were administered orally for the treatment of symptomatic paroxysmal atrial fibrillation or premature atrial contractions. The QRS duration, QTc, and...
Padmavathy, B; Niranjali, S; Devaraj, H
Administration of single dose (175 mg/kg body wt) of amiodarone dissolved in water through gavage for 3 weeks damaged the lung and changed the content of lung lavage. Activities of bronchoalveolar lavage (BAL) angiotensin converting enzyme (ACE) and lactate dehydrogenase (LDH) increased significantly. Also, the protein and lactate content of the lavage fluid increased significantly over the control. The drug also produced marked changes in morphology of the lung of experimental animals. PMID:1459640
Převorovská, Světlana; Maršík, František
Brno : Brno University of Technology, 2006 - (Burša, J.; Fuis, V.), s. 170-171 ISBN 80-214-3232-2. [ Human Biomechanics 2006. Hrotovice (CZ), 13.11.2006-16.11.2006] R&D Projects: GA ČR(CZ) GA106/03/1073; GA ČR(CZ) GA106/03/0958 Institutional research plan: CEZ:AV0Z20760514 Keywords : human cardiovascular system * cardiac action potential * antiarrhytmmic drugs-cell channel interaction Subject RIV: BK - Fluid Dynamics
Yu. A. Bunin
Full Text Available Highlights of primary prevention of death in patients with ventricular arrhythmias (VA are discussed. Overview of all main clinical trials exploring various anti-arrhythmic drugs in prevention of death in patients with VA is presented. It is emphasized that in patients with organic heart disease and VA only beta-blockers and amiodarone are able to reduce mortality, while other drugs have no effect on mortality, or they even increase mortality mainly due to arrhythmogenic effect. Recent clinical studies of the cardioverter-defibrillators efficacy in these patients are presented. It is shown that the use of cardioverter defibrillators compared with pharmacotherapy is more effective in prevention of fatal outcomes.
Matějovič, P.; Bahníková, M.; Pásek, Michal; Šimurdová, M.; Šimurda, J.
Brno : Brno University of Technology, 2002 - (Jan, J.; Kozumplík, J.; Provazník, I.), s. 214-216 ISBN 80-214-2633-0. ISSN 1211-412X. [Biosignal 2002. Brno (CZ), 26.06.2002-28.06.2002] Institutional research plan: CEZ:AV0Z2076919 Keywords : cardiac cell * sodium current * antiarrhythmic drugs Subject RIV: BO - Biophysics
Elming, Hanne; Brendorp, Bente; Pehrson, Steen;
relief. Since many patients experience a decrease in physical performance as well as a diminished quality of life during arrhythmia there is still a need for antiarrhythmic drug therapy. The development of new antiarrhythmic agents has changed the focus from class I to class III agents since it became...... evident that with class I drug therapy the prevalence of mortality is considerably higher. This review focuses on the benefits and risks of known and newer class III antiarrhythmic agents. The benefits discussed include the ability to maintain sinus rhythm in persistent atrial fibrillation patients, and...... reducing the need for implantable cardioverter defibrillator shock/antitachycardia therapy, since no class III antiarrhythmic agents have proven survival benefit. The risks discussed mainly focus on pro-arrhythmia as torsade de pointes ventricular tachycardia....
Brendorp, Bente; Pedersen, Oledyg; Torp-Pedersen, Christian;
With beta-blockers as the exception, increasing doubt is emerging on the value of antiarrhythmic drug therapy following a series of trials that have either shown no mortality benefit or even an excess mortality. Vaughan Williams class I drugs are generally avoided in patients with structural hear...
Full Text Available Objective: A drug interaction is defined as any alteration, pharmacokinetics and/or pharmacodynamics, produced by different substances, other drug treatments, dietary factors and habits such as drinking and smoking. These interactions can affect the antiarrhythmic drugs, altering their therapeutic efficacy and adverse effects. The aim of this study was to conduct a review of available data about interactions between antiarrhythmic drugs and food. Methods: The purpose of this review was to report an update of the existing literature data on the main findings with respect to food and antiarrhythmic drugs interactions by means of a search conducted in PubMed, which yielded a total of 250 articles initially. Results: After excluding different articles which were not focusing on the specific objective, the main results refer to interactions among antiarrhythmic drugs and food in general, grapefruit juice, and others like fibre or medicinal plants. Discussion: Food may affect the bioavailability of antiarrhythmic drugs and in some specific cases (dairy products, rich-in-protein diets, grapefruit juice, this should be carefully considered. The best recommendation seems to advise patients to remove the grapefruit juice from their diet when treatment with these drugs. Fibre should be separated from taking these drugs and regarding medicinal plants and given their increased use, the anamnesis must include information about its use, the reason for that use and what types of plants are used, all in order to give the corresponding recommendations.Objetivo: La interacción de medicamentos se define como cualquier alteración, farmacocinética y/o farmacodinámica, producida por diferentes sustancias, otros tratamientos, factores dietéticos y hábitos como beber y fumar. Estas interacciones pueden afectar a los fármacos antiarrítmicos, alterando su eficacia terapéutica y sus efectos adversos. El objetivo de este estudio fue realizar una revisión de los
Raatikainen, M J Pekka; Hakalahti, Antti; Uusimaa, Paavo; Nielsen, Jens Cosedis; Johannessen, Arne; Hindricks, Gerhard; Walfridsson, Håkan; Pehrson, Steen; Englund, Anders; Hartikainen, Juha; Kongstad, Ole; Mortensen, Leif Spange; Hansen, Peter Steen
BACKGROUND: The Medical ANtiarrhythmic Treatment or Radiofrequency Ablation in Paroxysmal Atrial Fibrillation (MANTRA-PAF) is a randomized trial comparing radiofrequency catheter ablation (RFA) to antiarrhythmic drugs (AADs) as first-line treatment of paroxysmal atrial fibrillation (PAF). In order...... events between the RFA, AAD and crossover groups (19% vs. 8% vs. 23%) (P=0.10). CONCLUSIONS: In the treatment of antiarrhythmic therapy naïve patients with PAF long-term efficacy of RFA was superior to AAD therapy. Thus, it is reasonable to offer RFA as first-line treatment for highly symptomatic...
IRAJ NAZERY; ARCHIMEDES SANATY
Propafenone HCI (p), is a relatively new Class IC antiarrhythmic agent. It has been reported to be superior to conventional antiarrhythmics in the control of supraventricular, ventricular and WPW associated tachyarrhythmias. It has been also shown to be well tolerated. In our study protocol, which extends over 2~ years period , we used (p) in 87 patients for management of various types of cardiac arrhythmias (most of whom were resistant to conventmonal antiarrhythmics) . Intravenously adminis...
Spath, Marian A.; Bernie J. O'Brien
The implantable cardioverter defibrillator (ICD) is a therapy for patients at risk of sudden cardiac death due to ventricular tachycardia (VT) or ventricular fibrillation (VF). But the apparent high cost of ICD therapy relative to antiarrhythmic drugs such as amiodarone has raised questions about the cost effectiveness of ICD therapy versus drug therapy. To inform this debate we reviewed the literature on ICD cost effectiveness. An electronic and manual search was conducted for articles publi...
Full Text Available Background. Atrial fibrillation (AF is the most common form of arrhythmia. Several trials have suggested that acupuncture may prevent AF. However, the efficacy of acupuncture for AF prevention has not been well investigated. Therefore, we designed a prospective, two-parallel-armed, participant and assessor blinded, randomized, sham-controlled clinical trial to investigate acupuncture in persistent AF (ACU-AF. Methods. A total of 80 participants will be randomly assigned to active acupuncture or sham acupuncture groups in a 1 : 1 ratio. Both groups will take the same antiarrhythmic medication during the study period. Patients will receive 10 sessions of acupuncture treatment once a week for 10 weeks. The primary endpoint is AF recurrence rate. Secondary endpoints are left atrium (LA and left atrial appendage (LAA changes in function and volume, and inflammatory biomarker changes. Ethics. This study protocol was approved by the institutional review boards (IRBs of Kyung Hee University Hospital (number 1335-04. This trial is registered with clinicaltrials.gov NCT02110537.
Mow, Tomas; Frederiksen, Kristen; Thomsen, Morten B.
Torsades de Pointes (TdP) is a potentially lethal cardiac arrhythmia and a known adverse effect of many drugs secondary to block of the rapidly activating delayed rectifier potassium current (IKr). In animal models antipsychotic drugs have shown reduced pro-arrhythmic potential compared to drugs...
Nabar, A; Rodriguez, L.; Timmermans, C; van Mechelen, R; Wellens, H
OBJECTIVE—To describe the electrocardiographic and electrophysiological findings of new atrial flutter developing in patients taking class IC antiarrhythmic drugs for recurrent atrial fibrillation, and to report the long term results of right atrial isthmus ablation in relation to the ECG pattern of spontaneous atrial flutter. DESIGN—Retrospective analysis. SETTING—Tertiary care academic hospital. PATIENTS—24 consecutive patients with atrial fibrillation (age 54 (12) years; 5 female, 19 male)...
Full Text Available Propafenone HCI (p, is a relatively new Class IC antiarrhythmic agent. It has been reported to be superior to conventional antiarrhythmics in the control of supraventricular, ventricular and WPW associated tachyarrhythmias. It has been also shown to be well tolerated. In our study protocol, which extends over 2~ years period , we used (p in 87 patients for management of various types of cardiac arrhythmias (most of whom were resistant to conventmonal antiarrhythmics . Intravenously administered, (P was effective in 85% of patients with paroxysmal reentrant supraventricular tachycardia (PRSVT, 75% of those with paroxysmal atrial fibrillation (PAF , 50% and 42% of those with refractory premature ventricular contractions (PVC and ventricular tachycardia (V. Tach, respectively. Orally administered, (P was effective in 73% of those with resistant PVCs and nonsustained ventricular tachycardia (NSV Tach, and 75% of those with resistant sustained ventricular tachycardia (RSVT •
Full Text Available The adenylyl cyclase (AC signaling system plays a crucial role in the regulation of cardiac contractility. Here we analyzed the key components of myocardial AC signaling in the developing chick embryo and assessed the impact of selected β-blocking agents on this system. Application of metoprolol and carvedilol, two commonly used β-blockers, at embryonic day (ED 8 significantly downregulated (by about 40% expression levels of AC5, the dominant cardiac AC isoform, and the amount of Gsα protein at ED9. Activity of AC stimulated by forskolin was also significantly reduced under these conditions. Interestingly, when administered at ED4, these drugs did not produce such profound changes in the myocardial AC signaling system, except for markedly increased expression of Giα protein. These data indicate that β-blocking agents can strongly derange AC signaling during the first half of embryonic heart development.
Ngo, Son Tung; Fang, Shang-Ting; Huang, Shu-Hsiang; Chou, Chao-Liang; Huy, Pham Dinh Quoc; Li, Mai Suan; Chen, Yi-Cheng
Alzheimer's disease (AD) is the most common form of dementia caused by the formation of Aβ aggregates. So far, no effective medicine for the treatment of AD is available. Many efforts have been made to find effective medicine to cope with AD. Curcumin is a drug candidate for AD, being a potent anti-amyloidogenic compound, but the results of clinical trials for it were either negative or inclusive. In the present study, we took advantages from accumulated knowledge about curcumin and have screened out four compounds that have chemical and structural similarity with curcumin more than 80% from all FDA-approved oral drugs. Using all-atom molecular dynamics simulation and the free energy perturbation method we showed that among predicted compounds anti-arrhythmic medication propafenone shows the best anti-amyloidogenic activity. The in vitro experiment further revealed that it can inhibit Aβ aggregation and protect cells against Aβ induced cytotoxicity to almost the same extent as curcumin. Our results suggest that propafenone may be a potent drug for the treatment of Alzheimer's disease. PMID:27304669
Aslam, Arif; Griffiths, Christopher E M
This article explores the current and emerging therapies for skin disease, with a particular focus on chronic plaque psoriasis and metastatic malignant melanoma. We discuss the current biological therapies used for psoriasis and those on the horizon, including small molecules and biosimilars. We also summarise the recent advances in the use of novel therapeutic agents in other dermatological diseases and outline the promise of translational research and stratified medicine approaches in dermatology. Better matching of patients with therapies is anticipated to have a major effect on both clinical practice and the development of new drugs and diagnostics. PMID:24532745
Koskela, Heikki; Naaranlahti, Toivo
An efficient therapy for cough usually requires identification and treatment of the underlying disease, like asthma. However an underlying disease in cough is not found in all cases and conventional treatment of the underlying disease is ineffective against cough. Drug therapy options are available also for these situations. Honey or menthol can be tried for cough associated with respitatory infections, antihistamines for cough associated with allergic rhinitis, blockers of the leukotriene receptor or muscarinic receptor for asthma-associated cough and morphine for cough associated with a malignant disease. Menthol, blockers of the muscarinic receptor, or dextrometorphan can be tried for prolonged idiopathic cough. Codeine is not necessary in the treatment of cough. Refraining from drug treatment should always be considered. PMID:27089619
The prevalence of atrial fibrillation (AF) is extensively increased. AF can cause a number of clinical serious outcomes, including stroke, life quantity and movable ability descent, hospitalization rate increment, left ventricular dysfunction and death. Based on updated clinical evidence, this review presents a solution for the treatment strategy of antiarrhythmic drugs in AF patients.%房颤(AF)病例分布广,发病率增长快,相关临床后果严重,如脑卒中、生活质量及活动能力下降、住院率增加、左室功能下降乃至死亡等.对AF患者的抗心律失常药物治疗,必须面对两种治疗策略的选择.本文综合近期陆续发表的一些临床研究结果,初步探讨临床治疗策略选择.
Full Text Available En la valoración de la Intoxicación Medicamentosa Aguda (IMA en pacientes graves con dosis potencialmente no tóxicas del teórico fármaco responsable es importante insistir en la anamnesis en la coingesta de otros fármacos o tóxicos. Inicialmente se prestará atención a las medidas de soporte vital, oxigenando, protegiendo la vía aérea y expandiendo la volemia. El ECG es una herramienta diagnóstica de primer orden en las IMA, sobre todo por antidepresivos tricíclicos (ADT y medicación cardiovascular. Su monitorización continua durante las primeras 12-24 horas suele ser necesaria en la mayoría de los casos. Las benzodiacepinas no suelen producir intoxicaciones graves. El uso del flumazenilo se reservará a los casos de depresión respiratoria, coma profundo o de causa no filiada. Pueden dar lugar a convulsiones, sobre todo en caso de intoxicación mixta con antidepresivos, y síndrome de abstinencia. Los ADT poseen una potencial gravedad enorme, pudiendo originar arritmias mortales. El rango terapéutico del litio es muy estrecho, pudiendo producirse signos de toxicidad fundamentalmente digestiva y neurológica. En caso de intoxicación por digoxina, se considerará el uso de anticuerpos antidigital en caso de bradiarritmias graves, bloqueos AV o PCR. El glucagón es el antídoto para la intoxicación grave por ß-bloqueantes y para la hipotensión refractaria en caso de calcioantagonistas.In the evaluation of Acute Drug Poisoning (ADP in patients seriously ill with a potentially non-toxic dose of the drug that is theoretically responsible, it is important to insist on anamnesis in the coingestion of other drugs or toxics. Initially attention is given to life support measures, oxygenation, protection of the airway and expanding the volemia. The ECG is a diagnostic tool of the first order in ADPs, above all for tricyclic antidepressants (TAD and cardio-vascular drugs. In the majority of cases continuous monitoring is usually
Osteoarthritis is one of the most common and economically important chronic diseases amongst adults, especially those of a senior age. There now exists a range of effective medications, which either alone or in combination can alleviate the symptoms of the disease and improve the quality of life. Because these medications are not always sufficiently effective and must sometimes be interrupted due to side effects, a large arsenal of active agents is necessary. Alleviation of pain and inhibition of inflammation are the primary goals of pharmacotherapy, whereby the objective is to return an active or transiently painful, decompensated osteoarthritis to a latent (silent, pain-free) condition. This therapeutic goal can almost always be accomplished by using analgesics, nonsteroidal anti-inflammatory drugs (NSAIDs), or intraarticular injection of glucocorticoids. The main problem in administering NSAIDs is their gastrointestinal toxicity,for which a prophylactic medication (e.g., simultaneous application of misoprostol or switching to a COX-2 selective NSAID) should be considered especially with risk groups. The newly developed COX-2 selective NSAIDs represent a true enrichment of our therapeutic options. The spectrum of indications for COX-2 selective NSAIDs should in the future correspond to that of older NSAID preparations, providing that no as yet unknown and serious side effects come to light from their use. Pharmacological results published until now confirm that a clinically relevant analgesic and/or anti-inflammatory effect is associated with the use of SYSA-DOAs (symptomatic slow acting drugs in osteoarthritis). However, no clinical studies exist which can positively confirm prevention of morphologically recognizable cartilage defects in man, or a slowing down or reversal of any progressively developing joint cartilage destruction by any individual medication. Neither the benefits, risks, pharmaceutical quality, nor composition of Orthokin are known, and for
Sumkauskaite, M; Bryant, M; Kortes, N; Stampfl, U; Radeleff, B
In the context of pre-interventional drug therapy, a premedication is given to patients who are known to have an allergy to contrast media, have renal impairment or hyperthyroidism. An already existing anticoagulation therapy, in anticipation of the planned intervention, must be reviewed and changed or even suspended as required. For peri-interventional drug therapy it is important to consider how strenuous the procedure will be as well as the general condition of the patient. Further discussion with anesthetists may be required for the planning of pain therapy or sedation during the procedure. These factors help to ensure maximum patient comfort as well as the success of the intervention. Post-interventional anticoagulation therapy, usually started peri-interventionally, plays an important role in minimizing the risk of acute thrombosis as well as in maintaining long-term functioning of the implanted material. The form of the anticoagulation therapy is set according to the type of intervention. PMID:26063076
The drug used in diarrhea must be effective in that they reduce the secretion and increase the absorption of the intestinal mucosa. This seems to be only possible with morphine derivatives. But these are not recommended as they may cause ileus. Antibiotics are indicated in only few cases of severe intestinal infections. Other frequently used drugs such as adsorbents are practically of no effect. Thus, rehydration, electrolyte substitution and realimentation remain the most effective method of...
Full Text Available The drug used in diarrhea must be effective in that they reduce the secretion and increase the absorption of the intestinal mucosa. This seems to be only possible with morphine derivatives. But these are not recommended as they may cause ileus. Antibiotics are indicated in only few cases of severe intestinal infections. Other frequently used drugs such as adsorbents are practically of no effect. Thus, rehydration, electrolyte substitution and realimentation remain the most effective method of treatment of acute diarrhea in infants.
Buclin, Thierry; Gotta, Verena; Fuchs, Aline; Widmer, Nicolas; Aronson, Jeffrey
Drug development has improved over recent decades, with refinements in analytical techniques, population pharmacokinetic-pharmacodynamic (PK-PD) modelling and simulation, and new biomarkers of efficacy and tolerability. Yet this progress has not yielded improvements in individualization of treatment and monitoring, owing to various obstacles: monitoring is complex and demanding, many monitoring procedures have been instituted without critical assessment of the underlying evidence and rationale, controlled clinical trials are sparse, monitoring procedures are poorly validated and both drug manufacturers and regulatory authorities take insufficient account of the importance of monitoring. Drug concentration and effect data should be increasingly collected, analyzed, aggregated and disseminated in forms suitable for prescribers, along with efficient monitoring tools and evidence-based recommendations regarding their best use. PK-PD observations should be collected for both novel and established critical drugs and applied to observational data, in order to establish whether monitoring would be suitable. Methods for aggregating PK-PD data in systematic reviews should be devised. Observational and intervention studies to evaluate monitoring procedures are needed. Miniaturized monitoring tests for delivery at the point of care should be developed and harnessed to closed-loop regulated drug delivery systems. Intelligent devices would enable unprecedented precision in the application of critical treatments, i.e. those with life-saving efficacy, narrow therapeutic margins and high interpatient variability. Pharmaceutical companies, regulatory agencies and academic clinical pharmacologists share the responsibility of leading such developments, in order to ensure that patients obtain the greatest benefit and suffer the least harm from their medicines. PMID:22360377
Various treatment modalities of acute and chronic pain have been an area of interest of medicine and investigators for centuries. There are two major classes of drugs that are used to control pain: opioid and non-opioid analgesics. They could be used in the case of monotherapy or combination therapy in pain management. However, these agents are not accepted as ideal drugs in clinical approaches against pain because of their serious side effects such as development of tolerance and addiction, ...
Vandemark, F. L.
Liquid chromatography has become a major analytical technique in the laboratory concerned with therapeutic drug monitoring. This acceptance arises from a number of important factors, including the unusual versatility of the technique, its potential use in the routine determination of drug substances, and the nondestructive nature of the detection systems commonly used.
Yan, Hong; Zeng, Fanyi
Hemophilia B is an X chromosome linked hereditary hemorrhagic disease, which is caused by the lose function mutation of factor IX (FIX), and significantly affects the patients' lifespan and life quality. The severity of hemophilia B depends on the FIX level in the plasma. By referring to the relevant literatures, we reviewed and summarized hemophilia B replacement therapies. Specifically, we focus on recombinant factor IX products on the market and those in the pipeline, especially on the long-acting factor IX drugs, to provide the basis for researches of new hemophilia B drugs. PMID:27382766
Jia, Jingying; Liu, Gangyi; Zhang, Mengqi; Lu, Youli; Lu, Chuan; Liu, Yun; Zheng, Hongcao; Wang, Wei; Gui, Yuzhou; Yu, Chen; Li, Shuijun; Wang, Yiping
Sulcardine sulfate (Sul), a novel antiarrhythmic agent, is currently in phase I and phase II clinical trials. To elucidate its clinical pharmacokinetic characteristics, a rapid and accurate liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed and validated for the quantification of Sul in human plasma. Plasma samples were precipitated by acetonitrile and isotope-labeled sulcardine was added as internal standard. The analysis was carried out on a Capcell Pak C18 MG III column (100 × 2.0 mm, 5 μm) with 0.1% formic acid in acetonitrile solution and water (17:83, v/v) as mobile phase. The linear range was 5.0-1000 ng/mL for Sul, with a lower limit of quantification of 5.0 ng/mL. The intra- and inter-batch CVs were within ±11.0% and the accuracies were 4.9-107.3%. Our method, for the first time, allows the rapid (only 3.0 min) and accurate quantification of Sul in human plasma. The method has been successfully applied in the pharmacokinetic study of Sul in a clinical trial following oral administration of Sul to healthy volunteers. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26715470
Knowing some basic principles about medicines would help patients to understand drug therapy and to help and encourage them to use it well. These principles relate to the categories and names of drugs, their different uses, how they reach the site of action (absorption, distribution, fate), how they produce their effects, both beneficial and harmful, the time courses of drug actions, how the pattern and intensity of the effects of a drug depend on dose and timing, drug interactions, how drug effects are demonstrated and investigated and sources of information and their trustworthiness. These basic principles are an essential part of health literacy and understanding them would enable individuals to comprehend better the information that they are likely to receive about medicines that they will take. Different populations need different types of education. For schoolchildren, the principles could fit into biology and domestic science teaching, starting in the later years of primary school or early in secondary school. A teaching package would also be needed for their teachers. For adults, web-based learning seems the most practical option. Web-based programmes could be supported by the NHS and professional bodies and through public libraries and local community health services. Specific groups for targeting could include young mothers and carers of chronically ill people. For retired people, one could envisage special programmes, perhaps in collaboration with the University of the Third Age. Conversations between patients and professionals would then become more effective and help shared decision making. PMID:22360596
R. D. Kurbanov
Full Text Available Aim. To assess propafenone antiarrhythmic efficacy and optimal timing of the drug administration for relief of persistent atrial fibrillation (PAF. Material and methods. 24 patients (19 men, 5 women, aged 53,8±13,3 with PAF (duration is more than 7 days were included in the study. PAF was confirmed clinically as well as by ECG and daily ECG monitoring. Indications for sinus rhythm recovery by propafenone were defined in according to the ACC/AHA/ESC recommendations (2006. 12-lead ECG was performed before the fist administration and 2, 4, 8, 12, 24 hours and some next days after propafenone therapy start. Echocardiography and thyroid hormone tests were also performed. Propafenone was administered additionally to standard treatment of the underlying disease and oral anticoagulants. The first dose of propafenone was 300 mg, after 4 hours patients received next dose of 300 mg if atrial fibrillation persisted and no side effects were observed, then doses of 300 mg were administered every 6-8 hours (but not more than 900-1200 mg per day during 5 days. Maintenance propafenone dose of 450-600 mg daily was used in case of sinus rhythm recovery. Results. Sinus rhythm was restored in 41,6% of patients taking propafenone, and time of sinus rhythm recovery was 53,1±28,9 hours after therapy start. Propafenone antiarrhythmic efficacy in the loading dose (300 mg was 4,2%. Propafenone efficacy during the first 24 hours (dose of 700±282,8 mg was 12,5%. The maximum rate of sinus rhythm recovery was observed during the first 2-3 days of propafenone receiving (60% of all patients with rhythm recovery. Patients with unrecovered sinus rhythm had longer duration of PAF in comparison with this in effectively treated patients, 105,8±89,0 vs 39,7±38,9 days (p<0,05, respectively, as well as the more prominent basal pulse deficit, 24,6±15,0 vs 13,56±5,7 beats per minute (p<0,05, respectively. Cardiac and transient noncardiac side effects were registered in 8,6 and 4
Jeffery, Christopher A; Shum, David W C; Hubbard, Ruth E
The metaphor of a frail older person as a car running out of petrol seems to have resonance in the lay media. Though it may be an over simplistic representation of a complex and dynamic process, it does facilitate discussion with patients and their relatives about the appropriateness of interventions, such as whether or not there is enough fuel (physiological reserves) to get up a really steep hill (undergo a coronary bypass graft). It can also be used as a way to emphasise what can be done to help. For example, in some longitudinal studies, 5% of older patients are less frail after 5 years follow up, suggesting there are things that can still be done to "fill up the tank". This review will consider whether drug therapies can fulfil this role. Frail older people are often prescribed long lists of medications but it is debatable whether current treatments actually address the causes or consequences of frailty itself. Here, we explore the associations between frailty and co-morbidity and evaluate whether the management of chronic disease may impact frailty development or progression. We consider how the management of hypertension may have an important role in the prevention of frailty, mediated by reduction of cerebrovascular disease, but why aggressive management of hypertension may have negative consequences for those who are already frail. We also summarise the evidence linking immunosenescence, inflammation and endocrine changes to frailty and investigate whether targeted drug therapy has the potential to influence frailty pathophysiology. PMID:23141547
Full Text Available Various treatment modalities of acute and chronic pain have been an area of interest of medicine and investigators for centuries. There are two major classes of drugs that are used to control pain: opioid and non-opioid analgesics. They could be used in the case of monotherapy or combination therapy in pain management. However, these agents are not accepted as ideal drugs in clinical approaches against pain because of their serious side effects such as development of tolerance and addiction, renal failure and gastrointestinal bleeding. As a consequent, developing new forms of pain relievers that are more safe and effective without any other side effects has became the main goal of researchers. In recent studies, it has been shown that conotoxin therapies are not addictive, and have tolerable indexes unlike opioids. In addition, conotoxins side effects are much milder and easier to manage than those of opioids. In this regard, it has been emphasized that biotoxins such as conotoxins obtained from marine creatures can be better choices in pain management for future prospects.
Antzelevitch, Charles; Burashnikov, Alexander; Sicouri, Serge; Belardinelli, Luiz
Ranolazine is an FDA-approved anti-anginal agent. Experimental and clinical studies have shown that ranolazine has anti-arrhythmic effects in both ventricles and atria. In the ventricles, ranolazine can suppress arrhythmias associated with acute coronary syndrome, long QT, heart failure, ischemia, and reperfusion. In atria, ranolazine effectively suppresses atrial tachyarrhythmias and fibrillation (AF). Recent studies have shown that the drug may be effective and safe in suppressing AF when u...
Motlagh, Farid Esmaeili; Ibrahim, Fatimah; Rashid, Rusdi Abd; Seghatoleslam, Tahereh; Habil, Hussain
Acupuncture therapy has been used to treat substance abuse. This study aims to review experimental studies examining the effects of acupuncture on addiction. Research and review articles on acupuncture treatment of substance abuse published between January 2000 and September 2014 were searched using the databases ISI Web of Science Core Collection and EBSCO's MEDLINE Complete. Clinical trial studies on the efficacy of acupuncture therapy for substance abuse were classified according to substance (cocaine, opioid, nicotine, and alcohol), and their treatment protocols, assessments, and findings were examined. A total of 119 studies were identified, of which 85 research articles addressed the efficacy of acupuncture for treating addiction. There were substantial variations in study protocols, particularly regarding treatment duration, frequency of electroacupuncture, duration of stimulation, and choice of acupoints. Contradictory results, intergroup differences, variation in sample sizes, and acupuncture placebo effects made it difficult to evaluate acupuncture effectiveness in drug addiction treatment. This review also identified a lack of rigorous study design, such as control of confounding variables by incorporating sham controls, sufficient sample sizes, reliable assessments, and adequately replicated experiments. PMID:27053944
Brendorp, B; Elming, H; Jun, L;
BACKGROUND: A prolonged QTc interval is considered a contraindication for class III antiarrhythmic drugs, but the influence of a normal or a slightly increased baseline QTc interval on the risk or benefit of treatment with a class III antiarrhythmic drug is not sufficiently clarified. METHODS AND...
Richard L. Page; 王琳
通常认为，在应用植入式复律除颤器（implantable cardioverter defibrillator，ICD）早期联合应用抗心律失常药物是多余的，这就像用了腰带又加吊带。直到不久前人们才发现，随着时间的推移，许多病人最终仍需在ICD的基础上使用抗心律失常药。在JAMA杂志中，Connolly及其同事报告了“植入式复律除颤器病人最佳药物治疗试验”（Optimal Pharmacological Therapy in Cardioverter Defibrillator Patients，OPTIC）。他们提出这样一个问题，即在植入ICD时是否应该应用抗心律失常药物并加上一种β-阻滞剂，以减少ICD放电。为了回答这个问题，关键是要了解ICD和抗心律失常药物的相互作用以及联合应用的效果。
... by drug therapy. Low-fat dairy products like milk, cottage cheese and yogurt also supply a good amount of protein and calcium, along with other important vitamins and minerals. People living with cancer have different nutrition goals ...
Pless, Stephan Alexander; Galpin, Jason D; Frankel, Adam; Ahern, Christopher A
Cardiac sodium channels are established therapeutic targets for the management of inherited and acquired arrhythmias by class I anti-arrhythmic drugs (AADs). These drugs share a common target receptor bearing two highly conserved aromatic side chains, and are subdivided by the Vaughan-Williams cl...
Rajasekaran, S.; Khandelwal, Gaurav
Although the discovery of effective anti-tuberculosis drugs has made uncomplicated spinal tuberculosis a medical disease, the advent of multi-drug-resistant Mycobacterium tuberculosis and the co-infection of HIV with tuberculosis have led to a resurgence of the disease recently. The principles of drug treatment of spinal tuberculosis are derived from our experience in treating pulmonary tuberculosis. Spinal tuberculosis is classified to be a severe form of extrapulmonary tuberculosis and henc...
B. A. Tatarskii
Full Text Available Characteristics and classification of different patterns of paroxysmal atrial fibrillation are presented. Main indications to restoration of sinus rhythm are discussed. The features of main medications used to terminate of atrial fibrillation are given. The choice of antiarrhythmic drug is considerate. Necessity of individual approach to therapy tactics is proved.
Motlagh, Farid Esmaeili; Ibrahim, Fatimah; Rashid , Rusdi Abd.; SEGHATOLESLAM, Tahereh; Habil, Hussain
Acupuncture therapy has been used to treat substance abuse. This study aims to review experimental studies examining the effects of acupuncture on addiction. Research and review articles on acupuncture treatment of substance abuse published between January 2000 and September 2014 were searched using the databases ISI Web of Science Core Collection and EBSCO’s MEDLINE Complete. Clinical trial studies on the efficacy of acupuncture therapy for substance abuse were classified according to substa...
Arts, Eric J.; Hazuda, Daria J.
The most significant advance in the medical management of HIV-1 infection has been the treatment of patients with antiviral drugs, which can suppress HIV-1 replication to undetectable levels. The discovery of HIV-1 as the causative agent of AIDS together with an ever-increasing understanding of the virus replication cycle have been instrumental in this effort by providing researchers with the knowledge and tools required to prosecute drug discovery efforts focused on targeted inhibition with ...
Nielsen, F.C.; Borregaard, N.
Pharmacogenetics traditionally designates the study of genetically determined variation in metabolism of drugs and toxins from the environment. The concept of phamacogenetics has been widened to encompass how essential genetic alterations central to the development of diseases may by used to target...
Hoang-Kim, Amy; Gelsomini, Letizia; Luciani, Deianira; Moroni, Antonio; Giannini, Sandro
Fracture repair has not been fully optimised and there is opportunity to increase the healing rate and reduce the number of complications using pharmacological means. While most anti-osteoporosis drugs have been widely tested for their ability to decrease the risk of osteoporotic fractures, fragility fractures still occur in patients under medical intervention. The primary purpose of this systematic review is to understand these underlying mechanisms between bone and drug therapies in osteopo...
Full Text Available Background: The behavior and dietary treatments are not so successful for extremely obese adolescents. Therefore, using drugs to treat extremely obese children and adolescents are among the modern approaches. This research aims to study the pharmaceutical interventions performed for treatment of obese children. Materials and Methods: The strategy of research was using of key words ‘obesity’, ‘adolescence’, ‘treatment’ and ‘anti-obesity drugs’ were searched in websites of PubMed, Iranian Medical Digital Library, SID, Iran Medex, Magiran. This study reviewed all the available published papers in English and Farsi languages during 2000-2010. The Criteria for exclusion was The papers that had been published on interventions and treatment of eating disorders, type II diabetes or the obesity caused by the secondary syndromes. Results: Twelve papers were found as short-term clinical trials and/or long-term follow-ups. In these studies, the positive effects of ‘sibutramine’ in some studies are shown; although some other side effects are reported as well. A significant weight-loss had been reported on ‘orlistat’ medicine, but digestive complications had been observed as well. None of the studies had followed up patients for more than one year. Apparently, ‘Metformin’ requires further studies.Conclusion: The FDA has only approved ‘sibutramine’ and ‘orlistat’ drugs. But side effects of long-term these drugs have already been unknown. However, it seems that ‘orlistat’ is applied for ≥12-year-old children and ‘sibutramine’ for ≥ 16-year-old children.
@@ In cooperation with colleagues from the China Pharmaceutical University over the past 15 years, researchers from the Shanghai Institute of Materia Medica (SIMM), a pharmaceutical research arm of CAS, have developed a new injection of acehytisine hydrochloride as a natural medication against heart rhythm disorders. The drug was officially approved on August 22, 2005 by China's State Food & Drug Administration (SFDA) as a new and marketable pharmaceutical for clinical therapy.
In the mid-1970's Dougherty and co-workers reintroduced hematoporphyrin derivative (HpD) as tumor localizer and photosensitizer for the detection and treatment of neoplastic disease. The efforts of this group led to the introduction of the combination of HpD and lasers for the treatment of a number of human neoplasms. During the late 1970's and throughout most of the 1980's efforts were made to determine the active component in the mixture of porphyrins which comprise HpO. The standard light source used in HpD was the argon-dye laser. Recently new photosensitizers for photodynamic therapy have been introduced. These newer photosensitizers are pure and not mixtures and are associated with less side effects than HpD. Concomitant with the development of new photosensitizers has been the development of new laser systems for photodynamic therapy. In this paper current developments in new drugs and new lasers for photodynamic therapy are presented
Full Text Available Carbon nanotubes and graphene are both low-dimensional sp2 carbon nanomaterials exhibiting many unique physical and chemical properties that are interesting in a wide range of areas including nanomedicine. Since 2004, carbon nanotubes have been extensively explored as drug delivery carriers for the intracellular transport of chemotherapy drugs, proteins, and genes. In vivo cancer treatment with carbon nanotubes has been demonstrated in animal experiments by several different groups. Recently, graphene, another allotrope of carbon, has also shown promise in various biomedical applications. In this article, we will highlight recent research on these two categories of closely related carbon nanomaterials for applications in drug delivery and cancer therapy, and discuss the opportunities and challenges in this rapidly growing field.
Dias Junior, Carlos A.C.; Ribeiro, Andréia; Soares, Adriana C; Pereira, Mariana L.; Nascimento, Mariana M.G.
The elderly population and the incidence of chronic diseases are growing rapidly in Brazil. This raises the demand for health services (like Nursing Homes - NH) and drugs, exposing this population to Potential Drug Therapy Problems (PDTP). A cross-sectional study in a Brazilian NH was developed through prescription analyses. PDTP were accounted when one of the following were detected: double therapy (DT); sub-dose; overdose; drug-drug interaction (DDI); food-drug interaction (FDI); Potentiall...
Full Text Available D00477 Drug Procainamide hydrochloride (JP16/USP); Procan SR (TN); Procanbid (TN); ...r agents 212 Antiarrhythmic agents 2121 Procainamides D00477 Procainamide hydrochloride (JP16/USP) Anatomica...TIARRHYTHMICS, CLASS I AND III C01BA Antiarrhythmics, class Ia C01BA02 Procainamide D00477 Procai...namide hydrochloride (JP16/USP) USP drug classification [BR:br08302] Cardiovascular Agents Antiarrhythmics Procai...namide D00477 Procainamide hydrochloride (JP16/USP) Target-based classification of drug
Spiro, Zoltan; Kovacs, Istvan A.; Csermely, Peter
Recently, a number of drug-therapy, disease, drug, and drug-target networks have been introduced. Here we suggest novel methods for network-based prediction of novel drug targets and for improvement of drug efficiency by analysing the effects of drugs on the robustness of cellular networks.
Sessa, Ben; Johnson, Matthew W
After a 40-year hiatus there is now a revisiting of psychedelic drug therapy throughout psychiatry, with studies examining the drugs psilocybin, ketamine, ibogaine and ayahuasca in the treatment of drug dependence. Limitations to these therapies are both clinical and legal, but the possibility of improving outcomes for patients with substance dependency imposes an obligation to research this area. PMID:25561484
Stage, Claus; Jürgens, Gesche; Dalhoff, Kim Peder; Rasmussen, Henrik Berg
Until now drug therapy has primarily been controlled by dose titration on the basis of effects and side effects. However, a lot of people being treated with a drug experience too little effect or too many side effects. Therefore it will be advantageous to improve drug therapy and make it even more "individualized". In this chase metabolomics is a hot topic. The aim of this paper is to review the concepts of metabolomics and the possible applications in regard to drug development, drug therapy and diagnosis, prognosis and monitoring of diseases. PMID:25096206
Stage, Claus; Jürgens, Gesche; Dalhoff, Kim Peder; Rasmussen, Henrik Berg
Until now drug therapy has primarily been controlled by dose titration on the basis of effects and side effects. However, a lot of people being treated with a drug experience too little effect or too many side effects. Therefore it will be advantageous to improve drug therapy and make it even mor...... "individualized". In this chase metabolomics is a hot topic. The aim of this paper is to review the concepts of metabolomics and the possible applications in regard to drug development, drug therapy and diagnosis, prognosis and monitoring of diseases....
Lundin, Andreas; Djärv, Therese; Engdahl, Johan; Hollenberg, Jacob; Nordberg, Per; Ravn-Fischer, Annika; Ringh, Mattias; Rysz, Susanne; Svensson, Leif; Herlitz, Johan; Lundgren, Peter
The aim of this study was to review the literature on human studies of drug therapy in cardiac arrest during the last 25 years. In May 2015, a systematic literature search was performed in PubMed, Embase, the Cochrane Library, and CRD databases. Prospective interventional and observational studies evaluating a specified drug therapy in human cardiac arrest reporting a clinical endpoint [i.e. return of spontaneous circulation (ROSC) or survival] and published in English 1990 or later were included, whereas animal studies, case series and reports, studies of drug administration, drug pharmacology, non-specified drug therapies, preventive drug therapy, drug administration after ROSC, studies with primarily physiological endpoints, and studies of traumatic cardiac arrest were excluded. The literature search identified a total of 8936 articles. Eighty-eight articles met our inclusion criteria and were included in the review. We identified no human study in which drug therapy, compared with placebo, improved long-term survival. Regarding adrenaline and amiodarone, the drugs currently recommended in cardiac arrest, two prospective randomized placebo-controlled trials, were identified for adrenaline, and one for amiodarone, but they were all underpowered to detect differences in survival to hospital discharge. Of all reviewed studies, only one recent prospective study demonstrated improved neurological outcome with one therapy over another using a combination of vasopressin, steroids, and adrenaline as the intervention compared with standard adrenaline administration. The evidence base for drug therapy in cardiac arrest is scarce. However, many human studies on drug therapy in cardiac arrest have not been powered to identify differences in important clinical outcomes such as survival to hospital discharge and favourable neurological outcome. Efforts are needed to initiate large multicentre prospective randomized clinical trials to evaluate both currently recommended and
Full Text Available D06172 Drug Tocainide (USAN/INN) C11H16N2O 192.1263 192.2575 D06172.gif Cardiac dep...01 CARDIAC THERAPY C01B ANTIARRHYTHMICS, CLASS I AND III C01BB Antiarrhythmics, class Ib C01BB03 Tocainide D06172 Tocai...HSA:6323] [KO:K04833] Tocainide [ATC:C01BB03] D06172 Tocainide (USAN/INN) voltage-gated sodium channel (SCN2...A) [HSA:6326] [KO:K04834] Tocainide [ATC:C01BB03] D06172 Tocainide (USAN/INN) voltage-gated sodium channel (...SCN3A) [HSA:6328] [KO:K04836] Tocainide [ATC:C01BB03] D06172 Tocainide (USAN/INN)
Full Text Available The objective of this study was to determine the association between the use of antiarrhythmic agents and the risk of malignant neoplasm of liver and intrahepatic bile ducts (MNLIHD.We used the research database of the Taiwan National Health Insurance Program to conduct a population-based, case-control study. We identified 9944 patients with antiarrhythmic history who were first diagnosed as having MNLIHD between 2005 and 2010. We identified an additional 19,497 patients with antiarrhythmic history in the same period who did not develop MNLIHD and were frequency-matched using age, sex, and index year to form a control group. Five commercially available antiarrhythmic agents, amiodarone, mexiletine, propafenone, quinidine, and procainamide, were analyzed.The adjusted odds ratio (OR of MNLIHD was 1.60 (95% confidence interval [CI], 1.45-1.77 for amiodarone users versus nonamiodarone users. In subgroup analysis, amiodarone use was significantly associated with an increased risk of MNLIHD with an adjusted OR of 18.0 (95% CI, 15.7-20.5 for patients with comorbidities compared to an OR of 2.43 (95% CI, 1.92-3.06 for those without comorbidities. After adjustment for age, sex, statins, anti-diabetes medications, non-steroidal antiinflammatory drugs, propafenone use, quinidine use, and comorbidities, the ORs were 1.49, 1.66, and 1.79 for MNLIHD associated with annual mean defined daily doses of ≤ 30, 31-145, and >145, respectively.The results of the present study indicated that amiodarone might be associated with the development of MNLIHD in a dose-dependent manner, particularly among patients with comorbidities.
Denisova, E V; Nazarov, V E
The article highlights the principles of individualized drug therapy of complicated duodenal ulcers in the postoperative period, based on the removal of the pathophysiological changes that occurred after different types of medical or surgical benefits. PMID:26415272
Full Text Available Potassium channels are the most variable ion channel group. They participate in numerous cardiovascular functions, for example regulation of vascular tone, maintenance of resting cardiac membrane potential and excitability of cardiac conduction tissue. Both drugs and endogenous ligands could modulate potassium channel function, belonging to the potassium channel blockers or openers. Modulation of potassium channels could be a therapeutic or adverse drug action. Class III antiarrhythmic agents block the potassium channels, thereby prolonging repolarization phase of action potential with resulting prolongation of effective refractory period. Their effectiveness against supraventricular and ventricular arrhythmias should be weighted against their proarrhythmogenic potential. In addition, numerous other antiarrhythmic agents could modulate potassium channels as well. Diazoxide, minoxidil and nicorandil (well known arterial vasodilators, as well as numerous newly synthesized substances with still unknown therapeutic potential, belong to the potassium channel activators/ openers. Therapeutic use of such vasodilators may involve treatment of hypertension (diazoxide, minoxidil and stable angina (nicorandil. Their use might be accompanied with side effects, such as vasodilation, edema, hypotension and reflex tachycardia. Potassium channel openers have also an important role in the treatment of peripheral vascular disease and pulmonary hypertension. In the future, drugs with selective effects on the vascular or cardiac potassium channels could be useful therapeutic agents.
Goodison, L; Schafer, H
Dance therapy can play a useful role in the treatment and rehabilitation of women with drug addiction. It works by raising self-esteem through an improved relationship with the body, giving women the strength to help combat their habit. The benefits of dance therapy for women at the detox unit of Holloway Prison have been confirmed by prison staff. PMID:10662323
Case reports show up, that bone scintigraphy during therapy of metastasing cancer of mamma or prostata with cytostatically acting drugs may reveal 'pseudonormal' results. False negative diagnosis can be excluded only by carefully regarding drug history. Gamma-camera with wholebody scan device for scintigraphy in two projections simplifies safe evaluation significantly. (orig.)
Encapsulating cytostatics into lipid vesicles, i.e. liposomes, improves tumour drug accumulation and reduce adverse effects. Liposomal doxorubicin (DXR) has been used in the treatment of a variety of cancers and may also be suitable for combining with other treatment modalities. By modulating liposomal membranes, liposomes can be made ultrasound (US) sensitive releasing encapsulated drug in tumour tissue upon external US stimulation and may thereby improve therapeutic outcome. Moreover, as DX...
Wainberg, M A; Friedland, G
Widespread use of antiretroviral agents and increasing occurrence of human immunodeficiency virus (HIV) strains resistant to these drugs have given rise to a number of important issues. Some of these concerns are distinct from the obvious question of the relationship between drug resistance and treatment failure and have potentially widespread public health implications. The relevant issues include but are not limited to the following: (1) frequency with which drug-resistant virus may be transmitted via sexual, intravenous, or mother-to-child routes; (2) ability of drug-resistant variants to be transmitted, a question that relates, in part, to the relative fitness of such strains; (3) effectiveness of antiviral therapy in diminishing viral burden in both blood and genital secretions, and whether this may be compromised in persons harboring resistant virus; and (4) importance of patient adherence to antiviral therapy and its relationship to sustained reduction in viral load to minimize the appearance in and transmission of drug-resistant virus from both blood and genital secretions. Thus, prevention of both development of HIV drug resistance as well as transmission of drug-resistant variants is a central issue of public health importance. Unless this topic is appropriately addressed, the likelihood is that drug-resistant variants of HIV, if able to successfully replicate, will sustain the epidemic and limit the effectiveness of antiviral therapy. PMID:9643862
Dvorak, R; Starling, R D; Callés-Escandon, J; Sims, E A; Poehlman, E T
The prevalence of obesity is increasing rapidly in the US and other developed countries. Even though the percentage of older individuals is increasing worldwide, obesity has only recently become a recognised problem in this population. Obesity occurs when energy intake chronically exceeds energy expenditure. Moreover, advancing age is associated with an inability to couple energy intake with energy expenditure. Obesity contributes to many adverse health outcomes, including non-insulin-dependent (type II) diabetes mellitus, as well as to an increase in both cardiovascular and all-cause mortality. Only recently has the medical community begun to accept obesity as a disease with a multifactorial pathogenesis that requires systematic lifestyle changes and pharmacological treatment. Several groups of drugs are available for the pharmacotherapy of obesity; anorectic medications (e.g. fenfluramine, dexfenfluramine); substances affecting energy expenditure and body composition [e.g. chromium (chromium picolinate), ephedrine, anabolic steroids, beta 3-adrenoceptor agonists]; and drugs affecting the absorption of nutrients (e.g. orlistat). To date, few drugs have produced and sustained a significant bodyweight loss. However, some drugs induce a significant short term reduction in bodyweight compared with placebo. Moreover, there is a paucity of information regarding the effectiveness of these drugs in the treatment of obesity in the elderly. Furthermore, it is even debated whether obesity should be treated with drug intervention in the elderly. Clinicians prescribing medications for obesity treatment in the elderly need to carefully consider the benefit: risk ratio, given the high prevalence of polypharmacy in elderly patients. Furthermore, physiological changes that occur with aging may affect the pharmacokinetics of administered drugs and need to be taken into consideration. PMID:9359021
Magnetic nanoparticles have been investigated for biomedical applications for more than 30 years. In medicine they are used for several approaches such as magnetic cell separation or magnetic resonance imaging (MRI). The development of biocompatible nanosized drug delivery systems for specific targeting of therapeutics is the focus of medical research, especially for the treatment of cancer and diseases of the vascular system. In an experimental cancer model, we performed targeted drug delivery and used magnetic iron oxide nanoparticles, bound to a chemotherapeutic agent, which were attracted to an experimental tumour in rabbits by an external magnetic field (magnetic drug targeting). Complete tumour remission could be achieved. An important advantage of these carriers is the possibility for detecting these nanoparticles after treatment with common imaging techniques (i.e. x-ray-tomography, magnetorelaxometry, magnetic resonance imaging), which can be correlated to histology
Říhová, Blanka; Strohalm, Jiří; Hoste, K.; Jelínková, Markéta; Hovorka, Ondřej; Kovář, Marek; Plocová, Daniela; Šírová, Milada; Šťastný, Marek; Ulbrich, Karel
Roč. 172, - (2001), s. 21-28. ISSN 1022-1360 R&D Projects: GA ČR GV307/96/K226; GA MZd NC5050 Institutional research plan: CEZ:AV0Z5020903 Keywords : doxorubicin * mitomycin * immunoprotective therapy Subject RIV: EC - Immunology Impact factor: 0.634, year: 2001
Prevention of adverse drug events that may result from medication errors is challenging. The safety of medication treatment is mostly determined on an average population and medication errors may be prevented when pharmacotherapy is better tailored to the individualized needs of the hospitalized pat
Broder, S; Fauci, A S
The discovery of effective therapies for HIV requires a fundamental knowledge of retroviral infections. Research by the Public Health Service and collaborating organizations on oncogenic viruses, including retroviruses, has provided much of the basic understanding of retroviruses in general and anti-retroviral therapeutic strategies in particular. Early work by the Viral Cancer and Developmental Therapeutic Programs of the National Cancer Institute and the Intramural Research Program of the N...
Stenvang, Jan; Kümler, Iben; Nygård, Sune Boris;
process. This research strategy is commonly known as drug repurposing or drug repositioning and provides a faster path to the clinics. We have developed and implemented a modification of the standard drug repurposing strategy that we review here; rather than investigating target-promiscuous non...... any non-standard chemotherapeutic drug will be relatively low in such a patient cohort it is a pre-requisite that such testing is based on predictive biomarkers. This review describes our strategy of biomarker-guided repurposing of chemotherapeutic drugs for cancer therapy, taking the repurposing of......Cancer is a leading cause of mortality worldwide and matters are only set to worsen as its incidence continues to rise. Traditional approaches to combat cancer include improved prevention, early diagnosis, optimized surgery, development of novel drugs, and honing regimens of existing anti...
Uhler, Ann S.; Parker, Olga V.
The authors suggest that action therapy, a group of techniques including psychodrama, drama therapy, and role training, warrants research attention to determine whether it is well suited to the special characteristics and needs of women clients. In addition, the authors call on researchers to develop a new standardized tool for counselors to use during initial interviews to determine whether women presenting for drug abuse treatment also have significant issues related to trauma. The authors ...
Soyka, M; Dittert, S; Gartenmeier, A; Schäfer, M
The driving ability of patients under therapy with antidepressives is seen less restrictive than some years ago. The inhibition of psychomotor performance is of special interest. Some empirical studies point at antidepressives increasing the risk for accidents at least in elderly patients. Different groups of antidepressants apparently show different effects. Tricyclic antidepressants were shown to worsen cognitive and psychomotor performance in some patients while serotonin reuptake inhibitors and some other new antidepressants may cause less behavioral toxicity. Methodological problems in assessing driving ability and some recent findings are discussed. PMID:9587241
Tilahun Ayane Debele
Full Text Available Photodynamic therapy (PDT is a non-invasive combinatorial therapeutic modality using light, photosensitizer (PS, and oxygen used for the treatment of cancer and other diseases. When PSs in cells are exposed to specific wavelengths of light, they are transformed from the singlet ground state (S0 to an excited singlet state (S1–Sn, followed by intersystem crossing to an excited triplet state (T1. The energy transferred from T1 to biological substrates and molecular oxygen, via type I and II reactions, generates reactive oxygen species, (1O2, H2O2, O2*, HO*, which causes cellular damage that leads to tumor cell death through necrosis or apoptosis. The solubility, selectivity, and targeting of photosensitizers are important factors that must be considered in PDT. Nano-formulating PSs with organic and inorganic nanoparticles poses as potential strategy to satisfy the requirements of an ideal PDT system. In this review, we summarize several organic and inorganic PS carriers that have been studied to enhance the efficacy of photodynamic therapy against cancer.
Parida, S K; Axelsson-Robertson, R; Rao, M V; Singh, N; Master, I; Lutckii, A; Keshavjee, S; Andersson, J; Zumla, A; Maeurer, M
The first cases of totally drug-resistant (TDR) tuberculosis (TB) were reported in Italy 10 years ago; more recently, cases have also been reported in Iran, India and South Africa. Although there is no consensus on terminology, it is most commonly described as 'resistance to all first- and second-line drugs used to treat TB'. Mycobacterium tuberculosis (M.tb) acquires drug resistance mutations in a sequential fashion under suboptimal drug pressure due to monotherapy, inadequate dosing, treatment interruptions and drug interactions. The treatment of TDR-TB includes antibiotics with disputed or minimal effectiveness against M.tb, and the fatality rate is high. Comorbidities such as diabetes and infection with human immunodeficiency virus further impact on TB treatment options and survival rates. Several new drug candidates with novel modes of action are under late-stage clinical evaluation (e.g., delamanid, bedaquiline, SQ109 and sutezolid). 'Repurposed' antibiotics have also recently been included in the treatment of extensively drug resistant TB. However, because of mutations in M.tb, drugs will not provide a cure for TB in the long term. Adjunct TB therapies, including therapeutic vaccines, vitamin supplementation and/or repurposing of drugs targeting biologically and clinically relevant molecular pathways, may achieve better clinical outcomes in combination with standard chemotherapy. Here, we review broader perspectives of drug resistance in TB and potential adjunct treatment options. PMID:24809736
Avinash De Sousa
Full Text Available Attention deficit hyperactivity disorder is a developmental disorder with an age onset prior to 7 years. Children with ADHD have significantly lower ability to focus and sustain attention and also score higher on impulsivity and hyperactivity. Stimulants, such as methylphenidate, have remained the mainstay of ADHD treatment for decades with evidence supporting their use. However, recent years have seen emergence of newer drugs and drug delivery systems, like osmotic release oral systems and transdermal patches, to mention a few. The use of nonstimulant drugs like atomoxetine and various other drugs, such as a-agonists, and a few antidepressants, being used in an off-label manner, have added to the pharmacotherapy of ADHD. This review discusses current trends in drug therapy of ADHD and highlights the promise pharmacogenomics may hold in the future.
Full Text Available Abdominal aortic aneurysm is often asymptomatic, less recognized, and causes considerable mortalityand morbidity, if missed. The incidence varies from country to country and the occurrence is influencedby modifiable (smoking, coronary heart disease, hypertension, dyslipidemia, and prolonged steroid therapyand non-modifiable risk factors (increasing age, male gender, and positive family history. Most ofthe patients with such aneurysm do not exhibit symptoms and the diagnosis is made accidentally duringroutine medical investigations, abdominal ultrasonography, or by an astute surgeon during an abdominalprocedure. Sometimes the diagnosis is made in an emergency room, if the attending resident/doctor isaware of it. Despite good diagnosis and effective management, the outcomes of complicated cases arepoor and the treatment cost is prohibitive. Hence, we reviewed the literature to find out the pathogenesisof such aneurysms and the usefulness of available drugs in its prevention.
Patel Pinal D.
Full Text Available This drug utilization or prescription-monitoring study was conducted to evaluate the drug-prescribing trend of anti-asthmatic drugs in retailed pharmacy outlets during 2009 and 2011 in urban and rural area of Saurashtra region, Gujarat, India. The study was conducted on 601 patients, using a developed prescription auditing Performa. Data was recorded from the co-operating patients by interviewing and information was filled in the performa. The data suggested that punctuality in professionalism like mentioning own (physicians name, patients name, diagnosis and minimum qualification of MD/MS was observed to be higher in urban than the rural. There was no significant sex difference. Bronchial asthma was found to be more prevalent in the age group 41 to 60 years. Patients were found to consult the doctor 2 to 7 days after symptoms and pay consulting fee more than Rs.20=00. The collected information suggested that bronchodilators were the most frequently prescribed anti-asthmatic drugs followed by corticosteroids and methylxanthine preparation. Analysis of prescription revealed that multiple drug therapy was opted for a significant number of patients as compared to single drug therapy. In combination therapy, the three-drug combination was the most often prescribed. Number of partial purchase of drugs as per the prescriptions was found to be higher in rural area than urban area. Lack of money was one of the reasons for partial prescription. Thus, it can be concluded that the present prescribing pattern of antiasthmatics in Saurashtra region does not completely meet standard guidelines for the asthma treatment. Hence there is a need of awareness amongst the physicians of Saurashtra region so that they can follow the guidelines while treating asthma. Also the patients must be encouraged to complete whole treatment for improving the health. It has been also concluded that a study may be more meaningful to further improve the dispensing practices of the
Turner, J Rick; Panicker, Gopi Krishna; Karnad, Dilip R; Cabell, Christopher H; Lieberman, Ronald; Kothari, Snehal
Assessments of cardiac and cardiovascular toxicity are prominent components of drug safety endeavors during drug development and clinical practice. Oncologic drugs bring several challenges to both domains. First, during drug development, it is necessary to adapt the ICH E14 "Thorough QT/QTc Study" because the cytotoxic nature of many oncologics precludes their being administered to healthy individuals. Second, appropriate benefit-risk assessments must be made by regulators: given the benefit these drugs provide in life-threatening illnesses, a greater degree of risk may be acceptable when granting marketing authorization than for drugs for less severe indications. Third, considerable clinical consideration is needed for patients who are receiving and have finished receiving pharmacotherapy. Paradoxically, although such therapy has proved very successful in many cases, with disease states going into remission and patients living for many years after cessation of treatment, cardiotoxicities can manifest themselves relatively soon or up to a decade later. Oncologic drugs have been associated with various off-target cardiovascular responses, including cardiomyopathy leading to heart failure, cardiac dysrhythmias, thromboembolic events, and hypertension. Follow-up attention and care are, therefore, critical. This article reviews the process of benefit-risk estimation, provides an overview of nonclinical and preapproval clinical assessment of cardiovascular safety of oncology drugs, and discusses strategies for monitoring and management of patients receiving drugs with known cardiotoxicity risk. These measures include cardiac function monitoring, limitation of chemotherapy dose, use of anthracycline analogs and cardioprotectants, and early detection of myocardial cell injury using biomarkers. PMID:24451296
The expenditure incurred in the German statutory health insurance (SHI) in relation to drugs, are characterized not only by the amount of drug prices, but also by their degree of efficient usage. The prevention of superfluous and inappropriate pharmaceutical supply leads to direct savings in expenditure, a drug-based guideline-oriented therapy, and prevention of diseases and deficiency symptoms leads to savings by avoiding hospitalizations, operations, and maintaining the ability to work. Prescriptions of new and expensive me-too drugs with no additional benefit bind financial resources of the SHI, which should be available for pharmaceutical therapeutic innovations. PMID:20552155
One of the mechanisms of external signal transduction (ionizing radiation, toxicants, stress) to the target cell is the existence of membrane and intracellular proteins with intrinsic tyrosine kinase activity. No wonder that etiology of malignant growth links to abnormalities in signal transduction through tyrosine kinases. The epidermal growth factor receptor (EGFR) tyrosine kinases play fundamental roles in development, proliferation and differentiation of tissues of epithelial, mesenchymal and neuronal origin. There are four types of EGFR: EGF receptor (ErbB1/HER1), ErbB2/Neu/HER2, ErbB3/HER3 and ErbB4/HER4. Abnormal expression of EGFR, appearance of receptor mutants with changed ability to protein-protein interactions or increased tyrosine kinase activity have been implicated in the malignancy of different types of human tumors. Bioinformatics is currently using in investigation on design and selection of drugs that can make alterations in structure or competitively bind with receptors and so display antagonistic characteristics. (authors)
Full Text Available Invasive fungal infections are on the rise. Amphotericin B and azole antifungals have been the mainstay of antifungal therapy so far. The high incidence of infusion related toxicity and nephrotoxicity with amphotericin B and the emergence of fluconazole resistant strains of Candida glabrata egged on the search for alternatives. Echinocandins are a new class of antifungal drugs that act by inhibition of β (1, 3-D- glucan synthase, a key enzyme necessary for integrity of the fungal cell wall. Caspofungin was the first drug in this class to be approved. It is indicated for esophageal candidiasis, candidemia, invasive candidiasis, empirical therapy in febrile neutropenia and invasive aspergillosis. Response rates are comparable to those of amphotericin B and fluconazole. Micafungin is presently approved for esophageal candidiasis, for prophylaxis of candida infections in patients undergoing hematopoietic stem cell transplant (HSCT and in disseminated candidiasis and candidemia. The currently approved indications for anidulafungin are esophageal candidiasis, candidemia and invasive candidiasis. The incidence of infusion related adverse effects and nephrotoxicity is much lower than with amphotericin B. The main adverse effect is hepatotoxicity and derangement of serum transaminases. Liver function may need to be monitored. They are, however, safer in renal impairment. Even though a better pharmacoeconomical choice than amphotericin B, the higher cost of these drugs in comparison to azole antifungals is likely to limit their use to azole resistant cases of candidial infections and as salvage therapy in invasive aspergillosis rather than as first line drugs.
D'Arcy, P F
The term ''iatrogenic disease'' means disease caused by therapy prescribed by doctors. Most such diseases are drug induced. Adverse effects of drugs have been more common in seriously ill patients who have received many drugs. Drug interaction has often been the cause. Most have been dose-related from cumulative pharmacologic effects. Reported data have been incomplete. Individual variability due to a genetic basis has been a factor. Environmental influences, such as smoking, atmospheric pollution, and hardness of the water supply may be involved. Sometimes the patient's metabolism has been impaired by concomitant liver or kidney malfunction. In such cases the drug, or its metabolites, may build up to a toxic level. A lowered threshold to the normal action of a drug is frequent among the very old and the very young. Geriatric patients have a considerable reduction in the reserve capacity of many organs. Hypersensitivity to a drug may be present. Skin rashes and eruptions are most common in this type of allergic reaction although jaundice and hemolytic anemia have followed. Polypharmacy increases the risk. Some patients make errors in taking prescribed drugs. Also, additional self-medication is common. Drug-food interactions may occur. Needed vitamins may be absorbed and eliminated by the use of liquid paraffin as a laxative. Intestinal flora-destroying antibiotics permit other organisms to grow. Alcohol is an additional hazard. Oral contraceptive use may be followed by anemia, and may react with other drugs. A list of such known reactions is given. Delayed iatrogenic neoplasia is being considered. Effects on the progeny have been shown with several drugs. Forewarning creates awareness and caution. PMID:798237
Skibsbye, Lasse; Wang, Xiaodong; Axelsen, Lene Nygaard;
period (ERP) and slowing the conduction velocity. We therefore aimed at elucidating these properties of SK channel inhibition and the underlying antiarrhythmic mechanisms by using; microelectrode action potential recordings and conduction velocity measurements in isolated rat atrium. Automated patch-clamping...... and two-electrode voltage-clamp was used to access INa and IK,ACh respectively. RESULTS: The SK channel inhibitor N-(pyridin-2-yl)-4-(pyridin-2-yl)thiazol-2-amine (ICA) exhibited antiarrhythmic effects. ICA prevented electrically induced runs of atrial fibrillation in the isolated right atrium and...... channel inhibition by ICA (10-30 µM) demonstrated prominent depression of other sodium channel-dependent parameters. ICA did not inhibit IK,ACh, but at concentrations above 10 µM ICA use-dependently inhibited INa. CONCLUSION: SK channel inhibition modulates multiple parameters of the action potential. It...
Full Text Available Abstract Introduction Sertraline and Risperidone are commonly used psychotropic drugs. Sertraline has previously been associated with eosinopilic pneumonia. Neither drug is recognised as a cause of diffuse fibrotic lung disease. Our report represents the first such case. Case Presentation We describe the case of a 33 year old Asian male with chronic schizophrenia who had been treated for three years with sertraline and risperidone. He presented to hospital in respiratory failure following a six month history of progressive breathlessness. High resolution CT scan demonstrated diffuse pulmonary fibrosis admixed with patchy areas of consolidation. Because the aetiology of this man's diffuse parenchymal lung disease remained unclear a surgical lung biopsy was undertaken. Histological assessment disclosed widespread fibrosis with marked eosinophillic infiltration and associated organising pneumonia - features all highly suggestive of drug induced lung disease. Following withdrawal of both sertraline and risperidone and initiation of corticosteroid therapy the patient's respiratory failure resolved and three years later he remains well albeit limited by breathlessness on heavy exertion. Conclusion Drug induced lung disease can be rapidly progressive and if drug exposure continues may result in respiratory failure and death. Prompt recognition is critical as drug withdrawal may result in marked resolution of disease. This case highlights sertraline and risperidone as drugs that may, in susceptible individuals, cause diffuse pulmonary fibrosis.
Full Text Available Cancer is a leading cause of mortality worldwide and matters are only set to worsen as its incidence continues to rise. Traditional approaches to combat cancer include improved prevention, early diagnosis, optimized surgery, development of novel drugs and honing regimens of existing anti-cancer drugs. Although discovery and development of novel and effective anti-cancer drugs is a major research area, it is well known that oncology drug development is a lengthy process, extremely costly and with high attrition rates. Furthermore, those drugs that do make it through the drug development mill are often quite expensive, laden with severe side-effects and, unfortunately, to date, have only demonstrated minimal increases in overall survival. Therefore, a strong interest has emerged to identify approved non-cancer drugs that possess anti-cancer activity, thus shortcutting the development process. This research strategy is commonly known as drug repurposing or drug repositioning and provides a faster path to the clinics. We have developed and implemented a modification of the standard drug repurposing strategy that we review here; rather than investigating target-promiscuous non-cancer drugs for possible anti-cancer activity, we focus on the discovery of novel cancer indications for already approved chemotherapeutic anti-cancer drugs. Clinical implementation of this strategy is normally commenced at clinical phase II trials and includes pre-treated patients. As the response rates to any non-standard chemotherapeutic drug will be relatively low in such a patient cohort it is a pre-requisite that such testing is based on predictive biomarkers. This review describes our strategy of biomarker-guided repurposing of chemotherapeutic drugs for cancer therapy, taking the repurposing of topoisomerase I inhibitors and topoisomerase I as a potential predictive biomarker as case in point.
Walfridsson, H; Walfridsson, U; Nielsen, J Cosedis;
AIMS: The Medical ANtiarrhythmic Treatment or Radiofrequency Ablation in Paroxysmal Atrial Fibrillation (MANTRA-PAF) trial assessed the long-term efficacy of an initial strategy of radiofrequency ablation (RFA) vs. antiarrhythmic drug therapy (AAD) as first-line treatment for patients with PAF. In...... made on an intention-to-treat basis. Both randomization groups showed significant improvements in assessments with both SF-36 and EQ-5D, at 24 months. Patients randomized to RFA showed significantly greater improvement in four physically related scales of the SF-36. The three most frequently reported...... improvement of HRQoL and symptom burden in patients with PAF. Patients randomized to RFA showed greater improvement in physical scales (SF-36) and the EQ-visual analogue scale. CLINICAL TRIAL REGISTRATION: URL http://www.clinicaltrials.gov. Unique identifier: NCT00133211....
Full Text Available Mucoadhesive drug therapy destined for localized drug treatment is gaining increasing importance in today’s drug development. Chitosan, due to its known biodegradability, bioadhesiveness and excellent safety profile offers means to improve mucosal drug therapy. We have used chitosan as mucoadhesive polymer to develop liposomes able to ensure prolonged residence time at vaginal site. Two types of mucoadhesive liposomes, namely the chitosan-coated liposomes and chitosan-containing liposomes, where chitosan is both embedded and surface-available, were made of soy phosphatidylcholine with entrapped fluorescence markers of two molecular weights, FITC-dextran 4000 and 20,000, respectively. Both liposomal types were characterized for their size distribution, zeta potential, entrapment efficiency and the in vitro release profile, and compared to plain liposomes. The proof of chitosan being both surface-available as well as embedded into the liposomes in the chitosan-containing liposomes was found. The capability of the surface-available chitosan to interact with the model porcine mucin was confirmed for both chitosan-containing and chitosan-coated liposomes implying potential mucoadhesive behavior. Chitosan-containing liposomes were shown to be superior in respect to the simplicity of preparation, FITC-dextran load, mucoadhesiveness and in vitro release and are expected to ensure prolonged residence time on the vaginal mucosa providing localized sustained release of entrapped model substances.
Carrizo, Aldo G; Morillo, Carlos A
Current guidelines include atrial fibrillation (AF) catheter ablation as part of the management strategy in patients that have failed at least one oral antiarrhythmic drug treatment course. However, growing evidence derived from both randomized and non-randomized studies demonstrate lower rates of AF recurrence and AF burden in patients with paroxysmal AF that are naïve to antiarrhythmic drug treatment. Furthermore, progression from paroxysmal AF to persistent AF appears to be delayed by early catheter ablation of AF. The current review addresses the question of the best timing for ablation in patients with paroxysmal AF and provides the rationale for offering AF ablation as first-line therapy based on the most updated evidence available. PMID:27300744
Tietze, Rainer; Zaloga, Jan; Unterweger, Harald; Lyer, Stefan; Friedrich, Ralf P; Janko, Christina; Pöttler, Marina; Dürr, Stephan; Alexiou, Christoph
Nanoparticles have belonged to various fields of biomedical research for quite some time. A promising site-directed application in the field of nanomedicine is drug targeting using magnetic nanoparticles which are directed at the target tissue by means of an external magnetic field. Materials most commonly used for magnetic drug delivery contain metal or metal oxide nanoparticles, such as superparamagnetic iron oxide nanoparticles (SPIONs). SPIONs consist of an iron oxide core, often coated with organic materials such as fatty acids, polysaccharides or polymers to improve colloidal stability and to prevent separation into particles and carrier medium . In general, magnetite and maghemite particles are those most commonly used in medicine and are, as a rule, well-tolerated. The magnetic properties of SPIONs allow the remote control of their accumulation by means of an external magnetic field. Conjugation of SPIONs with drugs, in combination with an external magnetic field to target the nanoparticles (so-called "magnetic drug targeting", MDT), has additionally emerged as a promising strategy of drug delivery. Magnetic nanoparticle-based drug delivery is a sophisticated overall concept and a multitude of magnetic delivery vehicles have been developed. Targeting mechanism-exploiting, tumor-specific attributes are becoming more and more sophisticated. The same is true for controlled-release strategies for the diseased site. As it is nearly impossible to record every magnetic nanoparticle system developed so far, this review summarizes interesting approaches which have recently emerged in the field of targeted drug delivery for cancer therapy based on magnetic nanoparticles. PMID:26271592
There main components of the program of radical therapy of breast cancer are distinguished: surgical, radiation and drug. The surgical operation continues to be one of the main therapeutic methods, though there is a trend towards limitation of the amount of surgical interventions. Investigations are carried out in the performance of rational operations of the cancer of the 1 and 2 stages supplemented with pre- and postoperative irradiation. Techniques of large dose fractionation are doveloped. It is shown that in case of 2b and 3a,b stages it is oppropriate to assign a combined or complex therapy: operation, irradiation and chemotherapy. The advantages of polychemotherapy via monochemotherapy are noted. The effect of immunotherapy on the efficiency of the therapy of brest cancer is studied. A conclusion is made that a certain progress has been reached recently in the treatment of breast cancer and that only an individual approach should be used when choosing therapy tactics taking into account all vital factors
Wallace Daniel J
Full Text Available Abstract Systemic lupus erythematosus (SLE is an autoimmune disorder that afflicts 500,000 people in the United States. There has not been a new SLE drug approved in the United States since 1958. However, a guidance document issued by the Food and Drug Administration in 2005 provided a roadmap for investigators which spawned numerous ongoing clinical trials. Among these, Belimumab, a monoclonal antibody to soluble B lymphocyte stimulator, met its primary endpoints in two large trials and will probably obtain FDA approval soon. Other promising agents targeting a variety of mechanisms of action are currently in development. This minireview highlights the latest therapies under investigation in SLE and gives an overview of the pathways that are specifically being targeted.
Full Text Available Psoriasis is a lifelong condition which is caused by the negative signals produced by immune system, which leads to hyper proliferation and other inflammatory reactions on the skin. In this case, keratinocytes which are the outermost layer of skin possess shortened life cycle and results in the alteration of desquamation process where the cytokines will come out through lesions of affected patients and as a result, scaling marks appears on the skin. These conditions may negatively affect the patient’s quality of life and lead to psychosocial stress. Psoriasis can be categorized as mild, moderate and severe conditions. Mild psoriasis leads to the formation of rashes, and when it becomes moderate, the skin turns into scaly. In severe conditions, red patches may be present on skin surface and becomes itchy. Topical therapy continues to be one of the pillars for psoriasis management. Drug molecules with target effect on the skin tissues and other inflammations should be selected for the treatment of psoriasis. Most of the existing drugs lead to systemic intoxication and dryness when applied in higher dose. Different scientific approaches for topical delivery are being explored by researches including emollient, modified gelling system, transdermal delivery, spray, nanogels, hydrogels, micro/nano emulsion, liposomes, nano capsules etc. These topical dosage forms are evaluated for various physico chemical properties such as drug content, viscosity, pH, extrudability, spreadability, toxicity, irritancy, permeability and drug release mechanism. This review paper focus attention to the impact of these formulation approaches on various anti-psoriasis drugs for their successful treatment.
Yager, Neil; Wang, Katherine; Keshwani, Najiba; Torosoff, Mikhail
We present a case of a 69-year-old woman presenting with polymorphic ventricular tachycardia caused by QT prolongation. Owing to known intolerances to a majority of antiarrhythmic medications, one remaining option was to initiate phenytoin. Phenytoin's narrow therapeutic window, multiple drug interactions and side effect profile make it an infrequently used antiarrhythmic. It is, however, a potent antiarrhythmic agent, which may be useful in treatment of ventricular tachycardia, especially in patients with multiple drug intolerances. PMID:26071440
Kling, Heather M; Nau, Gerard J; Ross, Ted M; Evans, Thomas G; Chakraborty, Krishnendu; Empey, Kerry M; Flynn, JoAnne L
Pulmonary diseases and infections are among the top contributors to human morbidity and mortality worldwide, and despite the successful history of vaccines and antimicrobial therapeutics, infectious disease still presents a significant threat to human health. Effective vaccines are frequently unavailable in developing countries, and successful vaccines have yet to be developed for major global maladies, such as tuberculosis. Furthermore, antibiotic resistance poses a growing threat to human health. The "Challenges and Future in Vaccines, Drug Development, and Immunomodulatory Therapy" session of the 2013 Pittsburgh International Lung Conference highlighted several recent and current studies related to treatment and prevention of antibiotic-resistant bacterial infections, highly pathogenic influenza, respiratory syncytial virus, and tuberculosis. Research presented here focused on novel antimicrobial therapies, new vaccines that are either in development or currently in clinical trials, and the potential for immunomodulatory therapies. These studies are making important contributions to the areas of microbiology, virology, and immunology related to pulmonary diseases and infections and are paving the way for improvements in the efficacy of vaccines and antimicrobials. PMID:25148426
Abellan-Pose, Raquel; Csaba, Noemi; Alonso, Maria Jose
The lymphatic system represents a major route of dissemination in metastatic cancer. Given the lack of selectivity of conventional chemotherapy to prevent lymphatic metastasis, in the last years there has been a growing interest in the development of nanocarriers showing lymphotropic characteristics. The goal of this lymphotargeting strategy is to facilitate the delivery of anticancer drugs to the lymph node-resident cancer cells, thereby enhancing the effectiveness of the anti-cancer therapies. This article focuses on the nanosystems described so far for the active or passive targeting of oncological drugs to the lymphatic circulation. To understand the design and performance of these nanosystems, we will discuss first the physiology of the lymphatic system and how physiopathological changes associated to tumor growth influence the biodistribution of nanocarriers. Second, we provide evidence on how the tailoring of the physicochemical characteristics of nanosystems, i.e. particle size, surface charge and hydrophilicity, allows the modulation of their access to the lymphatic circulation. Finally, we provide an overview of the relationship between the biodistribution and antimetastatic activity of the nanocarriers loaded with oncological drugs, and illustrate the most promising active targeting approaches investigated so far. PMID:26675222
Liver cancer was traditionally treated by surgery or interventional ablative treatments, or, if these options were not feasible, by best supportive care. Since 2008, systemic therapy with the multikinase inhibitor sorafenib has become available worldwide and has become the standard of care for unresectable/non-ablatable or advanced-stage hepatocellular carcinoma (HCC). Sorafenib is able to improve the median overall survival by approximately 3 months. Despite this significant advance in the non-surgical/non-interventional management of liver cancer, this improvement in overall survival is only a first step toward more potent, more targeted, and better tolerated oral antitumor treatments. Since the introduction of sorafenib into clinical practice, several attempts have been made to develop even more effective first-line treatments as well as an effective second-line treatment for HCC. None of these endeavors has been successful so far. The development of drug treatments for HCC has been particularly hampered by the unfortunate push to establish the diagnosis of liver cancer by non-invasive imaging alone, without requiring a liver biopsy for histologic confirmation: this precluded the very necessary search for informative biomarkers and the search for molecular targets for drug development in HCC. This important drawback is being increasingly recognized and corrected. Despite several obstacles remaining to be overcome, it seems reasonable to assume that using a rational, data-driven approach, we will be able to develop better drug treatments for liver cancer in the coming years. PMID:24945003
Beaty, Rachel S; Moffett, Brady S; Hall, Stuart; Kim, Jeffrey
Cardiac arrhythmias occurring during the intraoperative period for cardiac surgery have been associated with excess morbidity and mortality. Several antiarrhythmics have been utilized for the management of intraoperative arrhythmias. These antiarrhythmic medications can cause undesirable adverse outcomes in the intensive care setting. The incidence and treatment of adult intraoperative arrhythmias have been studied. In addition, the prevalence, risk factors, and optimal treatment of pediatric postoperative arrhythmias have also been studied. However, the literature has not been published on intraoperative antiarrhythmia treatment during pediatric cardiac surgery. The purpose of this study was to determine the safety of intraoperative antiarrhythmic medications utilized in pediatric cardiac surgery patients. This was a retrospective review of all patients who received an intraoperative antiarrhythmic in the cardiovascular operating room at Texas Children's Hospital. Patients were included if they underwent cardiovascular surgery from November 2008 to July 2013 and were excluded if antiarrhythmics were given intraoperatively for other indications (i.e., esmolol for hypertension) or if patients were older than 18 years of age. Safety of antiarrhythmic treatment was determined by the absence or presence of adverse events. Control or recurrence of the arrhythmia was analyzed as a secondary measure to help determine antiarrhythmic efficacy. A total of 45 patients were identified (53.3 % male). Patients were a median of 0.52 years at the time of surgery. Primary surgery types were tetralogy of Fallot repair (n = 6; 13.3 %) and ventricular septal defect closure (n = 5, 11.1 %). Thirty-one patients (68.9 %) had documented adverse events after the administration of antiarrhythmics. Most of these adverse events occurred after the administration of amiodarone (n = 16; 51.6 %) followed by esmolol (n = 15; 48.4 %). Fifty-one percent of the arrhythmias resolved in the operating
Objective To investigate the effectiveness and safety of various agents on paroxysmal atrial fibrillation in the elderly over 75 years old.Methods Totally 264 in-patients (75-91 years old, 185 males and 79 females) with atrial fibrillation history of less than 7 days were enrolled in this study. A total of 611 atrial fibrillation episodes were recorded, but 130 episodes (22. 3% ) of atrial fibrillation were auto-converted to sinus rhythm. The rest 481 episodes of atrial fibrillation were divided into six groups based on the drug used. Results The cardioversion ratio of atrial fibrillation were 9. 5%, 46.9%, 71.7%, 55.9%, 32.7%, and73.6%in control, cedilanid, amiodarone, propafenone, verapamil, and quinidine groups, respectively. Ventricular rate control were 5.4%, 83.6%, 84. 9%, 77.9%, 78.8%, and 11.3% in those groups, respectively. The total effective rates of amiodarone and cedilanid groups were the highest. When the ventricular rate was controlled to below 90 bpm, the patients would almost complain of no discomfort. No severe side-effect was observed in each group. Conclusion Amiodarone and cedilanid may be the proper drugs for the treatment of paroxysmal atrial fibrillation in the elderly. The above antiarrhythmics in each therapeutic group were relatively safe and effective.
Faiss, S; Scherübl, H; Riecken, E O; Wiedenmann, B
Successful treatment of neuroendocrine tumor disease of the gastroenteropancreatic system requires a multimodal approach. Radical tumor surgery is required before other therapies are initiated. So far, only surgery has proven to be curative. If surgical intervention is not possible or a tumor-free state cannot be achieved, biotherapy with the somatostatin analogues octreotide or lanreotide should then be preferably carried out in patients with functional tumors. Interferon-alpha can alternatively be given. In patients with gastrinoma, therapy with proton pump inhibitors (e.g., omeprazol) is the initial treatment of choice. In patients with nonfunctional tumors, indication for treatment is only given in cases of documented tumor progress. In case of progressive tumor disease or functionality under the above-mentioned therapies, treatment with somatostatin analogues can be intensified by dose escalation or alternatively by a combination therapy with interferon-alpha and a somatostatin analogue. On the basis of the less favorable response of neuroendocrine foregut tumors to biotherapy, chemotherapy should be initiated after failure of biotherapy in documented tumor progression. A combination of streptozotocin and 5-fluorouracil, possibly combined with D,L-folinic acid, is the treatment of choice, considering the response and side effect rates. In case of predominantly anaplastic neuroendocrine tumors in advanced stages, good tumor response rates with a chemotherapeutic scheme consisting of cisplatin and etoposide can be achieved. Since the chemotherapy scheme is less effective in patients with midgut or hindgut tumors, chemoembolization of liver metastases should follow biotherapy. The response to chemoembolization may be increased by simultaneous systemic chemotherapy. Attention should always be paid to an adequate analgesic drug administration. PMID:8893342
Bellamy, N; Grace, E; Hanna, B.; Grant, E; Tugwell, P.; Buchanan, W W
The ability to recall details of current and prior drug therapy was evaluated in two studies employing a total of 94 patients with inflammatory polyarthritis. Ten per cent of patients were unable to completely recall the names of their current anti-inflammatory drugs and eighty-three per cent of patients to completely recall the details of prior anti-inflammatory drug therapy. Prompting firstly with the proprietary names of drugs and thereafter with a pill board substantially enhanced recall ...
Eyileten, Ceren; Majchrzak, Kinga; Pilch, Zofia; Tonecka, Katarzyna; Mucha, Joanna; Taciak, Bartlomiej; Ulewicz, Katarzyna; Witt, Katarzyna; Boffi, Alberto; Krol, Magdalena; Rygiel, Tomasz P.
Recent studies indicate the critical role of tumour associated macrophages, tumour associated neutrophils, dendritic cells, T lymphocytes, and natural killer cells in tumourigenesis. These cells can have a significant impact on the tumour microenvironment via their production of cytokines and chemokines. Additionally, products secreted from all these cells have defined specific roles in regulating tumour cell proliferation, angiogenesis, and metastasis. They act in a protumour capacity in vivo as evidenced by the recent studies indicating that macrophages, T cells, and neutrophils may be manipulated to exhibit cytotoxic activity against tumours. Therefore therapy targeting these cells may be promising, or they may constitute drug or anticancer particles delivery systems to the tumours. Herein, we discussed all these possibilities that may be used in cancer treatment. PMID:27212807
A targeted delivery system based on the polymeric nanoparticles as a drug carrier represents a marvelous avenue for cancer therapy. The pivotal characteristics of this system include biodegradability, biocompatibility, non-toxicity, prolonged circulation and a wide payload spectrum of a therapeutic agent. Other outstanding features are their distinctive size and shape properties for tissue penetration via an active and passive targeting, specific cellular/subcellular trafficking pathways and facile control of cargo release by sophisticated material engineering. In this review, the current implications of encapsulation of anticancer agents within polyhydroxyalkanoates, poly-(lactic-co-glycolic acid) and cyclodextrin based nanoparticles to precisely target the tumor site, i.e., cell, tissue and organ are highlighted. Furthermore, the promising perspectives in this emerging field are discussed. PMID:26706565
Kressig, Reto W
The optimal management of Alzheimer's disease (AD) involves a close alliance with AD caregivers and requires early diagnosis, multimodal management, including non-drug and drug interventions, and multispecialty care. Non-pharmacological approaches such as cognitive stimulation programs mostly benefit behavior and psychiatric symptoms in dementia patients. Pharmacologic management of AD consists of eliminating therapeutic redundancies and potentially deleterious medications (Beers Criteria). A pharmacologic foundation of Ginkgo Biloba and combination therapy with a cholinesterase inhibitor and memantine reduces decline in cognition and function, decreases and/or delays the emergence and impact of neuropsychiatric symptoms, postpones institutionalization, and works best when appropriately instituted early and maintained. Despite an existing reimbursement limitation by the health-insurance system in Switzerland, the combination of cholinesterase inhibitor and memantine is possible within the admitted MMSE ranges. PMID:25791046
Full Text Available Abstract Background Patients' non-adherence to drug therapy is a major problem for society as it is associated with reduced health outcomes. Generally, approximately only 50% of patients with chronic disease in developed countries adhere to prescribed therapy, and the most common non-adherence refers to chronic under-use, i.e. patients use less medication than prescribed or prematurely stop the therapy. Patients' non-adherence leads to high additional costs for society in terms of poor health. Non-adherence is also related to the unnecessary sale of drugs. The aim of the present study was to estimate the drug acquisition cost related to non-adherence to drug therapy in a national population. Methods We constructed a model of the drug acquisition cost related to non-adherence to drug therapy based on patient register data of dispensed out-patient prescriptions in the entire Swedish population during a 12-month period. In the model, the total drug acquisition cost was successively adjusted for the assumed different rates of primary non-adherence (prescriptions not being filled by the patient, and secondary non-adherence (medication not being taken as prescribed according to the patient's age, therapies, and the number of dispensed drugs per patient. Results With an assumption of a general primary non-adherence rate of 3%, and a general secondary non-adherence rate of 50%, for all types of drugs, the acquisition cost related to non-adherence totalled SEK 11.2 billion (€ 1.2 billion, or 48.5% of total drug acquisition costs in Sweden 2006. With the assumption of varying primary non-adherence rates for different age groups and different secondary non-adherence rates for varying types of drug therapies, the acquisition cost related to non-adherence totalled SEK 9.3 billion (€ 1.0 billion, or 40.2% of the total drug acquisition costs. When the assumption of varying primary and secondary non-adherence rates for a different number of dispensed drugs
Hovstadius Bo; Petersson Göran
Abstract Background Patients' non-adherence to drug therapy is a major problem for society as it is associated with reduced health outcomes. Generally, approximately only 50% of patients with chronic disease in developed countries adhere to prescribed therapy, and the most common non-adherence refers to chronic under-use, i.e. patients use less medication than prescribed or prematurely stop the therapy. Patients' non-adherence leads to high additional costs for society in terms of poor health...
Abstract Adjusting drug therapy to the individual, a common approach in clinical practice, has evolved from 1) dose adjustments based on clinical effects to 2) dose adjustments made in response to drug levels and, more recently, to 3) dose adjustments based on deoxyribonucleic acid (DNA) sequencing of drug-metabolizing enzyme genes, suggesting a slow drug metabolism phenotype. This development dates back to the middle of the 20th century, when several different drugs were administered on the ...
Ge, Yanxiu; Ma, Yakun; Li, Lingbing
Single drug therapy that leads to the multidrug resistance of cancer cells and severe side-effect is a thing of the past. Combination therapies that affect multiple signaling pathways have been the focus of recent active research. Due to the successful development of prodrug-based nano-drug delivery systems (P-N-DDSs), their use has been extended to combination therapy as drug delivery platforms. In this review, we focus specifically on the P-N-DDSs in the field of combination therapy including the combinations of prodrugs with different chemotherapeutic agents, other therapeutic agents, nucleic acid or the combination of different types of therapy (e.g. chemotherapy and phototherapy). The relevant examples of prodrug-based nanoparticulate drug delivery strategy in combination cancer therapy from the recent literature are discussed to demonstrate the feasibilities of relevant technology. PMID:27400243
The aim of magnetic drug targeting (MDT) in cancer therapy is to concentrate chemotherapeutics to a tumor region while simultaneously the overall dose is reduced. This can be achieved with coated superparamagnetic nanoparticles bound to a chemotherapeutic agent. These particles are applied intra arterially close to the tumor region and focused to the tumor by a strong external magnetic field. The interaction of the particles with the field gradient leads to an accumulation in the region of interest (i.e. tumor). The particle enrichment and thereby the drug-load in the tumor during MDT has been proven by several analytical and imaging methods. Moreover, in pilot studies we investigated in an experimental in vivo tumor model the effectiveness of this approach. Complete tumor regressions without any negative side effects could be observed. - Research Highlights: →Iron oxide nanoparticles can be enriched in tumors by external magnetic fields. → Histology evidences the intravasation of particles enter the intracellular space. → Non-invasive imaging techniques can display the spatial arrangement of particles. → HPLC-analysis show outstanding drug enrichment in tumors after MDT.
Alexiou, Christoph, E-mail: firstname.lastname@example.org [Department of Oto-rhino-laryngology, Head and Neck Surgery, University Hospital Erlangen, Section for Experimental Oncology and Nanomedicine at the Else Kroener-Fresenius-Stiftung-Professorship (Germany); Tietze, Rainer; Schreiber, Eveline [Department of Oto-rhino-laryngology, Head and Neck Surgery, University Hospital Erlangen, Section for Experimental Oncology and Nanomedicine at the Else Kroener-Fresenius-Stiftung-Professorship (Germany); Jurgons, Roland [Franz Penzoldt Center, University Hospital Erlangen (Germany); Richter, Heike; Trahms, Lutz [PTB Berlin (Germany); Rahn, Helene; Odenbach, Stefan [TU Dresden, Chair of Magnetofluiddynamics, 01062 Dresden (Germany); Lyer, Stefan [Department of Oto-rhino-laryngology, Head and Neck Surgery, University Hospital Erlangen, Section for Experimental Oncology and Nanomedicine at the Else Kroener-Fresenius-Stiftung-Professorship (Germany)
The aim of magnetic drug targeting (MDT) in cancer therapy is to concentrate chemotherapeutics to a tumor region while simultaneously the overall dose is reduced. This can be achieved with coated superparamagnetic nanoparticles bound to a chemotherapeutic agent. These particles are applied intra arterially close to the tumor region and focused to the tumor by a strong external magnetic field. The interaction of the particles with the field gradient leads to an accumulation in the region of interest (i.e. tumor). The particle enrichment and thereby the drug-load in the tumor during MDT has been proven by several analytical and imaging methods. Moreover, in pilot studies we investigated in an experimental in vivo tumor model the effectiveness of this approach. Complete tumor regressions without any negative side effects could be observed. - Research Highlights: Iron oxide nanoparticles can be enriched in tumors by external magnetic fields. Histology evidences the intravasation of particles enter the intracellular space. Non-invasive imaging techniques can display the spatial arrangement of particles. HPLC-analysis show outstanding drug enrichment in tumors after MDT.
Gene D. Morse; Qing Ma; Star Khoza; Tinashe Mudzviti; Maponga, Charles C.
Background. The main objective was to determine the impact of herbal drug use on adverse drug reactions in patients on antiretroviral therapy (ART). Methodology. Patients receiving first-line ART from the national roll-out program participated in this cross-sectional study. Participants were interviewed and a data collection sheet was used to collect information from the corresponding medical record. Results. The majority (98.2%) of participants were using at least one herbal drug together wi...
Full Text Available Long QT syndrome is a cardiac repolarization disorder, which can be either idiopathic or congenital, and cause sudden cardiac death. The iatrogenic form is generally associated with drugs or electrolyte imbalance. Although prolonged QT interval is frequently seen due to antiarrhythmic agents, it can also be seen with antibiotics or anti-epileptics. Adverse drug interaction can manifest in several clinicopathological forms in elder individuals. In such cases, potential adverse effects of drugs used should be taken into consideration before prescribing additional drugs. Here, we present a case of clarithromycine-induced ventricular arrhythmia accompanied by QT prolongation on the third day of therapy, and the subsequent therapeutic approach, in a 91-year-old man. The patient was taking multiple drugs due to comorbid conditions and was prescribed clarithromycine therapy in the intensive care unit.
Dakof, Gayle A.; Henderson, Craig E.; Rowe, Cynthia L.; Boustani, Maya; Greenbaum, Paul E.; Wang, Wei; Hawes, Samuel; Linares, Clarisa; Liddle, Howard A.
The objective of this article is to examine the effectiveness of 2 theoretically different treatments delivered in juvenile drug court—family therapy represented by multidimensional family therapy (MDFT) and group-based treatment represented by adolescent group therapy (AGT)—on offending and substance use. Intent-to-treat sample included 112 youth enrolled in juvenile drug court (primarily male [88%], and Hispanic [59%] or African American [35%]), average age 16.1 years, randomly assigned to ...
Bürgi, U; Gerber, H; Peter, H J
Graves' disease and toxic uni- or multinodular goiter are the most frequent causes of hyperthyroidism. Graves' disease is caused by thyroid stimulating immunoglobulins which are directed against the TSH receptor of thyroid follicular cells. Graves' disease affects more females than males and is associated with diffuse goiter and a rapid appearance of symptoms and signs of hyperthyroidism. Patients with Graves' disease are on average younger than patients with toxic nodular goiter. The diagnosis of Graves' disease is usually easy, particularly if signs of endocrine opthalmopathy are present. Toxic nodular goiter is seen more often in older patients with pre-existing goiters. Symptoms and signs of hyperthyroidism often appear only slowly. Hyperthyroidism in these older patients can be oligosymptomatic. Older patients should therefore be investigated for the presence of hyperthyroidism, even if they present only a few symptoms or signs which could suggest this diagnosis. The development of ultrasensitive TSH assays has simplified the diagnosis of hyperthyroidism and made the TRH-test, often used in the past, almost superfluous. At the present time, it is practically always possible to differentiate between Graves' disease and toxic nodular goiter as the cause of hyperthyroidism on the basis of clinical and laboratory findings alone, and in many cases thyroid scintiscans are therefore no longer necessary. A patient with newly diagnosed Graves' disease is treated with antithyroid drugs (carbimazole or PTU) for one year. If hyperthyroidism persists after this one year of antithyroid drug treatment, or if it recurs, another year of therapy with carbimazole or PTU is indicated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7545825
Antiepileptic drug combination therapy remains an empirical second-line treatment approach in trigeminal neuralgia, after treatment with one antiepileptic drug or other nonantiepileptic drugs have failed. The results in three patients followed in our clinic are not sufficient to draw definitive conclusions, but suggest the possibility of developing this type of therapeutic approach further.
Flotte, Thomas J.; Anderson, T.; McAuliffe, Daniel J., Sr.; Hasan, Tayyaba; Doukas, Apostolos G.
A new approach to drug delivery has been developed at the Wellman Laboratories of Photomedicine that is analogous to photodynamic therapy except that it utilizes high pressure impulse waves to increase the effectiveness of a variety of drugs rather than light activated drugs. This therapeutic modality offers a generic technology that can be used in a variety of conditions including infections, abscesses, and cancer.
Boermeester, M A; van Sandick, J W; van Lanschot, J J; Boeckxstaens, G E; Tytgat, G N; Obertop, H
The principal mechanism leading to gastro-oesophageal reflux is an increased frequency of transient lower oesophageal sphincter relaxations; other factors are oesophageal hypersensitivity to gastric juice, hiatus hernia, and possible duodenal reflux. Patients with classical symptoms such as heartburn and regurgitation may be treated pharmaceutically combined with life style counselling. If the symptoms have not improved after 6 to 12 weeks, endoscopical examination is performed and, if necessary, 24-hour pH monitoring, barium radiographing and manometry. In the case of atypical symptoms such as dysphagia, laryngitis, asthma and chest pain, there is more reason to pursue diagnostic testing. In patients with dysphagia endoscopy is indicated to exclude malignancy. Drug treatment can be subdivided into antacids, H2 receptor antagonists, cytoprotective agents, prokinetics and proton pump inhibitors. In general practice a step-up approach to treatment is preferable, while for specialist treatment a stepdown approach is more (cost-)effective. Drawbacks of medical treatment are considerable frequency of recurrence of oesophagitis, persistence of regurgitation in 'volume refluxers' and controversial data on the possible development of (pre)malignant lesions of oesophagus and stomach. Surgical treatment is a good alternative for patients with persistent severe regurgitation during medical therapy and for young patients who prefer surgery to lifelong medication. Patients with Barrett's oesophagus should undergo regular endoscopic biopsy surveillance. PMID:9752035
Sukhanov, D S; Vinogradova, T I; Demidik, S N; Zabolotnyh, N V; Vasilieva, S N; Kovalenko, A L; Vitovskaya, M L
The results of pre-clinical research of cycloferon, remaxol and runihol on the model of experimental generalized tuberculosis, caused by the MBT with a different spectrum of drug sensitivity are presented. A considerable increase of the curative effect of the therapy with the used of cycloferon and remaxol. There was manifested the strengthening of lung clearance from the office, reducing the prevalence of specific inflammation in the lungs of the index of lung damage, stimulation of sorption and destructive ability of peritoneal macrophages, inhibited in the course of development of experimental tuberculosis infection. Runihol has no impact on the effectiveness of chemotherapy in the absence of a stimulating influence on the phagocytic function of the peritoneal macrophages. PMID:23805718
Full Text Available Lumbar disc degeneration is a disorder whose clinical manifestations are represented by episodic pain in the lumbar spine, without lumbar blockage and minor muscle contraction. Because lumbalgia caused by lumbar disc degeneration is not always very high intensity pain, the easiest to apply treatment is drug therapy. The aim of this study was to analyze the potential role of rehabilitation treatment in the recovery of patients and the prevention of complications compared to drug therapy alone. The study included 28 patients (17 women and 11 men aged between 23-60 years, assigned to two groups: 20 patients who received rehabilitation treatment (consisting of massage, kinesiotherapy, hydrokinesiotherapy, electrotherapy and medication and 8 patients who received drug treatment consisting of anti-inflammatory and analgesic drugs. The treatment duration was 10 days. For the evaluation of pain, the visual analogue scale was used, for the degree of disability, the Oswestry questionnaire, and for joint mobility and muscle strength, articular and muscular testing. At the end of treatment, the study group compared to the control group had a statistically significant result for pain (p=0.001, as well as for the Oswestry score (p=0.030. The mean age of the patients was 35.51±3.026, which shows an increased incidence among young adults. A possible connection between the development of the disease in women and age less than 45 years was also investigated, but the result was not statistically significant, p=0.22. Our data suggest the fact that rehabilitation treatment plays an important role in the reduction of pain and the improvement of the quality of life of patients with lumbar disc degeneration by decreasing the degree of disability. In the future, it can be proposed to monitor patients with lumbar disc degeneration over a longer time period in order to see the effects of kinetic rehabilitation programs in relation to the delay of chronicization. As
Full Text Available Abstract Cardiology has recently witnessed the production of an overwhelming amount of data through the advances made in genetics and molecular biology research. Understanding of genetics has tremendous potential to aid in the prevention, diagnosis and treatment of the majority of diseases. Despite the high level of publicity for research discoveries, clinicians have had difficulty in discriminating between what is still basic research and what can be applied to patients. The fact is that we still lack the technology to perform genetic testing in a time frame that is acceptable to clinicians. Meanwhile, then, the only option is to rely on clinical tests that can help us better stratify the individuals at risk for a disease. For example, Brugada syndrome has benefited tremendously from genetics and molecular biology since its initial description in 1992. Genetics will provide a more definitive diagnosis for the disease in the future. For the time being, though, research has shown that the administration of an intravenous class I antiarrhythmic is very useful in identifying patients with a concealed form of the disease.
Lee, Sang Joon; Seo, Eunseok; Cho, Yonghyun
Many antimalarial drugs kill malaria parasites, but antimalarial drug resistance (ADR) and toxicity to normal cells limit their usefulness. To solve this problem, we suggest a new therapy for drug-resistant malaria. The approach consists of data integration and inference through homology analysis of yeast–human–Plasmodium. If one gene of a Plasmodium synthetic lethal (SL) gene pair has a mutation that causes ADR, a drug targeting the other gene of the SL pair might be used as an effective tre...
Hrgović, Z; Hrgović, I; Thaci, D
The erectile disfunction (ED) represent a disease where diagnostic and therapy are maial standardized. However in the pharmacological there exists a lot of administer justice and legal-insurent problems because there are to few registered medicines. In respect towards the new revolutionary development in the therapy of erectile disfunction, the injectionary therapy of the corpus cavernous loses it is permanent place. Without questions the modilities of the new oral therapy with sildenafil will replace many patients using the "injectionary therapy", concerving psychogenic, neurogenic and soft disturbance into bloodvint during the erection. Simply, it must be said, that there are no further results in the oral therapy, because of the short time research regarding sildenofil. Therefore it is not know what kind of side effects would resulting inffens of sildenafil. After taking one tablet the effects could be expected after half on hour. According to literature recent success with the new therapy in about 90%. PMID:9769638
Warangkana Lohcharoenkal; Liying Wang; Yi Charlie Chen; Yon Rojanasakul
Nanoparticles have increasingly been used for a variety of applications, most notably for the delivery of therapeutic and diagnostic agents. A large number of nanoparticle drug delivery systems have been developed for cancer treatment and various materials have been explored as drug delivery agents to improve the therapeutic efficacy and safety of anticancer drugs. Natural biomolecules such as proteins are an attractive alternative to synthetic polymers which are commonly used in drug formula...
Viller, F; Guillemin, F; Briancon, S; Moum, T; Suurmeijer, T; van den Heuvel, W
Objective. To delineate compliance with drug therapy in rheumatoid arthritis parents, determine specific characteristics of compliant and noncompliant patients, and took for changes in compliance over time. Patients and methods. A prospective European cohort study (EURIDISS) recruited 556 patients i
Swatantra Kumar Singh Kushwaha; Saurav Ghoshal; Awani Kumar Rai; Satyawan Singh
Carbon nanotubes (CNTs) were discovered in 1991 and shown to have certain unique physicochemical properties, attracting considerable interest in their application in various fields including drug delivery. The unique properties of CNTs such as ease of cellular uptake, high drug loading, thermal ablation, among others, render them useful for cancer therapy. Cancer is one of the most challenging diseases of modern times because its therapy involves distinguishing normal healthy cells from affec...
Wang, Feng; Feng, Ting-Yi; Yang, Shilin; Preter, Maurice; Zhou, Jiang-Ning; Wang, Xiao-Ping
Dementia, which can be induced by diverse factors, is a clinical syndrome characterized by the decline of cognitive function. Behavioral and psychological symptoms of dementia (BPSD) include depression, agitation, and aggression. Dementia causes a heavy burden on patients and their caregivers. Patients with BPSD should be assessed comprehensively by practitioners and offered appropriate non-pharmacologic and pharmacologic therapy. Nonpharmacologic therapy has been recommended as the basal treatment for BPSD; however, pharmacologic therapy is required under many situations. Medications, including antipsychotic agents, antidepressants, sedative and hypnotic agents, mood stabilizers, cholinesterase inhibitors, and amantadine, are extensively used in clinical practice. We have reviewed the progression of pharmacologic therapy for BPSD. PMID:26644152
Zhi-fang YANG; Ci-zhen LI; Wei WANG; Ying-min CHEN; Ying ZHANG; Yuan-mou LIU; Hong-wei WANG
Aim: To examine the electrophysiological effects of sophocarpine on action potentials (AP) and ionic currents of cardiac myocytes and to compare some of these effects with those of amiodarone.Methods: Langendorff perfusion set-up was used in isolated guinea pig heart, and responses to sophocarpine were monitored using electrocardiograph. Conventional microelectrode, voltage clamp technique and perforated patch were employed to record fast response AP (fAP), slow response AP (sAP) and ionic currents in guinea pig papillary muscle or rabbit sinus node cells.Results: Tachyarrhythmia produced by isoprenaline (15 μmol/L) could be reversed by sophocarpine (300 μmol/L). Sophocarpine (10 μmol/L) decreased the amplitude by 4.0%, maximal depolarization velocity (Vmax) of the fAP by 24.4%, and Na+ current (INa) by 18.0%,while it prolonged the effective refractory period (ERP) by 21.1%. The same concentration of sophocarpine could also decrease the amplitude and Vmax of the sAP, by 26.8% and 25.7%, respectively, and attenuated the Ca2+ current (ICaL) and the K+ tail current substantially. Comparison of sophocarpine with amiodarone demonstrated that both prolonged the duration and the ERP of fAP and sAP, both decreased the amplitude and Vmax of the fAP and sAP, and both slowed the automatic heart rate.Conclusion: Sophocarpine could reverse isoprenaline-induced arrhythmia and inhibit INa, IcaL, and Ikr currents. The electrophysiological effects of sophocarpine are similar to those of amiodarone, which might be regarded as a prospective antiarrhythmic agent.
The article reviews the latest progress related to antiarrhythmic pharmacogenomics and cardiovascular diseases and health for women. It includes: (1) basic concepts; (2) cytochrome P450 polymorphisms and antiarrhythmic drugs; (3 ) polymorphisms coding ion channels and arrhythmias; (4) gender differences of expression for ion channel and transfer subunits; (5) gender differences of ventricular repolarization; (6) gender differences of inherrited and drug-induced long QT syndrome and treatment strategy; (7) selective estrogen receptor modulator raloxifene and QT interval; (8) the additive effects of naringenin and antiarrhythmic drug.%本文将从与女性心血管健康相关的角度,综述与心律失常相关的药物基因组学进展.主要内容包括:(1)药物基因组学的概念与研究范围；(2)细胞色素P450遗传多态对抗心律失常药物疗效的影响；(3)编码离子通道的基因多态与心律失常的关系；(4)离子通道及转运亚单位心脏表达的性别差异；(5)心室复极的性别差异及其成因；(6)先天性和药物引起的长QT综合征的性别差异及围产期长QT综合征患者的治疗策略；(7)女性雌激素治疗对QT间期的作用；(8)柚皮素与抗心律失常药物的叠加作用等.
Rowe, Cynthia L.
Just 15 years ago, Liddle and Dakof ("Journal of Marital and Family Therapy," 1995; 21, 511) concluded, based on the available evidence, that family therapy represented a "promising, but not definitive" approach for the treatment of drug problems among adolescents and adults. Seven years later, Rowe and Liddle (2003) review described considerable…
Myllylä, T.; Popov, A.; Surazyński, L.; Oinas, J.; Bibikova, O.; Bykov, A.; Wróbel, M. S.; Gnyba, M.; Jedrzejewska-Szczerska, M.; Meglinski, I.; Kuittinen, O.
Our aim is to optically monitor the delivery of the chemotherapy drugs for brain tumours, particularly used in the central nervous system (CNS) lymphoma therapy. In vivo monitoring would help to optimize the treatment and avoiding unnecessary medications. Moreover, it would be beneficial to be able to measure which of the multi-regimen drugs actually do penetrate and how well into the brain tissue. There exist several potential optical measurement techniques to be utilised for the purpose. The most desired method would allow the detection of the drugs without using optical biomarkers as a contrast agent. In this case, for non-invasive sensing of the drug in the brain cortex, the drug should have a reasonably strong optical absorption band somewhere in the range between 600 nm and 1700 nm, and not directly coincident with the strong bands of haemoglobin or water. Alternatively, mid-infrared (MIR) range has the potential for invasive drug monitoring techniques. In this paper, we report the optical properties of several chemotherapy drugs used in CNS lymphoma therapy, such as rituximabi, cyclophosphamide and etoposide. We measured their transmittance and reflectance spectra in near-infrared (NIR) range, particularly 900 nm - 2500 nm, to be considered when choosing the in vivo monitoring method to be developed. The absorption and scattering coefficients were retrieved from the measurements and applying Beer's law. For the measurement of the sum of total transmission and reflection in NIR range we used integrating sphere with spektralo to enable calculation of the scattering coefficient.
Lindstrøm, Maia; Filges, Trine; Jørgensen, Anne-Marie Klint
Purpose: This review evaluates the evidence on the effects of brief strategic family therapy (BSFT) on drug use reduction for young people in treatment for nonopioid drug use. Method: We followed Campbell Collaboration guidelines to prepare this review and ultimately located three studies for final analysis and interpretation. Results: The results…
There are several different types of drug delivery interfaces available on the market. Using the right interface for aerosol drug delivery to children is essential for effective inhalation therapy. However, clinicians usually focus on selecting the right drug-device combination and often overlook the importance of interface selection that lead to suboptimal drug delivery and therapeutic response in neonates and pediatrics. Therefore, it is necessary to critically assess each interface and understand its advantage and disadvantages in aerosol drug delivery to this patient population. The purpose of this paper is to provide a critical assessment of drug delivery interfaces used for the treatment of children with pulmonary diseases by emphasizing advantages and problems associated with their use during inhalation therapy. PMID:27610343
D. R. Khasanova; Yu V Zhitkova; L.M. Yu.V.
Objective: to compare a multimodal drug approach to treating poststroke cognitive impairments (CI).Patients and methods. Eighty patients with postroke CI in the early recovery period were examined. They were allocated to 4 groups:1) secondary stroke prevention only (a comparison nontreatment group); 2) actovegin infusions; 3) cerebrolysin infusions; 4) drug therapy in combination with non-drug cognitive training using the standard procedure. Follow-ups and neuropsychological assessments were ...
Xu, Ronald X.; Xu, Jeff S.; Zuo, Tao; Shen, Rulong; Huang, Tim H.; Michael F. Tweedle
We synthesize drug-loaded poly (lactic-co-glycolic acid) (PLGA) microspheres for image-guided combinatory epigenetic therapy in MCF-10A human mammary epithelial cells. LY294002 and Nile Red are encapsulated in microspheres for sustained drug release and fluorescence microscopic imaging. Drug-loaded microspheres target MCF-10A cells through a three-step binding process involving biotinylated antibody, streptavidin, and biotinylated microspheres. LY294002 loaded microspheres and 5-Aza-2-deoxycy...
Tatyana Andreyevna Lisitsyna; N. M. Kosheleva
The data available in the literature on experience in using antimalarial drugs in the treatment of systemic lupus erythematosus are summarized. A major emphasis is placed on therapy with hydroxychlorochine (plaquenil) versus chlorine. Possible mechanisms of action of the drug and its effect on the course of the disease itself and concomitant abnormalities are described. Data on the toxicity of the drug and its safe use in pregnancy and lactation are also discussed
Tatyana Andreyevna Lisitsyna
Full Text Available The data available in the literature on experience in using antimalarial drugs in the treatment of systemic lupus erythematosus are summarized. A major emphasis is placed on therapy with hydroxychlorochine (plaquenil versus chlorine. Possible mechanisms of action of the drug and its effect on the course of the disease itself and concomitant abnormalities are described. Data on the toxicity of the drug and its safe use in pregnancy and lactation are also discussed
Behrens, F; Thaçi, D; Wollenhaupt, J; Krüger, K
Psoriatic arthritis is a chronic inflammatory disease of the musculoskeletal system with association to skin psoriasis and is characterized by variable clinical symptoms with very heterogeneous degrees of disease suffering for patients. Clinical manifestations essentially include alterations to the skin and nails, peripheral arthritis, enthesitis, dactylitis and/or spinal involvement. This variability necessitates an individualized therapy of patients with different therapy targets. Apart from international guidelines no therapy recommendations are available in Germany for treatment of psoriatic arthritis. For this reason this article summarizes the established points, characteristics and aspects to be considered in the therapy of psoriatic arthritis in Germany, taking the various main forms of the disease into consideration. PMID:27259913
Shi, Changying; Guo, Dandan; Xiao, Kai; Wang, Xu; Wang, Lili; Luo, Juntao
The drug-loading properties of nanocarriers depend on the chemical structures and properties of their building blocks. Here we customize telodendrimers (linear dendritic copolymer) to design a nanocarrier with improved in vivo drug delivery characteristics. We do a virtual screen of a library of small molecules to identify the optimal building blocks for precise telodendrimer synthesis using peptide chemistry. With rationally designed telodendrimer architectures, we then optimize the drug-binding affinity of a nanocarrier by introducing an optimal drug-binding molecule (DBM) without sacrificing the stability of the nanocarrier. To validate the computational predictions, we synthesize a series of nanocarriers and evaluate systematically for doxorubicin delivery. Rhein-containing nanocarriers have sustained drug release, prolonged circulation, increased tolerated dose, reduced toxicity, effective tumour targeting and superior anticancer effects owing to favourable doxorubicin-binding affinity and improved nanoparticle stability. This study demonstrates the feasibility and versatility of the de novo design of telodendrimer nanocarriers for specific drug molecules, which is a promising approach to transform nanocarrier development for drug delivery.
Esmay, J B; Wertheimer, A I
The authors review the extent of the use of nonprescription drugs as well as possible variables influencing such consumption. Various studies indicate that age, sex, personality characteristics, perceptions of health status, socioeconomic factors, parental example, and pharmacists all play parts in determining over-the-counter (OTC) drug utilization. Several sources express concern about the inaccessibility of accurate OTC drug information to the consumer. Indeed, even the FDA has occasional difficulty obtaining reliable facts on both the numbers and formulae of such products. Several studies indicate that consumers acquire information about their home remedies through advertising, friends and relatives, physicians, pharmacists, and product labels. By far the most influential of these is advertising, and much concern has been voiced over consumers' unquestioning faith in drug ads. Examples are cited of deceptive, inaccurate, and unfair advertising practices used by some OTC drug manufacturers. The pros and cons of the "drug-oriented society" theory are discussed, including an analysis of its underlying origins. Testing of the safety and efficacy of nonrescription remedies has proved to be controversial, especially when considering the ramifications of the placebo effect. Different surveys report widespread misuse of OTC's by consumers through overuse, taking several drugs concurrently, and using home remedies to treat potentially serious diseases. PMID:500849
Neoadjuvant chemotherapy (NACT), neoadjuvant endocrine therapy (NAET), and neoadjuvant targeted therapy (NATT), more recently, have been adopted worldwide as standard of care in locally advanced and inoperable BC. These modalities, collectively called neoadjuvant systemic therapy (NAST), are also used for organ preservation and for mechanistic biological studies on drug response and resistance, drug development, and clinical trials. Furthermore, the response to NACT is a valuable indicator of long-term survival. In this work, the advantages and pitfalls of using NAST in BC for studying drug response and resistance for drug development and clinical trials are discussed as well as practical points on how to set up a NAST clinical trial in BC. PMID:26910079
K Allegaert; Van den Anker, J
Knowledge about the safe and effective use of medicines in neonates has increased substantially but has resulted in few label changes. Drugs developed for use in adults are reshaped and tailored to specific neonatal indications. However, the use of drugs in neonates should not only mirror adult pharmacotherapy, but should be driven by their own specific needs. Therefore, building collaborative networks may assist to develop a newborn-driven research agenda addressing their clinical needs and ...
Full Text Available Abstract Background Supraventricular arrhythmias after thoracotomy for pulmonary resections are well documented. There has been considerable interest in their incidence, nature, predictability from preoperative assessment and treatment. The purpose of this study is to define prevalence, type, risk factors for post-thoracotomy supraventricular arrhythmias and to assess the efficacy of amiodarone as an antiarrhythmic drug. Methods The records of 250 patients undergoing pulmonary resection for lung cancer during last two years were followed up in this prospective study with particular attention to possible risk factors (gender, age, extent and side of resection, diabetes mellitus, hypertension, tobacco smoking, beta-blocker ingestion. Patients underwent biopsy only were excluded. Once onset of supraventricular arrhythmia was monitored or documented in the electrocardiogram, intravenous infusion of amiodarone was started with a loading dose of 5 mg/kg in 30 minutes and a maintenance dose of 15 mg/kg until remission of it. Results Forty-three episodes (21.6% of supraventricular arrhythmias were documented with atrial fibrillation being the most common (88.3%. Rhythm disturbances were most likely to develop on the second postoperative day. Pneumonectomy, lobectomy and age >65 years were the statistically significant factors. The overall postoperative mortality was 3.2% and 2.3% for the patients with postoperative supraventricular arrhythmias. In none of the cases did supraventricular arrhythmia cause cardiac failure leading to death. Sinus rhythm was achieved with amiodarone in 37 out of 43 patients (86%. Electrical cardioversion was necessary for 6 patients who were hemodynamically unstable. The most common amiodarone-related complication was bradycardia (13.5%. Conclusions Postoperative supraventricular arrhythmias are a common complication in elderly patients undergoing lung resection surgery (especially pneumonectomy or lobectomy. Amiodarone is
Full Text Available D08421 Drug Procainamide (INN) C13H21N3O 235.1685 235.3253 D08421.gif Antiarrhythmi... CLASS I AND III C01BA Antiarrhythmics, class Ia C01BA02 Procainamide D08421 Procainamide (INN) USP drug cla...ssification [BR:br08302] Cardiovascular Agents Antiarrhythmics Procainamide D08421 Procainamide (INN) Target...a, NaV1.x voltage-gated sodium channel (SCN1A) [HSA:6323] [KO:K04833] Procainamid...e [ATC:C01BA02] D08421 Procainamide (INN) voltage-gated sodium channel (SCN2A) [HSA:6326] [KO:K04834] Procai
A novel functional‐genomics based concept of pharmacology that uses artificial intelligence techniques for mining and knowledge discovery in “big data” providing comprehensive information about the drugs’ targets and their functional genomics is proposed. In “process pharmacology”, drugs are associated with biological processes. This puts the disease, regarded as alterations in the activity in one or several cellular processes, in the focus of drug therapy. In this setting, the molecular drug targets are merely intermediates. The identification of drugs for therapeutic or repurposing is based on similarities in the high‐dimensional space of the biological processes that a drug influences. Applying this principle to data associated with lymphoblastic leukemia identified a short list of candidate drugs, including one that was recently proposed as novel rescue medication for lymphocytic leukemia. The pharmacological data science approach provides successful selections of drug candidates within development and repurposing tasks. PMID:27069773
Amundstuen Reppe, Linda; Spigset, Olav; Schjøtt, Jan
Polypharmacy and complex drug treatment regimens are becoming increasingly common, which may lead to adverse drug reactions, drug interactions, medication nonadherence, and increasing costs and thus challenge the rational use of drugs. At the same time, the accessibility of drug information increases, and health care professionals may have limited opportunities and capabilities to search and critically evaluate drug information. Clinicians have reported difficulties in searching the best evidence and translating study findings into clinically meaningful information applicable to specific patients. Consequently, it remains a challenge to ensure the rational use of drugs in the years to come. Drug information centers (DICs) have been established to promote the rational use of drugs. One of the most important tasks of DICs is the question and answer services for health care professionals posing drug-related questions. DICs staffed by pharmacists and clinical pharmacologists hold expertise in searching for drug information and critical evaluation of the literature. The uniqueness in this service lies not only in the identification and interpretation of the scientific literature but also in the adaptation of the findings into specific clinical situations and the discussion of possible solutions with the enquirer. Thus, DICs could provide valuable decision support to the clinic. Taking into account the increasing number of possible drug-related questions that will arise today and in the future, the DICs will remain highly relevant in the years to come. However, the DICs must follow the developments in health information technology to disseminate relevant, unbiased drug information to old and new users of the service. Moreover, the DICs are important tools to counterbalance the drug information published by the pharmaceutical industry. PMID:26831829
Goli, Veeraindar; Krishnan, Ranga; Ellinwood, Everett
An estimated three to seven million Americans suffer from obsessive compulsive disorder at some time in their lives. Until recently, obsessive compulsive disorder was considered refractory to most treatments. However, recent studies indicate a better prognosis with behavioral therapy, antidepressant medications, or both. Behavioral treatment is generally more effective for compulsions than for obsessions.
Contreras, Gabriel; Greene, Tom; Agodoa, Lawrence Y; Cheek, DeAnna; Junco, George; Dowie, Donna; Lash, James; Lipkowitz, Michael; Miller, Edgar R; Ojo, Akinlou; Sika, Mohammed; Wilkening, Beth; Toto, Robert D
The African American Study of Kidney Disease and Hypertension examined the effect on renal function decline of 2 blood pressure (BP) goals (low mean arterial pressure [MAP] disease (ESRD), death, or GFR decline by 50% or 25 mL/min per 1.73 m2. This report examines the effect of the BP intervention separately in the 3 drug groups. The BP effect was similar among the drug groups for either GFR slope or the main clinical composite. However, the BP effect differed significantly among the drug groups for the composite of ESRD or death (P=0.035) and ESRD alone (P=0.021). Higher event rates for amlodipine patients assigned to the usual BP goal (0.087 per patient-year for ESRD or death and 0.064 per patient-year for ESRD) were seen compared with the remaining groups of the factorial design (range, 0.041 to 0.050 for ESRD or death; and range, 0.027 to 0.036 for ESRD). The low BP goal was associated with reduced risk of ESRD or death (risk reduction 51%; 95% confidence interval, 13% to 73%) and ESRD (54%; 8% to 77%) for amlodipine patients, but not for patients assigned to the other drug groups. These secondary analyses suggest a benefit of the low BP goal among patients assigned to amlodipine, but they must be interpreted cautiously. PMID:15897360
For healthcare professionals, the volume of literature available on herb-drug interactions often makes it difficult to separate experimental/potential interactions from those deemed clinically relevant. There is a need for concise and conclusive information to guide pharmacotherapy in HIV/AIDS. In t...
Kunkel, Amber; Colijn, Caroline; Lipsitch, Marc; Cohen, Ted
Various forms of preventive and prophylactic antimicrobial therapies have been proposed to combat HIV (e.g. pre-exposure prophylaxis), tuberculosis (e.g. isoniazid preventive therapy) and malaria (e.g. intermittent preventive treatment). However, the potential population-level effects of preventative therapy (PT) on the prevalence of drug resistance are not well understood. PT can directly affect the rate at which resistance is acquired among those receiving PT. It can also indirectly affect resistance by altering the rate at which resistance is acquired through treatment for active disease and by modifying the level of competition between transmission of drug-resistant and drug-sensitive pathogens. We propose a general mathematical model to explore the ways in which PT can affect the long-term prevalence of drug resistance. Depending on the relative contributions of these three mechanisms, we find that increasing the level of coverage of PT may result in increases, decreases or non-monotonic changes in the overall prevalence of drug resistance. These results demonstrate the complexity of the relationship between PT and drug resistance in the population. Care should be taken when predicting population-level changes in drug resistance from small pilot studies of PT or estimates based solely on its direct effects. PMID:25918446
To determine compliance and factors affecting compliance to antiresorptive drugs in osteoporosis, and to compare compliant and non compliant groups in a tertiary care setting. A total of 800 patients with postmenopausal osteoporosis were included in the study. The demographic and reproductive characteristics of all the patients were recorded. Type of antiresorptive drugs prescribed, degree of compliance, time and reasons for discontinuation were studied and analyzed. The mean age of the patients was 64 (+-9) years and their mean duration of follow-up 18 (+-5) months. The prevalence of risk factors for osteoporosis were evenly distributed among treatment groups; 73% patients had a co-morbidity besides osteoporosis while 27% were osteoporotic alone. One or more previous vertebral fractures due to osteoporosis was reported by 14.5% of patients, whereas 35.5% had at least one non-vertebral fracture in their medical history. Out of the total patients 21.5% discontinued the prescribed drug before attending the bone mass re-evaluations, more than half of these within first six months of starting the drugs. The medication that was most frequently discontinued within one year was calcium and vitamin-D (33.7%, p<0.01) while the least discontinued medication was Alendronate (5.9%, p < 0.01) which is taken once a week. In this study the most important determinant of compliance was the type of drug prescribed and its dose frequency, with a definite preference for Alendronate once a week. Treatment compliance was particularly poor for calcium and vitamin-D regimen, thereby emphasizing the need to find new ways of administering supplements, particularly for vitamin-D. (author)
Swatantra Kumar Singh Kushwaha
Full Text Available Carbon nanotubes (CNTs were discovered in 1991 and shown to have certain unique physicochemical properties, attracting considerable interest in their application in various fields including drug delivery. The unique properties of CNTs such as ease of cellular uptake, high drug loading, thermal ablation, among others, render them useful for cancer therapy. Cancer is one of the most challenging diseases of modern times because its therapy involves distinguishing normal healthy cells from affected cells. Here, CNTs play a major role because phenomena such as EPR, allow CNTs to distinguish normal cells from affected ones, the Holy Grail in cancer therapy. Considerable work has been done on CNTs as drug delivery systems over the last two decades. However, concerns over certain issues such as biocompatibility and toxicity have been raised and warrant extensive research in this field.
Kushwaha, Swatantra Kumar Singh; Ghoshal, SauravI; Rai, Awani Kumar, E-mail: email@example.com [Pranveer Singh Institute of Technology, Kanpur (India); Singh, Satyawan [Saroj Institute of Technology and Management, Lucknow (India)
Carbon nanotubes (CNTs) were discovered in 1991 and shown to have certain unique physicochemical properties, attracting considerable interest in their application in various fields including drug delivery. The unique properties of CNTs such as ease of cellular uptake, high drug loading, thermal ablation, among others, render them useful for cancer therapy. Cancer is one of the most challenging diseases of modern times because its therapy involves distinguishing normal healthy cells from affected cells. Here, CNTs play a major role because phenomena such as EPR, allow CNTs to distinguish normal cells from affected ones, the Holy Grail in cancer therapy. Considerable work has been done on CNTs as drug delivery systems over the last two decades. However, concerns over certain issues such as biocompatibility and toxicity have been raised and warrant extensive research in this field. (author)
It is generally accepted that development of novel therapies to treat pregnancy-relates disorders, such as preeclampsia, is hampered to the paucity of research funding. Hence, it is with great interest to become aware of at least three novel therapeutic approaches for the treatment of this disorder, exploiting either the anticoagulant activity of antithrombin, the free radical scavenging activity of alpha-1-microglobulin, or the regenerative capacity of placenta-derived mesenchymal stem cells...
It is generally accepted that the development of novel therapies to treat pregnancy-related disorders, such as preeclampsia, is hampered by the paucity of research funding. Hence, it is with great interest to become aware of at least three novel therapeutic approaches for the treatment of this disorder: exploiting either the anticoagulant activity of antithrombin, the free radical scavenging activity of alpha-1-microglobulin, or the regenerative capacity of placenta-derived mesenchymal stem c...
Safar, Michel E.
Michel E SafarParis-Descartes University, Faculty of Medicine, Hôtel-Dieu Hospital, AP-HP, Diagnosis Center, Paris, FranceAbstract: In hypertensive subjects, cardiovascular risk reduction is critically related to the decrease of systolic blood pressure (SBP). De-stiffening therapy means that, in a controlled therapeutic trial of long duration, a selective reduction of SBP has been obtained in the studied group by comparison with the control group, and that this SBP reduction is due ...
Zhang, Ben-Gong; Tanaka, Gouhei; Aihara, Kazuyuki; Honda, Masao; Kaneko, Shuichi; Chen, Luonan
This paper studies the dynamics of the hepatitis B virus (HBV) model and the therapy regimens of HBV disease. First, we propose a new mathematical model of HBV with drug resistance, and then analyze its qualitative and dynamical properties. Combining the clinical data and theoretical analysis, we demonstrate that our model is biologically plausible and also computationally viable. Second, we demonstrate that the intermittent antiviral therapy regimen is one of the possible strategies to treat this kind of complex disease. There are two main advantages of this regimen, i.e. it not only may delay the development of drug resistance, but also may reduce the duration of on-treatment time compared with the long-term continuous medication. Moreover, such an intermittent antiviral therapy can reduce the adverse side effects. Our theoretical model and computational results provide qualitative insight into the progression of HBV, and also a possible new therapy for HBV disease.
Alimoradi, Houman; Matikonda, Siddharth S; Gamble, Allan B; Giles, Gregory I; Greish, Khaled
Hypoxia is a common characteristic of solid tumors. It is mainly determined by low levels of oxygen resulting from imperfect vascular networks supplying most tumors. In an attempt to improve the present chemotherapeutic treatment and reduce associated side effects, several prodrug strategies have been introduced to achieve hypoxia-specific delivery of cytotoxic anticancer agents. With the advances in nanotechnology, novel delivery systems activated by the consequent outcomes of hypoxia have been developed. However, developing hypoxia responsive drug delivery systems (which only depend on low oxygen levels) is currently naïve. This review discusses four main hypoxia responsive delivery systems: polymeric based drug delivery systems, oxygen delivery systems combined with radiotherapy and chemotherapy, anaerobic bacteria which are used for delivery of genes to express anticancer proteins such as tumor necrosis alpha (TNF-α) and hypoxia-inducible transcription factors 1 alpha (HIF1α) responsive gene delivery systems. PMID:26898739
Oliveira, Rudi; Miranda, Daniela; Magalhães, Joana; Capela, Rita; Perry, Maria J; O'Neill, Paul M; Moreira, Rui; Lopes, Francisca
The discovery of new drugs to treat malaria is a continuous effort for medicinal chemists due to the emergence and spread of resistant strains of Plasmodium falciparum to nearly all used antimalarials. The rapid adaptation of the malaria parasite remains a major limitation to disease control. Development of hybrid antimalarial agents has been actively pursued as a promising strategy to overcome the emergence of resistant parasite strains. This review presents the journey that started with simple combinations of two active moieties into one chemical entity and progressed into a delivery/targeted system based on major antimalarial classes of drugs. The rationale for providing different mechanisms of action against a single or additional targets involved in the multiple stages of the parasite's life-cycle is highlighted. Finally, a perspective for this polypharmacologic approach is presented. PMID:25913864
Palepu, Anita; Tyndall, Mark W.; Li, Kathy; Yip, Benita; O’Shaughnessy, Michael V.; Schechter, Martin T.; Montaner, Julio S.G.; Hogg, Robert S.
We conducted this study among HIV-infected injection drug users to determine the effect of self-reported alcohol use and prior incarceration at the time of initiating antiretroviral therapy on subsequent HIV-1 RNA suppression. We examined the demographics, recent incarceration history, and drug and alcohol use history from the Vancouver Injection Drug User Study (VIDUS) questionnaire closest to the date of initiating antiretroviral therapy. We linked these data to the HIV/AIDS Drug Treatment ...
Hananditia R. Pramestutie; Nina Silviana
Hypertension is a persistent blood pressure in which systolic pressure ≥140 mmHg and diastolic pressure ≥90 mmHg. The knowledge that should be owned by patients with hypertension is the meaning, causes, symptoms and treatment of hypertension. This knowledge is important to support the success of hypertension therapy. The aim of this research was to determine the knowledge level of hypertension patients about their drug therapy in the primary health care of Malang. This research used observati...
Selimović, Edin; Ibrahimagić-Šeper, Lejla; Petričević, Nikola; Nola-Fuchs, Petra
Purpose of this study was to compare the effects of combined therapy using nonsteroid anti-inflammatory analgetics and corticosteroids, and the effects of the mono-therapy with same drugs for post-operative pain after surgical removal of the impacted mandibular third molar. The study was completed at the Department of Oral Surgery and at the Department of Dental Medicine of the Public Institute Health Center Zenica in Zenica. The research included 60 patients divided into 3 groups...
Monteith, Teshamae S.; Goadsby, Peter J.
Opinion Statement The conceptual shift of our understanding of migraine from a vascular disorder to a brain disorder has dramatically altered the approach to the development of new medicines in the field. Current pharmacologic treatments of acute migraine consist of nonspecific and relatively specific agents. Migraine-specific drugs comprise two classes, the ergot alkaloid derivatives and the triptans, serotonin 5-HT1B/1D receptor agonists. The ergots, consisting of ergotamine and dihydroergo...
Full Text Available Objective: to compare a multimodal drug approach to treating poststroke cognitive impairments (CI.Patients and methods. Eighty patients with postroke CI in the early recovery period were examined. They were allocated to 4 groups:1 secondary stroke prevention only (a comparison nontreatment group; 2 actovegin infusions; 3 cerebrolysin infusions; 4 drug therapy in combination with non-drug cognitive training using the standard procedure. Follow-ups and neuropsychological assessments were made at the inclusion in the study and 3 and 6 months after stroke. The state of cognitive functions 6 months after stroke was considered to be an endpoint of the study.Results and discussion. At the inclusion in the study, the mini-mental state examination and the frontal lobe dysfunction scale showed no statistical differences in cognitive functions in different patient groups. At a 3-month follow-up, the cognitive status in the neuronal plasticity stimulation groups was significantly better than in the comparison group (p≤0.05. At a 6-month follow-up, there was a significant cognitive improvement in the combined stimulation group versus the drug-therapy and comparison groups (p≤0.05. Day-to-day activities and independent functioning also improved significantly more promptly in the patients receiving drug or combined therapies. More complex instrumental activities of daily living recovered significantly better during combined cognitive function stimulation than during pharmacological stimulation only. There was evidence that the drugs with proven stimulating effects on neuronal plasticity and nondrug cognitive training were effective in treating CI in the early recovery period of stroke. The combined drug and nondrug poststroke CI treatments reflecting the multimodal approach versus drug therapy were found to be most effective in these patients.
Gjini, Erida; Brito, Patricia H.
Antimicrobial resistance of infectious agents is a growing problem worldwide. To prevent the continuing selection and spread of drug resistance, rational design of antibiotic treatment is needed, and the question of aggressive vs. moderate therapies is currently heatedly debated. Host immunity is an important, but often-overlooked factor in the clearance of drug-resistant infections. In this work, we compare aggressive and moderate antibiotic treatment, accounting for host immunity effects. W...
Piktel, Ewelina; Niemirowicz, Katarzyna; Wątek, Marzena; Wollny, Tomasz; Deptuła, Piotr; Bucki, Robert
The rapid development of nanotechnology provides alternative approaches to overcome several limitations of conventional anti-cancer therapy. Drug targeting using functionalized nanoparticles to advance their transport to the dedicated site, became a new standard in novel anti-cancer methods. In effect, the employment of nanoparticles during design of antineoplastic drugs helps to improve pharmacokinetic properties, with subsequent development of high specific, non-toxic and biocompatible anti...
Wallace, Jill S; Hall, John C
Acute cutaneous necrosis is defined as a sudden onset of gangrenous skin changes in the skin, associated with significant morbidity and mortality. The following diseases are included in this discussion: coumadin necrosis, heparin necrosis, brown recluse spider bite, necrotizing fasciitis, vasculitis, pyoderma gangrenosum, calciphylaxis, clotting abnormalities and embolic phenomena. The importance of early diagnosis, early distinction and early drug therapy or drug withdrawal must match the diagnosis for maximal preservation of the skin and underlying tissue. PMID:20514791
Guerrier, Karine; Shamszad, Pirouz; Czosek, Richard J; Spar, David S; Knilans, Timothy K; Anderson, Jeffrey B
Supraventricular tachycardia (SVT) is the most frequent form of symptomatic tachyarrhythmia in infants. The purposes of this study were to describe practice patterns of the management of infants hospitalized with SVT and factors associated with 30-day hospital readmission. This was a multi-institutional, retrospective review of the pediatric health information system database of SVT hospitalizations from 2003 to 2013. High-volume centers (HVC) were defined as those at the upper quartile of admissions. Infants with an ICD-9 code of paroxysmal SVT were included. Antiarrhythmics investigated included amiodarone, atenolol, digoxin, esmolol, flecainide, procainamide, propafenone, propranolol, and sotalol. Frequency of antiarrhythmic use based on center volume was the primary end point. Rate of 30-day SVT readmission was the secondary end point. Analysis of factors associated with readmission was assessed by Chi-square analysis and expressed as odds ratio and 95 % confidence interval. A total of 851 patients (60 % male, 44 % neonates) were hospitalized at 43 hospitals. Propranolol, digoxin, and amiodarone were the most frequently utilized antiarrhythmics. HVCs represented 12 hospitals comprising 494 (58 %) patients. Although HVCs were more likely to utilize propranolol (OR 2.5, CI 1.5-4.1), there was no significant difference in the 30-day readmission rate between patients treated at HVCs versus non-HVCs (p = 0.9). The majority of infants with SVT are treated with a small number of antiarrhythmic medications during index hospitalization. Although hospital-to-hospital variation in antiarrhythmic choice exists, there appears to be no difference in readmission. The remaining practice variation may be related to intrinsic patient characteristics. PMID:27033244
Full Text Available An in silico chemical genomics approach is developed to predict drug repositioning (DR candidates for three types of cancer: glioblastoma, lung cancer, and breast cancer. It is based on a recent large-scale dataset of ~20,000 drug-induced expression profiles in multiple cancer cell lines, which provides i a global impact of transcriptional perturbation of both known targets and unknown off-targets, and ii rich information on drug's mode-of-action. First, the drug-induced expression profile is shown more effective than other information, such as the drug structure or known target, using multiple HTS datasets as unbiased benchmarks. Particularly, the utility of our method was robustly demonstrated in identifying novel DR candidates. Second, we predicted 14 high-scoring DR candidates solely based on expression signatures. Eight of the fourteen drugs showed significant anti-proliferative activity against glioblastoma; i.e., ivermectin, trifluridine, astemizole, amlodipine, maprotiline, apomorphine, mometasone, and nortriptyline. Our DR score strongly correlated with that of cell-based experimental results; the top seven DR candidates were positive, corresponding to an approximately 20-fold enrichment compared with conventional HTS. Despite diverse original indications and known targets, the perturbed pathways of active DR candidates show five distinct patterns that form tight clusters together with one or more known cancer drugs, suggesting common transcriptome-level mechanisms of anti-proliferative activity.
Lee, Haeseung; Kang, Seungmin; Kim, Wankyu
An in silico chemical genomics approach is developed to predict drug repositioning (DR) candidates for three types of cancer: glioblastoma, lung cancer, and breast cancer. It is based on a recent large-scale dataset of ~20,000 drug-induced expression profiles in multiple cancer cell lines, which provides i) a global impact of transcriptional perturbation of both known targets and unknown off-targets, and ii) rich information on drug's mode-of-action. First, the drug-induced expression profile is shown more effective than other information, such as the drug structure or known target, using multiple HTS datasets as unbiased benchmarks. Particularly, the utility of our method was robustly demonstrated in identifying novel DR candidates. Second, we predicted 14 high-scoring DR candidates solely based on expression signatures. Eight of the fourteen drugs showed significant anti-proliferative activity against glioblastoma; i.e., ivermectin, trifluridine, astemizole, amlodipine, maprotiline, apomorphine, mometasone, and nortriptyline. Our DR score strongly correlated with that of cell-based experimental results; the top seven DR candidates were positive, corresponding to an approximately 20-fold enrichment compared with conventional HTS. Despite diverse original indications and known targets, the perturbed pathways of active DR candidates show five distinct patterns that form tight clusters together with one or more known cancer drugs, suggesting common transcriptome-level mechanisms of anti-proliferative activity. PMID:26954019
Bermudez, José; Davies, Carolina; Simonazzi, Analía; Real, Juan Pablo; Palma, Santiago
One of the most significant health problems in the American continent in terms of human health, and socioeconomic impact is Chagas disease, caused by the protozoan parasite Trypanosoma cruzi. Infection was originally transmitted by reduviid insects, congenitally from mother to fetus, and by oral ingestion in sylvatic/rural environments, but blood transfusions, organ transplants, laboratory accidents, and sharing of contaminated syringes also contribute to modern day transmission. Likewise, Chagas disease used to be endemic from Northern Mexico to Argentina, but migrations have earned it global. The parasite has a complex life cycle, infecting different species, and invading a variety of cells - including muscle and nerve cells of the heart and gastrointestinal tract - in the mammalian host. Human infection outcome is a potentially fatal cardiomyopathy, and gastrointestinal tract lesions. In absence of a vaccine, vector control and treatment of patients are the only tools to control the disease. Unfortunately, the only drugs now available for Chagas' disease, Nifurtimox and Benznidazole, are relatively toxic for adult patients, and require prolonged administration. Benznidazole is the first choice for Chagas disease treatment due to its lower side effects than Nifurtimox. However, different strategies are being sought to overcome Benznidazole's toxicity including shorter or intermittent administration schedules-either alone or in combination with other drugs. In addition, a long list of compounds has shown trypanocidal activity, ranging from natural products to specially designed molecules, re-purposing drugs commercialized to treat other maladies, and homeopathy. In the present review, we will briefly summarize the upturns of current treatment of Chagas disease, discuss the increment on research and scientific publications about this topic, and give an overview of the state-of-the-art research aiming to produce an alternative medication to treat T. cruzi infection
Watts, Alan B; McConville, Jason T; Williams, Robert O
Recent advances in aerosolization technology have led to renewed interest in pulmonary delivery of a variety of drugs. Pressurized metered dose inhalers (pMDIs) and dry powder inhalers (DPIs) have experienced success in recent years; however, many limitations are presented by formulation difficulties, inefficient delivery, and complex device designs. Simplification of the formulation process as well as adaptability of new devices has led many in the pharmaceutical industry to reconsider aerosolization in an aqueous carrier. In the acute care setting, breath-enhanced air-jet nebulizers are controlling and minimizing the amount of wasted medication, while producing a high percentage of respirable droplets. Vibrating mesh nebulizers offer advantages in higher respirable fractions (RFs) and slower velocity aerosols when compared with air-jet nebulizers. Vibrating mesh nebulizers incorporating formulation and patient adaptive components provide improvements to continuous nebulization technology by generating aerosol only when it is most likely to reach the deep lung. Novel innovations in generation of liquid aerosols are now being adapted for propellant-free pulmonary drug delivery to achieve unprecedented control over dose delivered and are leading the way for the adaptation of systemic drugs for delivery via the pulmonary route. Devices designed for the metered dose delivery of insulin, morphine, sildenafil, triptans, and various peptides are all currently under investigation for pulmonary delivery to treat nonrespiratory diseases. Although these devices are currently still in clinical testing (with the exception of the Respimat), metered dose liquid inhalers (MDLIs) have already shown superior outcomes to current pulmonary and systemic delivery methods. PMID:18663654
This review summarizes the current status of neoadjuvantradiation approaches in the treatment of pancreatic cancer,including a description of modern radiation techniques,and an overview on the literature regarding neoadjuvantradio- or radiochemotherapeutic strategies both forresectable and irresectable pancreatic cancer. Neoadjuvantchemoradiation for locally-advanced, primarily non- orborderline resectable pancreas cancer results in secondaryresectability in a substantial proportion of patients withconsecutively markedly improved overall prognosisand should be considered as possible alternative inpretreatment multidisciplinary evaluations. In resectablepancreatic cancer, outstanding results in terms ofresponse, local control and overall survival have beenobserved with neoadjuvant radio- or radiochemotherapy inseveral phase Ⅰ/Ⅱ trials, which justify further evaluationof this strategy. Further investigation of neoadjuvantchemoradiation strategies should be performed preferentiallyin randomized trials in order to improvecomparability of the current results with other treatmentmodalities. This should include the evaluation of optimalsequencing with newer and more potent systemicinduction therapy approaches. Advances in patientselection based on new molecular markers might be ofcrucial interest in this context. Finally modern externalbeam radiation techniques （intensity-modulated radiationtherapy, image-guided radiation therapy and stereotacticbody radiation therapy）, new radiation qualities （protons,heavy ions） or combinations with alternative boostingtechniques widen the therapeutic window and contributeto the reduction of toxicity.
Full Text Available It is generally accepted that development of novel therapies to treat pregnancy-relates disorders, such as preeclampsia, is hampered to the paucity of research funding. Hence, it is with great interest to become aware of at least three novel therapeutic approaches for the treatment of this disorder, exploiting either the anticoagulant activity of antithrombin, the free radical scavenging activity of alpha-1-microglobulin, or the regenerative capacity of placenta-derived mesenchymal stem cells. As these projects are being carried out by small biotech enterprises, the question arises of how they are able to fund such undertakings. A novel strategy adopted by two of these companies is that they successfully petitioned US and EU agencies in order that preeclampsia be accepted in the register of rare or orphan diseases. This provides a number of benefits including market exclusivity, assistance with clinical trials and dedicated funding schemes. Other strategies to supplement meager research funds, especially to test novel approaches, could be crowdfunding, a venture which relies on intimate interaction with advocacy groups. In other words, preeclampsia meets Facebook. Perhaps similar strategies can be adopted to examine novel therapies targeting either the imbalance in angiogenic growth factors, complement activation, reduced levels of placenta protein 13 or excessive neutrophil activation evident in preeclampsia.
It is generally accepted that the development of novel therapies to treat pregnancy-related disorders, such as preeclampsia, is hampered by the paucity of research funding. Hence, it is with great interest to become aware of at least three novel therapeutic approaches for the treatment of this disorder: exploiting either the anticoagulant activity of antithrombin, the free radical scavenging activity of alpha-1-microglobulin, or the regenerative capacity of placenta-derived mesenchymal stem cells. As these projects are being carried out by small biotech enterprises, the question arises of how they are able to fund such undertakings. A novel strategy adopted by two of these companies is that they successfully petitioned US and EU agencies in order that preeclampsia is accepted in the register of rare or orphan diseases. This provides a number of benefits including market exclusivity, assistance with clinical trials, and dedicated funding schemes. Other strategies to supplement meager research funds, especially to test novel approaches, could be crowdfunding, a venture that relies on intimate interaction with advocacy groups. In other words, preeclampsia meets Facebook. Perhaps similar strategies can be adopted to examine novel therapies targeting either the imbalance in pro- or anti-angiogenic growth factors, complement activation, reduced levels of placenta protein 13, or excessive neutrophil activation evident in preeclampsia. PMID:25767802
It is generally accepted that the development of novel therapies to treat pregnancy-related disorders, such as preeclampsia, is hampered by the paucity of research funding. Hence, it is with great interest to become aware of at least three novel therapeutic approaches for the treatment of this disorder: exploiting either the anticoagulant activity of antithrombin, the free radical scavenging activity of alpha-1-microglobulin, or the regenerative capacity of placenta-derived mesenchymal stem cells. As these projects are being carried out by small biotech enterprises, the question arises of how they are able to fund such undertakings. A novel strategy adopted by two of these companies is that they successfully petitioned US and EU agencies in order that preeclampsia is accepted in the register of rare or orphan diseases. This provides a number of benefits including market exclusivity, assistance with clinical trials, and dedicated funding schemes. Other strategies to supplement meager research funds, especially to test novel approaches, could be crowdfunding, a venture that relies on intimate interaction with advocacy groups. In other words, preeclampsia meets Facebook. Perhaps similar strategies can be adopted to examine novel therapies targeting either the imbalance in pro- or anti-angiogenic growth factors, complement activation, reduced levels of placenta protein 13, or excessive neutrophil activation evident in preeclampsia. PMID:25767802
Full Text Available This opinion deals critically with the so-called complementary and alternative medical (CAM therapy on the basis of current data. From the authors’ perspective, CAM prescriptions and most notably the extensive current endeavours to the “integration” of CAM into conventional patient care is problematic in several respects.Thus, several CAM measures are used, although no specific effects of medicines can be proved in clinical studies. It is extensively explained that the methods used in this regard are those of evidence-based medicine, which is one of the indispensable pillars of science-oriented medicine. This standard of proof of efficacy is fundamentally independent of the requirement of being able to explain efficacy of a therapy in a manner compatible with the insights of the natural sciences, which is also essential for medical progress. Numerous CAM treatments can however never conceivably satisfy this requirement; rather they are justified with pre-scientific or unscientific paradigms. The high attractiveness of CAM measures evidenced in patients and many doctors is based on a combination of positive expectations and experiences, among other things, which are at times unjustified, at times thoroughly justified, from a science-oriented view, but which are non-specific (context effects. With a view to the latter phenomenon, the authors consider the conscious use of CAM as unrevealed therapeutic placebos to be problematic. In addition, they advocate that academic medicine should again systematically endeavour to pay more attention to medical empathy and use context effects in the service of patients to the utmost.The subsequent opinion discusses the following after an introduction to medical history: the definition of CAM; the efficacy of most common CAM procedures; CAM utilisation and costs in Germany; characteristics of science-oriented medicine; awareness of placebo research; pro and contra arguments about the use of CAM, not least
Anlauf, Manfred; Hein, Lutz; Hense, Hans-Werner; Köbberling, Johannes; Lasek, Rainer; Leidl, Reiner; Schöne-Seifert, Bettina
This opinion deals critically with the so-called complementary and alternative medical (CAM) therapy on the basis of current data. From the authors’ perspective, CAM prescriptions and most notably the extensive current endeavours to the “integration” of CAM into conventional patient care is problematic in several respects. Thus, several CAM measures are used, although no specific effects of medicines can be proved in clinical studies. It is extensively explained that the methods used in this regard are those of evidence-based medicine, which is one of the indispensable pillars of science-oriented medicine. This standard of proof of efficacy is fundamentally independent of the requirement of being able to explain efficacy of a therapy in a manner compatible with the insights of the natural sciences, which is also essential for medical progress. Numerous CAM treatments can however never conceivably satisfy this requirement; rather they are justified with pre-scientific or unscientific paradigms. The high attractiveness of CAM measures evidenced in patients and many doctors is based on a combination of positive expectations and experiences, among other things, which are at times unjustified, at times thoroughly justified, from a science-oriented view, but which are non-specific (context effects). With a view to the latter phenomenon, the authors consider the conscious use of CAM as unrevealed therapeutic placebos to be problematic. In addition, they advocate that academic medicine should again systematically endeavour to pay more attention to medical empathy and use context effects in the service of patients to the utmost. The subsequent opinion discusses the following after an introduction to medical history: the definition of CAM; the efficacy of most common CAM procedures; CAM utilisation and costs in Germany; characteristics of science-oriented medicine; awareness of placebo research; pro and contra arguments about the use of CAM, not least of all in terms
Mudzviti, Tinashe; Maponga, Charles C; Khoza, Star; Ma, Qing; Morse, Gene D
Background. The main objective was to determine the impact of herbal drug use on adverse drug reactions in patients on antiretroviral therapy (ART). Methodology. Patients receiving first-line ART from the national roll-out program participated in this cross-sectional study. Participants were interviewed and a data collection sheet was used to collect information from the corresponding medical record. Results. The majority (98.2%) of participants were using at least one herbal drug together with ART. The most common herbal remedies used were Allium Sativum (72.7%), Bidens pilosa (66.0%), Eucalyptus globulus (52.3%), Moringa oleifera (44.1%), Lippia javanica (36.3%), and Peltoforum africanum (34.3%). Two indigenous herbs, Musakavakadzi (OR = 0.25; 95% CI 0.076-0.828) and Peltoforum africanum (OR = 0.495; 95% CI 0.292-0.839) reduced the occurrence of adverse drug events. Conclusions. The use of herbal drugs is high in the HIV-infected population and there is need for pharmacovigilance programs to recognize the role they play in altering ADR profiles. PMID:22506106
... 42 Public Health 3 2010-10-01 2010-10-01 false Drug utilization management, quality assurance, and... management, quality assurance, and medication therapy management programs (MTMPs). (a) General rule. Each... utilization management program, quality assurance measures and systems, and an MTMP as described in...
Survey results showed a reduction of 22.3 percent in the use of major and minor tranquillizers, indicating that a change in the emphasis of care toward training and a less institutionalized environment may help to reduce the need for drug therapy to control deviant behavior in intellectually handicapped people. (Author/SW)
Piktel, Ewelina; Niemirowicz, Katarzyna; Wątek, Marzena; Wollny, Tomasz; Deptuła, Piotr; Bucki, Robert
The rapid development of nanotechnology provides alternative approaches to overcome several limitations of conventional anti-cancer therapy. Drug targeting using functionalized nanoparticles to advance their transport to the dedicated site, became a new standard in novel anti-cancer methods. In effect, the employment of nanoparticles during design of antineoplastic drugs helps to improve pharmacokinetic properties, with subsequent development of high specific, non-toxic and biocompatible anti-cancer agents. However, the physicochemical and biological diversity of nanomaterials and a broad spectrum of unique features influencing their biological action requires continuous research to assess their activity. Among numerous nanosystems designed to eradicate cancer cells, only a limited number of them entered the clinical trials. It is anticipated that progress in development of nanotechnology-based anti-cancer materials will provide modern, individualized anti-cancer therapies assuring decrease in morbidity and mortality from cancer diseases. In this review we discussed the implication of nanomaterials in design of new drugs for effective antineoplastic therapy and describe a variety of mechanisms and challenges for selective tumor targeting. We emphasized the recent advantages in the field of nanotechnology-based strategies to fight cancer and discussed their part in effective anti-cancer therapy and successful drug delivery. PMID:27229857
Bannister, Wendy P; Cozzi-Lepri, Alessandro; Kjær, Jesper;
Estimating the prevalence of accumulated HIV drug resistance in patients receiving antiretroviral therapy (ART) is difficult due to lack of resistance testing at all occasions of virological failure and in patients with undetectable viral load. A method to estimate this for 6498 EuroSIDA patients...
Page, Richard C; And Others
Used Hill Interaction Matrix to measure content and quality of interactions in 12-hour therapy group of 12 male drug addicts and 3 therapists. Categories of therapeutic work included conventional, assertive, speculative, and confrontive; categories of content included topic, group, personal, and relationship. Group was highly confrontive; most…
Full Text Available Tuberculosis appears to be a disease as old as human history. Tuberculosis is of great public health importance in the developing countries. Its clinical profile is different in developing countries in comparison to countries of Europe and North America. The recent epidemic of HIV has slowed down the declining trend in the incidence of tuberculosis. Bacilli are transmitted from one infected person to the others as an aerosol. In some cases contaminated milk may also be responsible. However despite effective regimens and addition of new drugs and improved pharmacokinetic knowledge the chemotherapy of tuberculosis still remains a challenge. Poor drug-compliance by patients being one of the foremost reason for frequent relapses and bacterial resistance. Some important and concrete steps to meet these challenges have been judicious use of two or more bactericidal drugs and introduction of short courses regiment. Multiple drugs therapy may shorten the duration of treatment and prevent emergence of drug resistance.
Full Text Available Introduction. For future health planning of our country, the type and amount of drugs used for treatment of chronic diseases should be known. Therefore, in the present study the treatment regimen of asthmatic children in the city of Mashhad was studied. Methods. To study the different types of drugs in the treatment regimen of asthmatic children in the city of Mashhad, we evaluated the treatment regimen of 366 primary school children with asthma disease. Starting, maximum and duration of action of three different bronchodilators (salbutamol inhaler, salbutamol syrup, and theophylline syrup were compared. Findings. The results of the first part of this study showed that only 31.6 percent of asthmatic children had history of treatment and only 10.6 percent had current medication. In addition, most of the treated children (38.8 percent had only bronchodilator (salbutamol syrup in their treatment regimen. The effect of salbutamol inhaler on lung function tests starts in 5 min, salbutamol syrup in 15 min and theophylline syrup at 30 min after administration. The maximum response to salbutamol inhaler, salbutamol syrup, and theophylline syrup occurred 15 min, 4 hr and 3 hr after administration, respectively. The reduction of response to salbutamol inhaler occurs after 3 hr, but there was no any reduction in response to salbutamol and theophylline syrup during study period. Conclusion. The prevalence of asthma among children in the city of Mashhad is relatively high, but most of asthmatic children are not treated. Although the oral bronchodilator in mild asthma is effective, salbutamol inhaler is needed for emergency use.
Boehm, Thomas; Folkman, Judah; Browder, Timothy; O'Reilly, Michael S.
Acquired drug resistance is a major problem in the treatment of cancer. Of the more than 500,000 annual deaths from cancer in the United States, many follow the development of resistance to chemotherapy. The emergence of resistance depends in part on the genetic instability, heterogeneity and high mutational rate of tumour cells. In contrast, endothelial cells are genetically stable, homogenous and have a low mutational rate. Therefore, antiangiogenic therapy directed against a tumour's endothelial cells should, in principle, induce little or no drug resistance. Endostatin, a potent angiogenesis inhibitor, was administered to mice bearing Lewis lung carcinoma, T241 fibrosarcoma or B16F10 melanoma. Treatment was stopped when tumours had regressed. Tumours were then allowed to re-grow and endostatin therapy was resumed. After 6, 4 or 2 treatment cycles, respectively, no tumours recurred after discontinuation of therapy. These experiments show that drug resistance does not develop in three tumour types treated with a potent angiogenesis inhibitor. An unexpected finding is that repeated cycles of antiangiogenic therapy are followed by prolonged tumour dormancy without further therapy.
This talk will introduce a new nanotechnology platform for cancer combination therapy that utilizes near infrared light activation not only for photodynamic damage but also as an extrinsic mechanism to initiate release of complimentary drugs to suppress dynamic bursts in molecular signaling networks that promote tumor cell survival and treatment escape. The goal is to achieve co-delivery with concomitant activity of photodynamic, molecular inhibitor and chemotherapeutic agents, selectively within the tumor. This approach overcomes challenges in achieving synergistic interactions using sequential drug delivery. Conventional drug delivery is compromised by the differential pharmacokinetics of individual agents and potentially antagonistic effects—such as vascular shutdown by one agent that limits delivery of the second. Here, photodynamic damage—which efficiently kills drug-resistant cells via damage of common proteins involved in drug-resistance (such as anti-apoptosis factors and drug-efflux transporters)—is synchronized spatially and temporally with the photo-initiated release of complimentary agents—to enable full interaction amongst the individual therapies. This spatiotemporal synchronization offers new prospects for exploiting time-sensitive synergistic interactions. Specific implementations of these concepts will be presented in preclinical models of cancer. Strategies to enable molecular-targeting of cancer cells via site-specific attachment of targeting moieties to the outer lipid shell of these nanovehicles will also be discussed. If successful in humans, this new paradigm for synchronized, tumor-focused combination therapy will ultimately supersede the present use of chronic drug injection by increasing efficacy per cycle whilst reducing systemic exposure to toxic drugs.
Raphemot, Rene; Posfai, Dora; Derbyshire, Emily R
Malaria remains a global public health threat, with half of the world's population at risk. Despite numerous efforts in the past decade to develop new antimalarial drugs to surmount increasing resistance to common therapies, challenges remain in the expansion of the current antimalarial arsenal for the elimination of this disease. The requirement of prophylactic and radical cure activities for the next generation of antimalarial drugs demands that new research models be developed to support the investigation of the elusive liver stage of the malaria parasite. In this Review, we revisit current antimalarial therapies and discuss recent advances for in vitro and in vivo malaria research models of the liver stage and their importance in probing parasite biology and the discovery of novel drug candidates. PMID:27249674
George L Drusano
Full Text Available Tuberculosis remains a worldwide problem, particularly with the advent of multi-drug resistance. Shortening therapy duration for Mycobacterium tuberculosis is a major goal, requiring generation of optimal kill rate and resistance-suppression. Combination therapy is required to attain the goal of shorter therapy.Our objective was to identify a method for identifying optimal combination chemotherapy. We developed a mathematical model for attaining this end. This is accomplished by identifying drug effect interaction (synergy, additivity, antagonism for susceptible organisms and subpopulations resistant to each drug in the combination.We studied the combination of linezolid plus rifampin in our hollow fiber infection model. We generated a fully parametric drug effect interaction mathematical model. The results were subjected to Monte Carlo simulation to extend the findings to a population of patients by accounting for between-patient variability in drug pharmacokinetics.All monotherapy allowed emergence of resistance over the first two weeks of the experiment. In combination, the interaction was additive for each population (susceptible and resistant. For a 600 mg/600 mg daily regimen of linezolid plus rifampin, we demonstrated that >50% of simulated subjects had eradicated the susceptible population by day 27 with the remaining organisms resistant to one or the other drug. Only 4% of patients had complete organism eradication by experiment end.These data strongly suggest that in order to achieve the goal of shortening therapy, the original regimen may need to be changed at one month to a regimen of two completely new agents with resistance mechanisms independent of the initial regimen. This hypothesis which arose from the analysis is immediately testable in a clinical trial.
Full Text Available Huzaifa I Adamali,1 Toby M Maher1–31Interstitial Lung Disease Unit, Royal Brompton Hospital, London, UK; 2National Heart and Lung Institute, Imperial College London, London, UK; 3Centre for Respiratory Research, University College London, London, UKAbstract: Over the past decade, there has been a cohesive effort from patients, physicians, clinical and basic scientists, and the pharmaceutical industry to find definitive treatments for idiopathic pulmonary fibrosis (IPF. As understanding of disease behavior and pathogenesis has improved, the aims of those treating IPF have shifted from reversing the disease to slowing or preventing progression of this chronic fibrotic illness. It is to be hoped that by slowing disease progression, survival will be improved from the current dismal median of 3.5 years following diagnosis. In Europe and Asia, a milestone has recently been reached with the licensing of the first IPF-specific drug, pirfenidone. This review assesses the current treatment modalities available for IPF, including pirfenidone. It also turns an eye to the future and discusses the growing number of promising compounds currently in development that it is hoped, in time, will make their way into the clinic as treatments for IPF.Keywords: interstitial lung disease, pirfenidone, clinical trials, usual interstitial pneumonia, acute exacerbations
Sprott, Haiko; Klauke, Wolfgang
The treatment of chronic, non-malignant low-back pain is based on the patients' history and the clinical examination. It can be assumed that half of the cases present with a neuropathic pain component which needs to be treated with antidepressive and antiepileptic drugs instead of "pure" analgesics. Opioids should be considered with extreme caution because of their toxicity. Chronic non-malignant back pain is the prototype for interdisciplinary treatment approaches and multi-modal interdisciplinary settings, including pain programmes. However, a personalised strategy has to be preferred in most cases. A quick relief of pain is important in order to improve function as well as to re-integrate the patient into professional life. Spinal infiltrations can be of both diagnostic as well as therapeutic benefits. Their indication must be considered carefully, especially if the invasive diagnostic intervention has no therapeutic consequences. The interventional procedures should only be used as part of a multimodal approach in patients without any psychological problem. The sole use of interventions supports the purely somatic orientation of many patients and thus leads us in the wrong direction. PMID:23985154
Full Text Available D03367 Drug Capobenate sodium (USAN) C16H22NO6. Na 347.1345 347.3387 D03367.gif Car...diac depressant [anti-arrhythmic] CAS: 27276-25-1 PubChem: 17397516 LigandBox: D03367 NIKKAJI: J21.180J ATOM
Full Text Available Background:The physiologic function of carnitine, oxidation of fatty acid and lipidmetabolism, is severely affected in carnitine deficiency, secondaryforms of which lead to renal tubular disorders and chronic renalfailure. Reduction in serum carnitine has been frequently reportedin patients and experimental animals treated with antiepileptic drugs,one of which, valproic acid has consistently been found to cause thedeficiency; the antiepileptic drugs, valproic acid, has consistentlybeen found to cause the deficiency. Previous results, however, regardingthe effects of other antiepileptic drugs have been less consistent.Considering the controversial results available in lterarure, the aim ofthis study was to determine the effect of Valproic acid, Carbamazepineand Phenobarbital on serum carnitine levels in epileptic children.Methods:In the present study, serum carnitine levels were randomly monitoredbefore and six months after therapy in 39 epileptic patients receivingthe antiepileptic drugs mentioned. Patient blood samples were takenbefore and six months after treatment and L-carnitine level wasdetermined using the UV enzymatic test (Rouche Kit spectronicGenesis 2, 340 nm.Results:Results showed a significant fall in the L-carnitine levels of epilepticchildren taking these drugs (P< 0.01.Conclusion:Considering the reducing effect of antiepileptic drugs on serumcarnitine levels, it is recommended that a carnitine supplement beadministered in pediatric epileptic patients to prevent the deficiencyand related consequences caused by such therapies.
Zhao, Pengfei; Zheng, Mingbin; Luo, Zhenyu; Gong, Ping; Gao, Guanhui; Sheng, Zonghai; Zheng, Cuifang; Ma, Yifan; Cai, Lintao
Smart nanoparticles (NPs) that respond to external and internal stimulations have been developing to achieve optimal drug release in tumour. However, applying these smart NPs to attain high antitumour performance is hampered by limited drug carriers and inefficient spatiotemporal control. Here we report a noninvasive NIR-driven, temperature-sensitive DI-TSL (DOX/ICG-loaded temperature sensitive liposomes) co-encapsulating doxorubicin (DOX) and indocyanine green (ICG). This theranostic system applies thermo-responsive lipid to controllably release drug, utilizes the fluorescence (FL) of DOX/ICG to real-time trace the distribution of NPs, and employs DOX/ICG to treat cancer by chemo/photothermal therapy. DI-TSL exhibits uniform size distribution, excellent FL/size stability, enhanced response to NIR-laser, and 3 times increased drug release through laser irradiation. After endocytosis by MCF-7 breast adenocarcinoma cells, DI-TSL in cellular endosomes can cause hyperthermia through laser irradiation, then endosomes are disrupted and DI-TSL ‘opens’ to release DOX simultaneously for increased cytotoxicity. Furthermore, DI-TSL shows laser-controlled release of DOX in tumour, enhanced ICG and DOX retention by 7 times and 4 times compared with free drugs. Thermo-sensitive DI-TSL manifests high efficiency to promote cell apoptosis, and completely eradicate tumour without side-effect. DI-TSL may provide a smart strategy to release drugs on demand for combinatorial cancer therapy.
Full Text Available Hui-Yin Chen,1 Hui-Ru Chang,2 Hui-Chu Lang3 1Department of Auditing, Mackay Memorial Hospital, Taipei, Taiwan; 2Department of Social Insurance, Ministry of Health and Welfare, Taipei, Taiwan; 3Institute of Hospital and Health Care Administration, National Yang-Ming University, Taipei, Taiwan Objectives: To evaluate the effects on physicians’ prescribing behavior and on the therapeutic outcome of non-insulin-dependent diabetes patients of substituting different generic brands of metformin. Methods: We adopt a retrospective cohort study involving 280 type-2 diabetes patients who regularly used the outpatient services of one medical center and who had changed metformin brands five times between 2003 and 2008. The aim was to examine the effects of switching brands. The generalized estimating equation was used to determine whether drug brand switching affected patient glycated hemoglobin A1c (HbA1c levels, their prescribed daily dose, or their adherence to medication with metformin. Results: HbA1c levels increased from 7.91 to 8.34 throughout the study period, although it was found that brand switching did not adversely affect HbA1c levels after controlling for patient characteristics and the time course of the study. Furthermore, the prescribed daily dose of metformin was stable throughout the study period, and was approximately 0.8 of the defined daily dose. Finally, although adherence was significantly higher with the original metformin than with the four generic brands, patients still maintained high levels of adherence of >0.8. Conclusion: Although switching between different brands of metformin slightly affected the prescribing behavior of the physicians, there was no unfavorable effect on patient HbA1c levels. Thus, the policy of substituting between different generic brands of metformin is a good cost-effective approach that does not adversely affect the quality of diabetes patient care. Keywords: metformin, generic substitution, glycemic
Tsoneva, Desislava; Stritzker, Jochen; Bedenk, Kristina; Zhang, Qian; Frentzen, Alexa; Cappello, Joseph; Fischer, Utz; Szalay, Aladar A
Blood tests are necessary, easy-to-perform and low-cost alternatives for monitoring of oncolytic virotherapy and other biological therapies in translational research. Here we assessed three candidate proteins with the potential to be used as biomarkers in biological fluids: two glucuronidases from E. coli (GusA) and Staphylococcus sp. RLH1 (GusPlus), and the luciferase from Gaussia princeps (GLuc). The three genes encoding these proteins were inserted individually into vaccinia virus GLV-1h68 genome under the control of an identical promoter. The three resulting recombinant viruses were used to infect tumor cells in cultures and human tumor xenografts in nude mice. In contrast to the actively secreted GLuc, the cytoplasmic glucuronidases GusA and GusPlus were released into the supernatants only as a result of virus-mediated oncolysis. GusPlus resulted in the most sensitive detection of enzyme activity under controlled assay conditions in samples containing as little as 1 pg/ml of GusPlus, followed by GusA (25 pg/ml) and GLuc (≥375 pg/ml). Unexpectedly, even though GusA had a lower specific activity compared to GusPlus, the substrate conversion in the serum of tumor-bearing mice injected with the GusA-encoding virus strains was substantially higher than that of GusPlus. This was attributed to a 3.2 fold and 16.2 fold longer half-life of GusA in the blood stream compared to GusPlus and GLuc respectively, thus a more sensitive monitor of virus replication than the other two enzymes. Due to the good correlation between enzymatic activity of expressed marker gene and virus titer, we conclude that the amount of the biomarker protein in the body fluid semiquantitatively represents the amount of virus in the infected tumors which was confirmed by low light imaging. We found GusA to be the most reliable biomarker for monitoring oncolytic virotherapy among the three tested markers. PMID:26348361
Full Text Available Rapid advances in the field of chemotherapy have resulted in the introduction of numerous antineoplastic drugs into clinical practice, which increased the efficiency of patient management. Also the prevalent use of combination treatment based on drug action synergy contributed to the improved clinical effect associated with cytotoxic drug administration. It seems, however, obvious that the multidirectional pharmacotherapy in oncology requires a thorough knowledge of drugs’ pharmaceutical behavior in order to maximize their collective action and prevent the occurrence of unintended drug interactions that could potentially impair treatment effectiveness. In fact, drug interactions constitute a serious problem for current oncology primarily resulting from a narrow therapeutic index specific for the majority of anticancer drugs. This, in turn, indicates that even slight deviations of their pharmacokinetics could cause significant clinical consequences, manifested by alteration of the toxicological profile or reduction of therapeutic efficiency. Hence, the investigation of molecular aspects underlying the mechanisms of various drug interactions seems to be essential for proper and safe patient management. The present article is devoted to the extensive subject of drug interactions occurring in the therapy of colorectal cancer. It presents the available literature data on both positive and negative effects of interactions and it discusses their mechanisms complying with their classification into pharmacokinetic and pharmacodynamic ones.
Cheng, Yin-Jia; Zeng, Xuan; Cheng, Dong-Bing; Xu, Xiao-Ding; Zhang, Xian-Zheng; Zhuo, Ren-Xi; He, Feng
Synergistic therapy involving two or more therapeutic agents with different anticancer mechanisms represents a promising approach to eradicate chemotherapy-refractory cancers. However, the preparation of a synergistic therapy platform generally involves complicated procedures to encapsulate different therapeutic agents and thereby increases the purification difficulty. In this work, we reported a simple but robust strategy to prepare a highly controllable drug delivery system (DDS) for synergistic cancer therapy. To construct this robust DDS, mesoporous silica nanoparticles (MSNs) were employed as a nanoplatform to encapsulate anticancer drug doxorubicin (DOX). After using a tumor-targeting cellular membrane-penetrating peptide (TCPP) and a mitochondria-targeting therapeutic peptide (TPP) to seal the surface pores via disulfide bonds, these newly developed MSNs can target cancer cells, penetrate cell membrane and rapidly release anticancer drug and mitochondria-targeted peptide in cytoplasm, inducing a remarkable synergistic anticancer effect. The new design concept reported here will promote the development of targeted and smart DDSs for synergistic cancer therapy. PMID:27182657
Chrysant, Steven G
Hypertension (HTN) affects an estimated 76.4 million US adults. Despite improvements in blood pressure (BP) control rates and the availability of effective antihypertensive agents, only 50% of these individuals achieve BP control. It is now recognized that many patients will require ≥ 2 antihypertensive agents to achieve BP control. Both the current US and reappraisal of the 2007 European guidelines include dual-combination regimens among recommended treatments for initial HTN therapy. For patients requiring 3 drugs, the combination of agents with complementary mechanisms of action (ie, renin-angiotensin-aldosterone system blocker, calcium channel blocker, and diuretic) has been recognized as rational and effective. Three single-pill triple-drug combinations have recently been approved for use in HTN in the United States: valsartan (VAL)/amlodipine (AML)/hydrochlorothiazide (HCTZ); olmesartan medoxomil (OM)/AML/HCTZ; and aliskiren (ALI)/VAL/HCTZ. Triple-combination regimens have resulted in a greater proportion of patients achieving BP control compared with dual-combination regimens, with significantly lower BP levels documented after only 2 weeks at maximum doses. Single-pill combinations offer convenience to address barriers to BP control such as poor adherence to therapy and therapeutic inertia. Additional benefits of combining antihypertensive agents from different classes include improved efficacy, safety, and reduction of cardiovascular risk. In patients with essential HTN for whom dual therapy is inadequate, single-pill triple-drug therapy can offer a simplified and effective treatment strategy. PMID:22104451
Full Text Available Pharmacist’s interventions (also known as pharmaceutical care plans are means of solving the drug therapy problems identified in pharmaceutical care. Outcomes are the results of pharmacists’ intervention activities. Patients’ satisfaction refers to patients’ feeling of fulfillment, pleasure or happiness with the services they have received. This study was designed to determine the types of pharmacist interventions applied in the pharmaceutical care of HIV patients receiving treatment at a tertiary hospital in southeast Nigeria, the types of outcomes of such interventions and level of patients’ satisfaction with their drug therapy. The components of the American society of health-system pharmacists (ASHP guidelines on ‘standardized method for pharmaceutical care was used as a data collection instrument to evaluate, document and intervene in the antiretroviral therapy of about one thousand four hundred and seventy three (1,473 patients. The results showed significant reductions in the frequency of the various interventions and parameters measured after the interventions. The study concluded that pharmaceutical interventions influences patients’ adherence, optimizes their drug therapy and improves rational prescribing and care resulting in significant improvements in the outcomes of their treatment and levels of satisfaction.
Full Text Available With the growing incidence of Multi-Drug-Resistant Tuberculosis (MDR-TB in newly identified patients, novel multimodality treatment methods are needed, aimed at reducing the time to sputum conversion and cavity healing, which would be applicable in MDR cases. Our experimental treatment consisted of the following: 1 chemotherapy based on the drug sensitivity profile, 2 local laser irradiation therapy for 25 days, and lymphotropic administration of isoniazid (to subcutaneous tissue in alternating locations: underarm area; fifth intercostal space along the sterna border; subclavian area where the first rib meets the sternum in a daily dose of 10mg/kg 5 times a week. This treatment was significantly more effective in newly detected destructive MDR-TB versus the standard Category IV regimen for MDR-TB in terms of reduced time for sputum culture conversion and cavity healing, estimated to be 6 months after initiation of treatment.
Roberta Balansin Rigon
Full Text Available Melanoma (MEL is a less common type of skin cancer, but it is more aggressive with a high mortality rate. The World Cancer Research Fund International (GLOBOCAN 2012 estimates that there were 230,000 new cases of MEL in the world in 2012. Conventional MEL treatment includes surgery and chemotherapy, but many of the chemotherapeutic agents used present undesirable properties. Drug delivery systems are an alternative strategy by which to carry antineoplastic agents. Encapsulated drugs are advantageous due to such properties as high stability, better bioavailability, controlled drug release, a long blood circulation time, selective organ or tissue distribution, a lower total required dose, and minimal toxic side effects. This review of scientific research supports applying a nanotechnology-based drug delivery system for MEL therapy.
We have already synthesized a boron-containing polymeric micellar drug delivery system for boron neutron capture therapy (BNCT). The synthesized diblock copolymer, boron-terminated copolymers (Bpin-PLA-PEOz), consisted of biodegradable poly(D,L-lactide) (PLA) block and water-soluble polyelectrolyte poly(2-ethyl-2-oxazoline) (PEOz) block, and a cap of pinacol boronate ester (Bpin). In this study, we have demonstrated that synthesized Bpin-PLA-PEOz micelle has great potential to be boron drug delivery system with preliminary evaluation of biocompatibility and boron content. - Highlights: • Herein, we have synthesized boron-modified diblock copolymer. • Bpin-PLA-PEOz, which will be served as new boron containing vehicle for transporting the boron drug. • This boron containing Bpin-PLA-PEOz micelle was low toxicity can be applied to drug delivery
Full Text Available We report a case of severe bradyarrythmia with hypotension and extremely large QRS due to proarrhythmic effect of drug combination (amiodarone following infusion of propafenone for the conversion of Paroxysmal Atrial Fibrillation (PAF in a 74 year old woman. The authors focus on the important side effects and complications due to aggressive treatment of not life-threatening arrhythmias, such as PAF without haemodinamic compromise in older patients. At conclusion “primum non nocere“.
Okumura, K; Hashimoto, Y.; Yasuhara, M; R. Hori
1. Antiarrhythmic actions of ajmaline against ischaemia (left coronary artery occlusion for 15 min) and subsequent reperfusion-induced arrhythmias were investigated in anaesthetized rats. 2. Ajmaline (2 mg kg-1, i.v.) was effective in suppressing ischaemia-induced arrhythmias whether given pre- or post-occlusion. 3. Ajmaline diminished the reperfusion-induced arrhythmias completely when given pre-occlusion but had little effect when given post-occlusion. 4. Reperfusion-induced increases in pl...
Tiurenkov, I N; Perfilova, V N
Clinical and experimental data available in the literature are summarized, which are indicative of the antiarrhythmogenic properties of GABA and substances possessing GABA-positive activity (phenibut, piracetam, sodium hydroxybutyrate, lithium hydroxybutyrate, etc.). The antiarrhythmic effects are manifested in various cases of the heart rhythm violation. The mechanism of this action is related to activation of the central and peripheral retarding GABAergic system, as well as to antihypoxant, antioxidant, and antistressor effects. PMID:12025796
Keller, Frieder; Schröppel, Bernd; Ludwig, Ulla
Patients with cancer have a high inherent risk of infectious complications. In addition, the incidence of acute and chronic kidney dysfunction rises in this population. Anti-infective drugs often require dosing modifications based on an estimate of kidney function, usually the glomerular filtration rate (GFR). However, there is still no preferential GFR formula to be used, and in acute kidney injury there is always a considerable time delay between true kidney function and estimated GFR. In most cases, the anti-infective therapy should start with an immediate and high loading dose. Pharmacokinetic as well as pharmacodynamic principles must be applied for further dose adjustment. Anti-infective drugs with time-dependent action should be given with the target of high trough concentrations (e.g., beta lactam antibiotics, penems, vancomycin, antiviral drugs). Anti-infective drugs with concentration-dependent action should be given with the target of high peak concentrations (e.g., aminoglycosides, daptomycin, colistin, quinolones). Our group created a pharmacokinetic database, called NEPharm, hat serves as a reference to obtain reliable dosing regimens of anti-infective drugs in kidney dysfunction as well as renal replacement therapy. To avoid the risk of either too low or too infrequent peak concentrations, we prefer the eliminated fraction rule for dose adjustment calculations. PMID:26167456
Full Text Available Abstract Background For the pharmacological treatment of bipolar depression several guidelines exist. It is largely unknown, to what extent the prescriptions in daily clinical routine correspond to these evidence based recommendations and which combinations of psychotropic drugs are frequently used. Methods The prescriptions of psychotropic drugs were investigated of all in-patients with bipolar depression (n = 2246; time period 1994–2009 from hospitals participating in the drug surveillance program AMSP. For the drug use in 2010, 221 cases were analysed additionally. Results From 1994 to 2009, 85% of all patients received more than one class of psychotropic substances: 74% received antidepressants in combination therapy, 55% antipsychotics, 48% anticonvulsants and 33% lithium. When given in combination, lithium is the most often prescribed substance for bipolar depression (33%, followed by valproic acid (23%, mirtazapine and venlafaxine (16% each, quetiapine (15%, lamotrigine (14% and olanzapine (13%. Both, lithium and valproic acid are often combined with selective serotonin reuptake inhibitors (SSRI, but also with mirtazapine und venlafaxine. Combinations of more than one antidepressant occur quite often, whereby combinations with bupropion, paroxetine, fluoxetine or fluvoxamine are very rare. In 2010, quetiapine (alone and combined was the most frequently prescribed drug (39%; aripiprazole was administered in 10%. Conclusion Combinations of antidepressants (SSRI, mirtazapine, venlafaxine with mood stabilizers (lithium, valproic acid, lamotrigine and / or atypical antipsychotics (quetiapine, olanzapine are common. Of most of those combinations the efficacy has not been studied. The use of aripiprazole and the concomitant use of two or three antidepressants contrast the guidelines.
Gary-Bobo, Magali; Hocine, Ouahiba; Brevet, David; Maynadier, Marie; Raehm, Laurence; Richeter, Sébastien; Charasson, Virginie; Loock, Bernard; Morère, Alain; Maillard, Philippe; Garcia, Marcel; Durand, Jean-Olivier
The synthesis of mesoporous silica nanoparticles (MSN) covalently encapsulating fluoresceine or a photosensitizer, functionalized with galactose on the surface is described. Confocal microscopy experiments demonstrated that the uptake of galactose-functionalized MSN by colorectal cancer cells was mediated by galactose receptors leading to the accumulation of the nanoparticles in the endosomal and lysosomal compartments. The MSN functionalized with a photosensitizer and galactose were loaded with the anti-cancer drug camptothecin. Those MSN combining drug delivery and photodynamic therapy were tested on three cancer cell lines and showed a dramatic enhancement of cancer cell death compared to separate treatments. PMID:22178618
Riyaz Ali M. Osmani
Full Text Available The intention behind the present work was to develop a microsponge based novel dosage form for sustained delivery of domperidone. Quasi-emulsion solvent diffusion method was employed using Eudragit RS-100 with various drug–polymer ratios for the preparation of microsponges. For optimization purposes, several factors which affect microparticles' physical properties were investigated. Characterization techniques followed for the formed microsponges were DSC, FTIR, SEM, XRD and particle size analysis, along with morphology, drug loading and in vitro drug release. It was found that there were no chemical interactions between drugs and polymers used as per DSC and FTIR results. The drug–polymer ratio showed remarkable impact on drug content, encapsulation efficiency and particle size. SEM micrographs revealed that microsponges were spherical in shape with porous surface, and had 104 ± 0.22 µm mean particle size. The microsponges were then loaded in capsules followed by in vitro drug release study; which depicted that microsponges with drug–polymer ratio of 1:2 were more proficient to give extended drug release of 76.38% at the end of 8 h, superior in contrast to conventional marketed formulation Domstal®, which got exhausted incredibly earlier by releasing 82.57% drug at the end of ½ h only. Hence, the developed microsponge based formulation of domperidone would be an expectant, promising substitute to conventional therapy of gastroparesis, emesis and alike gastric ailments.
Multidrug resistance (MDR) limits the success of many tumoricidal drugs. Non-significant accumulation of the drug into the target site is one major problem in photodynamic therapy. Nanoparticles are extensively used as efficient drug carriers in various local infectious and premalignant biological tissues. Due to their unique physical and chemical properties, PEGylated zinc oxide nanoparticles (ZnO NPs) exhibit high drug loading capacities, sustained drug release profiles and long-term anticancer efficacy. (Polyethylene glycol) PEG-zinc oxide nanoparticles were synthesized using the aquis chemical technique. Morphology/structural analysis of the said nanoparticles was confirmed by applying many techniques, e.g. scanning electron microscopy (SEM) and XRD. Average grain size of the nanoparticles, which was ≈100 nm, was calculated by applying the Scherrer formula. The PEGylated ZnO NPs were loaded with protoporphyrin IX (PpIX) to enhance the capability of drug carrying potency. Current work focused on the comparison of the cell killing effect (apoptosis/necrosis) by functionalizing different nanostructures via PEGylated ZnO NPs and bare ZnO NPs using the free-standing drug delivery procedure. ZnO NPs were used as anticancer drug vehicles because of their biocompatibility and bio-safety profile. The apoptotic effect of PEGylated tumoricidal drugs has been studied in human muscle carcinoma (RD cell line) in the dark as well as under laser exposure. It was concluded that PpIX localization was a significant time greater using encapsulation as compared to a conventional drug delivery system. This new technique may find excellent opportunities in the field of nanomedicine, especially in a multidrug delivery system. (letter)
Fakhar-e-Alam, M.; Rahim, S.; Atif, M.; Hammad Aziz, M.; Imran Malick, M.; Zaidi, S. S. Z.; Suleman, R.; Majid, A.
Multidrug resistance (MDR) limits the success of many tumoricidal drugs. Non-significant accumulation of the drug into the target site is one major problem in photodynamic therapy. Nanoparticles are extensively used as efficient drug carriers in various local infectious and premalignant biological tissues. Due to their unique physical and chemical properties, PEGylated zinc oxide nanoparticles (ZnO NPs) exhibit high drug loading capacities, sustained drug release profiles and long-term anticancer efficacy. (Polyethylene glycol) PEG-zinc oxide nanoparticles were synthesized using the aquis chemical technique. Morphology/structural analysis of the said nanoparticles was confirmed by applying many techniques, e.g. scanning electron microscopy (SEM) and XRD. Average grain size of the nanoparticles, which was ≈100 nm, was calculated by applying the Scherrer formula. The PEGylated ZnO NPs were loaded with protoporphyrin IX (PpIX) to enhance the capability of drug carrying potency. Current work focused on the comparison of the cell killing effect (apoptosis/necrosis) by functionalizing different nanostructures via PEGylated ZnO NPs and bare ZnO NPs using the free-standing drug delivery procedure. ZnO NPs were used as anticancer drug vehicles because of their biocompatibility and bio-safety profile. The apoptotic effect of PEGylated tumoricidal drugs has been studied in human muscle carcinoma (RD cell line) in the dark as well as under laser exposure. It was concluded that PpIX localization was a significant time greater using encapsulation as compared to a conventional drug delivery system. This new technique may find excellent opportunities in the field of nanomedicine, especially in a multidrug delivery system.
Objective To explore the efficacy of triple therapy and sequential therapy in the eradication of Helicobacter pylori(Hp) in patients receiving long-term non-steroidal antiinflammatorv drugs(NSAID) treatment. Methods Patients receiving long-term NSAID treatment were enrolled
Wallis, Robert S; Maeurer, Markus; Mwaba, Peter; Chakaya, Jeremiah; Rustomjee, Roxana; Migliori, Giovanni Battista; Marais, Ben; Schito, Marco; Churchyard, Gavin; Swaminathan, Soumya; Hoelscher, Michael; Zumla, Alimuddin
Tuberculosis is the leading infectious cause of death worldwide, with 9·6 million cases and 1·5 million deaths reported in 2014. WHO estimates 480 000 cases of these were multidrug resistant (MDR). Less than half of patients who entered into treatment for MDR tuberculosis successfully completed that treatment, mainly due to high mortality and loss to follow-up. These in turn illustrate weaknesses in current treatment regimens and national tuberculosis programmes, coupled with operational treatment challenges. In this Review we provide an update on recent developments in the tuberculosis drug-development pipeline (including new and repurposed antimicrobials and host-directed drugs) as they are applied to new regimens to shorten and improve outcomes of tuberculosis treatment. Several new or repurposed antimicrobial drugs are in advanced trial stages for MDR tuberculosis, and two new antimicrobial drug candidates are in early-stage trials. Several trials to reduce the duration of therapy in MDR and drug-susceptible tuberculosis are ongoing. A wide range of candidate host-directed therapies are being developed to accelerate eradication of infection, prevent new drug resistance, and prevent permanent lung injury. As these drugs have been approved for other clinical indications, they are now ready for repurposing for tuberculosis in phase 2 clinical trials. We assess risks associated with evaluation of new treatment regimens, and highlight opportunities to advance tuberculosis research generally through regulatory innovation in MDR tuberculosis. Progress in tuberculosis-specific biomarkers (including culture conversion, PET and CT imaging, and gene expression profiles) can support this innovation. Several global initiatives now provide unique opportunities to tackle the tuberculosis epidemic through collaborative partnerships between high-income countries and middle-income and low-income countries for clinical trials training and research, allowing funders to
Hallett, Rachel L; Colin J Sutherland; Alexander, Neal; Ord, Rosalynn; Jawara, Musa; Drakeley, Chris J.; Pinder, Margaret; Walraven, Gijs; Geoffrey A T Targett; Alloueche, Ali
Malaria parasites carrying genes conferring resistance to antimalarials are thought to have a selective advantage which leads to higher rates of transmissibility from the drug-treated host. This is a likely mechanism for the increasing prevalence of parasites with resistance to chloroquine (CQ) and sulfadoxine-pyrimethamine in sub-Saharan Africa. Combination therapy is the key strategy being implemented to reduce the impact of resistance, but its effect on the transmission of genetically resi...
Nasution, Azizah; Khairunnisa; Tanjung, Hari Ronaldo
Objective: This study aimed to evaluate the antihypertensive utilization and drug therapy problems (DTPs) in the treatment of patients with hypertension. Methods: This prospective analytical study used a self-determined questionnaire to collect 2-month period data of hypertensive patients (n=107) admitted to four primary health centers in Medan (Medan Deli, Helvetia, Glugur Darat, and Teladan). Inclusion criteria were patients diagnosed with hypertension, age ≥18 years, and under ...
A. Gauruder Burmester; A. Biskupskie; A. Rosahl; R. Tunn
PURPOSE: Evaluate the benefits of electromotive drug administration (EMDA) as an alternative technique in patients with chronic overactive bladder in terms of improvement of symptoms, quality of life, and sexuality. MATERIAL AND METHODS: A total of 72 patients with therapy-refractory overactive bladder according to the ICS (International Continence Society) definition, were treated by EMDA. The regimen consisted of three treatment cycles, each with 3 instillations at 2-week intervals. The sol...
Giovana Maria Fioramonti Calixto; Jéssica Bernegossi; Laura Marise de Freitas; Carla Raquel Fontana; Marlus Chorilli
Photodynamic therapy (PDT) is a promising alternative approach for improved cancer treatment. In PDT, a photosensitizer (PS) is administered that can be activated by light of a specific wavelength, which causes selective damage to the tumor and its surrounding vasculature. The success of PDT is limited by the difficulty in administering photosensitizers (PSs) with low water solubility, which compromises the clinical use of several molecules. Incorporation of PSs in nanostructured drug deliver...
Anish Babu; Templeton, Amanda K.; Anupama Munshi; Rajagopal Ramesh
The last decade has witnessed enormous advances in the development and application of nanotechnology in cancer detection, diagnosis, and therapy culminating in the development of the nascent field of “cancer nanomedicine.” A nanoparticle as per the National Institutes of Health (NIH) guidelines is any material that is used in the formulation of a drug resulting in a final product smaller than 1 micron in size. Nanoparticle-based therapeutic systems have gained immense popularity due to their ...
Velasquez, Elinor; Soto-Andrade, Jorge; Bongalon, Ben
A prototype for a web application was designed and implemented as a guide to be used by clinicians when designing the best drug therapy for a specific cancer patient, given biological data derived from the patients tumor tissue biopsy. A representation of the patients metabolic pathways is displayed as a graph in the application, with nodes as substrates and products and edges as enzymes. The top metabolically active sub- paths in the pathway, ranked using an algorithm based on both the patie...
Yanchick, J K
The development and implementation of a drug therapy monitoring clinic in the primary-care clinics of a military hospital are described. To improve patient care and decrease costs associated with treating chronic diseases, in August 1995 the pharmacy department established a drug therapy monitoring clinic. The clinic was responsible for initiating and monitoring treatment plans for patients with chronic diseases, implementing clinical guidelines, providing educational programs, collecting and analyzing outcome data, and handling requests for medication extensions. Treatment followed existing national standards and Department of Defense guidelines modified for the institution. The clinic began with one clinical pharmacy specialist, and within a year it added another clinical pharmacist and a technician. The clinic first obtained patients via consultations from providers in primary care; this was soon extended to all departments. In addition, the pharmacist was available to see walk-in patients needing medication extensions. Later, referrals came for inpatients and patients seen in the emergency room for asthma or diabetes mellitus, as well as for inpatients receiving oral anticoagulation therapy. For fiscal year 1999, the clinic saw 104 (+/- 44.3) patients per month seeking medication extensions. It also handled 24,873 clinical interventions that year, resulting in projected annual savings of $1,085,560. Chart review indicated that compliance with national standards improved dramatically for patients with diabetes mellitus or asthma followed by pharmacists compared with physician monitoring during the same period and before the clinic began. The wait time for reviewing laboratory results and for patients receiving anticoagulation therapy was eliminated, and doses were changed immediately, if needed. A comprehensive pharmacist-managed drug therapy monitoring clinic for outpatients with chronic diseases can result in positive patient outcomes and more cost
Full Text Available The last decade has witnessed enormous advances in the development and application of nanotechnology in cancer detection, diagnosis, and therapy culminating in the development of the nascent field of “cancer nanomedicine.” A nanoparticle as per the National Institutes of Health (NIH guidelines is any material that is used in the formulation of a drug resulting in a final product smaller than 1 micron in size. Nanoparticle-based therapeutic systems have gained immense popularity due to their ability to overcome biological barriers, effectively deliver hydrophobic therapies, and preferentially target disease sites. Currently, many formulations of nanocarriers are utilized including lipid-based, polymeric and branched polymeric, metal-based, magnetic, and mesoporous silica. Innovative strategies have been employed to exploit the multicomponent, three-dimensional constructs imparting multifunctional capabilities. Engineering such designs allows simultaneous drug delivery of chemotherapeutics and anticancer gene therapies to site-specific targets. In lung cancer, nanoparticle-based therapeutics is paving the way in the diagnosis, imaging, screening, and treatment of primary and metastatic tumors. However, translating such advances from the bench to the bedside has been severely hampered by challenges encountered in the areas of pharmacology, toxicology, immunology, large-scale manufacturing, and regulatory issues. This review summarizes current progress and challenges in nanoparticle-based drug delivery systems, citing recent examples targeted at lung cancer treatment.
Caecilia HC Sukowati, Natalia Rosso, Lory S Crocè, Claudio Tiribelli
Full Text Available Hepatocellular carcinoma (HCC is one of most common malignancies in the world. Systemic treatments for HCC, particularly for advanced stages, are limited by the drug resistance phenomenon which ultimately leads to therapy failure. Recent studies have indicated an association between drug resistance and the existence of the cancer stem cells (CSCs as tumor initiating cells. The CSCs are resistant to conventional chemotherapies and might be related to the mechanisms of the ATP Binding Cassette (ABC transporters and alterations in the CSCs signaling pathways. Therefore, to contribute to the development of new HCC treatments, further information on the characterization of CSCs, the modulation of the ABC transporters expression and function and the signaling pathway involved in the self renewal, initiation and maintenance of the cancer are required. The combination of transporters modulators/inhibitors with molecular targeted therapies may be a potent strategy to block the tumoral progression. This review summarizes the association of CSCs, drug resistance, ABC transporters activities and changes in signaling pathways as a guide for future molecular therapy for HCC.
Full Text Available Deregulation of cellular signal transduction, caused by gene mutations, has been recognized as a basic factor of cancer initiation, promotion and progression. Thus, the ability to control the activity of overstimulated signal molecules by the use of appropriate inhibitors became the idea of targeted cancer therapy, which has provided an effective tool to normalize the molecular disorders in malignant cells and to treat certain types of cancer. The molecularly targeted drugs are divided into two major pharmaceutical classes: monoclonal antibodies and small-molecule kinase inhibitors. This review presents a summary of their characteristics, analyzing their chemical structures, specified molecular targets, mechanisms of action and indications for use. Also the molecules subjected to preclinical trials or phase I, II and III clinical trials evaluating their efficiency and safety are presented. Moreover, the article discusses further perspectives for development of targeted therapies focusing on three major directions: systematic searching and discovery of new targets that are oncogenic drivers, improving the pharmacological properties of currently known drugs, and developing strategies to overcome drug resistance. Finally, the role of proper pharmacodiagnostics as a key to rational anticancer therapy has been emphasized since the verification of reliable predictive biomarkers is a basis of individualized medicine in oncology.
Full Text Available Pharmaceutical care (PC has been shown to improve the outcome of drug therapy in many disease conditions. HIV/AIDS is one of the disease conditions that are fraught with many problems that can benefit from this new emphasis of pharmacy practice also known as ‘pharmacists care’. Adverse drug reactions or effects are unintended and undesirable effects of drugs other than their known and expected actions which can be unpleasant and sometimes fatal. This study is designed to evaluate the impact of pharmaceutical care activities on the occurrence of side/adverse drug reactions in HIV/AIDS patients receiving antiretroviral drugs. The components of the American society of health-system pharmacists (ASHP guidelines on ‘standardized method for pharmaceutical care’ was used as a data collection instrument to evaluate, document and intervene in the antiretroviral therapy of about one thousand four hundred and seventy three (1,473 patients. The study identified about sixty (60 different types of side/adverse effects occurring among these patients through observation and patient complaints. The study also showed significant reduction in the incidence of side/adverse drug effects following the Pharmacist’s intervention activities, p ≥ 0.5. The study showed that pharmacists’ interventions in antiretroviral drug therapy through Pharmaceutical care can significantly reduce the incidence of side/adverse drug effects in HIV/AIDS patients receiving antiretroviral drugs.
Thompson, D; Oster, G
In this article we review published studies of the cost-effectiveness of drug therapy for hypercholesterolaemia to take stock of the principal findings that have been reported to date. We identified 9 studies that met all criteria for inclusion in our review, including 3 of bile-acid sequestrants (cholestyramine, colestipol), 2 of HMG-CoA reductase inhibitor (lovastatin), and 4 that considered both an HMG-CoA reductase inhibitor (simvastatin) and a bile-acid sequestrant (cholestyramine). While these studies were largely consistent in methodological approach, some differences were noted in the costs attributed to drug therapy. The cost-effectiveness of therapy with bile-acid sequestrants was found to range from $100 000 to $209 000 per year of life saved (1991 $US) for middle-aged men (42 to 55 years of age) with moderately high cholesterol levels (280 to 290 mg/dl) and otherwise average coronary risk characteristics. Corresponding cost-effectiveness ratios that have been reported for lovastatin range from $64 000 to $82 000, while those for simvastatin range from $45 000 to $65 000. Studies to date therefore suggest that therapy with HMG-CoA reductase inhibitors (i.e. lovastatin and simvastatin) is substantially more cost-effective than treatment with bile-acid sequestrants. PMID:10146977
Na, Han-Heom; Noh, Hee-Jung; Cheong, Hyang-Min; Kang, Yoonsung; Kim, Keun-Cheol
The efficacy of anticancer drugs depends on a variety of signaling pathways, which can be positively or negatively regulated. In this study, we show that SETDB1 HMTase is down-regulated at the transcriptional level by several anticancer drugs, due to its inherent instability. Using RNA sequence analysis, we identified FosB as being regulated by SETDB1 during anticancer drug therapy. FosB expression was increased by treatment with doxorubicin, taxol and siSETDB1. Moreover, FosB was associated with an increased rate of proliferation. Combinatory transfection of siFosB and siSETDB1 was slightly increased compared to transfection of siFosB. Furthermore, FosB was regulated by multiple kinase pathways. ChIP analysis showed that SETDB1 and H3K9me3 interact with a specific region of the FosB promoter. These results suggest that SETDB1-mediated FosB expression is a common molecular phenomenon, and might be a novel pathway responsible for the increase in cell proliferation that frequently occurs during anticancer drug therapy. [BMB Reports 2016; 49(4): 238-243] PMID:26949019
Calixto, Giovana Maria Fioramonti; Bernegossi, Jéssica; de Freitas, Laura Marise; Fontana, Carla Raquel; Chorilli, Marlus
Photodynamic therapy (PDT) is a promising alternative approach for improved cancer treatment. In PDT, a photosensitizer (PS) is administered that can be activated by light of a specific wavelength, which causes selective damage to the tumor and its surrounding vasculature. The success of PDT is limited by the difficulty in administering photosensitizers (PSs) with low water solubility, which compromises the clinical use of several molecules. Incorporation of PSs in nanostructured drug delivery systems, such as polymeric nanoparticles (PNPs), solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), gold nanoparticles (AuNPs), hydrogels, liposomes, liquid crystals, dendrimers, and cyclodextrin is a potential strategy to overcome this difficulty. Additionally, nanotechnology-based drug delivery systems may improve the transcytosis of a PS across epithelial and endothelial barriers and afford the simultaneous co-delivery of two or more drugs. Based on this, the application of nanotechnology in medicine may offer numerous exciting possibilities in cancer treatment and improve the efficacy of available therapeutics. Therefore, the aim of this paper is to review nanotechnology-based drug delivery systems for photodynamic therapy of cancer. PMID:26978341
Giovana Maria Fioramonti Calixto
Full Text Available Photodynamic therapy (PDT is a promising alternative approach for improved cancer treatment. In PDT, a photosensitizer (PS is administered that can be activated by light of a specific wavelength, which causes selective damage to the tumor and its surrounding vasculature. The success of PDT is limited by the difficulty in administering photosensitizers (PSs with low water solubility, which compromises the clinical use of several molecules. Incorporation of PSs in nanostructured drug delivery systems, such as polymeric nanoparticles (PNPs, solid lipid nanoparticles (SLNs, nanostructured lipid carriers (NLCs, gold nanoparticles (AuNPs, hydrogels, liposomes, liquid crystals, dendrimers, and cyclodextrin is a potential strategy to overcome this difficulty. Additionally, nanotechnology-based drug delivery systems may improve the transcytosis of a PS across epithelial and endothelial barriers and afford the simultaneous co-delivery of two or more drugs. Based on this, the application of nanotechnology in medicine may offer numerous exciting possibilities in cancer treatment and improve the efficacy of available therapeutics. Therefore, the aim of this paper is to review nanotechnology-based drug delivery systems for photodynamic therapy of cancer.
Puri, K; Puri, N
In the treatment of intracanal and periodontal infections, the local application of antibiotics and other therapeutic agents in the root canal or in periodontal pockets may be a promising approach to achieve sustained/controlled drug release, high antimicrobial activity and low systemic side effects. The conventional method for the elimination of subgingival microbial infection includes mechanical debridement, irrigation with antimicrobial agents or surgical access. But, the effectiveness of conventional nonsurgical treatment is limited by lack of accessibility to bacteria in deeper periodontal pockets, and/or does not completely eliminate intracanal microorganisms. Surgical intervention may be beneficial but cannot be done in all cases, medically compromised cases and also in patients not willing to be subjected to surgical therapy. Development of local drug delivery systems provides an answer to all such difficulties. This comprehensive review tries to cover the detailed information about the latest advances in the various local drug delivery systems, their indications, contraindications and their advantages over systemic drug therapy. PMID:24868252
Mukundraj S. Keny
Full Text Available Knee osteoarthritis (OA is a disease of the whole knee joint occurring due to an interaction between inflammatory, hypoxic, and mechanical pathways. Initial management includes monotherapy with analgesics or anti and #8209;inflammatory agents, eventually switching over to combination therapy with steroids and/or newer drugs. Cardiovascular risks associated with non and #8209;steroidal anti and #8209;inflammatory drugs (NSAIDs limit their long term use. Hence, novel target receptors or pathways, which remain unaffected by conventional therapy and modify disease are being increasingly looked for. Newer drugs such as glucosamine, chondroitin, methylsulfonylmethane, diacerein along with vitamins/minerals are commonly used as adjuncts to NSAIDs or as monotherapy. Because of their novel mechanisms of action and better safety profile they seem to be promising as disease modifying agents in the treatment of OA. Google, PubMed, Cochrane databases and Science Direct search was performed, and relevant articles were identified. This review focuses on the pathological targets which these drugs modify in order to bring about a symptom modifying effect. [Int J Basic Clin Pharmacol 2014; 3(3.000: 424-430
Tathiana Silva de Souza Martins
Full Text Available The aim of this study was: to identify and classify the main drugs administered by intravenous method in the prescriptions of the pediatric units and to verify the occurrence of potentially medicamentous interactions. It is an exploratory descriptive research, with quantitative treatment of the data. The population was formed by 1,248 pediatric prescriptions and the sample of 205, having as inclusion criteria prescriptions with intravenous therapy of two or more drugs. Data collection was made at the Medical Files of a University Hospital. It was verified that most of the drugs used presented interactive potential; 60% of the sample had been exposed to the co-administration of antimicrobials. The vancomycin was the most present agent, and all the children used an antimicrobial during the institutionalization period. It was concluded that the co-administration of potentially interactive drugs associated to simultaneous scheduling of administration of such agents could predispose the patients to undesired events, affecting, this way, the safety of the therapy.
Angell, Chava; Xie, Sibai; Zhang, Liangfang; Chen, Yi
Nanomedicine has been growing exponentially due to its enhanced drug targeting and reduced drug toxicity. It uses the interactions where nanotechnological components and biological systems communicate with each other to facilitate the delivery performance. At this scale, the physiochemical properties of delivery systems strongly affect their capacities. Among current delivery systems, DNA nanotechnology shows many advantages because of its unprecedented engineering abilities. Through molecular recognition, DNA nanotechnology can be used to construct a variety of nanostructures with precisely controllable size, shape, and surface chemistry, which can be appreciated in the delivery process. In this review, different approaches that are currently used for the construction of DNA nanostructures are reported. Further, the utilization of these DNA nanostructures with the well-defined parameters for the precise control in drug delivery and gene therapy is discussed. PMID:26725041
The aim of my Ph. D. research is to develop drug-polyester nanoconjugates (NCs) as a novel translational polymeric drug delivery system that can successfully evade non-specific uptake by reticuloendothelial system (RES) and facilitate targeted cancer diagnosis and therapy. By uniquely integrating well-established chemical reaction-controlled ring opening polymerization (ROP) with nanoprecipitation technique, I successfully developed a polymeric NC system based on poly(lactic acid) and poly(O-carboxyanhydrides) (OCA) that allows for the quantitative loading and controlled release of a variety of anticancer drugs. The developed NC system could be easily modified with parmidronate, one of bisphosphonates commonly used as the treatment for disease characterized by osteolysis, to selectively deliver doxorubicin (Doxo) to the bone tissues and substantially to improve their therapeutic efficiency in inhibiting the growth of osteosarcoma in both murine and canine models. More importantly, the developed NCs could avidly bind to human serum albumin, a ubiquitous protein in the blood, to bypass the endothelium barrier and penetrate into tumor tissues more deeply and efficiently. When compared with PEGylated NCs, these albumin-bound NCs showed significantly reduced accumulation in RES and enhanced tumor accumulation, which consequently contributed to higher their tumor inhibition capabilities. In addition, the developed NC system allows easy incorporation of X-ray computed tomography (CT) contrast agents to largely facilitate personalized therapy by improving diagnosis accuracy and monitoring therapeutic efficacy. Through the synthetic and formulation strategy I developed, a large quantity (grams or larger-scale) of drug-polyester NCs can be easily obtained, which can be used as a model drug delivery system for fundamental studies as well as a real drug delivery system for disease treatment in clinical settings.
Tuininga, Y S; Crijns, H J; Oosterhuis, B; Wiesfeld, A C; van Wijk, L M; Albronda, F; de Bruin, H; Jonkman, J H; Kozma, C; Lie, K I
The hemodynamic and pharmacokinetic effects of the novel class 1c antiarrhythmic drug restacorin were investigated in two groups of patients. Group I consisted of 5 patients with normal left ventricular (LV) function, and group II consisted of 10 patients with mild heart failure [New York Heart Association (NYHA) II; mean LV ejection fraction 33 +/- 6%]. The study had an open label, baseline-controlled, single-dose design. Restacorin was infused in a total dosage of 1.2 mg/kg. In group I, the only significant change as compared with baseline findings was a 25% increase in right atrial pressure. In group II; cardiac output (CO), dP/dt, and stroke work index (SWI) decreased significantly (-18, -11, and -24%, respectively). In addition, a significant 32% increase was noted in pulmonary artery wedge pressure (PAWP), and a 27% increase occurred in systemic vascular resistance (SVR). No changes were observed in heart rate (HR) or mean arterial blood pressure (MAP). CO and SVR at baseline correlated with the average plasma concentrations (r = -0.65 and p = 0.009 and r = 0.56 and p = 0.028 respectively). Creatinine clearance was inversely correlated to the restacorin plasma concentration (r = -0.51, p = 0.05). The half-life (t1/2) elimination time of restacorin was 2.60 h for group I, and 4.06 h for group II. Clearance was 51.4 and 32.2 L.h-1, respectively. Restacorin appears to be well tolerated in patients with normal LV function. The drug is not recommended for use in patients with reduced LV function because of its moderate negative inotropic effect. PMID:7515984
Jerjian, Taleen V; Glode, Ashley E; Thompson, Lisa A; O'Bryant, Cindy L
Antibody-drug conjugates (ADCs) combine highly specific monoclonal antibodies with potent cytotoxic drugs. Their synergy allows for targeted delivery of toxic drugs to cancer cells while sparing systemic exposure. In this review, we focus on the history and clinical applications of ADCs approved by the U.S. Food and Drug Administration (FDA) for the treatment of cancer and highlight new ADCs in the drug development pipeline. Three ADCs have received FDA approval thus far. Gemtuzumab ozogamicin, although withdrawn from the U.S. market, may still be an effective treatment modality in subsets of patients with acute myeloid leukemia. Brentuximab vedotin and ado-trastuzumab emtansine have shown improved efficacy and safety data compared with standard chemotherapy for the treatment of advanced lymphoma and breast cancer, respectively. With a number of ADCs with promising preliminary data in the clinical trial pipeline, cancer therapy is moving forward from traditional chemotherapy to targeted treatment modalities driven by the specificity of monoclonal antibodies and advancing biotechnology. PMID:26799352
Kuo, Chih-Yu; Liu, Ting-Yu; Chan, Tzu-Yi; Tsai, Sung-Chen; Hardiansyah, Andri; Huang, Li-Ying; Yang, Ming-Chien; Lu, Ruey-Hwa; Jiang, Jeng-Kai; Yang, Chih-Yung; Lin, Chi-Hung; Chiu, Wen-Yen
Magnetic silica core/shell nanovehicles presenting atherosclerotic plaque-specific peptide-1 (AP-1) as a targeting ligand (MPVA-AP1 nanovehicles) have been prepared through a double-emulsion method and surface modification. Amphiphilic poly(vinyl alcohol) was introduced as a polymer binder to encapsulate various drug molecules (hydrophobic, hydrophilic, polymeric) and magnetic iron oxide (Fe3O4) nanoparticles. Under a high-frequency magnetic field, magnetic carriers (diameter: ca. 50 nm) incorporating the anti-cancer drug doxorubicin collapsed, releasing approximately 80% of the drug payload, due to the heat generated by the rapidly rotating Fe3O4 nanoparticles, thereby realizing rapid and accurate controlled drug release. Simultaneously, the magnetic Fe3O4 themselves could also kill the tumor cells through a hyperthermia effect (inductive heating). Unlike their ungrafted congeners (MPVA nanovehicles), the AP1-grafted nanovehicles bound efficiently to colorectal cancer cells (CT26-IL4Rα), thereby displaying tumor-cell selectivity. The combination of remote control, targeted dosing, drug-loading flexibility, and thermotherapy and chemotherapy suggests that magnetic nanovehicles such as MPVA-AP1 have great potential for application in cancer therapy. PMID:26705859
Menéndez-Arias, Luis; Alvarez, Mar
One to two million people worldwide are infected with the human immunodeficiency virus type 2 (HIV-2), with highest prevalences in West African countries, but also present in Western Europe, Asia and North America. Compared to HIV-1, HIV-2 infection undergoes a longer asymptomatic phase and progresses to AIDS more slowly. In addition, HIV-2 shows lower transmission rates, probably due to its lower viremia in infected individuals. There is limited experience in the treatment of HIV-2 infection and several antiretroviral drugs used to fight HIV-1 are not effective against HIV-2. Effective drugs against HIV-2 include nucleoside analogue reverse transcriptase (RT) inhibitors (e.g. zidovudine, tenofovir, lamivudine, emtricitabine, abacavir, stavudine and didanosine), protease inhibitors (saquinavir, lopinavir and darunavir), and integrase inhibitors (raltegravir, elvitegravir and dolutegravir). Maraviroc, a CCR5 antagonist blocking coreceptor binding during HIV entry, is active in vitro against CCR5-tropic HIV-2 but more studies are needed to validate its use in therapeutic treatments against HIV-2 infection. HIV-2 strains are naturally resistant to a few antiretroviral drugs developed to suppress HIV-1 propagation such as nonnucleoside RT inhibitors, several protease inhibitors and the fusion inhibitor enfuvirtide. Resistance selection in HIV-2 appears to be faster than in HIV-1. In this scenario, the development of novel drugs specific for HIV-2 is an important priority. In this review, we discuss current anti-HIV-2 therapies and mutational pathways leading to drug resistance. PMID:24345729
Full Text Available “Prolonged medical starvation” as the method of cancer therapy was borrowed from folk healers Omelchenko A and Breuss R. Author was convinced in efficiency of this method of cancer treatment via examination of cured patients and on own experience. The mechanism of this method of cancer therapy operates via Warburg effect targeting that promotes efficient cancer treatment with small cytotoxic drugs. Just it was described the mechanism of Warburg effect as well as mechanism transmutation of mitochondrial function in cancer metabolism which are exhibited in connection with operation of described method cancer therapy. There were described the biochemical and biophysical mechanisms of formations resistance to some cytotoxic drugs and recurrence cancer disease after disease remission which occur sometimes as result of treatment with great dosage of cytotoxic drugs. Also it was described the benefits of use the method “Prolonged medical starvation” with decreased dosage of cytotoxic drugs for cancer treatment. The significance of this work that it was substantiated the mechanism operation of combination “Prolonged medical starvation” with small dosages cytotoxic drugs of cancer treatment, which mechanism leads to prevention recurrence cancer disease and resistance to anticancer drugs in comparison with intensive anticancer chemotherapy with great dosages of cytotoxic drugs in cancer therapy. Also the offered concepts of cancer therapy mechanism gave possibility to explain mechanisms of some results of experiments eliminating the doubts of the authors these experiments.
Full Text Available A significant case report of a HIV infected patient in his fifties who experienced an excellent virological and immunological response to antiretroviral therapy (which has been modified just to prevent or avoid some adverse events, but developed a severe, sudden acute kidney failure while under a polypharmacy due to some underlying and overwhelming disorders (i.e. arterial hypertension, non-insulin-dependent diabetes mellitus, a recent acute heart infarction with remarkable remnants, and finally an anecdotal muscle-joint pain with self-prescription of non-steroideal anti-inflammatory drugs, represents the key point for a debate around the increasing frequency of “polypharmacy” in the field of HIV infection, even when HIV resistance to antiretroviral is not a concern. The continuing increase of mean age of HIV-infected population, plus the existing, sometimes unmodifiable risk factors for cardiovascular, dysmetabolic, and renal disorders, plus the adjunct of anecdotal illnesses prompting the resort to different drugs and medications, either prescribed for HIV infection itself, or taken for concurrent or subsequent diseases, or self-prescribed occasionally due to an intercurrent, trivial disorders per se, may prompt a complicated scenario culminating with a life-threatening acute renal failure of tubular origin. Our report gives us the opportunity to revise and discuss the expected interactions between antiretroviral therapy and the even growing exposure to multiple different drug and drug classes, which may be responsible for relevant drug interactions and direct or adjunctive end-organ impairment, up to life-threatening conditions, which may be avoided or prevented by considering carefully all comorbidites and co-treatments potentially administered to HIV infected patients, thirty years after the discovery of AIDS.