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Conventional Drugs (conventional + drug)
Selected AbstractsGentamicin fails to increase dystrophin expression in dystrophin-deficient muscleMUSCLE AND NERVE, Issue 5 2003Patrick Dunant PhD Abstract A recent report that aminoglycoside antibiotics restored the expression of functional dystrophin to skeletal muscles of mdx mice, a model of Duchenne muscular dystrophy (DMD), raised hopes that DMD may be treatable by a conventional drug. Subsequently, several human trials were initiated for evaluating gentamicin therapy in selected DMD patients. An increase of dystrophin expression was not detected in one human trial that was fully reported. Here, we report that we were unable to replicate previously published beneficial results by gentamicin treatment in the mdx mouse. Therefore, we believe that additional animal experimentation is required to further evaluate the possibility of in vivo aminoglycoside therapy of DMD. Muscle Nerve 27: 624,627, 2003 [source] Cardiac side effects of psychiatric drugs,HUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue S1 2008Paul Mackin Abstract This review describes the common effects of psychotropic drugs on the cardiovascular system and offers guidance for practical management. Selected reports from the literature describing common side effects associated with psychotropic drugs are reviewed, and suggestions for further reading are given throughout the text. Orthostatic hypotension is the most common adverse autonomic side effect of antipsychotic drugs. Among the atypical antipsychotics the risk of orthostatic hypotension is highest with clozapine and among the conventional drugs the risk is highest with low potency agents. Rarely, orthostatic hypotension may result in neurocardiogenic syncope. QTc prolongation can occur with all antipsychotics but an increased risk is seen with pimozide, thioridazine, sertindole and zotepine. QTc prolongation is a marker of arrhythmic risk. Torsade de pointe, a specific arrhythmia, may lead to syncope, dizziness or ventricular fibrillation and sudden death. Heart muscle disease presents most commonly in the elderly as chronic heart failure, but myocarditis and cardiomyopathy, although relatively rare, are devastating, but potentially reversible complications of psychotropic drug therapy have been particularly linked to clozapine treatment. Patients with severe mental illness (SMI) are a ,high risk' population with regard to cardiovascular morbidity and mortality. It is probable that many patients accumulate an excess of ,traditional' risk factors for the development of cardiovascular disease, but other mechanisms including psychotropic drugs may also be influential in increasing risk in this vulnerable group. These risks need to be seen in the context of the undoubted therapeutic efficacy of the psychotropic armamentarium and the relief that these drugs bring to those suffering from mental disorder. Copyright © 2007 John Wiley & Sons, Ltd. [source] Neurological complications of psychiatric drugs: clinical features and management,HUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue S1 2008Peter M. Haddad Abstract This paper reviews the main neurological complications of psychiatric drugs, in particular antipsychotics and antidepressants. Extrapyramidal syndromes include acute dystonia, parkinsonism, akathisia, tardive dyskinesia and tardive dystonia. Extrapyramidal symptoms (EPS) are less frequent with atypical than with conventional antipsychotics but remain common in clinical practice partly due to lack of screening by health professionals. Neuroleptic malignant syndrome (NMS) consists of severe muscle rigidity, pyrexia, change in conscious level and autonomic disturbance but partial forms also occur. NMS is particularly associated with the initiation and rapid increase in dose of high-potency antipsychotics but it has been reported with all the atypical antipsychotics and rarely with other drugs including antidepressants. Serotonin toxicity comprises altered mental state (agitation, excitement, confusion), neuromuscular hyperactivity (tremor, clonus, myoclonus, hyper-reflexia) and autonomic hyperactivity and occurs on a spectrum. Severe cases, termed serotonin syndrome, usually follow the co-prescription of drugs that increase serotonergic transmission by different pathways, for example a monoamine oxidase inhibitor (MAOI) and a selective serotonin reuptake inhibitor (SSRI). Most antipsychotics and antidepressants lower the seizure threshold and can cause seizures; the risk is greater with clozapine than with other atypical antipsychotics and greater with tricyclic antidepressants (TCAs) than with SSRIs. In randomised controlled trials in elderly patients with dementia atypical antipsychotics are associated with a higher risk of stroke and death than placebo. Cohort studies suggest that conventional drugs carry at least the same risk. Cessation of treatment with antipsychotics and antidepressants can lead to a wide range of discontinuation symptoms which include movement disorders and other neurological symptoms. Clinicians need to be familiar with strategies to reduce the risk of these adverse events and to manage them when they arise. Their occurrence needs to be balanced against the benefits of psychiatric drugs in terms of efficacy and improved quality of life in a range of disorders. Copyright © 2007 John Wiley & Sons, Ltd. [source] Cutaneous leishmaniasis: successful treatment with itraconazoleINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 1 2006Javier Consigli MD Background, Leishmaniasis is a disease produced by several species of protozoa of the Leishmania genus. These protozoa are injected into the human bloodstream by sandflies. The symptomathology, either cutaneous, mucocutaneous or visceral, depends on the infective species and the immune status of the patient. Antimonial drugs are the mainstay treatment for all the clinical forms of the disease. Amphotericin B is the second-choice drug. Methods We report two clinical cases of cutaneous leishmaniasis treated with itraconazole. One case was a relapsing form unresponsive to conventional therapy. Results, Both patients achieved fast resolution of their lesions with no secondary effects. Conclusions, Itraconazole may be a valid option for the treatment of cutaneous leishmaniasis, mainly in those cases unresponsive to conventional drugs. [source] Safety and efficacy of granulocyte and monocyte adsorption apheresis in patients with active ulcerative colitis: A multicenter studyJOURNAL OF CLINICAL APHERESIS, Issue 1 2001Takashi Shimoyama Abstract Active ulcerative colitis (UC) is characterized by activation and infiltration of granulocytes and monocytes/macrophages into the colonic mucosa. The infiltrated leukocytes can cause mucosal damage by releasing degradative proteases, reactive oxygen derivatives, and proinflammatory cytokines. The aim of this trial (conducted in 14 specialist centers) was to assess safety and efficacy of granulocyte and monocyte adsorption apheresis in patients with active UC most of whom were refractory to conventional drug therapy. We used a new adsorptive type extracorporeal column (G-1 Adacolumn) filled with cellulose acetate beads (carriers) of 2 mm in diameter, which selectively adsorb granulocytes and monocytes/macrophages. Patients (n = 53) received five apheresis sessions, each of 60 minutes duration, flow rate 30 ml per minute for 5 consecutive weeks in combination with 24.4 ± 3.60 mg prednisolone (mean ± SE per patient per day, baseline dose). During 60 minutes apheresis, 26% of granulocytes, 19.5% of monocytes and 2% of lymphocytes adsorbed to the carriers. At week 7, 58.5% of patients had remission or improved, the dose of prednisolone was reduced to 14.2 ± 2.25 mg (n = 37). The apheresis treatment was fairly safe, only eight non-severe side effects (in 5 patients) were reported. Based on our results, we believe that in patients with active severe UC, patients who are refractory to conventional drugs, granulocyte and monocyte adsorption apheresis is a useful adjunct to conventional therapy. This procedure should have the potential to allow tapering the dose of corticosteroids, shorten the time to remission and delay relapse. J. Clin. Apheresis. 16:1-9, 2001. © 2001 Wiley-Liss, Inc. [source] Adulteration of Chinese herbal medicines with synthetic drugs: a systematic reviewJOURNAL OF INTERNAL MEDICINE, Issue 2 2002E. Ernst Abstract.,Ernst E. (University of Exeter, Exeter, UK). Adulteration of Chinese herbal medicines with synthetic drugs: a systematic review (Review Article). J Intern Med 2002; 252: 107,113. The popularity of Chinese herbal medicines (CHMs) demands a critical analysis of safety issues. The aim of this systematic review is to summarize data regarding adulterations of CHMs with conventional drugs. Literature searches were carried out in six databases. Articles containing original data on adulterations were considered without language restrictions. Eighteen case reports, two case series and four analytical investigations were identified. The list of adulterants contains drugs associated with serious adverse effects like corticosteroids. In several instances, patients were seriously harmed. One report from Taiwan suggests that 24% of all samples were contaminated with at least one conventional pharmacological compound. It is concluded that adulteration of CHMs with synthetic drugs is a potentially serious problem which needs to be addressed by adequate regulatory measures. [source] Pharmacokinetics of CPX-351 (cytarabine/daunorubicin HCl) liposome injection in the mouseJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 7 2009William F. Bayne Abstract CPX-351 (cytarabine/daunorubicin liposome injection) is a liposomal formulation of a synergistic, fixed combination of the antineoplastic drugs cytarabine and daunorubicin for intravenous infusion. The two drugs are contained within the liposome in a 5:1 molar ratio, shown to be synergistic in vitro and in murine models of hematological malignancies. Mice were given a single intravenous dose of CPX-351 or conventional cytarabine and daunorubicin in saline and plasma and bone marrow were assayed for drug and lipid concentrations. A pharmacokinetic model was developed to assess the disposition of the coencapsulated drugs in mice, including the free and encapsulated fractions after measurement of the total plasma concentrations. Through the measurement of the loss of both encapsulated drug and liposomal lipid from the plasma, the routes of elimination, extravasation (uptake of encapsulated drugs into the tissues) and leak (passage of the drugs across the liposome membrane into the plasma), could be discerned. Knowing the leak rates from the liposome into the plasma and the plasma pharmacokinetics of the conventional drugs, the free drug concentrations could be predicted. The free concentrations in the bone marrow from the liposome leak in plasma could also be predicted using the bone marrow responses to the conventional drugs. © 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:2540,2548, 2009 [source] The effects of the phytoestrogenic isoflavone genistein on the hepatic disposition of preformed and hepatically generated gemfibrozil 1- O -acyl glucuronide in the isolated perfused rat liverJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 10 2003Anthony N. Lucas ABSTRACT Foods and complementary medicines contain phytoestrogenic isoflavones such as genistein, which undergo hepatic glucuronidation and excretion into bile and can potentially interfere with the hepatic elimination of other compounds. To investigate this potential, livers from Sprague-Dawley rats were perfused in single-pass mode with preformed gemfibrozil 1- O -acyl glucuronide (GG) (1 ,M, n = 12) for 60 min followed by a 30-min washout phase, or with gemfibrozil (1 ,M n = 10) for 120 min. Half of each group of livers were co-perfused with genistein (10 ,M) throughout the experiment. Perfusate and bile were analyzed for GG and gemfibrozil by HPLC. Co-perfusion with genistein significantly (P < 0.05) decreased the biliary extraction ratio of preformed GG from a mean of 0.82 to 0.65 and the first-order rate constant for transport of GG into bile from 0.054 + 0.010 to 0.032 + 0.008 min,1, but increased the first-order rate constant for sinusoidal efflux of GG from 0.128 + 0.023 to 0.227 + 0.078 min,1. Co-perfusion with genistein also significantly decreased the biliary extraction ratio of hepatically generated GG from 0.95 + 0.01 to 0.83 + 0.05. The findings confirm that genistein increases the potential for hepatic and systemic exposure to hepatically generated glucuronides, which may be important for patients on conventional drugs who consume isoflavones. [source] Targeted delivery of proteins by nanosized carriersJOURNAL OF POLYMER SCIENCE (IN TWO SECTIONS), Issue 1 2008Roberto Solaro Abstract Proteic drug administration poses some additional issues as compared with conventional drugs because of protein high molecular weight and short half-life in plasma. It is well known that protein delivery canbe significantly improved by using targeted nanocarriers. Among the diverse investigated systems, this overview focuses onliposomes and nanoparticles. Indeed, because of their subcellular size, nanocarriers can cross the fenestration of the vascular epithelium and penetrate tissues. Moreover, nanosystems can be confined at the location of choice by conjugation to molecules that strongly bind the target cells. In spite of the significant progress made in the design and engineering of liposomes and nanoparticles tailored to the targeted delivery of proteins, these nanocarriers seldom succeed in delivering proteins directly inside the cell cytosol. Accordingly, some attention is also paid to virosomes and fusion proteins. These systems have a few advantages over conventional nanocarriers, particularly the ability to cross the cell membrane. They also share the main drawback of being highly immunogenic. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 1,11, 2008 [source] Effectiveness of acupuncture for Parkinson's disease: A systematic reviewMOVEMENT DISORDERS, Issue 11 2008Myeong Soo Lee PhD Abstract The objective of this review is to assess the clinical evidence for or against acupuncture as a treatment for Parkinson's disease (PD). We searched the literature using 17 databases from their inception to September 2007 (searched again 3rd January 2008), without language restrictions. We included all randomized clinical trials (RCTs) regardless of their design. Methodological quality was assessed using the Jadad score. Eleven RCTs met all inclusion criteria. Three RCTs assessed the effectiveness of acupuncture on Unified Parkinson's Disease Rating Scale (UPDRS) compared with placebo acupuncture. A meta-analysis of these studies showed no significant effect (n = 96, WMD, 5.7; 95% CI ,2.8 to 14.2, P = 0.19, heterogeneity: tau2 = 0, ,2 = 0.97, P = 0.62, I2 = 0%). Another six RCTs compared acupuncture plus conventional drugs on improvement of symptoms of PD with drugs only. A meta-analysis of two of these studies suggested a positive effect of scalp acupuncture (n = 106, RR, 1.46, 95% CI = 1.15 to 1.87, P = 0.002; heterogeneity: tau2 = 0.00, ,2 = 1.14, P = 0.29, I2 = 12%). Two further RCTs tested acupuncture versus no treatment. The meta-analysis of these studies also suggested beneficial effects of acupuncture. The results of the latter two types of RCTs fail to adequately control for nonspecific effects. In conclusion, the evidence for the effectiveness of acupuncture for treating PD is not convincing. The number and quality of trials as well as their total sample size are too low to draw any firm conclusion. Further rigorous trials are warranted. © 2008 Movement Disorder Society [source] Patients' dependence on a nurse for the administration of their intravenous anti-TNF therapy: A phenomenographic studyMUSCULOSKELETAL CARE, Issue 2 2009Ingrid Larsson RN Abstract Background:,Pain, stiffness and functional restriction of the joints are the main problems for many patients with inflammatory rheumatic conditions. When conventional drugs fail to delay the development of the disease, the patient may require biological treatment such as anti-TNF therapy. Some biological drugs are administered in the form of intravenous infusions and thus the patient is obliged to attend a clinic in order to receive his/her medication, which can affect everyday life as well as independence. It is therefore important to focus on the patient perspective. Aim:,The aim of this study was to describe variations in how patients with rheumatic conditions conceive their dependence on a nurse for the administration of their intravenous anti-TNF therapy. Method:,The study had a descriptive qualitative design with a phenomenographic approach. Interviews were conducted with 20 patients. Result:,Three descriptive categories and seven sub-categories emerged: Dependence that affords security (encountering continuity, encountering competence and obtaining information); Dependence that creates involvement (being allowed influence and being given freedom); Dependence that invigorates (obtaining relaxation and encountering the environment). Conclusion:,The patients had not reflected on the fact that they were dependent on a nurse for the administration of their intravenous anti-TNF therapy, which may be due to their possibility to influence the treatment. The patients' needs should constitute the basis for the nurse's role in the provision of care. Copyright © 2008 John Wiley & Sons, Ltd. [source] Herb,drug interactions: Review and assessment of report reliabilityBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 5 2001Adriane Fugh-Berman Aims, The aim of this systematic review was to assess the published clinical evidence on interactions between herbal and conventional drugs. Methods, Four electronic databases were searched for case reports, case series or clinical trials of such interactions. The data were extracted and validated using a scoring system for interaction probability. Results, One hundred and eight cases of suspected interactions were found. 68.5% were classified as ,unable to be evaluated', 13% as ,well-documented' and 18.5% as ,possible' interactions. Warfarin was the most common drug (18 cases) and St John's wort the most common herb (54 cases) involved. Conclusion, Herb,drug interactions undoubtedly do occur and may put individuals at risk. However our present knowledge is incomplete and more research is urgently needed. [source] Jostling for Position: Optimizing Linker Location in the Design of Estrogen Receptor-Targeting PROTACsCHEMMEDCHEM, Issue 7 2010Kedra Cyrus Dr. Abstract Estrogen receptor-, (ER) antagonists have been widely used for breast cancer therapy. Despite initial responsiveness, hormone-sensitive ER-positive cancer cells eventually develop resistance to ER antagonists. It has been shown that in most of these resistant tumor cells, the ER is expressed and continues to regulate tumor growth. Recent studies indicate that tamoxifen initially acts as an antagonist, but later functions as an ER agonist, promoting tumor growth. This suggests that targeted ER degradation may provide an effective therapeutic approach for breast cancers, even those that are resistant to conventional therapies. With this in mind, we previously demonstrated that proteolysis targeting chimeras (PROTACs) effectively induce degradation of the ER as a proof-of-concept experiment. Herein we further refined the PROTAC approach to target the ER for degradation. The ER-targeting PROTACs are composed of an estradiol on one end and a hypoxia-inducing factor,1, (HIF-1,)-derived synthetic pentapeptide on the other. The pentapeptide is recognized by an E3 ubiquitin ligase called the von,Hippel Lindau tumor suppressor protein (pVHL), thereby recruiting the ER to this E3 ligase for ubiquitination and degradation. Specifically, the pentapeptide is attached at three different locations on estradiol to generate three different PROTAC types. With the pentapeptide linked through the C7, position of estradiol, the resulting PROTAC shows the most effective ER degradation and highest affinity for the estrogen receptor. This result provides an opportunity to develop a novel type of ER antagonist that may overcome the resistance of breast tumors to conventional drugs such as tamoxifen and fulvestrant (Faslodex). [source] | |||||||||||||