Clinical pharmacology

Drug therapy to achieve the recommended target blood pressure remains the cornerstone of the management of hypertension. Today, there are strong evidences from randomized controlled trials that antihypertensive drugs are more effective than placebo at reducing cardiovascular mortality and morbidity.

8p vifaye 20-09-2024 3 1   Download

The low-density lipoprotein cholesterol (LDL-C) is established as a causative agent of atherosclerotic cardiovascular disease (ASCVD) and lowering plasma LDL-C levels represents the main approach to reduce the risk of cardiovascular events. Statins remain the cornerstone of drug therapy for dyslipidemia.

11p vifaye 20-09-2024 1 1   Download

The aim of this study was to investigate the potential impact of obesity on patients’ clinical outcome and response to the usual post orthopaedic surgery thromboprophylaxis enoxaparin or aspirin. Additionally, the participants perceived barrier(s) to adherence to the prescribed prophylaxis were explored.

224p runthenight04 02-02-2023 2 1   Download

The aims of this study are to (1) review the fundamental knowledge of AR from the perspectives of the Western medicine and CM perspectives, (2) investigate the effectiveness and the safety of CHM used for the management of AR by conducting a systematic review (SR) of the RCTs, (3) elucidate the pharmacological effects and the mechanisms of actions of the five herbs commonly used in the RCTs, and (4) extract the herbs used in retrospective diagnosis of ARlike signs and symptoms from the classical texts, conduct pattern analyses of the herbs used classically by employing principal component a...

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trans-[PtCl2NH3(4-Hydroxymethylpyridine)] (trans-PtHMP) is an analogue of clinically ineffective transplatin, which is cytotoxic in the human leuke-mia cancer cell line. As DNA is a major pharmacological target of anti-tumor platinum compounds, modifications of DNA by trans-PtHMP and recognition of these modifications by active tumor suppressor protein p53 were studied in cell-free media using the methods of molecular biology and biophysics.

14p dell39 27-03-2013 49 4   Download

Because clinical trials of pharmacological neuroprotective strategies in stroke have been disappointing, attention has turned to the brain’s own endogenous strategies for neuroprotection. Two endogenous mechanisms have been characterized so far, namely ischemic preconditioning and ische-mic postconditioning.

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Clinical evidence continuous medical education: a randomised educational trial of an open access e-learning program for transferring evidence-based information – ICEKUBE (Italian Clinical Evidence Knowledge Utilization Behaviour Evaluation) – study protocol Lorenzo Moja*1, Ivan Moschetti1, Michela Cinquini2, Valeria Sala1, Anna Compagnoni3, Piergiorgio Duca4, Christian Deligant5, Roberto Manfrini5, Luca Clivio6, Roberto Satolli5, Antonio Addis7, Jeremy M Grimshaw8, Pietro Dri5 and Alessandro Liberati1 Address: 1Italian Cochrane Centre, Mario Negri Institute for Pharmacological Research, M...

11p toshiba23 11-12-2011 67 3   Download

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học quốc tế cung cấp cho các bạn kiến thức về ngành y đề tài: Bench-to-bedside review: Molecular pharmacology and clinical use of inert gases in anesthesia and neuroprotection...

12p coxanh_6 30-10-2011 52 3   Download

of Clinical Pharmacology, Department of Medicine, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA Biology Institute, Department of Medicine Winthrop-University Hospital, 222 Station Plaza, North, Mineola, NY 11501, USA 3Division of Rheumatology, Allergy and Immunology, Department of Medicine Winthrop-University Hospital, 222 Station Plaza, North, Mineola, NY 11501, USA 2Vascular Corresponding author: Allison B Reiss, AReiss@winthrop.org Received: 11 Oct 2006 Revisions requested: 23 Nov...

11p thulanh13 15-10-2011 37 1   Download

Diuretics increase the rate of urine flow and sodium excretion and are used to adjust the volume and/or composition of body fluids in a variety of clinical situations, including hypertension, heart failure, renal failure, nephrotic syndrome, and cirrhosis. The objective of this chapter is to provide the reader with unifying concepts as to how the kidney operates and how diuretics modify renal function. The chapter begins with a description of renal anatomy and physiology, as this information is prerequisite to a discussion of diuretic pharmacology....

281p vanass 01-04-2011 78 11   Download

Harrison's Internal Medicine Chapter 15. Headache Headache: Introduction Headache is among the most common reasons that patients seek medical attention. Diagnosis and management is based on a careful clinical approach that is augmented by an understanding of the anatomy, physiology, and pharmacology of the nervous system pathways that mediate the various headache syndromes. General Principles A classification system developed by the International Headache Society characterizes headache as primary or secondary (Table 15-1).

5p ongxaemnumber1 26-11-2010 90 6   Download

Diagnosis and Treatment of Adverse Drug Reactions The manifestations of drug-induced diseases frequently resemble those of other diseases, and a given set of manifestations may be produced by different and dissimilar drugs. Recognition of the role of a drug or drugs in an illness depends on appreciation of the possible adverse reactions to drugs in any disease, on identification of the temporal relationship between drug administration and development of the illness, and on familiarity with the common manifestations of the drugs.

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Epidemiology Patients receive, on average, 10 different drugs during each hospitalization. The sicker the patient, the more drugs are given, and there is a corresponding increase in the likelihood of adverse drug reactions. When 15 drugs are given, the probability is 40%. Retrospective analyses of ambulatory patients have revealed adverse drug effects in 20%.

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Drug Interactions Not Mediated by Changes in Drug Disposition Drugs may act on separate components of a common process to generate effects greater than either has alone. Antithrombotic therapy with combinations of antiplatelet agents (glycoprotein IIb/IIIa inhibitors, aspirin, clopidogrel) and anticoagulants (warfarin, heparins) are often used in the treatment of vascular disease, although such combinations carry an increased risk of bleeding.

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Pharmacokinetic Interactions Causing Decreased Drug Effects Gastrointestinal absorption can be reduced if a drug interaction results in drug binding in the gut, as with aluminum-containing antacids, kaolin-pectin suspensions, or bile acid sequestrants. Drugs such as histamine H 2 receptor antagonists or proton pump inhibitors that alter gastric pH may decrease the solubility and hence absorption of weak bases such as ketoconazole.

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Multiple Variants Modulating Drug Effects As this discussion makes clear, for each drug with a defined mechanism of action and disposition pathways, a set of "candidate genes," in which polymorphisms may mediate variable clinical responses, can be identified. Indeed, polymorphisms in multiple genes have been associated with variability in the effect of a single drug. CYP2C9 loss-of-function variants are associated with a requirement for lower maintenance doses of the vitamin K antagonist anticoagulant warfarin. In rarer (...

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Principles of Genetic Variation and Human Traits (See also Chaps. 62 and 64) Variants in the human genome resulting in variation in level of expression or function of molecules important for pharmacokinetics and pharmacodynamics are increasingly recognized. These may be mutations (very rare variants, often associated with disease) or polymorphisms, variants that are much more common in a population. Variants may occur at a single nucleotide [known as single nucleotide polymorphism (SNP)] or involve insertion or deletion of one or more nucleotides.

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Transferase Variants One of the most extensively studied phase II polymorphisms is the PM trait for thiopurine S-methyltransferase (TPMT). TPMT bioinactivates the antileukemic drug 6-mercaptopurine. Further, 6-mercaptopurine is itself an active metabolite of the immunosuppressive azathioprine. Homozygotes for alleles encoding the inactive TPMT (1 in 300 individuals) predictably exhibit severe and potentially fatal pancytopenia on standard doses of azathioprine or 6-mercaptopurine.

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Principles of Dose Selection The desired goal of therapy with any drug is to maximize the likelihood of a beneficial effect while minimizing the risk of adverse effects. Previous experience with the drug, in controlled clinical trials or in postmarketing use, defines the relationships between dose (or plasma concentration) and these dual effects and provides a starting point for initiation of drug therapy. Figure 5-1 illustrates the relationships among dose, plasma concentrations, efficacy, and adverse effects and carries with it several important implications: 1.

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Renal Disease Renal excretion of parent drug and metabolites is generally accomplished by glomerular filtration and by specific drug transporters, only now being identified. If a drug or its metabolites are primarily excreted through the kidneys and increased drug levels are associated with adverse effects, drug dosages must be reduced in patients with renal dysfunction to avoid toxicity. The antiarrhythmics dofetilide and sotalol undergo predominant renal excretion and carry a risk of QT prolongation and arrhythmias if doses are not reduced in renal disease.

5p tubreakdance 26-11-2010 114 5   Download