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Clinical Pharmacology and Therapeutics

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Страница 1 Table of Contents List of Tables List of Illustrations Guide Pages Clinical Pharmacology and Therapeutics Lecture Notes Страница 8 Preface Contributors Страница 11 1 Pharmacodynamics and pharmacokinetics Clinical scenario Introduction KEY POINTS – PHARMACODYNAMICS AND PHARMACOKINETICS Principles of drug action (pharmacodynamics) Mechanism of drug action Action on a receptor Action on an enzyme Action on membrane ionic channels Cytotoxic actions Dose–response relationship Principles of pharmacokinetics Absorption Distribution Clinical relevance of volume of distribution Plasma protein binding Clearance Single intravenous bolus dose Linear versus non‐linear kinetics Principles of drug elimination Drug metabolism Metabolic drug interactions Clinical scenario Induction KEY POINTS ‐ ENZYME INDUCTION AND INHIBITION Clinical scenario Inhibition Genetic factors in metabolism Renal excretion Clinical pharmacokinetics: dosage individualisation Clinical scenario KEY POINTS Introduction Therapeutic drug monitoring Clearance estimates Interpretation of serum concentrations Clinical examples of therapeutic drug monitoring Digoxin Clinical scenario Is this concentration expected? What dose adjustment should be made? Gentamicin Clinical scenario What dosage regimen should be prescribed? Has steady state been reached? How should the dose be adjusted? Phenytoin Clinical scenario Why was the first concentration so low? Why was the second concentration so high? Influence of renal function on pharmacokinetics and pharmacodynamics Clinical scenario Influence of impaired renal function KEY POINTS Altered pharmacokinetics Elimination Decreased protein binding Influence hepatic disease on pharmacokinetics and pharmacodynamics Hepatic metabolism Altered drug effect Worsening of the existing clinical condition Enhancement of adverse drug effects Influence of liver disease Altered pharmacokinetics Decreased first‐pass metabolism Decreased elimination by liver metabolism and decreased protein binding High extraction drugs Low extraction drugs Altered drug effect deranged brain function Decreased clotting factors Worsening of metabolic state Drug‐induced alkalosis Fluid overload Hepatotoxic drugs Prescribing for the young and the elderly Prescribing for the young Clinical scenario Introduction Pharmacokinetics Pharmacodynamics Practical aspects of prescribing in children Safety Development and regulation of medicines for children Prescribing for the elderly Clinical scenario Introduction Drug absorption Drug distribution Drug metabolism and age Renal excretion Receptor sensitivity Impairment of homeostasis Polypharmacy KEY POINTS: PRESCRIBING FOR THE ELDERLY Drugs in pregnant and breastfeeding women Drugs in pregnancy Clinical scenario KEY POINTS Introduction Effect of drugs on the foetus Fertilisation and implantation period Organogenesis Growth and development Drugs given at the end of pregnancy Effect of pregnancy on drug absorption, distribution and elimination Drug distribution Drug elimination Drug treatment of common medical problems during pregnancy Infection Nausea and vomiting Diabetes Asthma Epilepsy KEY POINTS IN THE MANAGEMENT OF PREGNANT WOMEN WITH EPILEPSY Hypertension Hyperthyroidism Thrombosis Depression Connective tissue disease Drug use in breastfeeding Clinical scenario KEY POINTS 2 Clinical trials and drug development Clinical scenario KEY POINTS Introduction Drug discovery Models of drug development Preclinical development In vitro studies In vivo animal studies of efficacy and toxicity Clinical trials Phase I clinical trials Specific types of Phase I clinical studies First in human studies Dose ranging studies Interaction studies Safety studies Phase II clinical trials Phase III clinical trials Factors to consider in Phase III trial design Newer approaches to Phase III clinical trial design Clinical scenario Phase IIIb and IV studies Pharmacovigilance Yellow card scheme 3 Pharmacoeconomics: the economic evaluation of new drugs Clinical scenario Introduction – why do we need economic evaluations? KEY POINTS Economic evaluation Perspective Costs Linking costs to benefits Cost‐minimisation analysis Cost‐effectiveness analysis Cost–benefit analysis Cost–utility analysis Why use CUA and QALYs? How are the constituent parts of QALYs estimated? How is cost‐effectiveness then assessed? Sensitivity analysis Pharmacoeconomics and decision‐making REFERENCES 4 Practical prescribing Good prescribing: questions to ask yourself before prescribing a drug Is drug treatment really necessary? Which drug should I choose? By what route should it be administered? What dose and how often? Writing the prescription: practical aspects General pointers on good prescribing Adverse drug reactions Drug allergy Drug interactions Pharmacodynamic interactions Pharmacokinetic interactions Adherence Clinical scenario Emergency prescribing Страница 168{buyButton}

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