Pharmacokinetics & Pharmacodynamics PDF

10. Pharmacokinetics and pharmacodynamics in the older persons (L5.5B) Pha mac d amic d g effec b d 1. Additive or antagonistic response 2. Therapeutic, eg. antihypertensives, cancer chemotherapy, pain management. 3. Harmful, eg., in patients receiving several drugs with anti...

10. Pharmacokinetics and pharmacodynamics in the older persons (L5.5B) Pha mac d amic d g effec b d 1. Additive or antagonistic response 2. Therapeutic, eg. antihypertensives, cancer chemotherapy, pain management. 3. Harmful, eg., in patients receiving several drugs with anticholinergic effect Pha mac ki e ic b d effec d g Absorption GI absorption may be inhibited (to various extents) by: Drugs with large surface area (eg. antacids) Binding resins (eg. cholestyramine) Drugs which affect GI motility Drugs which affect GI pH (eg. antacids, iron, kaolin-pectin, cholestyramine, colestipol) Distribution Drugs may compete with each other for binding sites on proteins or tissues (lasts for a few days). That is not clinically important, unless: The displaced drug is highly bound The displaced drug has limited VoD (volume of distribution). The displaced drug is slowly eliminated The displaced drug has low therapeutic index, Eg. dramatic in hypoprothrombinemia when phenylbutazone is added to warfarin (warfarin displaced from pl. protein binding sites + inhibition of hepatic w. metabolism). Eg. of precipitant drugs: sulphonamides, phenytoin, NSAIDs, sulphonylureas. Metabolism Can be or by the concurrent administration of other drugs. Effect on metabolism of drugs Examples “Enzyme-inducers” drug metabolism effect Barbiturates, Carbamazepine, Phenytoin, takes 1- weeks to kick in “takes longer” to Primidone, Rifampicin disappear) “Enzyme-inhibitors” All of these are due to P450 3A4 activity: Metabolism concentration drug Amiodarone, fluoxetine, Chloramphenicol, response possible toxicity isoniazid, Cimetidine, Ciprofloxacin, Diltiazem, Mostly occurs from using drugs that are Erythromycin, Valproic acid, ketoconazole, broken down by the same subtype of cytochrome propoxyphene, quinidine, Sulphonamides, P450. Inhibition of drug metabolism begins fairly verapamil quickly & is usually maximal by the time steady state concentration is reached. Renal excretion - pH, nephrotoxicity & competition Part of renal excretion affected Examples of drugs Alkalinisation of the urine ionization of drugs Quinidine that are weak bases: lipid solubility drug Methadone reabsorption from renal tubule into the blood Sympathomimetics plasma drug concentration. But if the drug is a weak acid the urinary pH Salicylates renal excretion plasma levels. Nephrotoxic Elimination of other drugs by Aminoglycosides, amphotericin B, pentamidine glomerular filtration Many drugs are excreted via active tubular Amphotericin B, Cephalosporins, Methotrexate, secretion Competition for excretion NSAIDs, Penicillins, Probenecid, Salicylates, Thiazides