Drug Interactions.ppt

Drug Interactions New Zealand College of Pharmacists Purpose of Presentation This presentation supplements the course materials Risk Factors for Drug Interactions High Risk Patients Elderly, young, very sick, multiple disease Multiple drug therapy Renal, liver impairment High Risk Drugs Narrow therapeutic index drugs Recognised enzyme inhibitors or inducers Pharmacodynamic Drug Interactions One drug causes a change in patient response to another drug without altering that drug’s pharmacokinetics Eg increase toxicity of digoxin caused by diuretic induced hypokalaemia Additive effects of alcohol and benzodiazepines Beta-blocker given with beta-agonist Pharmaceutical Interactions Interactions that occur prior to systemic administration. For example incompatibility between two drugs mixed in an IV fluid. These interactions can be physical (e.g. with a visible precipitate) or chemical with no visible sign of a problem PharmacokineticDrug Interactions One drug alters the rate or extent of absorption, distribution, metabolism or excretion of another drug. A change in blood concentration causes a change in the drug’s effect. Altered Absorption (Availability) Change in gastrointestinal pH Ketoconazole needs acidic conditions in gut Drug binding in GI tract E.g. tetracycline and calcium Change in gastrointestinal flora Antibiotics with OCs??????? ? Change in gastrointestinal motility Metoclopramide and digoxin Malabsorption caused by other drugs Orlistat (Xenical) and fat soluble vitamins CYP450 Nomenclature CYP 450 SystemDefinitions Substrate:Drug is metabolised by the enzyme system Inducer:Drug that will increase the synthesis of CYP450 enzymes InhibitorDrug that will decrease the metabolism of a substrate Enzyme Induction 1 Leads to production of more enzyme, usually after 3-4 days of exposure to inducer Most CYPs are inducible but not CYP2D6 Time course of interaction depends on half-life of inducer. Enzyme Induction 2 Rifampicin has short hal