Critical Illness and Pharmacology 2/11/10 - critical illness changes many aspects of pharmacodynamics and pharmacokinetics Pharmacokinetics – how the body handles the drug - Absorption: unpredictable oral bioavailablity due to ileus & diarrhoea, slower IM absorption due to impaired peripheral blood flow - Distribution: Vd commonly increased by increased total body water, decreased protein binding -> shorter t1/2 and increased free drug. - Metabolism: may be slowed by acute hepatic impairment or reduced hepatic blood flow. - Elimination: hepatic clearance -> decreased by biliary obstruction, renal clearance -> impaired by renal failure and variably restored by dialysis Pharmacodynamics – how the drug effects the body - effects can be therapeutic and toxic. - close relationship with pharmacokinetics. - drug effect decreased from: increased Vd, impaired tissue blood flow - drug effect may be increased from: failure to excrete. - cardiovascular: more susceptible to cardiotoxicity because of myocardial dysfunction - renal: more susceptible to impairment because of dehydration and impaired renal blood flow - nervous system: more susceptible to cerebral toxicity because of encephalopathy - haematological system: more susceptible to anti-coagulation c/o sepsis and DIC, also increased risk of DVT -> require prophylaxis Jeremy Fernando (2011)