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)