Pharmacokinetics and pharmacodynamics in critically ill patients

Abstract

The rapidly changing physiology of critically ill patients causes variations in the absorption, distribution, metabolism, excretion, and pharmacodynamic effect of drugs used to treat these patients. Alterations in fluid status, cardiac, renal and hepatic function, and circulating serum proteins necessitate increased attention to drug selection and dosage modification. Cardiac failure results in decreased absorption, metabolism, and excretion of drugs while renal failure results in parent drug and metabolite accumulation, increases in unbound drug, and changes in distribution volume. The changes in hepatic blood flow and protein binding, and decreases in hepatocellular mass and enzyme function that occur in hepatic failure may alter the clearance of several drugs. Serum drug concentrations are helpful in defining the pharmacokinetics and ultimately the pharmacodynamic effect of the drugs used in critically ill patients. The serum drug concentrations must be interpreted in association with their pharmacodynamic effect and the clinical situation. Adjusting drug therapy based on pharmacokinetic principles is discussed in detail with specific suggestions for dosage modifications in renal and hepatic failure.

Bioavailability of Oral Fluconazole in Critically Ill Abdominal Trauma Patients With and Without Abdominal Wall Closure: a Randomized Crossover Clinical Trial

“…22 Altered pharmacokinetics of many commonly used drugs in the critically ill is reported in the literature. 23,24 The pharmacokinetic parameters changed include volume of distribution, elimination (hepatic and renal) rate for parent and metabolites as well as protein binding. Intrapatient variability has been reported in critically ill patients receiving antimicrobial agents and phenytoin.…”

Proton Pump Inhibitor Formulary Considerations in the Acutely III: Part 1: Pharmacology, Pharmacodynamics, and Available Formulations

“…5, 56 Clearly, patients who are likely to absorb a medication should receive it orally or enterally if possible. However, in cases where drug absorption is questionable or likely impaired, intravenous formulations should be considered.…”

Adaptation des thérapeutiques médicamenteuses en cas d’insuffisance hépatocellulaire

“…L'hyperthermie et l'hypothermie sont aussi à l'origine d'une diminution du débit sanguin hépatique artériel et veineux et donc, par ce biais, d'une diminution de la clairance hépatique [21].…”

“…L'hypotension artérielle de l'état de choc, quelle que soit son origine s'accompagne d'une vasoconstriction systémique à l'origine d'une diminution du débit sanguin hépatique et, par conséquent, d'une diminution de la clairance hépatique [21].…”