Pharmacology and Pharmacotherapy
Pharmacology tests altered pharmacokinetics in critical illness, drug dosing, interactions and toxicology.
Core rules
- Sepsis increases volume of distribution for hydrophilic drugs; loading doses may need to be higher.
- Renal and hepatic clearance change maintenance doses; CRRT dosing is not equivalent to normal renal function.
- CYP interactions matter: azoles, rifampicin and antiepileptics affect sedatives and anticoagulants.
- Propofol infusion syndrome: metabolic acidosis, rhabdomyolysis and arrhythmia; avoid high-dose or prolonged infusion.
- Vancomycin: AUC-guided dosing. Aminoglycosides: extended-interval dosing with trough monitoring.
Worked example
An 80-kg septic patient needs vancomycin. Give a loading dose of 25–30 mg/kg actual body weight, about 2,000–2,400 mg, to fill the increased volume of distribution, then dose by renal function and AUC. A standard 1-g dose may under-treat early sepsis.
Traps
- Underdosing beta-lactams in sepsis.
- Assuming CRRT removes all drugs.
- Missing withdrawal syndromes after prolonged sedation.
- Using dexmedetomidine in unstable bradycardia.