Clinical meaning
Pharmacotherapeutics at the advanced practice level requires mastery of pharmacokinetics (absorption, distribution, metabolism, excretion), pharmacodynamics (drug-receptor interactions, dose-response relationships), and pharmacogenomics (genetic variations affecting drug metabolism).
Absorption is influenced by route of administration, formulation, GI pH, blood flow, and first-pass metabolism. Bioavailability varies significantly: IV administration has 100% bioavailability, while oral medications undergo first-pass hepatic metabolism that can substantially reduce systemic availability (e.g., propranolol oral bioavailability ~25%).
Drug metabolism occurs primarily in the liver via cytochrome P450 (CYP) enzymes. Key isoforms include CYP3A4 (metabolizes ~50% of drugs), CYP2D6 (codeine, tamoxifen, many antidepressants), CYP2C19 (clopidogrel, PPIs), and CYP2C9 (warfarin, phenytoin). Genetic polymorphisms create poor metabolizers, intermediate metabolizers, extensive metabolizers, and ultra-rapid metabolizers, significantly affecting drug response.
Renal dosing adjustments are critical for drugs with significant renal elimination. The Cockcroft-Gault equation or CKD-EPI formula estimates kidney function for dosing decisions. Drugs requiring renal adjustment include metformin, DOACs, gabapentin, vancomycin, aminoglycosides, and lithium.
Hepatic dosing considerations use the Child-Pugh classification. Phase I reactions (oxidation, reduction, hydrolysis via CYP enzymes) are more affected by liver disease than Phase II reactions (conjugation, glucuronidation).
Prescribing in special populations requires attention to physiologic changes. Pregnancy drug safety uses FDA Letter Categories (being replaced by the Pregnancy and Lactation Labeling Rule). Pediatric dosing often uses weight-based calculations. Geriatric prescribing follows the Beers Criteria to avoid potentially inappropriate medications, and START/STOPP criteria guide prescribing optimization.