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...