Pathophysiology
Clinical meaning
Evidence-based medication selection requires the clinician to integrate pharmacokinetic principles, pharmacodynamic targets, patient-specific variables, and guideline-concordant evidence to optimize therapeutic outcomes while minimizing harm. Pharmacokinetics governs how the body processes a drug through four phases: absorption (bioavailability influenced by route, formulation, gastric pH, P-glycoprotein efflux pumps, and first-pass hepatic metabolism), distribution (affected by protein binding -- highly protein-bound drugs like warfarin at 99% are susceptible to displacement interactions -- volume of distribution, lipophilicity, and blood-brain barrier penetration), metabolism (primarily hepatic via cytochrome P450 enzymes where CYP3A4 metabolizes approximately 50% of all drugs, CYP2D6 metabolizes 25%, and CYP2C9/2C19 handle additional substrates), and elimination (renal clearance calculated by CKD-EPI eGFR determines dose adjustments for drugs like gabapentin, metformin, and aminoglycosides; hepatic clearance assessed by Child-Pugh classification guides dose reduction for drugs like opioids and benzodiazepines). Pharmacodynamics describes what the drug does to the body: receptor agonism or antagonism, enzyme inhibition, ion channel modulation, and the dose-response relationship defined by the therapeutic index (ratio of TD50 to ED50). Narrow therapeutic index (NTI) drugs -- digoxin (0.8-2.0 ng/mL), lithium (0.6-1.2 mEq/L), phenytoin (10-20 mcg/mL),...