Pharmacology and Therapeutics: kinetics, dosing, and interactions
Pharmacology and Therapeutics tests how drugs move, how they act, and how to choose and adjust them safely. PLE items combine pharmacokinetic calculations with autonomic, antimicrobial, and cardiovascular therapeutics.
Core rules
- First-order elimination removes a constant fraction per time; t1/2 = 0.693 × Vd/CL, and steady state is reached after about 4-5 half-lives.
- Loading dose = (Vd × target concentration)/F; maintenance dose = (CL × target concentration)/F. Loading dose is independent of clearance.
- Zero-order drugs include phenytoin, ethanol, and high-dose salicylate; small dose increases can cause toxicity.
- Receptors: agonists activate, antagonists block; competitive antagonism is surmountable, noncompetitive antagonism is not.
- CYP interactions: inhibitors such as ketoconazole, macrolides, and grapefruit raise drug levels; inducers such as rifampin, carbamazepine, and phenytoin lower them.
Worked example
A drug has Vd 50 L, target concentration 2 mg/L, and bioavailability 1. Loading dose = 50 × 2 = 100 mg. If clearance is 5 L/h, maintenance = 5 × 2 = 10 mg/h, or 240 mg/day. If bioavailability were 0.5, both doses would be doubled. Reasoning: Vd sets the loading dose; clearance sets the maintenance rate; bioavailability adjusts both.
Traps
Do not adjust a loading dose for renal failure unless Vd changes; maintenance dosing is what usually needs adjustment. Do not apply first-order half-life to phenytoin at high levels. Do not choose antibiotics by spectrum alone without culture and site penetration. Do not ignore CYP inducers when a drug suddenly loses effect.