Pharmacology: Pharmacokinetics, Pharmacodynamics and Dosing
Pharmacology: what is tested
Pharmacology tests pharmacokinetics, pharmacodynamics, dose calculations and clinically important interactions. The exam expects you to predict how absorption, distribution, metabolism and excretion change a drug's effect.
Core rules
- Bioavailability F is the fraction reaching systemic circulation; first-pass metabolism lowers oral F. Volume of distribution Vd = dose / plasma concentration. Clearance Cl = rate of elimination / plasma concentration.
- Half-life t1/2 = 0.693 x Vd / Cl. Steady state is reached after about 4-5 half-lives; a loading dose fills Vd faster.
- First-order kinetics eliminate a constant fraction per unit time; zero-order kinetics eliminate a constant amount and occur with phenytoin, ethanol and high-dose salicylate. Small dose increases then cause large level rises.
- Loading dose = (Vd x target concentration) / F. Maintenance dose rate = Cl x target concentration.
- Agonists activate receptors; competitive antagonists shift the dose-response curve right; potency is EC50, efficacy is maximal response. CYP inducers (rifampicin, carbamazepine) lower drug levels; inhibitors (erythromycin, ketoconazole) raise them.
Worked example. A drug has Vd 50 L, clearance 5 L/h and target concentration 4 mg/L; give it intravenously. Reasoning: loading dose = 50 L x 4 mg/L = 200 mg. Maintenance rate = 5 L/h x 4 mg/L = 20 mg/h. With F 0.8 orally, the loading dose would be 200 / 0.8 = 250 mg.
Traps that cost marks
- Including clearance in the loading-dose calculation.
- Forgetting to divide by F for an oral loading dose.
- Expecting steady state after one half-life.
- Missing zero-order kinetics when phenytoin toxicity follows a small dose increase.