Clinical Pharmacology and Rational Pharmacotherapy
The pharmacology section tests whether you can choose a drug, a dose and a duration for a specific patient, and predict what will go wrong. Expect pharmacokinetics, drug interactions, renal and hepatic adjustment, pregnancy safety, antibiotic stewardship and prescription rules.
Core rules
- Half-life governs the dosing interval; steady state is reached after four to five half-lives; a loading dose is needed when the volume of distribution is large or the drug is urgently required.
- Cytochrome P450 interactions are examinable: rifampicin and carbamazepine are inducers, macrolides and azole antifungals are inhibitors. Warfarin is the classic victim drug - monitor the INR.
- Adjust renally cleared drugs by creatinine clearance (Cockcroft–Gault), not by serum creatinine alone. Metformin is reduced at eGFR 30–45 and stopped below 30.
- Prescriptions in Kazakhstan are written by international non-proprietary name, with dose, route, frequency and duration; antibiotics and most chronic-therapy drugs are prescription-only.
- Antibiotic stewardship: culture before treatment where feasible, narrow the spectrum on results, respect duration limits, reserve fluoroquinolones.
- Pregnancy: avoid ACE inhibitors, warfarin, isotretinoin and tetracyclines; paracetamol, penicillins and insulin are acceptable.
Worked example
A patient stabilised on warfarin develops bronchitis and is prescribed clarithromycin. Reasoning: clarithromycin inhibits CYP3A4 and raises the INR with bleeding risk. The safer choice is an antibiotic without this interaction, or if a macrolide is essential, close INR monitoring with dose adjustment.
Traps
- Doubling the next dose after a missed one instead of resuming the schedule.
- Continuing NSAIDs in heart failure or CKD.
- Stopping anti-tuberculosis treatment when the patient feels better.
- Ignoring hepatic impairment when dosing a drug with high first-pass metabolism.