Pharmacology and Pharmacotherapeutics
What the domain tests
This domain connects drug action at receptors and enzymes to bedside prescribing: dose–response, therapeutic index, elimination kinetics, interactions, and special populations. Israeli vignettes often ask you to predict an effect, choose monitoring, or identify the mechanism behind a toxicity.
Core rules and concepts
- Efficacy is the maximal response; potency is the dose needed to produce a given effect. A partial agonist cannot match a full agonist even at saturation.
- Narrow therapeutic index drugs demand TDM or close clinical monitoring: digoxin, warfarin, lithium, phenytoin, aminoglycosides, vancomycin, theophylline.
- For first-order elimination, steady state is reached after about 4–5 half-lives; loading doses fill volume of distribution faster but do not change maintenance requirements.
- CYP inhibition usually raises substrate concentrations quickly; CYP induction develops over days to weeks and lowers concentrations. P-glycoprotein affects digoxin, dabigatran, and some statins.
- Renal and hepatic impairment change the fraction unbound, clearance, and accumulation risk; older adults have reduced renal reserve and altered body composition.
Worked example
A patient stable on warfarin starts fluconazole for candidiasis. Fluconazole inhibits CYP2C9 and CYP3A4, reducing warfarin metabolism; INR rises over several days. Because warfarin has a narrow therapeutic index, the correct reasoning is pharmacokinetic interaction plus monitoring: check INR sooner, anticipate dose reduction, and counsel on bleeding signs. Stopping warfarin abruptly without a plan is also unsafe because it removes protection against thrombosis.
Traps that cost marks
Do not confuse half-life with duration of action; do not assume every interaction is pharmacokinetic (some are pharmacodynamic, such as NSAID plus anticoagulant bleeding risk). Do not ignore active metabolites, such as those of codeine or tramadol. Do not apply adult doses to children by simple proportion without weight-based or surface-area calculation.
Key points
- Efficacy ≠ potency; partial agonists cap response.
- Narrow-index drugs need TDM or tight monitoring.
- Inhibition is fast; induction is slow.
- Adjust for renal/hepatic function and age.
- Separate PK from PD interactions.