Pharmaceutical Sciences and Drug Knowledge
Domain 3 - Pharmaceutical Sciences and Drug Knowledge
This domain tests the science behind the label: why a formulation behaves the way it does, how the body handles the drug, and what that means at the bedside or the counter. Expect pharmacokinetic reasoning, formulation questions, and small calculations.
Core pharmacokinetic rules to have automatic
- Half-life to steady state: about 4–5 half-lives; the same applies to washout. A drug with a 36-hour half-life needs roughly a week.
- Loading dose depends on volume of distribution; maintenance dose depends on clearance.
- Bioavailability is reduced by first-pass metabolism; food, gastric pH and transporters change it.
- When clearance falls in renal or hepatic impairment, the maintenance dose changes - not the loading dose.
Metabolism and interactions
- CYP3A4 handles a large share of drugs. Strong inhibitors (clarithromycin, ketoconazole, ritonavir, grapefruit) raise concentrations; inducers (rifampin, carbamazepine, St John's wort) lower them, with effects taking 1–2 weeks to appear or resolve.
- Induction and inhibition matter most for narrow-therapeutic-index substrates: warfarin, tacrolimus, phenytoin, digoxin and the DOACs.
Formulations
- Extended-release: never crush or split unless the product is designed for it; dose dumping is a real risk, especially with tube feeding.
- Enteric-coated: designed to bypass gastric acid; crushing defeats the purpose.
- Bioequivalence: Health Canada accepts a generic when the 90% confidence interval for the AUC and Cmax ratio falls within 80.0–125.0% of the comparator. That standard does not remove the need for monitoring when switching narrow-therapeutic-index drugs.
- Also know excipients (lactose, sulfites, tartrazine), preservative-free products for neonates, cold chain, and beyond-use dates after reconstitution.
Worked example
A patient with a nasogastric tube is prescribed nifedipine extended-release 60 mg daily. Crushing it releases the whole dose at once and can cause profound hypotension.
- Reasoning: the formulation, not the molecule, is the problem.
- Action: switch to an agent available in a crushable, dispersible form (for example amlodipine tablets, which can be crushed and dispersed), flush the tube adequately, and recheck blood pressure after the change.
Traps that cost marks
- Confusing half-life with duration of action.
- Adjusting the loading dose in renal failure while leaving the maintenance dose unchanged.
- Assuming every generic substitution is clinically neutral for a narrow-therapeutic-index drug.
- Ignoring the effect of food or tube feeding on absorption.