Clinical Pharmacology Flashcards

What is the mechanism of action of proton pump inhibitors (PPIs) such as omeprazole?

Answer: Irreversible inhibition of the H⁺/K⁺-ATPase enzyme (proton pump) in gastric parietal cells

PPIs covalently and irreversibly bind to the H⁺/K⁺-ATPase proton pump in activated parietal cells, preventing acid secretion regardless of stimulant type.

Why is warfarin dose adjustment required when a patient starts rifampicin therapy?

Answer: Rifampicin is a potent CYP2C9 inducer that increases warfarin metabolism, reducing its anticoagulant effect

Rifampicin strongly induces CYP2C9 and CYP3A4, accelerating warfarin metabolism and reducing its plasma levels, which can cause subtherapeutic anticoagulation and clot formation.

What is the clinical importance of therapeutic drug monitoring (TDM) for vancomycin?

Answer: To ensure AUC/MIC targets are achieved for efficacy while avoiding nephrotoxicity

Vancomycin TDM using AUC/MIC-guided dosing balances optimal bactericidal exposure against nephrotoxicity risk, which is enhanced in critically ill or renally impaired patients.

Which drug is used to reverse the anticoagulant effect of dabigatran (a direct thrombin inhibitor)?

Answer: Idarucizumab (Praxbind)

Idarucizumab is a humanised monoclonal antibody fragment that specifically and rapidly reverses dabigatran's anticoagulant effect by binding it with very high affinity.

What is the pharmacological rationale for combining a beta-lactam with a beta-lactamase inhibitor (e.g., amoxicillin-clavulanate)?

Answer: The beta-lactamase inhibitor irreversibly binds and deactivates bacterial beta-lactamases, protecting the beta-lactam antibiotic from enzymatic degradation

Beta-lactamase inhibitors like clavulanate irreversibly inactivate bacterial beta-lactamases that would otherwise degrade the co-administered beta-lactam, restoring its antibacterial activity against resistant organisms.

Why must MAO-B inhibitors (e.g., selegiline) used in Parkinson's disease be distinguished from non-selective MAOIs in clinical practice?

Answer: MAO-B inhibitors at low doses are selective for dopamine metabolism and have fewer dietary tyramine interactions than non-selective MAOIs

Selective MAO-B inhibitors at standard Parkinson's doses primarily break down dopamine without significantly affecting tyramine metabolism, reducing the hypertensive 'cheese effect' risk of non-selective MAOIs.