Drug interactions and QTc — consultant viva

Station structure

Time: 8–10 minutes. Depth: consultant teaching registrar. Expect named trials, CYP enzyme precision, and action thresholds stated as teaching bands rather than invented universal statutes.[1][5]

Core questions and model points

1. PK vs PD? PK changes exposure (ADME/CYP); PD changes effect at same exposure (additive QTc, serotonin toxicity). Multi-hit long QT is PD synergy on a PK-raised level.[1][5]

2. Smoking and clozapine? Smoke PAHs induce CYP1A2 → lower levels; cessation raises levels/toxicity risk; plan dose and plasma level; NRT ≠ full induction.[3]

3. Fluvoxamine? Potent CYP1A2 inhibitor → elevated clozapine; high-risk combination without intensive TDM.[4]

4. Why correct QT? Rate dependence; Bazett overcorrects at high HR; Fridericia often preferred; never trust automation alone.[7][6]

5. Action thresholds? Teaching band: escalate near QTc ≥500 ms or Δ≈60 ms; strip culprits, electrolytes, monitor.[5][6]

6. TdP first drugs? Unstable → defibrillate; IV magnesium even if Mg normal; high-normal K+; stop QT drugs.[6][1]

7. Ray 2009? Atypical antipsychotics: dose-related sudden cardiac death risk comparable to typicals — not class-safe by marketing.[2]

8. Methadone? ECG screening principles; avoid extra QT drugs; coordinate OAT.[8]

9. Citalopram? Greater QTc signal vs many SSRIs in EHR data; respect dose maxima and risk stacking.[9][5]

10. Hospital risk tools? Tisdale score components (age, sex, diuretics, K+, baseline QTc, sepsis, MI, HF, number of QT drugs) as stratification language.[10]

Distinctions that score

Score by mapping CYP1A2 vs 2D6 vs 3A4 with one concrete pair each, using reduced repolarisation reserve (Roden) as the unifying multi-hit model, and risk-stratifying rather than abandoning indicated clozapine for theoretical QTc fear without measurement and monitoring.[1][3][4][5]