Drug Interactions

On this page

Fundamentals of Interactions - The Chemical Tango

  • Drug interactions: one drug alters another's clinical effects or concentration.
  • Two main types:
    • Pharmacokinetic (PK): Body's effect on drug (ADME).
      • Altered Absorption, Distribution, Metabolism (e.g., CYP450 enzyme induction/inhibition), Excretion.
    • Pharmacodynamic (PD): Drug's effect on body.
      • Receptor binding (synergism/antagonism), or altered signal transduction.
  • Clinical impact: ↑toxicity, ↓efficacy, or new adverse effects.
  • Risk factors: Polypharmacy, elderly, genetic polymorphisms, hepatic/renal impairment.

⭐ Cytochrome P450 (CYP) enzymes, particularly CYP2D6 and CYP3A4, are central to many psychotropic drug interactions.

CYP450 & PK Interactions - Enzyme Traffic Jams

Cytochrome P450 (CYP450) enzymes in liver metabolize most psychotropics. Interactions via induction (↓ effect) or inhibition (↑ toxicity) alter drug levels.

  • CYP Inducers: 📌 "CRAPS" - Carbamazepine, Rifampicin, Alcohol (chronic), Phenytoin, Smoking.
    • Effect: ↓ levels of substrates (e.g., OCPs, antipsychotics).
  • CYP Inhibitors: 📌 Key examples: Valproate, Fluoxetine, Fluvoxamine, Erythromycin, Grapefruit Juice.
    • Effect: ↑ levels of substrates, risk of toxicity.
  • Key Psychotropic Pathways:
    • CYP2D6: TCAs, venlafaxine, risperidone, aripiprazole. (SSRIs often inhibit)
    • CYP3A4: Benzodiazepines (alprazolam), quetiapine, lurasidone.
    • CYP1A2: Clozapine, olanzapine. (Smoking induces)
  • Other PK: Absorption (antacids), distribution (protein binding), excretion ($Li^+$ & NSAIDs).

⭐ Fluvoxamine is a potent inhibitor of CYP1A2 & CYP2C19, significantly impacting clozapine & olanzapine levels.

Pharmacodynamic Dangers - When Drugs Collide

  • Serotonin Syndrome:
    • Cause: SSRI/SNRI + MAOI, triptans, linezolid.
    • Triad: Cognitive (agitation), Autonomic (hyperthermia), Neuromuscular (myoclonus).
    • 📌 Mnemonic: SHIVERS.

    ⭐ MAOIs need a 2-week washout before SSRIs (fluoxetine: 5 weeks) to prevent serotonin syndrome.

  • Hypertensive Crisis (MAOIs):
    • Cause: + Tyramine-rich foods (cheese, wine), sympathomimetics.
    • Symptoms: Severe headache, ↑↑BP.
  • Additive CNS Depression:
    • Cause: Benzodiazepines + Alcohol, opioids, antihistamines.
    • Effect: ↑Sedation, respiratory depression.
  • QTc Prolongation:
    • Drugs: Antipsychotics (haloperidol), TCAs, macrolides.
    • Risk: Torsades de Pointes (TdP).
    • ⚠️ Monitor ECG if QTc > 500 ms.
  • Anticholinergic Burden:
    • Drugs: TCAs, 1st gen antipsychotics, antihistamines.
    • Symptoms: Dry mouth, blurred vision, constipation, urinary retention, confusion.
    • 📌 Mnemonic: "Dry as a bone..." oka

Noteworthy Psychiatric Drug Pairs - Risky Mixes

  • SSRIs/SNRIs + MAOIs: ⚠️ Serotonin Syndrome (hyperthermia, rigidity, myoclonus). Min 2-week washout (Fluoxetine 5 weeks).
  • Lithium + NSAIDs/Thiazides/ACEIs: ↑ Lithium levels → Toxicity. Monitor levels.
  • Valproate + Lamotrigine: ↑ Lamotrigine levels (avg. 2x) → ↑ Risk of Stevens-Johnson Syndrome (SJS). (📌 VDL: Valproate Doubles Lamotrigine)
  • Clozapine + Carbamazepine: ↑ Risk of agranulocytosis/bone marrow suppression. Avoid.
  • Benzodiazepines + Opioids: Severe respiratory depression, coma, death.
  • TCAs + MAOIs: Hypertensive crisis, Serotonin Syndrome.

⭐ Valproate inhibits Lamotrigine metabolism (UGT glucuronidation), doubling its levels and SJS risk.

High‑Yield Points - ⚡ Biggest Takeaways

  • Serotonin Syndrome: High risk with SSRIs/SNRIs + MAOIs, linezolid, triptans.
  • Hypertensive Crisis: From MAOIs + tyramine-rich foods or sympathomimetics.
  • CYP450 Inducers (e.g., carbamazepine) ↓ drug levels; Inhibitors (e.g., fluoxetine) ↑ drug levels.
  • Lithium Toxicity: Increased by NSAIDs, thiazides, ACE inhibitors.
  • Clozapine Levels: Altered by CYP1A2 inhibitors (e.g., fluvoxamine) & inducers (smoking).
  • Benzodiazepines + Opioids: Potent risk of severe CNS & respiratory depression.
  • Valproate + Lamotrigine: Valproate inhibits lamotrigine metabolism, ↑ SJS risk.

Practice Questions: Drug Interactions

Test your understanding with these related questions

Pharmacodynamics deals with:-

1 of 5

Flashcards: Drug Interactions

1/10

Which antidepressants respond well in patients of hysteroid dysphoria?_____

TAP TO REVEAL ANSWER

Which antidepressants respond well in patients of hysteroid dysphoria?_____

MAO inhibitors

browseSpaceflip

Enjoying this lesson?

Get full access to all lessons, practice questions, and more.

Start Your Free Trial