Study Guide Antiemesis Management in Cancer Therapy

Monday, March 24, 2025 📌 1⃣ 10:47 PM Study Guide: Antiemesis Management in Cancer Therapy Pathophysiology of CINV • Chemotherapy-Induced Nausea & Vomiting (CINV) is triggered by the vomiting center (medulla) and chemoreceptor trigger zone (CTZ). • Key neurotransmitters involved: • Serotonin (5-HT3) • Dopamine (D2) • Substance P (NK-1) • Others: Histamine, Acetylcholine, Prostaglandins 2⃣ Types of CINV Type Timing Key Features Acute ≤ 24 hrs post-chemo Mediated by serotonin (5-HT3) Delayed > 24 hrs, peaks at 48-72 hrs Mediated by Substance P (NK-1) Anticipatory Before chemotherapy Conditioned response (psychological) Breakthrough Occurs despite prophylaxis Refractory 3⃣ Requires rescue antiemetics Persistent N/V in later cycles Previous regimens failed Emetogenic Risk Classifica;on (IV Chemotherapy) Risk Level Emetogenic Agents High (>90%) Cisplatin, Carboplatin AUC ≥ 4, Cyclophosphamide > 1500 mg/m², Ifosfamide ≥ 2 g/m² Moderate (30-90%) Carboplatin AUC < 4, Cyclophosphamide ≤ 1500 mg/m², Oxaliplatin, Methotrexate > 50 mg/m² Low (10-30%) 5-FU, Methotrexate ≤ 50 mg/m², Vinblastine, Vincristine Minimal (<10%) Bleomycin, Rituximab, Trastuzumab An;eme;c Agents by Class (A) 5-HT3 Receptor Antagonists (Acute CINV) 4⃣ • • • • • • • • • • • • Drugs: Ondansetron, Granisetron, Dolasetron, Palonosetron MOA: Blocks serotonin in CTZ and GI tract Key ADRs: QTc prolongation, headache, constipation Special Notes: Palonosetron (Aloxi) → Best for delayed nausea (long t½: ~40 hrs) Ondansetron max IV dose = 16 mg (due to QT risk) (B) NK-1 Receptor Antagonists (Delayed CINV) Drugs: Aprepitant (Emend), Fosaprepitant (IV), Rolapitant, Netupitant MOA: Blocks Substance P in the CTZ Key ADRs: Hiccups, constipation, fatigue, LFT elevation Drug Interactions: ↓ Warfarin INR ↑ Dexamethasone levels (dose adjust needed) (C) Corticosteroids (Delayed CINV) • • • • • • • • • • • • • • Drug: Dexamethasone (Decadron) MOA: Reduces inflammation and prostaglandin activity Key ADRs: Hyperglycemia, insomnia, mood changes, increased appetite Used in: Acute & delayed nausea prevention (D) Dopamine (D2) Antagonists (Breakthrough CINV) Drugs: Prochlorperazine, Metoclopramide, Haloperidol, Olanzapine MOA: Blocks dopamine (D2) receptors in CTZ Key ADRs: EPS (tardive dyskinesia, dystonia), sedation, QTc prolongation Special Notes: Olanzapine → Strong evidence for breakthrough CINV Metoclopramide → Not first-line due to EPS risk (E) Benzodiazepines (Anticipatory CINV) Drug: Lorazepam (Ativan) MOA: Binds GABA receptors, reducing conditioned nausea Used in: Anticipatory nausea (NOT direct antiemetic) Key ADRs: Sedation, confusion, dependence (F) Cannabinoids (Breakthrough CINV) • Drugs: Dronabinol (Marinol), Nabilone (Cesamet) • MOA: Binds CB1 & CB2 receptors, reducing nausea • Key ADRs: Drowsiness, dizziness, euphoria, increased appetite Recommended An;eme;c Regimens (A) High Emetogenic Risk (e.g., Cisplatin) 5⃣ ✅ 1. 2. 3. 4. 4-Drug Regimen 5-HT3 antagonist (palonosetron preferred) NK-1 receptor antagonist (e.g., aprepitant) Dexamethasone Olanzapine (B) Moderate Emetogenic Risk ✅ 3-Drug Regimen 5. 5-HT3 antagonist 6. Dexamethasone 7. +/- NK-1 antagonist (optional) (C) Low Emetogenic Risk ✅ 1-Drug Regimen • Dexamethasone OR Prochlorperazine (D) Breakthrough CINV ✅ Add to previous regimen: • Olanzapine, prochlorperazine, or metoclopramide • Cannabinoids (dronabinol/nabilone) if refractory (E) Anticipatory Nausea ✅ Benzodiazepines + behavioral therapy • Lorazepam (Ativan) the night before & 1 hr before chemo 6⃣ Special Popula;ons & Considera;ons Scenario Best Option Avoid Long QT Syndrome Palonosetron Ondansetron, Dolasetron Diabetes 5-HT3 antagonists Dexamethasone (↑ BG) Substance Use History Olanzapine Warfarin Patient Dexamethasone, 5-HT3 antagonists Aprepitant (↓ INR) 7⃣ Key Exam Takeaways ✔ Palonosetron = Best for delayed nausea ✔ ✔ ✔ ✔ 🚀 Cannabinoids, Benzos NK-1 receptor antagonists = Best for delayed CINV Olanzapine = Strong option for breakthrough nausea Lorazepam = Best for anticipatory CINV QTc prolongation risk = Avoid ondansetron, dolasetron Final Exam Tip: When in doubt, match the CINV type with the drug class: • • • • Acute → 5-HT3 antagonist (Ondansetron, Granisetron) Delayed → NK-1 receptor antagonist (Aprepitant, Fosaprepitant) Breakthrough → Olanzapine or Dopamine Antagonists Anticipatory → Lorazepam Would you like flashcards or a quiz format for further review? 😊