SN3 SHORT NOTE 5M ★ High-yield

Describe the antiemetics used in chemotherapy-induced nausea and vomiting.

Pharmacology · 2nd Professional — Para-Clinical

Types of Chemotherapy-induced Nausea and Vomiting

Type	Timing	Chief mediator	Most effective drugs
Acute	Within 24 hours, peaking at 5–6 hours	Serotonin (5-HT) released from gut enterochromaffin cells acting on vagal 5-HT3 receptors	5-HT3 antagonists with dexamethasone
Delayed	After 24 hours, up to 5 days	Substance P acting on central NK1 receptors	NK1 antagonists (aprepitant) with dexamethasone; 5-HT3 antagonists are much less effective here
Anticipatory	Before the next cycle	A conditioned (learned) response, triggered by the sight or smell of the unit	Benzodiazepines and behavioural therapy; conventional antiemetics do not work
Breakthrough and refractory	Despite prophylaxis	Mixed	Olanzapine, metoclopramide, cannabinoids

CLINICAL PEARL

Acute and delayed vomiting have different mediators, which is why one drug cannot cover both. The acute phase is a serotonin event and responds to ondansetron. The delayed phase is a substance P event and largely does not. Giving a 5-HT3 antagonist alone and calling it prophylaxis protects the first day and leaves the patient unprotected for the next four — which is when most of the distress and dehydration actually occur.

The Drugs

5-HT3 antagonists — ondansetron, granisetron, and palonosetron, which has a much longer half-life (about 40 hours) and higher receptor affinity, giving it some activity in the delayed phase. Adverse effects: headache, constipation, and QT prolongation
NK1 antagonists — aprepitant and intravenous fosaprepitant; they block substance P centrally. Aprepitant is a moderate CYP3A4 inhibitor and interacts with dexamethasone (whose dose is reduced), warfarin and oral contraceptives
Dexamethasone — effective in both acute and delayed phases and part of nearly every regimen; the mechanism is not fully understood
Olanzapine — blocks multiple receptors (D2, 5-HT3, H1, muscarinic) and is highly effective for breakthrough and refractory vomiting; causes sedation, which some patients welcome
Metoclopramide at high dose blocks 5-HT3 as well as D2, but the extrapyramidal risk limits it to second-line use

Prophylaxis BY Emetogenic Risk

Emetogenic risk	Examples	Prophylaxis
High (over 90% vomit)	Cisplatin, high-dose cyclophosphamide, anthracycline with cyclophosphamide	5-HT3 antagonist + dexamethasone + NK1 antagonist (± olanzapine)
Moderate (30–90%)	Carboplatin, oxaliplatin, doxorubicin	5-HT3 antagonist + dexamethasone (+ NK1 for carboplatin)
Low (10–30%)	Paclitaxel, gemcitabine, fluorouracil	Dexamethasone or a 5-HT3 antagonist alone
Minimal (under 10%)	Vincristine, bleomycin, most biologicals	No routine prophylaxis

Prophylaxis must be given before the chemotherapy and continued for the days at risk; treating established vomiting is far less effective and the patient remembers it, which sets up anticipatory vomiting for the next cycle

Applied Aspects

Preventing vomiting at the first cycle is the best protection against anticipatory vomiting at later cycles, since it is a learned response and the learning happens on the first exposure
Ondansetron is not a general antiemetic — it is poor for motion sickness and vestibular vomiting, which are histamine- and muscarinic-mediated
Watch for QT prolongation where ondansetron is combined with other QT-prolonging drugs or where potassium and magnesium are low, which is common in vomiting patients
Constipation from 5-HT3 antagonists compounds opioid constipation in cancer patients; a laxative should be prescribed alongside
Cost limits NK1 antagonists in India; where they are unaffordable, olanzapine is a cheap, widely available and genuinely effective substitute with good trial evidence
Attend to nutrition, hydration and electrolytes, and to the patient's expectations — uncontrolled vomiting is a common reason for refusing further chemotherapy

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