✅ 1. PROMETHAZINE — 20% VERSION

⭐ Class

• Antihistamine (H1-blocker) + anticholinergic

⭐ Mechanism (PD)

• Blocks H1 receptors + muscarinic receptors →

✔ Sedation

✔ Prevents motion sickness & vomiting

⭐ Uses

• Motion sickness
• Hyperemesis gravidarum
• Nausea in early pregnancy
• Vertigo

⭐ Side Effects

• Sedation
• Dry mouth
• Dizziness
• Hypotension

⭐ Contra

❌ Severe liver disease

❌ Glaucoma (anticholinergic)

Mini-summary:

👉 Promethazine = sedating H1 blocker for pregnancy nausea & motion sickness.

🟦🟦🟦

✅ 2. METOCLOPRAMIDE — 20% VERSION

⭐ Class

• D2 antagonist + prokinetic

⭐ Mechanism (PD)

• Blocks dopamine D2 receptors in CTZ
• ↑ GI motility (pro-kinetic) via ↑ ACh release

⭐ Uses

• Hyperemesis gravidarum
• Post-operative nausea
• Gastroparesis
• Nausea in early pregnancy

⭐ Side Effects

⚠ Extrapyramidal symptoms (EPS)

⚠ Acute dystonia

• Diarrhoea
• Drowsiness

⭐ Contra

❌ Parkinson’s disease

❌ Bowel obstruction / perforation

Mini-summary:

👉 Metoclopramide = D2 blocker + prokinetic. Watch for dystonia.

🟦🟦🟦

✅ 3. PROCHLORPERAZINE — 20% VERSION

⭐ Class

• Phenothiazine antipsychotic
• Potent D2 antagonist

⭐ Mechanism (PD)

• Blocks dopamine (D2) in CTZ → strong antiemetic
• Mild anticholinergic & antihistamine effects

⭐ Uses

• Severe vomiting
• Vertigo
• Migraine-associated nausea

⭐ Side Effects

• EPS (dystonia, Parkinsonism)
• Sedation
• Hypotension

⭐ Contra

❌ Parkinson’s

❌ Elderly with confusion

Mini-summary:

👉 Prochlorperazine = strong D2 blocker for severe vomiting, but causes EPS.

🟦🟦🟦

✅ 4. ONDANSETRON — 20% VERSION

⭐ Class

• 5-HT3 (serotonin) antagonist

⭐ Mechanism (PD)

• Blocks 5-HT3 receptors in:

✔ GI tract

✔ Vagus nerve

✔ CTZ

→ Very strong antiemetic

⭐ Uses

• First-line for postoperative nausea
• Chemotherapy-induced vomiting
• Hyperemesis gravidarum (moderate–severe)

⭐ Side Effects

• Constipation
• Headache
• QT prolongation
• Mild ↑ liver enzymes

⭐ Contra

❌ QT prolongation

❌ Using other QT-prolonging drugs

Mini-summary:

👉 Ondansetron = BEST antiemetic (5-HT3 blocker). Watch QT interval.

🟦🟦🟦

✅ 5. CORTICOSTEROIDS (DEXAMETHASONE) — 20% VERSION

⭐ Class

• Glucocorticoid anti-inflammatory

⭐ Mechanism (PD)

• Reduces inflammatory mediators in vomiting pathways
• Potentiates other antiemetics

⭐ Uses

• Chemotherapy vomiting
• Postoperative nausea
• Adjunct with ondansetron/metoclopramide

⭐ Side Effects

• Mood changes
• Hyperglycemia
• Immunosuppression (long-term)
• Gastric irritation

⭐ Contra

❌ Uncontrolled infection

❌ Uncontrolled diabetes

Mini-summary:

👉 Dexamethasone = adjunct antiemetic, especially in chemo & post-op settings.

🟦🟦🟦

✅ ULTIMATE SUPER-SUMMARY (ALL 5 DRUGS)

Famotidine – Key Clinical Note

Drug class

• Histamine-2 receptor antagonist (H2RA)

Mechanism

• Reversibly blocks H2 receptors on gastric parietal cells

→ ↓ gastric acid secretion

→ ↓ gastric volume + hydrogen ion concentration

• Works on both basal and stimulated acid secretion

Indications

Common & exam-relevant:

• Peptic ulcer disease (PUD)
• GERD/acid reflux
• Stress ulcer prophylaxis (hospitalized patients)
• Dyspepsia
• Zollinger–Ellison syndrome (adjunct)

Dose (adult typical ranges – NOT pregnancy-specific)

• 20–40 mg PO once or twice daily
• IV forms used inpatient

(Always adjust to local guidelines + renal function)

Onset & duration

• Onset: ~1 hour
• Duration: 10–12 hours

Adverse effects

Generally well tolerated

• Headache
• Dizziness
• Constipation/diarrhea
• Rare: confusion in elderly/renal impairment

⚠ Compared to cimetidine, famotidine has:

• Minimal CYP450 inhibition
• Much lower endocrine side effects

Contraindications / cautions

• Hypersensitivity to H2 blockers
• Dose reduction in renal impairment (renal clearance)

Pregnancy & lactation

• Considered relatively safe; commonly used for reflux in pregnancy
• Minimal transfer into breast milk and low oral infant absorption

(Always weigh risk/benefit and use lowest effective dose.)

Drug interactions

• Less interaction risk than cimetidine
• Can ↓ absorption of drugs needing acidic pH:
• ketoconazole
• atazanavir
• May mask gastric cancer symptoms

Comparison with PPIs

Clinical pearls

• Good for nocturnal acid breakthrough
• Useful when rapid symptom relief needed
• Watch renal function in elderly/hospital patients

CIMETIDINE — Full Pharmacology Note

CLASS

• H₂-receptor antagonist (H2 blocker)
• First in class (others = ranitidine, famotidine, nizatidine)

MECHANISM OF ACTION

• Competitive antagonism of histamine H₂ receptors on gastric parietal cells

→ ↓ basal + nocturnal + meal-stimulated acid secretion

• Reduces:
• Hydrogen ion secretion
• Gastric acid output
• Pepsin secretion (indirect via ↓ acid)

Main trigger blocked: histamine pathway

(does NOT block ACh or gastrin pathways strongly)

PHARMACOKINETICS

• Route: oral, IM, IV
• Onset: ~60 minutes PO
• Peak acid suppression: 1–3 hrs
• Duration: 6–8 hrs
• Crosses BBB + placenta + breast milk
• Renal excretion → dose adjust in renal failure

THERAPEUTIC USES

• Peptic ulcer disease
• GERD / reflux symptoms
• Dyspepsia
• Zollinger-Ellison (less preferred than PPIs)
• Stress ulcer prophylaxis (historical)
• Prevention of aspiration pneumonitis before surgery (rare now)

UNIQUE, CLASSIC SIDE EFFECT PROFILE

1. Anti-androgenic effects (VERY HIGH-YIELD)

• Gynecomastia (men)
• Galactorrhea (women)
• ↓ libido, impotence

Mechanism:

• Blocks DHT binding to androgen receptors
• ↑ prolactin via dopamine antagonism

2. CNS effects

More common in elderly or renal impairment:

• Confusion
• Dizziness
• Delirium

3. GI

• Diarrhea
• Constipation
• Abdominal discomfort

4. Hematologic (rare)

• Thrombocytopenia
• Neutropenia
• Agranulocytosis (very rare)

5. Hypersensitivity

• Rash
• Fever

BIGGEST EXAM FACT: CYP450 inhibition

Cimetidine is a potent inhibitor of:

• CYP1A2
• CYP2C9
• CYP2D6
• CYP3A4

→ increases levels of:

• Warfarin → ↑ bleeding risk
• Phenytoin → toxicity
• Theophylline → arrhythmias/seizures
• Benzodiazepines
• Lidocaine
• Quinidine
• Propranolol

Newer H2 blockers avoid this issue.

DRUG INTERACTIONS

• Warfarin (INR ↑)
• Theophylline
• Antiarrhythmics
• TCAs
• Benzodiazepines
• Beta-blockers metabolised by CYPs

Avoid chronic use with polypharmacy elderly patients.

Contraindications / caution

• Renal failure (reduce dose)
• Elderly (CNS effects)
• Hepatic impairment
• Polypharmacy

COMPARISON WITH OTHER H₂ BLOCKERS

USE IN PREGNANCY + LACTATION

• Historically considered safe
• Category B (older classification)
• Crosses placenta + in breast milk
• Preferred alternatives in current practice = famotidine

Used in pregnancy for:

• Reflux
• Dyspepsia
• GERD
• Peptic ulcer disease

NO known teratogenicity at therapeutic doses.

CLINICAL PEARLS (for exams & practice)

• First H₂ blocker discovered
• Only one with:
• CYP450 inhibition
• Anti-androgen effects
• Avoid chronic therapy in elderly + polypharmacy
• Treat nocturnal acid breakthrough when PPIs alone insufficient

TOXICITY MANAGEMENT

Stop drug + supportive care

If severe CNS/hematologic symptoms → discontinue permanently

WHEN TO CHOOSE CIMETIDINE

Rarely first-line today

Indications where appropriate:

• Cost constraints
• Short-term relief for dyspepsia/GERD
• As alternative when PPIs unavailable/contraindicated

Integrated clinical scenario (covers all drugs + every key fact you listed)

Setting

A 28-year-old primigravida at 9+4 weeks comes to the antenatal clinic with:

• Severe nausea/vomiting for 10 days (can’t keep food down, ketones + on dipstick → hyperemesis gravidarum picture)
• Vertigo when she turns in bed
• Bad heartburn + reflux (worse at night)
• She also says she’s traveling by bus daily and gets motion sickness.

Past history + risks you must screen before choosing drugs:

• She previously had acute angle-closure glaucoma (important!)
• Her father has congenital long QT; she once had “palpitations” (so you decide to be careful with QT drugs)
• She is not diabetic, no active infection
• No bowel obstruction symptoms (no severe colicky pain, no absolute constipation)
• No Parkinson’s history
• No known severe liver disease

1) First problem: Pregnancy nausea / motion sickness / vomiting + vertigo

Step A — Mild–moderate nausea + motion sickness component

Because she has motion sickness + early pregnancy nausea, you think of promethazine.

Promethazine

• Class: H1 antihistamine + anticholinergic
• Mechanism: blocks H1 + muscarinic receptors

→ sedation + helps motion sickness & vomiting

• Uses here: motion sickness, early pregnancy nausea, hyperemesis gravidarum, vertigo
• Key side effects: sedation, dry mouth, dizziness, hypotension
• Key contraindications:

❌ Glaucoma (anticholinergic can worsen)

❌ Severe liver disease

• Clinical decision in THIS patient: because she had glaucoma, you avoid promethazine (even though it matches the symptom pattern).

Mini-summary you’d tell her: Promethazine is a sedating H1 blocker helpful for pregnancy nausea/motion sickness, but glaucoma makes it a bad choice for you.

Step B — Hyperemesis gravidarum with dehydration risk

You need a stronger antiemetic and something that also improves gastric emptying.

Metoclopramide

• Class: D2 antagonist + prokinetic
• Mechanism:
• blocks D2 in CTZ → antiemetic
• ↑ GI motility via ↑ ACh release → pro-kinetic
• Uses here: hyperemesis gravidarum, nausea in early pregnancy, gastroparesis, post-op nausea
• Key risks: ⚠ EPS, especially acute dystonia; also diarrhea, drowsiness
• Contraindications: ❌ Parkinson’s disease (dopamine block worsens)

❌ Bowel obstruction/perforation (prokinetic danger)

• In this patient: no Parkinson’s, no obstruction signs → metoclopramide is reasonable, but you warn about acute dystonia/EPS and to come back urgently if neck/eye/jaw spasms occur.

Mini-summary: Metoclopramide = D2 blocker + prokinetic; watch for dystonia.

Step C — If vomiting becomes severe or metoclopramide inadequate

You consider a potent D2 antiemetic.

Prochlorperazine(stematil)

• Class: phenothiazine antipsychotic; potent D2 antagonist
• Mechanism: blocks D2 in CTZ → strong antiemetic
• mild anticholinergic/antihistamine effects
• Uses here: severe vomiting, vertigo, migraine nausea
• Side effects: EPS (dystonia/parkinsonism), sedation, hypotension
• Contra: ❌ Parkinson’s

❌ elderly with confusion

• In this patient: young → confusion issue not relevant, but EPS risk overlaps with metoclopramide. You’d typically use one strategy, not stack EPS-heavy drugs unless necessary.

Mini-summary: Prochlorperazine = strong D2 blocker for severe vomiting, but EPS common.

Step D — When you need the “strongest” antiemetic effect (esp. moderate–severe HG / post-op / chemo-type pathways)

You consider ondansetron, but you must think QT.

Ondansetron

• Class: 5-HT3 antagonist(a serotonin receptor (subtype 3))
• Mechanism: blocks 5-HT3 receptors in:
• GI tract
• vagus nerve
• CTZ

→ very strong antiemetic

• Uses: first-line for post-op nausea, chemotherapy vomiting, hyperemesis gravidarum (moderate–severe)
• Side effects: constipation, headache, QT prolongation, mild ↑ liver enzymes
• Contra: ❌ known QT prolongation

❌ taking other QT-prolonging drugs

• In THIS patient: family history of long QT + her palpitations → you check ECG / avoid if QT concern is real. If QT is normal and no other QT-prolongers, it can be used carefully.

Mini-summary: Ondansetron = best antiemetic (5-HT3 blocker). Watch QT.

Step E — “Adjunct booster” option (post-op/chemo style, or refractory vomiting)

If vomiting is refractory (and especially in hospital protocols), you add steroid adjunct.

Dexamethasone

• Class: glucocorticoid anti-inflammatory
• Mechanism: reduces inflammatory mediators in vomiting pathways + potentiates other antiemetics
• Uses: chemotherapy vomiting, post-op nausea, adjunct with ondansetron/metoclopramide
• Side effects: mood changes, hyperglycemia, immunosuppression (long term), gastric irritation
• Contra: ❌ uncontrolled infection

❌ uncontrolled diabetes

• In this patient: not diabetic, no infection → could be considered as adjunct if severe/refractory.

Mini-summary: Dexamethasone = adjunct antiemetic, useful in chemo/post-op style regimens; watch glucose/infection.

2) Second problem: Heartburn / reflux (especially nocturnal)

Her vomiting + pregnancy + reflux symptoms suggest acid suppression is needed. You choose between H2 blockers.

Option 1 — Famotidine (preferred modern H2RA)

Famotidine

• Class: H2 receptor antagonist (H2RA)
• Mechanism: reversible block of H2 receptors on parietal cells

→ ↓ gastric acid secretion

→ ↓ gastric volume + hydrogen ion concentration

Works on basal + stimulated secretion

• Indications: PUD, GERD/reflux, stress ulcer prophylaxis (inpatients), dyspepsia, Zollinger–Ellison (adjunct)
• Dose ranges (adult typical, not pregnancy-specific): 20–40 mg PO once/twice daily; IV inpatient; adjust to local guidance + renal function
• Onset/duration: onset ~1 hour; duration 10–12 hours
• Adverse effects: headache, dizziness, constipation/diarrhea; rare confusion in elderly/renal impairment
• Key comparison to cimetidine: minimal CYP450 inhibition + much fewer endocrine effects
• Cautions: hypersensitivity; dose reduce in renal impairment
• Pregnancy/lactation: relatively safe; commonly used; minimal transfer to milk and low infant oral absorption (use lowest effective dose)
• Interactions: can ↓ absorption of drugs needing acidic pH (ketoconazole, atazanavir); may mask gastric cancer symptoms
• H2RA vs PPI: faster onset, shorter duration, moderate effectiveness, tolerance can develop over days; PPIs slower onset, longer duration, stronger effect, minimal tolerance
• Pearls: good for nocturnal acid breakthrough, rapid symptom relief; watch renal function in elderly/hospital patients

In this patient: nocturnal reflux → famotidine is a neat fit, especially if you want something quick and safer interaction-wise.

Option 2 — Cimetidine (classic exam drug; mostly avoided now)

You consider it mainly for exams/cost constraints and because it’s the “unique one”.

Cimetidine

• Class: H2 receptor antagonist (first in class)
• Mechanism: competitive H2 block on parietal cells

→ ↓ basal/nocturnal/meal-stimulated acid secretion

↓ H+ secretion + gastric acid output; ↓ pepsin indirectly

Mainly blocks histamine pathway (not ACh/gastrin strongly)

• PK: PO/IM/IV; onset ~60 min; peak 1–3 h; duration 6–8 h

crosses BBB + placenta + breast milk

renal excretion → dose adjust in renal failure

• Uses: PUD, GERD, dyspepsia, Zollinger–Ellison (less preferred than PPIs), stress ulcer prophylaxis (historical), aspiration pneumonitis prophylaxis (rare now)
• Unique “classic” side effects (high-yield):
1. Anti-androgenic: gynecomastia, galactorrhea, ↓ libido/impotence

Mechanism: blocks DHT binding at androgen receptor + ↑ prolactin via dopamine antagonism

2. CNS (elderly/renal): confusion, dizziness, delirium
3. GI: diarrhea/constipation/abdominal discomfort
4. Rare hematologic: thrombocytopenia, neutropenia, agranulocytosis (very rare)
5. Hypersensitivity: rash, fever
• Biggest exam fact: potent CYP450 inhibitor (1A2, 2C9, 2D6, 3A4)

→ increases levels of warfarin (bleeding), phenytoin, theophylline (arrhythmias/seizures), benzodiazepines, lidocaine, quinidine, propranolol

• Interactions: warfarin, theophylline, antiarrhythmics, TCAs, benzodiazepines, beta-blockers metabolized by CYPs
• Cautions: renal failure, elderly, hepatic impairment, polypharmacy
• Pregnancy/lactation: historically considered safe; crosses placenta/milk; preferred alternative now = famotidine; no known teratogenicity at therapeutic doses
• Toxicity management: stop drug + supportive care; discontinue permanently if severe CNS/hematologic effects
• When to choose now: rarely first-line; cost constraints, short-term dyspepsia/GERD, when PPIs unavailable/contraindicated

In THIS patient: she’s pregnant and may take other meds later; you want fewer interactions → you pick famotidine over cimetidine unless a specific reason forces cimetidine.

Final integrated plan in the scenario (logic chain)

1. Hyperemesis gravidarum: start metoclopramide (D2 blocker + prokinetic), monitor for acute dystonia/EPS; avoid if obstruction/Parkinson’s.
2. If vomiting becomes severe: consider prochlorperazine (strong D2) but remember EPS + sedation + hypotension.
3. If you need a very strong antiemetic: ondansetron (5-HT3) only if QT risk is acceptable (avoid with known QT prolongation or other QT-prolonging drugs).
4. If refractory and inpatient-style regimen: add dexamethasone as adjunct, but avoid in uncontrolled infection/diabetes; watch mood, glucose, gastric irritation.
5. Motion sickness/vertigo option: promethazine fits symptom-wise (H1 + anticholinergic) but avoid here due to glaucoma; also causes sedation/dry mouth/hypotension.
6. Reflux control: choose famotidine (fast onset ~1h, duration 10–12h, fewer interactions), and keep cimetidine mainly as the exam classic (CYP inhibition + antiandrogen effects + CNS effects in elderly/renal).

🧠 ANTIEMETICS + ACID SUPPRESSANTS — COMPLETE MASTER TABLE (ZERO-OMISSION)

🔑 ULTRA-HIGH-YIELD EXAM LOCKS

• EPS drugs → metoclopramide + prochlorperazine
• QT issue → ondansetron
• Motion sickness + sedation → promethazine
• Adjunct only → dexamethasone
• Safest H2 blocker → famotidine
• CYP inhibition + gynecomastia → cimetidine