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PHARMACOLOGY MASTER SETS

Anti-Ulcers | Antiemetics | Anti-Diarrhoea/Constipation | Cough | Anti-Asthma

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🔴 SET 1 — ANTI-ULCER DRUGS

Classification

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ANTACIDS

⭐ Super Point: "Al constipates, Mg loosens" — combined formulations balance each other. CaCO₃ causes acid rebound due to Ca²⁺-stimulated gastrin release.

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H₂-RECEPTOR ANTAGONISTS

⭐ Super Point – Cimetidine is the oddball H₂ blocker:

• Inhibits CYP1A2, CYP2C9, CYP2D6, CYP3A4 → major drug interactions (warfarin, phenytoin, theophylline, lidocaine)
• Blocks renal tubular secretion of creatinine → falsely elevates serum creatinine
• Anti-androgenic: gynaecomastia, impotence, loss of libido (blocks androgen receptors)
• Crosses BBB: confusion, dizziness, headache (especially elderly)
• Ranitidine was withdrawn worldwide due to NDMA carcinogen contamination

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PROTON PUMP INHIBITORS (PPIs)

• Oral bioavailability ~65% (first-pass)
• t½ = 1–2 hours but acid suppression lasts 24–36 hrs (due to irreversible binding)
• Take 30–60 min before meals (pump must be active for drug to work)
• Only active pumps are inhibited; maximal effect after 3–4 days of daily dosing

• Peptic ulcer disease (PUD), GERD, Zollinger-Ellison syndrome
• H. pylori eradication (as part of combination therapy)
• Prevention of NSAID-induced ulcers
• IV omeprazole 80 mg bolus + 8 mg/hr infusion for peptic ulcer bleeding (pre-endoscopy)

• ↓ Mg²⁺ (hypomagnesaemia) → arrhythmias, tetany
• ↓ Ca²⁺ absorption → osteoporosis, hip fractures
• ↓ Vit B₁₂ absorption (needs acid for release from food)
• ↑ Risk of C. difficile colitis
• ↑ Risk of community-acquired pneumonia
• Drug interactions: ↓ clopidogrel activation (omeprazole > pantoprazole – inhibits CYP2C19)

⭐ Super Points:

• PPIs are prodrugs activated in acid → give before meal (not after)
• Pantoprazole has least CYP2C19 inhibition → preferred with clopidogrel
• Omeprazole = CYP2C19 inhibitor → ↑ diazepam, warfarin, phenytoin levels
• Esomeprazole = S-enantiomer of omeprazole (longer half-life)

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SUCRALFATE

• Requires acidic pH for activation → Do NOT give with antacids/PPIs simultaneously (give 30 min apart)
• Minimal systemic absorption (<5%)
• Binds many drugs → give 2 hrs before other medications (reduces absorption of fluoroquinolones, digoxin, warfarin, phenytoin)
• Used for: stress ulcer prophylaxis (especially in ICU), peptic ulcers
• Safe in: pregnancy, renal failure (minimal absorption), not safe in severe renal failure (aluminium toxicity risk)

⭐ Super Point: Sucralfate works at LOW pH — activated by stomach acid. Antacids and PPIs abolish its activation. Space them apart.

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MISOPROSTOL

• Indication: Prevention of NSAID-induced ulcers in high-risk patients (reduces incidence to <3%; ↓ complications by 50%)
• Adverse effects: Dose-dependent diarrhoea + abdominal cramping (limits use)
• Contraindicated in pregnancy (uterotonic → cervical ripening, abortion) — used therapeutically for medical abortion (with mifepristone)

⭐ Super Point: Misoprostol = only PGE₁ analogue anti-ulcer drug. Its uterotonic action is exploited in obstetrics (cervical ripening, PPH, medical abortion).

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BISMUTH COMPOUNDS

• Coats ulcer base → physical barrier
• Stimulates mucus, bicarbonate, prostaglandin secretion
• Direct antimicrobial vs H. pylori
• Binds enterotoxins (useful in traveller's diarrhoea)

• Black stool + black tongue (harmless — distinguish from melaena!)
• Long-term: encephalopathy (ataxia, confusion, seizures) — rare
• High-dose subsalicylate → salicylate toxicity
• Avoid in renal insufficiency

⭐ Super Point: Bismuth blackens stool → mimic melaena. Always tell patients. Encephalopathy is a warning sign with prolonged use.

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H. PYLORI ERADICATION

• PPI (bid) + Clarithromycin (500 mg bid) + Amoxicillin (1 g bid)
• OR: PPI + Clarithromycin + Metronidazole (if penicillin allergy)

• PPI (bid) + Bismuth (qid) + Tetracycline (qid) + Metronidazole (qid)

⭐ Super Point: Test-and-treat strategy: urea breath test or stool antigen test for H. pylori. Most sensitive post-treatment test = urea breath test (wait ≥4 weeks after stopping PPI).

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🟠 SET 2 — ANTIEMETICS

Vomiting Reflex — Key Receptors

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Classification & Drug Details

1. DOPAMINE (D₂) ANTAGONISTS

Metoclopramide

• MOA: Blocks D₂ in CTZ + peripherally → ↑ LOS tone, ↑ gastric emptying, ↑ peristalsis (prokinetic). Also has 5-HT₄ agonist activity (enhances Ach release in gut)
• Uses: Chemotherapy-induced nausea (mild), gastroparesis, GERD, post-op nausea, hyperemesis gravidarum (drug of choice in hyperemesis + headache-associated vomiting)
• Adverse effects:
  • Extrapyramidal symptoms (EPS): Acute dystonia, akathisia, parkinsonism, tardive dyskinesia (long-term)
  • Hyperprolactinaemia → galactorrhoea, gynaecomastia
  • Does not cross BBB well → lower EPS vs prochlorperazine
  • Contraindicated in GI obstruction, phaeochromocytoma

⭐ Super Point: Metoclopramide + 5-HT₄ agonism = prokinetic antiemetic. Drug of choice in gastroparesis. Pre-treat with diphenhydramine to reduce EPS risk.

Domperidone

• Peripheral D₂ antagonist only (does NOT cross BBB → minimal CNS EPS)
• Prolonged QTc (cardiac risk) → restricted use
• Useful in Parkinson's patients (does not worsen motor symptoms)

Prochlorperazine (Stemetil)

• Phenothiazine D₂ antagonist
• Used for labyrinthitis, vertigo, post-op nausea
• Higher EPS risk than metoclopramide

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2. 5-HT₃ ANTAGONISTS ("Setrons")

• Headache (most common)
• Constipation
• QTc prolongation (avoid with other QT-prolonging drugs)
• Ondansetron: rare serotonin syndrome (high dose), not effective for motion sickness or apomorphine-induced vomiting

⭐ Super Point: Setrons are useless for motion sickness (no H₁/M₁ blockade). They work on the serotonin pathway released by gut enterochromaffin cells during chemo.

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3. NK₁ RECEPTOR ANTAGONISTS

⭐ Super Point: Triple antiemetic prophylaxis for highly emetogenic chemo = Ondansetron + Dexamethasone + Aprepitant (given on Day 1; aprepitant continues days 2–3 for delayed nausea).

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4. ANTIHISTAMINES (H₁ Antagonists)

⭐ Super Point: Best drugs for motion sickness = hyoscine (scopolamine) > meclizine > promethazine. Ondansetron and metoclopramide do NOT work for motion sickness.

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5. ANTICHOLINERGICS

• Hyoscine (Scopolamine): Most effective for motion sickness; given as transdermal patch (behind ear, 4–6 hrs before travel). Anticholinergic ADRs: dry mouth, blurred vision, urinary retention, sedation.

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6. DEXAMETHASONE

• MOA in nausea: unknown (possibly ↓ prostaglandins at CTZ, ↓ gut 5-HT release)
• Used as adjunct in CINV regimens and post-op nausea
• Enhanced antiemetic effect when combined with ondansetron

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7. CANNABINOIDS

• Dronabinol / Nabilone (CB₁ receptor agonists)
• Indicated for: chemotherapy-induced nausea refractory to other antiemetics
• ADRs: euphoria, dysphoria, sedation, increased appetite

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Antiemetic Choice by Context

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🟡 SET 3 — ANTIDIARRHOEAL & LAXATIVE DRUGS

ANTIDIARRHOEALS

1. OPIOID RECEPTOR AGONISTS

Loperamide (Drug of Choice for Acute Non-infectious Diarrhoea)

• MOA: Activates μ-opioid receptors in the myenteric plexus → ↓ peristalsis (↑ transit time), ↑ anal sphincter tone, ↓ intestinal secretion. Also blocks calmodulin → ↓ Cl⁻ secretion
• Does NOT cross BBB → no CNS effects, no abuse potential
• Used in: acute diarrhoea, IBS-D, ileostomy control
• Avoid in: infectious/febrile diarrhoea (delays clearance of pathogens), pseudomembranous colitis

Codeine / Diphenoxylate + Atropine

• Diphenoxylate: Opioid that does cross BBB → abuse potential. Combined with atropine (subtherapeutic dose) to discourage abuse (causes unpleasant effects if misused in high doses)
• Codeine: Also reduces motility; has CNS/analgesic effects

⭐ Super Point: Loperamide = safe, no CNS penetration, OTC. Diphenoxylate + Atropine = Lomotil = has abuse potential; atropine added as deterrent.

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2. BISMUTH SUBSALICYLATE (Pepto-Bismol)

• Useful in traveller's diarrhoea (antimicrobial + binds enterotoxins)
• Reduces stool frequency via salicylate → ↓ intestinal prostaglandins and chloride secretion

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3. OCTREOTIDE (Somatostatin Analogue)

• ↓ Splanchnic blood flow, ↓ gut hormone secretion (insulin, glucagon, VIP, gastrin), ↓ intestinal motility
• Used in: secretory diarrhoea (VIPoma, carcinoid syndrome), AIDS-related diarrhoea, short bowel syndrome, post-surgical diarrhoea
• ADRs: Steatorrhoea, gallstones (↓ gallbladder motility), nausea, hyperglycaemia or hypoglycaemia, bradycardia, hypothyroidism (long-term)

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4. ALOSETRON (5-HT₃ antagonist — IBS-D)

• Blocks 5-HT₃ on enteric neurons → ↓ visceral afferent pain, ↓ colonic transit
• Used in: severe IBS with predominant diarrhoea (IBS-D) in women (restricted prescribing programme — risk of ischaemic colitis)
• ADRs: Ischaemic colitis, severe constipation — black box warning

⭐ Super Point: Alosetron is approved only for women with severe IBS-D who fail conventional therapy. Risk of ischaemic colitis limits use. Requires REMS programme.

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5. ORS (Oral Rehydration Solution)

• Glucose-coupled Na⁺ absorption (SGLT-1) remains intact even in secretory diarrhoea
• WHO-ORS: 75 mEq/L Na⁺, 20 mEq/L K⁺, 65 mEq/L Cl⁻, 10 mEq/L citrate, 75 mmol/L glucose
• First-line in cholera and paediatric diarrhoea

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LAXATIVES

Classification

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Key Drug Notes

• Osmotic; non-fermentable → no gas
• Used for chronic constipation, bowel prep before colonoscopy
• Safe in pregnancy and children
• Mixed electrolyte solution (GoLYTELY) for colonoscopy prep

• Non-absorbed disaccharide → fermented by colonic bacteria → organic acids → osmotic diarrhoea
• Also used in hepatic encephalopathy (acidifies colon → NH₃ → NH₄⁺ → trapped, eliminated)
• ADRs: bloating, flatulence, abdominal cramps (from gas production)

• Prodrugs activated by colonic bacteria → stimulate enteric nervous system
• Bisacodyl also available as suppository
• Avoid long-term → melanosis coli (brown discolouration of colonic mucosa — from anthraquinone), cathartic colon (long-term motility damage)

• ClC-2 chloride channel activator → ↑ luminal fluid → soften stool
• Used in: chronic idiopathic constipation, IBS-C (especially women ≥18), opioid-induced constipation
• ADRs: nausea (main), diarrhoea, dyspnoea (transient)

• GC-C agonists → ↑ cGMP in enterocytes → ↑ CFTR Cl⁻ channel activity → ↑ fluid secretion + ↓ visceral pain (cGMP also inhibits pain-sensing afferents)
• Used in: IBS-C, chronic idiopathic constipation
• ADRs: Diarrhoea (most common); contraindicated in paediatric patients <6 yrs (risk of severe dehydration)

⭐ Super Points:

• Lactulose = laxative AND hepatic encephalopathy treatment
• Melanosis coli = marker of anthraquinone (senna/cascara) overuse
• Bisacodyl suppository → fastest onset (15–60 min) vs oral (6–12 hrs)
• Lubiprostone is not absorbed systemically → safe profile but causes nausea

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🟢 SET 4 — COUGH (Antitussives, Expectorants, Mucolytics)

Classification

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CENTRAL ANTITUSSIVES

Codeine

• MOA: Opioid μ-receptor agonist in the medullary cough centre → raises threshold for cough reflex
• Also analgesic, constipating (useful as antidiarrhoeal)
• ADRs: Constipation, sedation, respiratory depression, dependence
• Metabolised by CYP2D6 → ultra-rapid metabolisers get excessive morphine → toxicity
• Contraindicated in children <12 yrs (morphine toxicity risk)

Dextromethorphan (DXM)

• MOA: Blocks NMDA receptor and σ-receptor in cough centre; also weak μ-opioid agonist
• No analgesic or addiction potential at therapeutic doses
• ADRs: At high doses → serotonin syndrome (combined with MAOIs), dissociative hallucinations (recreational misuse)
• Drug interactions: Contraindicated with MAOIs (risk of serotonin syndrome)
• Metabolised by CYP2D6

⭐ Super Point: Dextromethorphan does NOT cause constipation (unlike codeine). It is an NMDA antagonist at high doses — hence abuse potential ("robotripping"). Avoid with MAOIs.

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PERIPHERAL ANTITUSSIVE

Benzonatate (Tessalon)

• MOA: Local anaesthetic → inhibits stretch receptors in bronchi, alveoli, pleura → interrupts cough reflex peripherally
• Structurally related to procaine/tetracaine
• ADRs: If chewed/sucked (not swallowed whole) → oral anaesthesia, bronchospasm, cardiac arrest
• Onset: 15–20 min; Duration: 3–8 hrs

⭐ Super Point: Benzonatate pearls/capsules must be swallowed intact — chewing releases drug → severe oropharyngeal anaesthesia → choking, cardiovascular collapse.

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EXPECTORANTS

Guaifenesin (Guaiphenesin)

• MOA: Reflexly stimulates increased secretion of respiratory tract fluid (by stimulating gastric irritant receptors) → ↓ viscosity of mucus → facilitates mucociliary clearance
• First-line OTC expectorant; poorly supported by strong clinical trial evidence
• ADRs: Nausea, vomiting (at high doses), headache

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MUCOLYTICS

Acetylcysteine (NAC)

• MOA: Free –SH (thiol) group → cleaves disulphide bonds in mucus glycoproteins → ↓ mucus viscosity
• Uses:
  • Mucolytic in COPD, bronchiectasis, cystic fibrosis (nebulised)
  • Antidote for paracetamol (acetaminophen) overdose (repletes glutathione)
  • Contrast nephropathy prevention (IV/oral before contrast)
• ADRs: Bronchospasm (inhaled), nausea, flushing, anaphylactoid reactions (IV)

Bromhexine / Ambroxol

• MOA: Bromhexine → depolymerises mucopolysaccharide fibres in mucus; Ambroxol is the active metabolite of bromhexine
• Ambroxol also stimulates surfactant production
• Used in COPD, bronchitis, post-surgical respiratory care (Ambroxol IV/oral)

⭐ Super Points:

• NAC = both mucolytic AND paracetamol antidote (glutathione precursor)
• Ambroxol = active metabolite of bromhexine (clinically more potent)
• Erdosteine: newer mucolytic with antioxidant properties — prodrug activated in liver

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Antitussive Choice by Context

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🔵 SET 5 — ANTI-ASTHMA DRUGS

Classification

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β₂-AGONISTS

SABAs (Salbutamol / Albuterol)

• MOA: Activate β₂-adrenergic receptors → ↑ adenylyl cyclase → ↑ cAMP → bronchial smooth muscle relaxation; also inhibit mast cell degranulation
• First-line reliever medication (rescue inhaler)
• Onset: 3–5 min inhaled; Duration: 4–6 hrs
• ADRs: Tachycardia, tremor, hypokalaemia (K⁺ shifts into cells via Na⁺/K⁺-ATPase), hyperglycaemia
• Tolerance (tachyphylaxis): Overuse → receptor downregulation → decreased bronchodilator response (marker of poor asthma control)

LABAs (Salmeterol / Formoterol)

• Duration: 12 hrs (salmeterol, formoterol); Indacaterol: 24 hrs
• Salmeterol: slow onset (20–30 min) — NOT for acute attacks
• Formoterol: fast onset (3–5 min) → can be used as reliever in MART strategy
• NEVER use LABAs as monotherapy in asthma (without ICS) → increased mortality risk (LABAs suppress symptoms but don't control inflammation)
• LABAs are first-line maintenance in COPD (without ICS required)

⭐ Super Points:

• Salmeterol = long-acting BUT slow onset → NOT a rescue drug. Formoterol = long-acting AND fast onset → can be reliever.
• Salbutamol IV/nebulised → drives K⁺ into cells → treats hyperkalaemia (used in ICU)
• β₂ agonists + hypokalaemia + tachycardia = classic side effect triad

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ANTICHOLINERGICS

Ipratropium Bromide (SAMA)

• MOA: Blocks M₁, M₂, M₃ muscarinic receptors in bronchi → ↓ bronchoconstriction, ↓ mucus secretion
• Less effective than SABAs in asthma, but synergistic in acute severe asthma (combine ipratropium + salbutamol nebuliser)
• First-line maintenance bronchodilator in COPD (not asthma)
• Minimal systemic absorption (quaternary ammonium → doesn't cross BBB)
• ADRs: Dry mouth, blurred vision (if mist contacts eye), urinary retention, constipation

Tiotropium (LAMA)

• Once-daily inhalation; binds M₃ (long duration 24 hrs)
• Kinetically selective for M₃ over M₂ (dissociates quickly from M₂ → avoids tachycardia)
• Used in COPD (first-line LAMA) + as add-on in step 4–5 asthma

⭐ Super Point: In acute severe asthma, nebulised salbutamol + ipratropium together → superior bronchodilation. In COPD, LAMA ± LABA is the backbone maintenance therapy.

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INHALED CORTICOSTEROIDS (ICS)

1. ↓ Transcription of inflammatory genes (IL-4, IL-5, IL-13, TNF-α, eotaxin)
2. ↑ Anti-inflammatory proteins (lipocortin → ↓ phospholipase A₂ → ↓ prostaglandins, leukotrienes, PAF)
3. ↓ Mucosal oedema, ↓ goblet cell hyperplasia, ↓ eosinophil recruitment
4. ↑ β₂ receptor expression → restore β₂ agonist sensitivity

• Most effective long-term controller medication in asthma
• Regular ICS use → ↓ exacerbations, ↓ hospitalisations, ↓ mortality
• Local ADRs: Oropharyngeal candidiasis (Candida albicans), dysphonia (hoarseness) — use spacer + rinse mouth after
• Systemic ADRs (high dose/long-term): HPA axis suppression, growth retardation in children, osteoporosis, cataracts, glaucoma, skin thinning

⭐ Super Points:

• ICS do NOT relieve acute bronchospasm — they are preventers, not relievers
• Ciclesonide = prodrug activated in lung → lower systemic bioavailability
• Rinse and spit after ICS to prevent candidiasis
• ICS + LABA (combination inhalers): Fluticasone/Salmeterol (Seretide), Budesonide/Formoterol (Symbicort/Turbohaler — also used in MART)

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METHYLXANTHINES (Theophylline / Aminophylline)

1. Inhibits phosphodiesterase (PDE) → ↑ cAMP + cGMP → bronchial smooth muscle relaxation
2. Adenosine receptor antagonism → bronchodilation + CNS stimulation
3. Anti-inflammatory (↑ HDAC activity at low doses → ↓ steroid resistance)
4. Stimulates respiratory muscles + diaphragm contractility

• Narrow therapeutic index: Target plasma level = 10–20 mg/L (toxic >20 mg/L)
• Metabolised by CYP1A2, CYP3A4 — MULTIPLE drug interactions
• Half-life variably affected: smoking ↓ t½ (induces CYP1A2), heart failure ↑ t½, liver disease ↑ t½

• Mild (10–20 mg/L): Nausea, vomiting, headache, irritability, insomnia
• Moderate (20–30 mg/L): Tachycardia, arrhythmias, tremor
• Severe (>30–40 mg/L): Seizures, life-threatening arrhythmias

• ↑ Theophylline levels: Erythromycin, Ciprofloxacin, Cimetidine, Allopurinol, Fluvoxamine, Oral contraceptives
• ↓ Theophylline levels: Rifampicin, Phenytoin, Phenobarbitone, Smoking, Carbamazepine

⭐ Super Points:

• Aminophylline = theophylline + ethylenediamine (IV formulation; 80% theophylline)
• Smoking DECREASES theophylline levels (induces CYP1A2) → smokers need higher doses
• If patient stops smoking → levels RISE → toxicity risk
• Toxicity: seizures + arrhythmias can occur without preceding nausea
• Low-dose theophylline (5–10 mg/L) → anti-inflammatory via HDAC-2 activation

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LEUKOTRIENE MODIFIERS

Montelukast / Zafirlukast (CysLT₁ Receptor Antagonists)

• MOA: Block CysLT₁ receptors for LTC₄, LTD₄, LTE₄ → ↓ bronchoconstriction, ↓ mucosal oedema, ↓ eosinophil recruitment
• Uses: Mild-moderate asthma; especially effective in:
  • Aspirin-exacerbated respiratory disease (AERD/aspirin-sensitive asthma)
  • Exercise-induced bronchoconstriction
  • Allergic rhinitis (montelukast approved for both asthma + rhinitis)
• Oral, once daily (montelukast); not for acute attacks
• ADRs: Generally well-tolerated; neuropsychiatric effects — agitation, depression, suicidal ideation (Black Box Warning added by FDA in 2020)

Zileuton (5-Lipoxygenase Inhibitor)

• Blocks 5-LOX → ↓ synthesis of ALL leukotrienes (LTA₄, LTB₄, LTC₄, LTD₄, LTE₄)
• Inhibits CYP1A2 → ↑ theophylline, warfarin levels
• ADRs: Hepatotoxicity (monitor LFTs); less used than montelukast

⭐ Super Points:

• Montelukast = first choice for aspirin-sensitive asthma + exercise-induced asthma
• FDA Black Box 2020: Neuropsychiatric risk (suicidality) → reserve for cases where benefit clearly outweighs risk
• Zafirlukast = CYP2C9 inhibitor → ↑ warfarin levels

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MAST CELL STABILISERS

• Sodium Cromoglicate (Cromolyn) / Nedocromil
• MOA: Inhibit mast cell degranulation → ↓ release of histamine, leukotrienes, prostaglandins; also inhibit type I and III hypersensitivity reactions in lung; ↓ sensory C-fibre activation
• Used for: Exercise-induced and allergen-induced asthma (prophylactic only — no role in acute attack)
• Inhaled only; minimal systemic absorption
• Excellent safety profile — used in children and pregnancy
• ADRs: Cough, throat irritation, bronchospasm on inhalation

⭐ Super Point: Cromoglicate is PROPHYLACTIC ONLY — must be used before exercise/allergen exposure. Completely useless in acute attack. No bronchodilator activity.

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BIOLOGICS (Targeted Therapy)

⭐ Super Point: Tezepelumab targets TSLP (thymic stromal lymphopoietin) — the most upstream cytokine in airway inflammation — effective across eosinophilic, allergic, AND non-eosinophilic severe asthma.

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STEPWISE ASTHMA MANAGEMENT (GINA Framework)

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ACUTE SEVERE ASTHMA — Emergency Treatment

1. High-flow O₂ (target SpO₂ 94–98%)
2. Nebulised salbutamol + ipratropium (back-to-back or continuous)
3. IV/oral systemic corticosteroids (hydrocortisone 100 mg IV qds; prednisolone 40–50 mg oral)
4. IV magnesium sulphate (1.2–2 g over 20 min) — inhibits Ca²⁺-dependent smooth muscle contraction → bronchial smooth muscle relaxation
5. IV aminophylline (if no response — monitor levels, toxicity risk)
6. Heliox (He/O₂ mixture) — reduces airway resistance
7. Intubation + ventilation if life-threatening

⭐ Super Point: Mg²⁺ sulphate → works by antagonising Ca²⁺ in smooth muscle → bronchodilation. Safe, well-tolerated. Also used in status asthmaticus in children.

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⭐ MEGA SUPER-POINT SUMMARY TABLE

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What's Inside Each Set

🔴 SET 1 — Anti-Ulcer Drugs

🟠 SET 2 — Antiemetics

🟡 SET 3 — Antidiarrhoeals & Laxatives

🟢 SET 4 — Cough

🔵 SET 5 — Anti-Asthma

PHARMACOLOGY EXAM QUESTION BANK

Anti-Ulcers | Antiemetics | Anti-Diarrhoea/Constipation | Cough | Anti-Asthma

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🔴 PART A — MCQs (Multiple Choice Questions)

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SET 1 — ANTI-ULCER MCQs

• A) Omeprazole
• B) Esomeprazole
• C) Pantoprazole ✓
• D) Lansoprazole

Explanation: Pantoprazole has the least CYP2C19 inhibitory activity among PPIs, minimising interference with clopidogrel activation (which requires CYP2C19 for conversion to active metabolite). Omeprazole and esomeprazole are the strongest CYP2C19 inhibitors.

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• A) With the antacid simultaneously for synergistic effect
• B) At least 30 minutes before the antacid ✓
• C) Only at bedtime
• D) After meals only

Explanation: Sucralfate requires an acidic environment (pH <4) for polymerization into its protective gel. Antacids raise gastric pH and inactivate sucralfate. Space them at least 30 minutes apart.

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• A) Famotidine
• B) Omeprazole
• C) Cimetidine ✓
• D) Sucralfate

Explanation: Cimetidine uniquely blocks androgen receptors → anti-androgenic effects → gynaecomastia, impotence, decreased libido. No other H₂ blocker has this effect.

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• A) Magnesium hydroxide
• B) Calcium carbonate
• C) Aluminium hydroxide ✓ (in moderate doses) / actually all systemic absorbed ones
• D) Sodium bicarbonate ✓ (best answer in CKD context)

Exam-smart answer: D — Sodium bicarbonate. Causes systemic alkalosis and sodium load, harmful in CKD and hypertension. Aluminium can accumulate in severe CKD causing encephalopathy. NaHCO₃ also causes CO₂ gas and acid rebound.

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• A) They are direct-acting drugs that inhibit the pump immediately
• B) They work best when taken after a meal
• C) They are prodrugs activated in the acidic environment of parietal cell canaliculi ✓
• D) They competitively block H₂ receptors

Explanation: PPIs (omeprazole etc.) are benzimidazole prodrugs. They are acid-activated to form sulfenamide, which irreversibly binds cysteine residues of H⁺/K⁺-ATPase. Must be taken 30–60 min before meals so the pump is active.

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• A) Sucralfate
• B) Bismuth subcitrate
• C) Misoprostol ✓
• D) Omeprazole

Explanation: Misoprostol (PGE₁ analogue) has uterotonic properties causing cervical ripening and uterine contractions. It is a Category X in pregnancy for ulcer prophylaxis but used therapeutically for medical abortion (with mifepristone).

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• A) Stop the drug immediately and perform endoscopy
• B) Order stool occult blood test
• C) Reassure — this is a harmless side effect of bismuth ✓
• D) Start IV PPI therapy

Explanation: Bismuth compounds cause harmless blackening of stool (and tongue with liquids). This must be distinguished from melaena (digested blood). Melaena has a tarry consistency and offensive odour. Reassurance is correct if the patient is on bismuth.

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• A) PPI
• B) Bismuth
• C) Metronidazole
• D) Clarithromycin ✓

Explanation: Quadruple therapy = PPI + Bismuth + Tetracycline + Metronidazole. Clarithromycin is part of standard triple therapy (PPI + Clarithromycin + Amoxicillin), used when clarithromycin resistance is low.

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SET 2 — ANTIEMETIC MCQs

• A) Ondansetron
• B) Prochlorperazine
• C) Metoclopramide ✓
• D) Aprepitant

Explanation: Metoclopramide is the drug of choice for hyperemesis gravidarum AND vomiting associated with headache/migraine. Ondansetron is preferred for chemotherapy-induced vomiting. Prochlorperazine has higher EPS risk.

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• A) Ondansetron alone
• B) Metoclopramide + dexamethasone
• C) Ondansetron + Dexamethasone + Aprepitant ✓
• D) Promethazine + ondansetron

Explanation: Triple antiemetic therapy = 5-HT₃ antagonist (ondansetron) + corticosteroid (dexamethasone) + NK₁ antagonist (aprepitant). This covers both acute (ondansetron) and delayed (aprepitant) CINV phases.

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• A) Ondansetron
• B) Metoclopramide
• C) Hyoscine (Scopolamine) ✓
• D) Aprepitant

Explanation: Motion sickness is mediated via vestibular-cerebellar pathways using H₁ and muscarinic (M₁) receptors. Scopolamine (anticholinergic) and antihistamines (meclizine, promethazine) are effective. Ondansetron (5-HT₃) and metoclopramide (D₂) do NOT work for motion sickness.

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• A) Metoclopramide
• B) Prochlorperazine
• C) Domperidone ✓
• D) Haloperidol

Explanation: Domperidone is a peripheral D₂ antagonist that does NOT cross the blood–brain barrier. It controls nausea without worsening Parkinson's motor symptoms. All other D₂ antagonists (metoclopramide, prochlorperazine, haloperidol) cross the BBB and will block striatal dopamine → worsen parkinsonism.

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• A) Blocks D₂ receptors in the CTZ
• B) Blocks histamine H₁ receptors in the vestibular nucleus
• C) Blocks NK₁ receptors in the vomiting centre
• D) Blocks 5-HT₃ receptors on vagal afferents and in the CTZ ✓

Explanation: Chemotherapy damages gut enterochromaffin cells → release 5-HT → activates 5-HT₃ on vagal afferents → triggers vomiting. Ondansetron blocks this peripherally (gut) and centrally (CTZ).

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• A) It is a prodrug
• B) It has a half-life of ~40 hours and binds receptor differently ✓
• C) It blocks NK₁ receptors
• D) It stimulates 5-HT₄ receptors

Explanation: Palonosetron has t½ ≈ 40 hours (vs ondansetron 3–4 hrs), binds 5-HT₃ receptor with different allosteric properties, and is effective for both acute and delayed CINV, unlike earlier setrons.

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• A) Ondansetron
• B) Metoclopramide ✓
• C) Domperidone
• D) Hyoscine

Explanation: Acute dystonic reactions (including oculogyric crisis, torticollis, trismus) are EPS caused by D₂ blockade in the nigrostriatal pathway. Metoclopramide crosses the BBB and causes this. Treatment: IV/IM diphenhydramine or benztropine.

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SET 3 — ANTIDIARRHOEAL/LAXATIVE MCQs

• A) Loperamide
• B) Bismuth subsalicylate
• C) Diphenoxylate ✓
• D) Codeine

Explanation: Diphenoxylate can cross the BBB at high doses → euphoria/abuse. Atropine (subtherapeutic dose) causes unpleasant anticholinergic effects if high doses are taken recreationally, acting as a deterrent. This combination = Lomotil.

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• A) Oral vancomycin
• B) Loperamide ✓
• C) Cholestyramine
• D) Probiotics

Explanation: Loperamide reduces gut motility → prolongs retention of C. difficile toxins → risk of toxic megacolon. Contraindicated in infectious/inflammatory diarrhoea. Treat the underlying cause with metronidazole/oral vancomycin.

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• A) Lubricates the colon
• B) Directly kills gut bacteria
• C) Acidifies colon → converts NH₃ to NH₄⁺ → traps and eliminates ammonium ✓
• D) Stimulates gut motility via 5-HT₄ receptors

Explanation: Lactulose is fermented by colonic bacteria → lactic/acetic acid → ↓ colonic pH → NH₃ + H⁺ → NH₄⁺ (ionised, non-absorbable) → excreted in stool. Also osmotic laxative effect → rapid bowel evacuation of ammonia.

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• A) Lactulose
• B) Psyllium
• C) PEG (polyethylene glycol)
• D) Senna ✓

Explanation: Senna (and other anthraquinone glycosides like cascara) cause brown-black pigmentation of colonic mucosa (melanosis coli) due to apoptosis of colonic epithelial cells and subsequent phagocytosis by macrophages. Benign but indicates chronic stimulant laxative overuse.

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• A) IBS-C in men; hepatotoxicity
• B) IBS-D in children; constipation
• C) IBS-D in women; ischaemic colitis ✓
• D) CINV; QTc prolongation

Explanation: Alosetron (5-HT₃ antagonist) slows colonic transit, specifically approved for women with severe IBS-D failing conventional therapy. Ischaemic colitis (Black Box Warning) and severe constipation led to initial withdrawal and now a REMS programme.

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• A) Bisacodyl
• B) Psyllium
• C) Methylnaltrexone (Relistor) ✓
• D) Lubiprostone (also correct but less specific)

Best answer: Methylnaltrexone — peripheral μ-opioid receptor antagonist that does NOT cross BBB → reverses opioid-induced constipation without affecting analgesia. Lubiprostone also approved for opioid-induced constipation.

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• A) Blocking 5-HT₃ receptors in the colon
• B) Lubricating stool with mineral oil
• C) Inhibiting Na⁺/K⁺-ATPase in colonocytes
• D) Activating guanylate cyclase-C → ↑ cGMP → ↑ CFTR Cl⁻ secretion ✓

Explanation: Linaclotide is a GC-C (guanylate cyclase-C) agonist. ↑ cGMP activates CFTR → ↑ Cl⁻ and HCO₃⁻ secretion → ↑ intestinal fluid → softer stool + faster transit. cGMP also acts on pain-sensing afferents → ↓ visceral pain in IBS-C.

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SET 4 — COUGH MCQs

• A) Prescribe codeine syrup
• B) Prescribe dextromethorphan syrup
• C) Prescribe promethazine + codeine combination syrup
• D) Advise against OTC antitussives; recommend honey and fluids ✓

Explanation: OTC antitussives are NOT recommended in children <4 years (FDA 2007 guidance; most guidelines extend caution to <12 years). Codeine is contraindicated <12 yrs. Honey (≥1 yr) has evidence for cough suppression. Safety first.

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• A) Enhanced antitussive effect
• B) Serotonin syndrome ✓
• C) QTc prolongation
• D) Respiratory depression

Explanation: Dextromethorphan weakly inhibits serotonin reuptake. Combined with MAOIs (which prevent serotonin degradation) → serotonin accumulation → serotonin syndrome (hyperthermia, agitation, clonus, autonomic instability). Strict contraindication.

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• A) Inhibiting phosphodiesterase
• B) Activating mucociliary transport
• C) Breaking disulphide bonds in mucus glycoproteins ✓
• D) Blocking M₃ receptors in bronchial glands

Explanation: NAC's free thiol (-SH) group reduces disulphide bonds (-S-S-) holding mucus gel together → depolymerises mucus → ↓ viscosity → easier expectoration.

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• A) Severe diarrhoea
• B) Bronchospasm only
• C) Oropharyngeal anaesthesia → choking + potential cardiovascular collapse ✓
• D) Acute dystonic reaction

Explanation: Benzonatate is a local anaesthetic (related to tetracaine). If chewed, it causes oropharyngeal anaesthesia → loss of gag reflex, choking, aspiration, as well as CNS toxicity (seizures) and cardiovascular collapse. Capsules must be swallowed whole.

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• A) Carbocisteine
• B) Erdosteine
• C) Acetylcysteine
• D) Ambroxol ✓

Explanation: Ambroxol is the active metabolite of bromhexine; it depolymerises mucus AND stimulates type II pneumocytes to produce surfactant. This additional property makes it useful in premature neonates and post-surgical respiratory care.

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SET 5 — ANTI-ASTHMA MCQs

• A) Good asthma control
• B) Salbutamol tolerance requiring dose increase
• C) Poor asthma control requiring step-up in controller therapy ✓
• D) Need to switch to ipratropium

Explanation: According to GINA guidelines, SABA use >2 days/week (excluding pre-exercise use) indicates inadequate asthma control. Step up — add or increase ICS. Overuse of SABA (>3 canisters/year) is associated with ↑ mortality.

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• A) It can be used as a rescue inhaler due to its potency
• B) Its onset is rapid (3–5 min) making it ideal for acute attacks
• C) It can be used as monotherapy in asthma
• D) It has a slow onset (20–30 min) and should never be used without ICS in asthma ✓

Explanation: Salmeterol has partial agonist activity with slow onset — NOT suitable for acute bronchospasm. FDA black box warning: LABAs must NOT be used as monotherapy in asthma (associated with increased asthma deaths in the SMART trial). Always combine with ICS.

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• A) Rifampicin
• B) Omeprazole
• C) Ciprofloxacin ✓
• D) Salbutamol

Explanation: Ciprofloxacin inhibits CYP1A2 → ↓ theophylline metabolism → toxic plasma levels. Therapeutic range is 10–20 mg/L. At 35 mg/L, seizures and arrhythmias occur. Other inhibitors: erythromycin, cimetidine, fluvoxamine. Rifampicin DECREASES levels.

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• A) Omalizumab
• B) Montelukast ✓
• C) Salmeterol
• D) Cromoglicate

Explanation: Aspirin/NSAID-exacerbated respiratory disease (AERD) — COX inhibition shunts arachidonic acid toward the 5-LOX pathway → excess LTC₄/LTD₄ → bronchoconstriction. Montelukast (CysLT₁ antagonist) directly blocks this pathway. Drug of choice in AERD.

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• A) Omalizumab
• B) Mepolizumab
• C) Benralizumab
• D) Tezepelumab ✓

Explanation: Tezepelumab blocks TSLP (thymic stromal lymphopoietin) — the most upstream cytokine in airway inflammation, present across all asthma endotypes (eosinophilic, allergic, and non-eosinophilic). Others target specific downstream pathways (IgE, IL-5) and require specific biomarker criteria.

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• A) Bronchodilation via β₂ receptor activation
• B) Inhibition of phosphodiesterase
• C) Inhibition of mast cell degranulation → prevention of mediator release ✓
• D) 5-HT₃ receptor blockade in bronchi

Explanation: Cromoglicate is a mast cell stabiliser. Taken prophylactically 15–20 min before exercise, it prevents mast cell degranulation triggered by osmotic changes in airway surface fluid during exercise. It is purely preventive with NO bronchodilator activity.

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• A) Blocking β₂ receptors
• B) Inhibiting phosphodiesterase
• C) Antagonising calcium → relaxing bronchial smooth muscle ✓
• D) Blocking leukotriene receptors

Explanation: Mg²⁺ competes with Ca²⁺ in smooth muscle contraction. Ca²⁺ is required for smooth muscle contraction via calmodulin–myosin light chain kinase pathway. By blocking Ca²⁺ entry, Mg²⁺ causes bronchodilation. Dose: 1.2–2 g IV over 20 min.

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• A) Formoterol has slower onset
• B) Formoterol has shorter duration
• C) Formoterol should not be used as a reliever
• D) Formoterol has fast onset (3–5 min) and can be used as both reliever and maintenance (MART strategy) ✓

Explanation: Formoterol is a full agonist at β₂ receptors with fast onset (unlike salmeterol which is a partial agonist with slow onset). This allows its use in the MART (Maintenance And Reliever Therapy) strategy with budesonide/formoterol.

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🟠 PART B — SAQs (Short Answer Questions)

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SAQ 1

Model Answer:

• PPIs (e.g., omeprazole, lansoprazole) are prodrugs — inactive at neutral pH
• In the acidic secretory canaliculi of parietal cells, they are protonated → converted to active sulfenamide
• Sulfenamide irreversibly (covalent) binds to cysteine residues on the H⁺/K⁺-ATPase (proton pump)
• This blocks the final step of acid secretion regardless of stimulus (histamine, gastrin, ACh)
• Effect lasts 24–36 hrs despite short plasma t½ (1–2 hrs) — new pump synthesis needed for recovery
• Maximal suppression achieved after 3–4 days of daily dosing
• Must be taken 30–60 min before meals (pumps must be active/stimulated for drug to work)

⭐ Exam point: PPIs do NOT directly block receptors — they block the pump itself. Pantoprazole is preferred with clopidogrel (least CYP2C19 inhibition).

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SAQ 2

Model Answer:

• Central: Blocks D₂ receptors in the CTZ → antiemetic
• Peripheral: Blocks D₂ in gut + activates 5-HT₄ → ↑ ACh release from myenteric plexus → ↑ LOS tone + ↑ gastric emptying + ↑ intestinal peristalsis = prokinetic

1. Nausea/vomiting (post-op, drug-induced, mild CINV)
2. Hyperemesis gravidarum (drug of choice)
3. Headache/migraine-associated vomiting (drug of choice)
4. Gastroparesis (diabetic + post-surgical)
5. GERD (augments LOS tone)

• EPS: Acute dystonia, akathisia, tardive dyskinesia (long-term) — D₂ blockade in nigrostriatal pathway
• Hyperprolactinaemia → galactorrhoea, menstrual irregularities, gynaecomastia (D₂ blockade in tuberoinfundibular pathway)
• Sedation, fatigue
• Restlessness

⭐ Exam point: Pretreat with diphenhydramine/benztropine to reduce EPS. Domperidone is preferred in Parkinson's as it doesn't cross BBB.

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SAQ 3

Model Answer:

• Lactulose = dual use: laxative + hepatic encephalopathy (↓ ammonia absorption)
• Bisacodyl suppository: onset 15–60 min (vs oral 6–12 hrs)
• Senna long-term → melanosis coli (anthraquinone pigment)
• Linaclotide contraindicated in children <6 yrs (dehydration risk)

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SAQ 4

Model Answer:

1. Inhibits phosphodiesterase (PDE) → ↑ cAMP → bronchodilation + ↓ mast cell degranulation
2. Adenosine receptor antagonism → bronchodilation + CNS stimulation (explains CNS toxicity)
3. At low doses: Activates HDAC-2 → ↑ corticosteroid sensitivity (anti-inflammatory; useful in steroid-resistant asthma)
4. ↑ Diaphragm contractility → useful in COPD and respiratory failure

• Narrow therapeutic index: Target = 10–20 mg/L
• Metabolised by CYP1A2 and CYP3A4
• Half-life varies: 3–5 hrs in healthy adults; up to 24 hrs in liver disease/heart failure
• Smoking ↓ t½ (CYP1A2 induction); stopping smoking → levels rise → toxicity risk
• Aminophylline = theophylline + ethylenediamine (IV use; 80% theophylline content)

• ↑ Levels: Erythromycin, Ciprofloxacin, Cimetidine, Allopurinol, Oral contraceptives
• ↓ Levels: Rifampicin, Phenytoin, Carbamazepine, Smoking, Phenobarbitone

• 10–20: Nausea, vomiting, headache, insomnia
• 20–30: Tachycardia, arrhythmias, tremor

• 30: Seizures, life-threatening arrhythmias (may occur without warning nausea)

⭐ Exam point: Seizures from theophylline toxicity may occur WITHOUT prior nausea/vomiting — monitor levels carefully, especially when CYP inhibitors are added.

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SAQ 5

Model Answer:

1. Salbutamol (nebulised/IV) — β₂ agonist → ↑ cAMP → bronchodilation. Continuous or back-to-back nebulisation. Also used IV in life-threatening asthma.
2. Ipratropium bromide (nebulised) — Muscarinic M₃ antagonist → ↓ bronchoconstriction. Synergistic with salbutamol. Add in moderate-severe attack.
3. Systemic corticosteroids — IV hydrocortisone (100 mg qds) or oral prednisolone (40–50 mg). Onset delayed 4–6 hrs (gene transcription). Suppress airway inflammation, restore β₂ receptor responsiveness.
4. Oxygen — Target SpO₂ 94–98%. Hypoxaemia is the main cause of death.

1. IV Magnesium sulphate (1.2–2 g over 20 min) — Antagonises Ca²⁺ in bronchial smooth muscle → relaxation. Safe, effective add-on.
2. IV Aminophylline — PDE inhibitor → ↑ cAMP bronchodilation. Narrow TI; monitor levels. Rarely used now.

⭐ Key: Antibiotics NOT routinely given (most acute asthma is viral/inflammatory not bacterial). MgSO₄ is now standard in severe attacks.

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🔵 PART C — LAQs (Long Answer Questions)

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LAQ 1

Model Answer:

I. Classification of Anti-Ulcer Drugs (2 marks)

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II. Proton Pump Inhibitors (PPIs) (8 marks)

• Oral bioavailability ~65% (first pass hepatic metabolism)
• Absorbed in small intestine (enteric-coated to prevent degradation in stomach)
• Plasma t½ = 1–2 hours
• Duration of action = 24–36 hours (irreversible binding)
• Extensively protein bound (>95%)
• Hepatic metabolism via CYP2C19 and CYP3A4
• Accumulate in acidic parietal cell canaliculi (trapped by protonation)

• PPI (prodrug) → enters blood → accumulates in parietal cell secretory canaliculi → protonated (activated) in acid → forms sulfenamide (active form)
• Sulfenamide: covalent bond with Cys813 and Cys892 of H⁺/K⁺-ATPase α subunit
• Irreversibly blocks the pump → complete cessation of acid secretion from that cell
• Only affects actively secreting pumps → maximum effect with meal-stimulated pumps
• Recovery requires synthesis of new pump protein (18–24 hrs)
• Full effect after 3–4 days of daily dosing

• Peptic ulcer disease (gastric + duodenal)
• GERD / erosive oesophagitis
• Zollinger-Ellison syndrome (high doses; e.g., omeprazole 60–120 mg/day)
• NSAID-induced ulcer prevention
• H. pylori eradication (as part of combination therapy)
• Upper GI bleeding (IV omeprazole 80 mg bolus + 8 mg/hr for 72 hrs post-endoscopy)
• Stress ulcer prophylaxis (ICU patients)

• Clopidogrel: Omeprazole/esomeprazole inhibit CYP2C19 → ↓ clopidogrel activation → ↓ antiplatelet effect → use pantoprazole instead
• ↑ Diazepam, warfarin, phenytoin levels (CYP2C19 inhibition)
• ↓ Absorption of: ketoconazole, itraconazole, iron, ampicillin esters (require acid)

• Short-term: headache, diarrhoea, nausea, abdominal pain
• Long-term:
  • Hypomagnesaemia (impairs Mg²⁺ absorption) → tetany, arrhythmias
  • Hypocalcaemia → osteoporosis, fractures (↓ Ca²⁺ absorption)
  • Vitamin B₁₂ deficiency (requires acid for release from food proteins)
  • C. difficile colitis (↑ risk — loss of acid barrier)
  • Community-acquired pneumonia (↑ risk)
  • Acute interstitial nephritis (rare, idiosyncratic)
  • Fundic gland polyps (benign, regress on stopping)

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III. H. pylori Eradication (2 marks)

PPI (bid) + Clarithromycin (500 mg bid) + Amoxicillin (1 g bid)

PPI (bid) + Bismuth + Tetracycline + Metronidazole (all qid)

• Pre-treatment: Urea breath test or stool antigen test (most sensitive non-invasive)
• Post-treatment: Urea breath test (wait ≥4 weeks after stopping PPI to avoid false negatives)

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LAQ 2

Model Answer:

I. Classification of Bronchodilators (2 marks)

• Short-acting (SABAs): Salbutamol, Terbutaline
• Long-acting (LABAs): Salmeterol, Formoterol, Indacaterol

• Short-acting (SAMAs): Ipratropium bromide
• Long-acting (LAMAs): Tiotropium, Aclidinium

• ICS: Beclomethasone, Budesonide, Fluticasone
• Leukotriene antagonists: Montelukast, Zafirlukast
• Biologics: Omalizumab, Mepolizumab, Tezepelumab

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II. Pharmacology of β₂-Agonists (5 marks)

• Bind β₂ receptors (Gs-coupled) → activate adenylyl cyclase → ↑ cAMP → activates PKA
• PKA phosphorylates myosin light chain kinase (MLCK) → inactivation → smooth muscle relaxation → bronchodilation
• Additionally: inhibit mast cell mediator release, ↑ mucociliary clearance

• Onset: 3–5 min inhaled; Duration: 4–6 hrs
• Rescue reliever — use for breakthrough symptoms
• ADRs: Tremor, tachycardia, hypokalaemia (K⁺ shift into cells), hyperglycaemia
• Tachyphylaxis with overuse (receptor downregulation)

• LABAs must ALWAYS be combined with ICS in asthma (FDA black box warning — SMART trial: LABA monotherapy → ↑ asthma deaths)
• In COPD: LABAs can be used without ICS (first-line)
• Salbutamol drives K⁺ into cells → used for emergency hyperkalaemia management

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III. Inhaled Corticosteroids (ICS) (4 marks)

1. Bind intracellular glucocorticoid receptors (GR) → GR-drug complex → translocates to nucleus
2. Trans-repression: ↓ NF-κB and AP-1 activity → ↓ transcription of IL-4, IL-5, IL-13, TNF-α, eotaxin
3. Trans-activation: ↑ Lipocortin-1 synthesis → ↓ phospholipase A₂ → ↓ prostaglandins, leukotrienes
4. ↓ Mucosal oedema, ↓ eosinophil recruitment, ↓ goblet cell hyperplasia
5. ↑ β₂ receptor synthesis → restore/maintain bronchodilator responsiveness

• Most effective long-term controller in asthma
• Reduce exacerbations, hospitalisations, and asthma mortality
• NOT bronchodilators — DO NOT relieve acute bronchospasm

• Local: Oropharyngeal candidiasis (Candida albicans), dysphonia (hoarseness) — use spacer, rinse mouth
• Systemic (high dose/long-term): HPA suppression, growth retardation in children, osteoporosis, cataracts, glaucoma, easy bruising

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IV. Stepwise Asthma Management (GINA 2023) (4 marks)

• SABA-only treatment at Step 1 no longer preferred (increased mortality risk)
• ICS-formoterol as reliever across all steps (MART = Maintenance And Reliever Therapy)

• Anti-IgE (Omalizumab): allergic asthma, high IgE
• Anti-IL-5 (Mepolizumab, Benralizumab): eosinophilic asthma (eos ≥150–300)
• Anti-IL-4Rα (Dupilumab): type 2 asthma
• Anti-TSLP (Tezepelumab): any severe uncontrolled asthma

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LAQ 3

Model Answer:

I. Physiological Basis of Vomiting (1 mark)

• CTZ (chemoreceptor trigger zone) — Area postrema, outside BBB; senses drugs, toxins, metabolic changes (D₂, 5-HT₃, NK₁ receptors)
• Vestibular apparatus — motion sickness (H₁, M₁ receptors)
• Vagal afferents from gut — 5-HT₃ receptors
• Higher cortical centres (anticipatory nausea)

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II. Classification with Mechanisms (6 marks)

• Metoclopramide: D₂ block (CTZ) + 5-HT₄ agonism (gut) → antiemetic + prokinetic
• Domperidone: Peripheral D₂ only (doesn't cross BBB) → no EPS; safe in Parkinson's
• Prochlorperazine: Phenothiazine; D₂ block; used in vertigo/labyrinthitis

• Ondansetron, Granisetron, Palonosetron
• Block 5-HT₃ on vagal afferents and CTZ
• Most effective for CINV; no effect on motion sickness

• Aprepitant, Fosaprepitant
• Block substance P/NK₁ in vomiting centre
• Specifically effective for delayed CINV

• Promethazine, Meclizine, Cyclizine, Diphenhydramine
• Block H₁ in vestibular nucleus + vomiting centre; also anticholinergic
• Best for motion sickness; sedating

• Hyoscine (Scopolamine): M₁ block; most effective for motion sickness; transdermal patch

• Dexamethasone: Mechanism unclear (↓ prostaglandins, ↓ 5-HT release); adjunct in CINV

• Dronabinol, Nabilone: CB₁ receptor agonists; refractory CINV

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III. Drug of Choice by Scenario (3 marks)

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IV. Key Adverse Effects (2 marks)

⭐ Exam emphasis: Know the five receptor types at the CTZ/vomiting centre, which drug blocks which receptor, and match the drug to the clinical context. The Parkinson's-domperidone link and hyperemesis-metoclopramide link are high-yield.

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📋 QUICK MCQ REVISION GRID

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