PH5.1-2 | Respiratory Pharmacology — Practice Quiz

Correct. GINA Step 2 mandates a low-dose ICS as the first add-on controller for persistent asthma. ICS reduces eosinophilic airway inflammation, decreases exacerbation frequency, and is superior to oral corticosteroids for long-term control due to a far safer systemic safety profile.

GINA Step 2: low-dose ICS is the first-line controller; LABA monotherapy in asthma carries a black-box warning.

Review GINA step therapy. Low-dose ICS is the cornerstone of Step 2. LABA monotherapy (without ICS) is contraindicated in asthma due to increased risk of severe asthma-related death (FDA black-box warning). Oral steroids and aminophylline are reserved for later steps or acute exacerbations.

Correct. Salbutamol selectively activates beta-2 adrenoceptors (Gs-coupled). This activates adenylyl cyclase, increasing intracellular cAMP, which activates protein kinase A (PKA). PKA phosphorylates myosin light-chain kinase, reducing its activity and causing smooth muscle relaxation — bronchodilation within minutes.

Beta-2 agonists activate Gs-coupled beta-2 receptors → adenylyl cyclase → cAMP → PKA → myosin light-chain kinase phosphorylation → bronchodilation.

Salbutamol is a selective beta-2 agonist, not a muscarinic antagonist (that is tiotropium/ipratropium), not a phosphodiesterase inhibitor (that is theophylline), and not a leukotriene antagonist (that is montelukast). Each bronchodilator class has a distinct target.

Correct. GOLD 2023 guidelines support dual bronchodilation (LAMA + LABA) as the preferred step-up for patients with inadequate symptom control on LAMA monotherapy. Combining anticholinergic and beta-2 agonist mechanisms provides additive bronchodilation with complementary sites of action. ICS is added only when blood eosinophils ≥300 cells/μL or ongoing exacerbations persist.

GOLD Step 2 for COPD: dual bronchodilation (LAMA + LABA) is preferred before adding ICS; ICS is added only when eosinophil count is high or exacerbations persist on dual bronchodilation.

In COPD, dual bronchodilation (LAMA + LABA) is the evidence-based step-up before ICS. Unlike asthma, ICS monotherapy is ineffective in COPD and may increase pneumonia risk. Theophylline is third-line. SABA alone (without a controller) does not address the persistent obstruction.

Correct. The FDA black-box warning on LABAs in asthma was driven by trials showing increased asthma-related deaths with LABA monotherapy. Subsequent studies (SMART trial, FDA mandated studies) confirmed that ICS co-administration mitigates this risk. Therefore, LABA + ICS as a fixed combination or prescribed together is the Step 3 standard of care.

LABA must always be co-prescribed with ICS in asthma. The ICS-LABA combination is the Step 3 standard. LABAs alone increase mortality risk in asthma.

LABA monotherapy in asthma is contraindicated regardless of cost constraints — this is a patient safety issue, not a preference. Salmeterol has a slow onset (15–30 min) and is not suitable for acute attacks. Treatment decisions should follow evidence, not cost compromise.

Correct. Tiotropium is a long-acting muscarinic antagonist (LAMA). It competitively blocks M3 receptors on bronchial smooth muscle and submucosal glands. M3 blockade prevents acetylcholine-mediated bronchoconstriction and excessive mucus secretion. Its kinetic selectivity (slow dissociation from M3 vs rapid dissociation from prejunctional M2 autoreceptors) preserves feedback inhibition of ACh release while sustaining M3 blockade for ~24 hours.

Tiotropium is a LAMA: long-acting muscarinic antagonist (M3 blockade); its kinetic selectivity (dissociates slowly from M3, rapidly from M2) prolongs duration to 24 hours.

Tiotropium is a muscarinic antagonist (anticholinergic), not a beta-2 agonist. It does not affect mast cells or leukotriene receptors. Remember the two major bronchodilator classes: beta-2 agonists (SABA/LABA) and muscarinic antagonists (SAMA/LAMA) — each has a distinct receptor target.

Correct. Oral candidiasis from ICS results from local immunosuppression in the oropharynx due to deposited ICS particles. Rinsing and gargling with water after each dose removes most of the deposited drug before it is absorbed by oropharyngeal tissues. This is the primary prevention strategy. Use of a spacer (for MDI) also reduces oropharyngeal deposition.

ICS local adverse effects (candidiasis, dysphonia) are caused by oropharyngeal deposition; mouth-rinsing after each dose removes residual drug and is the standard preventive strategy.

Switching to oral steroids would cause far greater systemic immunosuppression and much higher candidiasis risk. Stopping ICS entirely is not appropriate for persistent asthma. Bedtime-only dosing and dose reduction are not recognised preventive strategies for this specific adverse effect.

Correct. Montelukast blocks CysLT1 receptors, which are expressed in both nasal mucosa and bronchial tissue. Since cysteinyl leukotrienes (LTC4, LTD4, LTE4) drive both allergic rhinitis and asthma via the same mediator pathway, a single oral LTRA addresses both conditions simultaneously. This operationalises the united airway disease concept.

Montelukast, an oral LTRA, addresses both allergic rhinitis and asthma because cysteinyl leukotrienes drive inflammation in both the upper and lower airways — the united airway disease concept.

Option B (separate nasal + inhaled steroids) would also treat both conditions but involves two devices rather than a single oral agent. Option A uses two bronchodilators without anti-inflammatory coverage for rhinitis. Option D (antihistamine + SABA) fails to address the underlying inflammation of either condition.

Correct. Dextromethorphan (the D-isomer of levorphanol) acts on sigma receptors and as an NMDA receptor antagonist in the brainstem cough centre. Crucially, it does NOT have mu-opioid receptor agonist activity — hence no analgesia, minimal addiction potential, and no respiratory depression at therapeutic doses. This distinguishes it from codeine, the classic opioid antitussive.

Dextromethorphan is a non-opioid central antitussive acting via sigma receptors and NMDA antagonism; it lacks mu-opioid activity and therefore has minimal analgesic/addiction potential.

Mu-opioid agonism describes codeine (and morphine, which was the original antitussive). Dextromethorphan works via sigma receptors and NMDA antagonism — this is the key pharmacological distinction. Peripheral sensory nerve desensitisation is the mechanism of benzonatate (peripherally-acting antitussive).

Correct. N-acetylcysteine (NAC) contains a free thiol (-SH) group that directly cleaves disulphide (S-S) bonds within mucus glycoprotein chains (mucins). This depolymerises the mucin network, reducing sputum viscosity and elasticity — making mucociliary clearance easier. It is used both as an inhaled mucolytic and, at higher doses, as an acetaminophen antidote via glutathione replenishment.

Acetylcysteine is a mucolytic that directly breaks disulphide bonds (via its free -SH thiol group) in mucus glycoproteins, reducing viscosity; guaifenesin is an expectorant (increases secretions); bromhexine stimulates mucus gland secretion of less viscous mucus.

Guaifenesin is an expectorant — it increases secretion volume and hydration but does not break chemical bonds in mucus. Codeine is an antitussive, not appropriate for productive cough (contraindication: suppresses productive cough). Bromhexine stimulates serous gland secretion, producing less viscous mucus — a different mechanism from direct bond cleavage.

Correct. This is a major prescribing error. In productive cough, coughing is the mechanism by which the patient clears potentially infected secretions. Suppressing the cough with an antitussive (dextromethorphan, codeine) traps purulent sputum in the airways, worsening the respiratory infection, potentially leading to lobar pneumonia or respiratory failure in a COPD patient. The correct management is an expectorant/mucolytic + treat the infection + bronchodilator.

Antitussives are CONTRAINDICATED in productive (wet) cough — suppressing cough traps secretions, worsening infection and obstruction. The fundamental prescribing rule: determine cough type FIRST.

Antitussives + productive cough is not merely suboptimal — it is harmful. The cough reflex is the primary defence against retained secretions in productive illness. Never suppress a productive cough. This is the most important clinical application of cough pharmacotherapy classification.