6.1 Respiratory Pharmacology

Asthma and COPD: the Pharmacological Backbone

Respiratory pharmacology is examined heavily within Clinical Pharmacology & Therapeutic Decision Making, the largest content area (20%) of the DHA pharmacist assessment. The exam expects you to know mechanisms, class-specific adverse effects and the counselling points a Dubai community or hospital pharmacist actually gives at the counter.

Beta-2 Agonists

Short-acting beta-2 agonists (SABAs) - salbutamol (albuterol) and terbutaline - relax bronchial smooth muscle by stimulating beta-2 adrenoceptors, raising cyclic adenosine monophosphate. Onset by inhalation is within minutes, making them the reliever of choice for acute symptoms. Adverse effects are extensions of beta stimulation: tremor (skeletal muscle beta-2), tachycardia and palpitations, and hypokalemia from beta-2-mediated shift of potassium into cells - clinically relevant with repeated high-dose nebulised salbutamol in acute asthma.

Long-acting beta-2 agonists (LABAs) - salmeterol (slow onset) and formoterol (fast onset) - provide 12-hour bronchodilation. The critical exam rule: LABAs are never used as monotherapy in asthma. LABA-only treatment masks bronchospasm while airway inflammation progresses, and safety trials showed increased asthma-related deaths. In asthma a LABA is always co-prescribed with an inhaled corticosteroid, usually in a fixed ICS/LABA combination inhaler (budesonide/formoterol, fluticasone/salmeterol). In COPD, LABA monotherapy is acceptable. Non-selective beta-blockers (for example propranolol) antagonise these drugs and can provoke bronchospasm - a classic pharmacist-intervention scenario.

Inhaled Corticosteroids

Inhaled corticosteroids (ICS) - beclometasone, budesonide, fluticasone - are the foundation of persistent asthma control, suppressing airway inflammation. They are preventers, not relievers, and must be taken regularly. Because deposition is oropharyngeal as well as pulmonary, the signature local adverse effects are oral candidiasis (thrush) and dysphonia (hoarse voice). Counselling: rinse the mouth with water and spit after every dose, and use a spacer with a metered-dose inhaler to cut oral deposition. High-dose ICS over years can cause systemic effects (adrenal suppression, reduced bone density), but at usual doses systemic absorption is minimal.

Antimuscarinics

Long-acting muscarinic antagonists (LAMAs) - tiotropium (once daily) - block M3 receptors, preventing acetylcholine-mediated bronchoconstriction. They are first-line maintenance therapy in COPD and an add-on option in asthma. Adverse effects are anticholinergic: dry mouth, constipation, urinary retention (caution in benign prostatic hyperplasia) and risk of precipitating narrow-angle glaucoma, especially if nebulised drug contacts the eye. Ipratropium is the short-acting counterpart used in acute exacerbations.

Leukotriene Receptor Antagonists

Montelukast blocks cysteinyl leukotriene receptors, useful as add-on therapy in asthma, exercise-induced bronchoconstriction and allergic rhinitis. It is taken orally once daily - a compliance advantage - but carries a regulatory warning for neuropsychiatric effects including agitation, sleep disturbance, depression and suicidal ideation; advise patients and parents to report mood or behaviour changes.

Theophylline

Theophylline, a methylxanthine (phosphodiesterase inhibitor and adenosine receptor antagonist), is now a reserve agent because of its narrow therapeutic index - target plasma concentration 10-20 mg/L. Toxicity begins with nausea and tremor and progresses to cardiac arrhythmias and seizures. It is metabolised by CYP1A2, so levels are increased by inhibitors such as ciprofloxacin, erythromycin and cimetidine, and decreased by inducers including tobacco smoke, carbamazepine and rifampicin. Dose-check whenever interacting drugs start or stop, and when a patient quits smoking.

Biologics and Oxygen

Omalizumab, a monoclonal antibody against immunoglobulin E, represents the biologic class for severe allergic asthma with elevated IgE despite optimised inhaler therapy; it is given by subcutaneous injection and carries an anaphylaxis risk, so doses are administered under observation. In COPD exacerbations use controlled oxygen therapy (24-28% via Venturi mask) targeting SpO2 88-92%: a minority of chronic hypercapnic patients depend on hypoxic drive, and uncontrolled high-flow oxygen can cause dangerous CO2 retention and respiratory acidosis.

Inhaler Technique and Spacer Counselling

Poor technique is the commonest reason inhaled therapy fails. Key counselling points:

• Metered-dose inhaler (MDI): shake, exhale fully, seal lips, start a slow deep inhalation and fire the canister simultaneously, then hold the breath ~10 seconds. Coordination problems are solved with a spacer, which also improves lung deposition and reduces thrush with ICS; wash spacers in detergent and air-dry to limit static.
• Dry-powder inhaler (DPI): requires a forceful, deep inhalation - unsuitable for patients with very poor inspiratory flow; do not exhale into the device.
• Check technique at every refill; rinse-and-spit after ICS-containing inhalers.

Antihistamines and Decongestants

First-generation H1 antihistamines (chlorphenamine, promethazine, diphenhydramine) cross the blood-brain barrier, causing sedation and marked anticholinergic effects (dry mouth, urinary retention, blurred vision) - avoid in the elderly and warn about driving. Second-generation agents (cetirizine, loratadine, fexofenadine) are minimally sedating and preferred for allergic rhinitis and urticaria. For nasal congestion, topical oxymetazoline works rapidly but use beyond about 5-7 days causes rebound congestion (rhinitis medicamentosa) - a favourite exam point. Oral pseudoephedrine is an alternative but is cautioned in hypertension, ischaemic heart disease and hyperthyroidism.

Stepwise Management and Acute Exacerbations

Asthma follows a stepwise approach: low-dose ICS is the preferred controller from the earliest persistent stage, with the ICS dose stepped up or a LABA added when control is poor - always checking adherence and inhaler technique first. Heavy SABA use (more than one reliever canister a month) is a red flag for uncontrolled asthma and increased exacerbation risk, and many guidelines now prefer as-needed low-dose ICS/formoterol over SABA-only reliever therapy. In an acute severe asthma attack, give repeated inhaled or nebulised salbutamol (ipratropium is added in severe episodes), a course of systemic corticosteroids (oral prednisolone 40-50 mg for 5-7 days), and controlled oxygen to keep saturation at 93-95%. COPD exacerbations are managed with increased bronchodilator therapy, a short prednisolone course (30-40 mg for 5 days), antibiotics when sputum becomes purulent, and the controlled 88-92% oxygen target described above. Long-term azithromycin prophylaxis and phosphodiesterase-4 inhibition with roflumilast are specialist options for frequently exacerbating COPD - know that they exist rather than their dosing detail.