Respiratory & GI Pharmacology

Respiratory and gastrointestinal pharmacology encompasses treatments for asthma, COPD, peptic ulcer disease, nausea, and constipation.

Bronchodilators are the mainstay of obstructive airways disease. Short-acting beta-2 agonists (SABA — salbutamol, terbutaline) stimulate β2 adrenergic receptors in bronchial smooth muscle, activating adenylyl cyclase, increasing cAMP, activating PKA, which phosphorylates myosin light chain kinase — causing smooth muscle relaxation and bronchodilation. Onset is within 5 minutes, duration 4–6 hours. SABAs are reliever medications for acute symptoms. Long-acting beta-2 agonists (LABA — salmeterol, formoterol) have duration >12 hours. They should not be used without inhaled corticosteroids in asthma (risk of masking worsening inflammation and increased mortality — SMART trial). Short-acting muscarinic antagonists (SAMA — ipratropium) block M3 muscarinic receptors in bronchial smooth muscle and glands, reducing bronchoconstriction and secretions. They are preferred in COPD exacerbations. Long-acting muscarinic antagonists (LAMA — tiotropium) are a cornerstone of COPD maintenance therapy.

Inhaled corticosteroids (ICS — budesonide, fluticasone, beclometasone) are the most effective anti-inflammatory therapy in asthma. They suppress eosinophilic airway inflammation by reducing cytokine and chemokine production, downregulating inflammatory gene expression. Local adverse effects include oropharyngeal candidiasis and dysphonia — mitigated by rinsing mouth after use. Systemic absorption is minimised by delivery to the lungs. High-dose ICS can cause adrenal suppression.

Combination inhalers (ICS + LABA) provide both anti-inflammatory and bronchodilator effects conveniently — e.g., budesonide/formoterol (Symbicort), fluticasone/salmeterol (Seretide).

For gastrointestinal pharmacology, proton pump inhibitors (PPIs — omeprazole, pantoprazole, esomeprazole) are the most potent acid-suppressive agents. They are prodrugs that are activated in the acidic canaliculi of the parietal cell, where they form covalent disulfide bonds with H+/K+-ATPase (the proton pump), irreversibly inhibiting acid secretion. They are used for peptic ulcer disease (especially H. pylori eradication — triple therapy: PPI + amoxicillin + clarithromycin), GORD, and Zollinger-Ellison syndrome.

Antiemetics act at multiple receptors. Ondansetron is a 5-HT3 receptor antagonist — serotonin in the GI tract and the chemoreceptor trigger zone (CTZ) triggers nausea/vomiting; blocking 5-HT3 suppresses this. It is highly effective for chemotherapy-induced and post-operative nausea. Metoclopramide is a D2 receptor antagonist centrally (CTZ and vomiting centre) and also promotes gastric motility — useful for diabetic gastroparesis and nausea but can cause extrapyramidal side effects (tardive dyskinesia with long-term use).

Laxatives: bulk-forming agents (psyllium/ispaghula) absorb water and increase stool bulk. Osmotic laxatives (lactulose, macrogol) draw water into the bowel. Stimulant laxatives (bisacodyl, senna) stimulate enteric nerve plexuses, increasing colonic motility. Docusate is a stool softener (detergent action).