Asthma SMART Protocol
Single Maintenance and Reliever Therapy: Inhaled Corticosteroid (Budesonide) + Formoterol (rapid-onset LABA) is now preferred first-line across all steps.
Theophylline Toxicity
Phosphodiesterase inhibitor with narrow therapeutic index; toxicity (cardiac arrhythmias, seizures) precipitated by CYP1A2 inhibitors (Ciprofloxacin).
Long-Term PPI Risks
Omeprazole irreversibly inhibits H+/K+ ATPase; long-term risks: hypomagnesemia, C. diff colitis, microscopic colitis, hip fractures (osteoporosis), and B12 deficiency.
Antiemetic 5-HT3 Antagonists
Ondansetron: blocks serotonin 5-HT3 receptors in chemoreceptor trigger zone and vagal afferents; high-yield adverse effect: QT interval prolongation.
Bronchodilators & Anti-Inflammatory Respiratory Therapeutics
Pulmonary drug classes target airway smooth muscle tone and eosinophilic/neutrophilic inflammation:
| Drug Class | Representative Agents | Mechanism of Action | Key Board Facts & Adverse Effects |
|---|---|---|---|
| SABA & LABA | Albuterol (SABA); Salmeterol, Formoterol (LABA) | β2 agonist → ↑ cAMP → bronchial smooth muscle relaxation | Tremor, tachycardia, hypokalemia (shifts K+ into cells); LABA monotherapy in asthma is CONTRAINDICATED (increases asthma mortality) |
| Inhaled Corticosteroids (ICS) | Fluticasone, Budesonide, Beclomethasone | Inhibits NF-κB → ↓ inflammatory cytokines and eosinophil recruitment | First-line chronic asthma controller; rinse mouth after use to prevent oral candidiasis (thrush) and dysphonia |
| Muscarinic Antagonists (SAMA / LAMA) | Ipratropium (SAMA), Tiotropium (LAMA) | Competitively block M3 receptors → block bronchoconstriction and reduce mucus secretion | First-line maintenance for COPD; dry mouth, urinary retention in elderly BPH patients |
| Leukotriene Modifiers | Montelukast, Zafirlukast (CysLT1 receptor antagonists); Zileuton (5-lipoxygenase inhibitor) | Block leukotriene LTD4 receptors (Montelukast) or synthesis (Zileuton) | Excellent for aspirin-exacerbated respiratory disease (AERD) and exercise-induced asthma; Montelukast: neuropsychiatric boxed warning; Zileuton: hepatotoxicity |
Gastrointestinal Acid Suppression & Motility Agents
Gastric acid secretion by parietal cells is driven by histamine (H2), acetylcholine (M3), and gastrin (CCK-B), converging on the H+/K+ ATPase proton pump:
| Agent Class | Specific Drugs | Mechanism of Action | Adverse Reactions & Drug Interactions |
|---|---|---|---|
| Proton Pump Inhibitors (PPIs) | Omeprazole, Pantoprazole, Esomeprazole | Irreversibly inhibits H+/K+ ATPase proton pump in gastric parietal cells | Decreased calcium absorption (↑ osteoporotic fractures), hypomagnesemia, C. difficile colitis; Omeprazole inhibits CYP2C19 (reduces clopidogrel activation) |
| H2 Receptor Antagonists | Famotidine, Ranitidine, Cimetidine | Competitively block histamine H2 receptors on parietal cells → ↓ cAMP → ↓ acid | Cimetidine: Potent CYP450 inhibitor, antiandrogenic effects (gynecomastia, impotence, prolactin release) |
| Prokinetic / Antiemetic | Metoclopramide | D2 dopamine receptor antagonist in CTZ and upper GI tract → ↑ LES tone and gastric emptying | Diabetic gastroparesis; Extrapyramidal symptoms (dystonia, parkinsonism), Tardive dyskinesia; contraindicated in bowel obstruction |
| Motility Stimulant | Erythromycin | Binds motilin receptors on gastrointestinal smooth muscle → stimulates migrating motor complex (MMC) | Used acutely in diabetic gastroparesis or acute upper GI bleeding to clear stomach before endoscopy; rapid tachyphylaxis |
Board Traps & Common Distractors
- LABA monotherapy in asthma without an inhaled corticosteroid is strictly contraindicated; it increases the risk of severe asthma exacerbations and asthma-related death.
- Metoclopramide carries a black-box warning for irreversible tardive dyskinesia with long-term use (> 12 weeks); discontinue immediately if abnormal facial or tongue movements appear.
- Cimetidine is a notorious inhibitor of multiple CYP450 enzymes (1A2, 2C9, 2D6, 3A4) and interacts with Warfarin, Theophylline, and Phenytoin; prefer Famotidine.