12.3 Respiratory & Gastrointestinal Agents
Key Takeaways
Inhaled beta-2 agonists relax airway smooth muscle through Gs-cAMP; current asthma guidance favors an inhaled corticosteroid-formoterol reliever over short-acting beta-agonist monotherapy for adolescents and adults.
Montelukast blocks the CysLT1 leukotriene receptor and carries a boxed warning for neuropsychiatric events; zileuton inhibits 5-lipoxygenase; tiotropium and ipratropium block airway M3 receptors.
Theophylline has a narrow therapeutic index and is cleared by CYP1A2, so ciprofloxacin can cause theophylline toxicity with seizures and arrhythmias.
Proton pump inhibitors irreversibly inhibit the parietal-cell H+/K+-ATPase; long-term use is linked to C. difficile infection, hypomagnesemia, vitamin B12 deficiency and fractures, and omeprazole reduces clopidogrel activation.
Ondansetron blocks 5-HT3 receptors and prolongs the QT interval; metoclopramide blocks D2 receptors and carries a boxed warning for tardive dyskinesia; loperamide abuse at high doses causes torsades de pointes.
12.3 Respiratory & Gastrointestinal Agents
The outline lists respiratory agents (bronchodilators, beta-2 agonists, leukotriene inhibitors, anticholinergics, steroids and biologics) and gastrointestinal agents (proton pump inhibitors, H2 blockers, antiemetics, motility agents and antidiarrheals). Podiatric surgeons manage patients with asthma and COPD, prescribe NSAIDs that need gastroprotection, treat postoperative nausea and constipation, and must recognize interactions with antibiotics.
Respiratory Agents
| Class | Examples | Mechanism | Key adverse effects and pearls |
|---|---|---|---|
| Short-acting beta-2 agonists | Albuterol, levalbuterol | Beta-2 (Gs) raises cAMP and relaxes airway smooth muscle | Tremor, tachycardia, hypokalemia (used to shift K+ into cells in hyperkalemia) |
| Long-acting beta-2 agonists | Salmeterol, formoterol | Same, with longer duration | Not used as monotherapy in asthma because of increased asthma-related deaths; paired with inhaled corticosteroids |
| Inhaled corticosteroids | Fluticasone, budesonide, beclomethasone | Suppress airway inflammation (NF-kB transrepression) | Oral candidiasis and dysphonia (rinse after use); high doses affect bone density |
| Systemic corticosteroids | Prednisone, methylprednisolone | Broad anti-inflammatory action | Hyperglycemia, infection, poor wound healing |
| Muscarinic antagonists | Ipratropium (short-acting), tiotropium and umeclidinium (long-acting) | Block airway M3 receptors | Dry mouth, urinary retention; mainstay of COPD therapy |
| Leukotriene modifiers | Montelukast, zafirlukast (CysLT1 receptor antagonists); zileuton (5-lipoxygenase inhibitor) | Block leukotriene-mediated bronchoconstriction | Montelukast boxed warning for neuropsychiatric events; zileuton hepatotoxicity |
| Methylxanthine | Theophylline | Phosphodiesterase inhibition and adenosine antagonism | Narrow therapeutic index; cleared by CYP1A2, so ciprofloxacin and cimetidine cause toxicity (seizures, arrhythmias) |
| PDE4 inhibitor | Roflumilast | Raises cAMP in inflammatory cells | Weight loss, diarrhea; severe COPD with chronic bronchitis |
| Biologics | Omalizumab (anti-IgE); mepolizumab, reslizumab (anti-IL-5); benralizumab (anti-IL-5 receptor); dupilumab (anti-IL-4 receptor alpha); tezepelumab (anti-TSLP) | Target Th2 and eosinophilic inflammation | Severe asthma phenotypes; injection reactions; anaphylaxis risk with omalizumab |
Asthma and COPD strategy. For adolescents and adults, international asthma guidance no longer recommends short-acting beta-agonist treatment alone. It prefers as-needed low-dose inhaled corticosteroid-formoterol as the reliever, with daily controller therapy added by severity. COPD therapy centers on long-acting bronchodilators (LAMA and/or LABA). Inhaled corticosteroids are added mainly for frequent exacerbations with higher blood eosinophil counts.
Perioperative point. Patients with asthma should bring their reliever inhaler. Non-selective beta-blockers can precipitate bronchospasm (10.3), and some patients with aspirin-exacerbated respiratory disease develop bronchospasm with any COX-1-inhibiting NSAID.
Gastrointestinal Agents
Acid Suppression and Mucosal Protection
| Drug | Mechanism | Key points |
|---|---|---|
| Proton pump inhibitors (omeprazole, pantoprazole, esomeprazole) | Prodrugs activated in the acid canaliculus that irreversibly bind the H+/K+-ATPase | Take 30–60 minutes before breakfast; long-term risks include C. difficile infection, hypomagnesemia, vitamin B12 deficiency, fracture risk and acute interstitial nephritis; omeprazole and esomeprazole inhibit CYP2C19, reducing clopidogrel activation |
| H2 receptor antagonists (famotidine, cimetidine) | Block parietal cell H2 receptors | Cimetidine inhibits several CYP enzymes and has antiandrogenic effects; ranitidine was withdrawn in 2020 because of NDMA contamination |
| Antacids (calcium carbonate, magnesium and aluminum hydroxide) | Neutralize acid | Chelate fluoroquinolones and tetracyclines; magnesium causes diarrhea, aluminum causes constipation |
| Sucralfate | Forms a protective barrier over ulcer bases in acid | Binds fluoroquinolones and other drugs |
| Misoprostol | PGE1 analog; increases mucus and bicarbonate, reduces acid | Prevents NSAID ulcers; contraindicated in pregnancy (uterine contractions) |
NSAID gastroprotection. Patients at higher GI risk (older age, prior ulcer, anticoagulants or steroids) who need an NSAID should take a PPI or misoprostol, or use a COX-2-selective agent with its cardiovascular trade-offs (11.3).
Antiemetics
| Class | Examples | Adverse effects |
|---|---|---|
| 5-HT3 antagonists | Ondansetron, granisetron | QT prolongation, headache, constipation |
| D2 antagonists | Metoclopramide, prochlorperazine, promethazine | Extrapyramidal effects; metoclopramide carries a boxed warning for tardive dyskinesia with long-term use; IV promethazine can cause severe tissue injury and gangrene with extravasation or intra-arterial injection |
| NK1 antagonists | Aprepitant, fosaprepitant | CYP3A4 interactions |
| Corticosteroid | Dexamethasone | Transient hyperglycemia, which matters in diabetic surgical patients |
| Anticholinergic | Transdermal scopolamine | Confusion and urinary retention in older adults |
| Cannabinoids | Dronabinol, nabilone | Used for chemotherapy-induced nausea (12.5) |
Postoperative nausea prevention often combines drugs from different classes.
Motility, Laxatives and Opioid-Induced Constipation
- Prokinetics: metoclopramide (D2 blockade with 5-HT4 effects) and erythromycin (motilin receptor agonist) speed gastric emptying in diabetic gastroparesis.
- Laxatives: osmotic (polyethylene glycol, lactulose), stimulant (senna, bisacodyl) and stool softeners (docusate). Prescribe a bowel regimen with every postoperative opioid, because no tolerance develops to opioid constipation (11.3).
- Peripherally acting mu-opioid antagonists: methylnaltrexone, naloxegol and naldemedine reverse opioid-induced constipation without reversing analgesia, because they do not cross the blood-brain barrier.
Antidiarrheals
- Loperamide: a peripheral mu-opioid agonist. Very high doses (misuse) cause QT prolongation and torsades de pointes.
- Diphenoxylate-atropine: atropine is added to discourage abuse.
- Bismuth subsalicylate: causes black stool and tongue; it contains salicylate, which matters with anticoagulants and aspirin allergy.
- Avoid antimotility drugs in suspected C. difficile colitis or bloody infectious diarrhea, because slowing transit can worsen toxin-mediated disease.
A patient with COPD maintained on theophylline is given ciprofloxacin for osteomyelitis. Five days later she has vomiting, tachycardia and a generalized seizure. What explains this?
Ciprofloxacin displaces theophylline from alpha-1 acid glycoprotein without changing clearance
Ciprofloxacin induces CYP3A4, converting theophylline to a convulsant metabolite
Ciprofloxacin inhibits CYP1A2, reducing theophylline clearance into the toxic range
Ciprofloxacin chelates theophylline in the gut, causing withdrawal seizures
A patient on long-term omeprazole after a coronary stent is now taking clopidogrel. What is the main pharmacologic concern with this combination?
Omeprazole induces CYP2C19, producing excess active metabolite and bleeding
Omeprazole chelates clopidogrel in the stomach, preventing its absorption
Omeprazole irreversibly inhibits platelet COX-1, doubling the bleeding risk
Omeprazole inhibits CYP2C19, reducing clopidogrel's conversion to its active form
Which antiemetic is most likely to cause tardive dyskinesia with prolonged use?
Metoclopramide
Transdermal scopolamine
Ondansetron
Aprepitant
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