33.2 Respiratory Pharmacology: Cough and Colds, Allergic Rhinitis, Asthma (Controllers, Relievers, Exacerbations), COPD, Anti-TB Drugs, Antibiotics for Pneumonia and Bronchitis, and Lung Cancer Therapy

Why this area matters

The TOS respiratory area covers:

• cough and colds;
• allergic rhinitis;
• bronchial asthma;
• COPD;
• infections (pulmonary TB, pneumonia, bronchitis, pneumonitis);
• lung cancer.

Respiratory complaints are the most common reason for consultation in the Philippines. Misuse of antibiotics for colds and poor inhaler technique are frequent problems, so rational prescribing is tested.

Cough, colds and allergic rhinitis

• The common cold: viral and self-limited. Antibiotics do not help. Symptomatic options are:
  • paracetamol;
  • saline irrigation;
  • honey for children over 1 year;
  • decongestants (oral pseudoephedrine or phenylephrine; topical oxymetazoline for no more than 3 to 5 days, to avoid rhinitis medicamentosa). Avoid them in uncontrolled hypertension.
  • Over-the-counter cough and cold medicines are not recommended for young children, because of toxicity and little benefit.
• Antitussives:
  • dextromethorphan (NMDA antagonist; serotonergic interactions);
  • codeine (an opioid; avoided in children and in CYP2D6 ultrarapid metabolizers).
• Expectorants and mucolytics: guaifenesin, carbocisteine, ambroxol and N-acetylcysteine.
• Allergic rhinitis:
  • intranasal corticosteroids (fluticasone, mometasone, budesonide) are the most effective, especially for congestion;
  • second-generation H1 antihistamines (cetirizine, loratadine, fexofenadine) are less sedating than first-generation drugs (chlorphenamine, diphenhydramine), which are anticholinergic and sedating;
  • montelukast (neuropsychiatric warnings) and intranasal antihistamines are alternatives;
  • allergen immunotherapy is used for selected patients.

Asthma pharmacology

• Beta-2 agonists:
  • SABA (salbutamol): rapid relief;
  • LABA (salmeterol, formoterol; formoterol has a rapid onset);
  • adverse effects are tremor, tachycardia and hypokalemia;
  • LABAs must never be used without an inhaled corticosteroid because of increased asthma deaths.
• Inhaled corticosteroids (budesonide, fluticasone, beclomethasone): the controller of choice. Local effects are oral thrush and dysphonia (rinse the mouth, use a spacer). High doses have systemic effects.
• GINA (Global Initiative for Asthma) approach:
  • track 1 uses as-needed low-dose ICS-formoterol as the reliever at all steps, and ICS-formoterol as maintenance and reliever at higher steps;
  • track 2 uses SABA as the reliever with a daily ICS-containing controller;
  • SABA-only treatment is no longer recommended for adults and adolescents.
• Other drugs:
  • LAMA (tiotropium) as an add-on;
  • leukotriene receptor antagonists (montelukast), useful in aspirin-exacerbated and exercise-induced asthma;
  • theophylline, a phosphodiesterase inhibitor and adenosine antagonist with a narrow range (toxicity causes nausea, arrhythmias and seizures, and CYP1A2 inhibitors such as ciprofloxacin raise its level);
  • biologics (omalizumab, mepolizumab) for severe allergic or eosinophilic asthma.
• Acute exacerbation:
  • repeated SABA (by spacer or nebulizer) and ipratropium in severe attacks;
  • systemic corticosteroids early (prednisolone 40 to 50 mg for 5 to 7 days in adults);
  • oxygen to keep saturation at 93% to 95%;
  • IV magnesium sulfate for severe attacks;
  • avoid sedatives;
  • in life-threatening asthma, intubation is done by experts.
• Drugs that worsen asthma: beta-blockers, including eye drops, and aspirin and NSAIDs in aspirin-exacerbated respiratory disease.

COPD pharmacology

• Smoking cessation: the most effective intervention. Options are nicotine replacement, varenicline (a partial nicotinic agonist) and bupropion.
• Maintenance bronchodilators:
  • a LAMA (tiotropium) or LABA;
  • a LAMA plus LABA for more symptoms or exacerbations;
  • add an ICS only for frequent exacerbations, especially with blood eosinophils of 300/uL or more, because ICS increase pneumonia risk in COPD;
  • roflumilast (a PDE4 inhibitor) for chronic bronchitis with exacerbations;
  • long-term azithromycin for selected frequent exacerbators.
• Exacerbations:
  • SABA with or without ipratropium;
  • prednisone 40 mg for 5 days;
  • antibiotics when sputum purulence increases;
  • controlled oxygen (target 88% to 92%) to avoid CO2 retention;
  • non-invasive ventilation for hypercapnic respiratory failure.
• Vaccines: influenza and pneumococcal.
• Long-term oxygen for chronic hypoxemia improves survival.

Drugs for TB, pneumonia and bronchitis

• First-line anti-TB drugs:

• Drug-resistant TB uses bedaquiline (QT prolongation), linezolid (myelosuppression, neuropathy), fluoroquinolones and pretomanid, in all-oral regimens. Streptomycin (ototoxic and nephrotoxic) is no longer routine.
• Drug-induced hepatitis during TB treatment (ALT over 3 times normal with symptoms, or over 5 times without): stop the hepatotoxic drugs and reintroduce them one at a time when the liver recovers.
• Pneumonia:
  • Low-risk outpatient adults: amoxicillin, or a macrolide or doxycycline for atypical organisms. Use amoxicillin-clavulanate or a cephalosporin plus a macrolide with comorbidities.
  • Hospitalized patients: a beta-lactam (ceftriaxone, ampicillin-sulbactam) plus a macrolide, or a respiratory fluoroquinolone (levofloxacin, moxifloxacin).
  • Pseudomonas or MRSA risk: antipseudomonal beta-lactams and vancomycin or linezolid.
  • Aspiration: amoxicillin-clavulanate or clindamycin.
• Acute bronchitis is viral, so no antibiotics. Pertussis is the exception: macrolides.
• Pneumonitis:
  • drug-induced pneumonitis (amiodarone, methotrexate, nitrofurantoin, bleomycin): stop the drug and give steroids;
  • aspiration chemical pneumonitis: supportive care.

Lung cancer therapy

• Non-small cell lung cancer:
  • surgery for early stages;
  • chemoradiation (platinum doublets: cisplatin or carboplatin with pemetrexed, paclitaxel or gemcitabine) for locally advanced disease;
  • advanced disease is guided by molecular testing:
    • EGFR mutations, common in Asian non-smokers: osimertinib and other EGFR tyrosine kinase inhibitors (rash, diarrhea, interstitial lung disease);
    • ALK rearrangements: alectinib or crizotinib;
    • PD-L1-high tumors: immune checkpoint inhibitors (pembrolizumab), which cause immune-related adverse events (pneumonitis, colitis, hepatitis, thyroiditis) treated with steroids.
• Small cell lung cancer: platinum with etoposide, plus immunotherapy. It is very chemosensitive but relapses early.
• Platinum toxicities: cisplatin causes nephrotoxicity, ototoxicity, neuropathy and severe emesis (prevent with hydration and antiemetics). Carboplatin causes myelosuppression.