Pulmonary Pharmacology · Medications for Lung Diseases

💊 Pulmonary Pharmacology Current Medications in Lung Diseases · Medical Student Reference

1. Obstructive Lung Diseases (COPD & Asthma)

Bronchodilators

Class	Drugs	Mechanism	Clinical Use	Adverse Effects
SABA (Short‑acting β₂ agonist)	Albuterol (salbutamol), Levalbuterol	β₂‑adrenergic receptor agonist → ↑ cAMP → bronchodilation	Rescue inhaler for asthma/COPD exacerbations	Tachycardia, tremor, hypokalemia
LABA (Long‑acting β₂ agonist)	Salmeterol, Formoterol, Vilanterol, Olodaterol	Same as SABA; longer duration (12‑24h)	Maintenance therapy for asthma (with ICS) and COPD	Same as SABA; never use as monotherapy in asthma (↑ mortality)
SAMA (Short‑acting muscarinic antagonist)	Ipratropium	Blocks M3 receptors → ↓ cGMP → bronchodilation	COPD exacerbation; sometimes added to SABA in severe asthma	Dry mouth, urinary retention (rare with inhaled)
LAMA (Long‑acting muscarinic antagonist)	Tiotropium, Umeclidinium, Aclidinium, Glycopyrrolate	Same as SAMA; 24‑h duration	First‑line maintenance for COPD; add‑on in severe asthma	Dry mouth, caution in narrow‑angle glaucoma
Methylxanthines	Theophylline, Aminophylline	Phosphodiesterase inhibition (↑ cAMP), adenosine antagonist	Rarely used (refractory COPD/asthma)	Narrow therapeutic index: seizures, arrhythmias, nausea

Anti‑Inflammatory Agents

Class	Drugs	Mechanism	Clinical Use	Key Points
Inhaled Corticosteroids (ICS)	Fluticasone, Budesonide, Beclomethasone, Mometasone, Ciclesonide	Binds glucocorticoid receptor → ↓ inflammatory gene transcription	First‑line controller for persistent asthma; COPD with frequent exacerbations	Local: oral candidiasis, dysphonia. Systemic effects minimal at standard doses.
Systemic Corticosteroids	Prednisone, Methylprednisolone	Same as ICS, systemic effect	Acute asthma/COPD exacerbations; severe refractory disease	Short course (5‑7 days). Long‑term: osteoporosis, diabetes, adrenal suppression.
Leukotriene Receptor Antagonists (LTRA)	Montelukast, Zafirlukast	Blocks CysLT₁ receptor → ↓ bronchoconstriction, inflammation	Mild persistent asthma, exercise‑induced asthma, allergic rhinitis	Well tolerated. FDA black box warning: neuropsychiatric events (rare).
5‑Lipoxygenase Inhibitor	Zileuton	Inhibits leukotriene synthesis	Asthma (rarely used)	Hepatotoxicity, CYP interactions.
Mast Cell Stabilizers	Cromolyn, Nedocromil	Prevents mast cell degranulation	Prophylaxis for exercise/allergen‑induced asthma	Very safe, but less effective than ICS.

Biologics for Severe Asthma

Drug	Target	Indication	Notes
Omalizumab	Anti‑IgE	Moderate‑severe allergic asthma	SC injection q2‑4 weeks; risk of anaphylaxis
Mepolizumab, Reslizumab	Anti‑IL‑5	Severe eosinophilic asthma	Reduces exacerbations; lowers eosinophil count
Benralizumab	Anti‑IL‑5Rα	Severe eosinophilic asthma	Depletes eosinophils via ADCC
Dupilumab	Anti‑IL‑4Rα	Moderate‑severe asthma, atopic dermatitis, nasal polyps	Blocks IL‑4/IL‑13 signaling; can cause eosinophilia
Tezepelumab	Anti‑TSLP	Severe asthma (broad phenotype)	Blocks upstream alarmin; effective regardless of eosinophils

💡 GINA Stepwise Therapy (Asthma):
Step 1: PRN low‑dose ICS‑formoterol (or SABA).
Step 2: Low‑dose ICS daily.
Step 3: Low‑dose ICS‑LABA.
Step 4: Medium‑dose ICS‑LABA.
Step 5: Add‑on LAMA, biologics, or high‑dose ICS‑LABA.

💡 GOLD Guidelines (COPD): LAMA or LABA initial; dual LAMA/LABA for persistent symptoms; ICS added if eosinophils ≥300 or frequent exacerbations. Triple therapy (LAMA/LABA/ICS) for frequent exacerbators.

2. Restrictive Lung Diseases (ILD / Pulmonary Fibrosis)

Drug	Mechanism	Indication	Adverse Effects / Monitoring
Pirfenidone	Antifibrotic; inhibits TGF‑β, reduces fibroblast proliferation	Idiopathic Pulmonary Fibrosis (IPF)	GI upset, photosensitivity, LFT elevation
Nintedanib	Tyrosine kinase inhibitor (VEGFR, FGFR, PDGFR)	IPF, systemic sclerosis‑ILD, progressive fibrosing ILD	Diarrhea, nausea, LFT elevation, bleeding risk
Corticosteroids	Anti‑inflammatory / immunosuppressive	Sarcoidosis, hypersensitivity pneumonitis, COP, CTD‑ILD	Long‑term toxicity; taper to lowest effective dose
Immunosuppressants (Azathioprine, Mycophenolate, Methotrexate, Cyclophosphamide)	Various; steroid‑sparing agents	CTD‑ILD, sarcoidosis, refractory HP	Myelosuppression, hepatotoxicity, infection risk
Biologics (Infliximab, Adalimumab, Rituximab)	Anti‑TNF, anti‑CD20	Refractory sarcoidosis, CTD‑ILD	Infection, infusion reactions

3. Pulmonary Infections

Community‑Acquired Pneumonia (CAP) – Empiric Therapy

Setting	Regimen	Coverage
Outpatient, no comorbidities	Amoxicillin OR Doxycycline OR Macrolide (if low resistance)	S. pneumoniae, atypicals
Outpatient, with comorbidities	Amoxicillin‑clavulanate + macrolide OR Respiratory fluoroquinolone (Levofloxacin, Moxifloxacin)	S. pneumoniae, H. influenzae, atypicals
Inpatient, non‑severe	β‑lactam (Ceftriaxone, Cefotaxime) + Macrolide OR Respiratory FQ	Broad CAP coverage
Inpatient, severe (ICU)	β‑lactam + Macrolide OR β‑lactam + Respiratory FQ	Add MRSA coverage (Vancomycin) if risk factors

Tuberculosis (TB)

First‑line (RIPE): Rifampin, Isoniazid, Pyrazinamide, Ethambutol (2 months), then Rifampin + Isoniazid (4 months).
Latent TB: Isoniazid for 9 months OR Rifampin for 4 months OR Isoniazid + Rifapentine weekly for 3 months (3HP).

Drug	Mechanism	Major Adverse Effects
Isoniazid (INH)	Inhibits mycolic acid synthesis	Hepatotoxicity, peripheral neuropathy (give pyridoxine/B6), lupus‑like syndrome
Rifampin	Inhibits RNA polymerase	Orange body fluids, hepatotoxicity, potent CYP inducer (drug interactions!)
Pyrazinamide (PZA)	Unknown (requires acidic pH)	Hepatotoxicity, hyperuricemia (gout)
Ethambutol	Inhibits arabinosyl transferase	Optic neuritis (color blindness, visual acuity ↓) — reversible if caught early

💡 RIPE monitoring: Rifampin (LFTs, CYP), INH (LFTs, B6), PZA (LFTs, uric acid), Ethambutol (visual acuity, color vision).

Fungal Pneumonia & Opportunistic Infections

Pneumocystis jirovecii (PJP): TMP‑SMX (first‑line). Alternatives: Pentamidine, Atovaquone, Clindamycin + Primaquine. Add corticosteroids if PaO₂ <70 mmHg or A‑a gradient >35.
Aspergillus: Voriconazole (first‑line), Isavuconazole, Liposomal Amphotericin B.
Histoplasma / Blastomyces / Coccidioides: Itraconazole (mild‑moderate), Amphotericin B (severe).

4. Pulmonary Hypertension (PAH)

Pathway	Drug Class	Examples	Notes
Nitric Oxide / cGMP	PDE5 inhibitors Soluble guanylate cyclase stimulators	Sildenafil, Tadalafil Riociguat	Contraindicated with nitrates. Riociguat also for CTEPH.
Endothelin pathway	Endothelin receptor antagonists (ERA)	Bosentan, Ambrisentan, Macitentan	Hepatotoxicity (bosentan), fluid retention, teratogenic (monthly pregnancy test).
Prostacyclin pathway	Prostacyclin analogs / IP receptor agonists	Epoprostenol (IV), Treprostinil (IV/SC/inhaled/PO), Iloprost (inhaled), Selexipag (oral)	Most potent vasodilators. Epoprostenol requires continuous infusion.

⚠️ Vasoreactivity Testing: Inhaled nitric oxide or IV epoprostenol during right heart catheterization. Only positive responders (rare) get calcium channel blockers (Nifedipine, Diltiazem, Amlodipine). Never use CCB empirically in PAH — can worsen RV failure.

5. Other Pulmonary Medications

Antitussives & Mucolytics

Dextromethorphan: Centrally acting antitussive (NMDA antagonist).
Benzonatate: Local anesthetic on stretch receptors.
Guaifenesin: Expectorant; increases respiratory tract fluid.
N‑acetylcysteine (NAC): Mucolytic (breaks disulfide bonds in mucus). Also used for acetaminophen overdose.
Dornase alfa (Pulmozyme): Recombinant DNase; breaks down DNA in thick mucus. Indicated in cystic fibrosis.

Smoking Cessation

Drug	Mechanism	Notes
Nicotine Replacement Therapy (NRT)	Partial nicotinic agonist (reduces craving)	Patch, gum, lozenge, inhaler, nasal spray
Varenicline	Partial nicotinic acetylcholine receptor agonist	Most effective oral agent; monitor for neuropsychiatric symptoms (rare)
Bupropion	Norepinephrine/dopamine reuptake inhibitor; nicotinic antagonist	Also antidepressant; contraindicated in seizure disorder

Pleurodesis Agents

Talc slurry / poudrage: Most effective for malignant pleural effusion or recurrent pneumothorax.
Doxycycline, Bleomycin: Alternative sclerosing agents.

6. High‑Yield Drug Interactions & Safety Pearls

Drug / Class	Interaction / Caution
Rifampin	Potent CYP inducer → ↓ efficacy of OCPs, warfarin, antiretrovirals, antifungals, immunosuppressants.
Macrolides (Azithromycin, Clarithromycin)	CYP3A4 inhibitors → ↑ levels of statins, warfarin, colchicine. Clarithromycin much stronger inhibitor than azithromycin.
Fluoroquinolones	QTc prolongation. Tendon rupture risk. Avoid with divalent cations (Ca, Mg, Al, Fe) — separate by 2‑4 hours.
LABA monotherapy in asthma	Without ICS, ↑ risk of asthma‑related death. Always combine LABA with ICS in asthma.
Beta‑blockers	Non‑selective (propranolol) can worsen bronchospasm. Use cardioselective (metoprolol, atenolol) with caution.
NSAIDs / Aspirin	Avoid in aspirin‑exacerbated respiratory disease (AERD / Samter's triad: asthma, nasal polyps, aspirin sensitivity).
PDE5 inhibitors + Nitrates	Profound hypotension — absolute contraindication.

7. Quick Reference: Drug Classes by Disease

Asthma

SABA (rescue)
ICS (controller)
ICS/LABA (maintenance)
LTRA (add‑on)
LAMA (severe)
Biologics (severe)
Systemic steroids (exacerbation)

COPD

SABA/SAMA (rescue)
LAMA or LABA (maintenance)
LAMA/LABA dual
ICS/LABA/LAMA triple
Roflumilast (PDE4 inhibitor, severe with chronic bronchitis)
Azithromycin (prophylaxis, select patients)

IPF / ILD

Pirfenidone
Nintedanib
Corticosteroids (inflammatory ILD)
Immunosuppressants

PAH

ERA (Bosentan, Ambrisentan, Macitentan)
PDE5i (Sildenafil, Tadalafil)
sGC stimulator (Riociguat)
Prostacyclins (Epoprostenol, Treprostinil, Selexipag)
CCB (only if vasoreactive)

💊 Pulmonary Pharmacology Reference — Updated with current guidelines (GOLD 2024, GINA 2024, ATS/ERS).
Covers bronchodilators, anti‑inflammatories, antimicrobials, PAH therapies, and essential drug interactions.