USMLE (Fach) / Pharmacology - Respiratory (Lektion)
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- Histamine-1 blockers Reversible inhibitors of H1 histamine receptors. First generation: Diphenhydramine, dimenhydrinate, chlorpheniramine ("-en/-ine" or "-en/-ate")- Clinical use: Allergy, motion sickness, sleep aid- Adverse effects: Sedation, antimuscarinic, anti-α-adrenergic Second generation: Loratadine, fexofenadine, desloratadine, cetirizine ("-adine)- Clinical use: Allergy- Adverse effects: Less sedating than 1st generation because of ↓ entry into CNS
- Guaifenesin Expectorant – thins respiratory secretions; does not suppress cough reflex.
- N-acetylcysteine Mucolytic – liquifies mucus in chronic bronchopulmonary diseases (eg, COPD, CF) by disrupting disulfide bonds. Also used as an antidote for acetaminophen (paracetamol) overdose.
- Dextromethorphan Antitussive (antagonizes NMDA glutamate receptors). - Synthetic codeine analog.- Has mild opioid effect when used in excess. - Mild abuse potential. - Nalaxone can be given for overdose. Adverse effects:- Dissociative symptoms- Hallucinations- May cause serotonin syndrome if combined with other serotonergic agents.
- Pseudoephedrine, phenylephrine α-adrenergic agonists, used as nasal decongestants. Clinical use: Reduce hyperemia, edema, nasal congestion; open obstructed eustachian tubes. Adverse effects: Hypertension. Rebound congestion if used more than 4-6 days. Can also cause CNS stimulation/anxiety (pseudoephedrine).
- Pulmonary hypertension drugs Endothelin receptor antagonists (Bosentan): - Competitively antagonizes endothelin-1 receptors → ↓ pulmonary vascular resistance.- Heptatotoxic (monitor LFTs) PDE-5 inhibitors (Sidenafil):- Inhibits PDE-5 → ↑ cGMP → prolonged vasodilatory effect of nitric oxide.- Also used to treat erectile dysfunction.- Contraindicated when taking nitroglycerin or other nitrates. Prostacyclin analogs (Epoprostenol, iloprost):- PGI2 (prostacyclin) with direct vasodilatory effects on pulmonary and systemic arterial vascular beds. Inhibits platelet aggregation.- Side effects: flushing, jaw pain
- β2-agonists Albuterol – relaxes bronchial smooth muscle (short acting β2-agonist). Used during acute exacerbation. Salmeterol, formoterol – long-acting agents for prophylaxis. Adverse effects are tremor and arrhythmia.
- Inhaled corticosteroids Fluticasone, budesonide – inhibit the synthesis of virtually all cytokines. Inactivate NF-κB, the transcription factor that induces production of TNF-α and other inflammatory agents. 1st-line therapy for chronic asthma. Use spacer or rinse mouth after use to prevent oral thrush.
- Muscarinic antagonists Tiotropium, ipratropium – competitively block muscarinic receptors, preventing bronchoconstriction. - Also used for COPD. - Tiotropium is long acting.
- Zileuton 5-lipoxygenase pathway inhibitor. Blocks conversion of arachidonic acid to leukotriens. Hepatotoxic.
- Omalizumab Anti-IgE monoclonal therapy.Binds mostly unbound serum IgE and blocks binding to FcεRI. Used in allergic asthma with ↑ IgE levels resistant to inhaled steroids and long-acting β2-agonists.
- Methylxanthines Theophylline – likely causes bronchodilation by inhibiting phosphodiesterase → ↑ cAMP levels due to ↓ cAMP hydrolysis. Usage is limited because of narrow therapeutic index (cardiotoxicity, neurotoxicity). - Metabolized by cytochrome P-450. - Blocks actions of adenosine.
- Methacholine Nonselective muscarinic receptor (M3) agonist. Used in bronchial challenge test to help diagnose asthma.
- Diphenhydramine First generation histamine-1 blocker
- Dimenhydrinate First generation histamine-1 blocker
- Loratadine Second generation histamine-1 blocker
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- Montelukast, zafirlukast Block leukotriene receptors (CysLT1). Especially good for aspirin-induced and exercise-induced asthma.
- Fexofenadine Second generation histamine-1 blocker
- Desloratadine Second generation histamine-1 blocker
- Cetirizine Second generation histamine-1 blocker
- Mast cell stabilizers Cromolyn, nedocromil – prevent release of inflammatory mediators from mast cells. Used for prevention of bronchospasm, not for acute bronchodilation.
- Chlorpheniramine First generation histamine-1 blocker
- Nedocromil Mast cell stabilizer
- Cromolyn Mast cell stabilizer
- Promethazine Histamine-1 blocker
- Hydroxyzine Histamine-1 blocker