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HY points followed by a quiz at the end
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Bosentan
MOA of bosentan?
- Endothelin 1 receptor antagonist.
- Endothelin is a vasoconstrictor of pulmonary vessels.
- Bosentan is used to treat pulmonary hypertension –> decreased vasoconstriction of pulmonary vasculature.
- One of the highest yield drugs on the Step 1 NBME forms.
When is endothelin increased?
- In any situation where there is increased pulmonary capillary pressure. This includes:
- Any cause of pulmonary hypertension (i.e., primary pulmonary hypertension due to BMPR2 mutation; COPD; CF; systemic sclerosis).
- Cor pulmonale (right heart failure due to a pulmonary cause).
- Drugs causing pulmonary fibrosis, including methotrexate, amiodarone, bleomycin, busulfan.
- Left heart failure (due to increased pulmonary capillary wedge pressure, which means increased pulmonary capillary hydrostatic pressure).
How will the USMLE ask about it?
- 68M + lateralized apex beat + S3 heart sound + systemic hypertension; which of the following would be expected in this patient? –> answer = up arrow for endothelin; up arrow for beta-myosin gene transcription (due to left ventricular hypertrophy); up arrow for c-jun (a transcription factor, because of left ventricular hypertrophy).
- Patient has dilated cardiomyopathy secondary to HTN –> increased left-sided heart pressure –> increased left atrial pressure –> increased pulmonary capillary wedge pressure (since LAP = PCWP) –> increased pulmonary vascular pressure means constriction of pulmonary vessels (mediated by endothelin).
- 32F + non-smoker + 6-month Hx of worsening dyspnea + loud pulmonary component of S2 (loud P2); which of the following is most likely associated with her condition? –> answer = “increased endothelin activity.”
- Patient has primary pulmonary hypertension (genetic; usually due to BMPR2 mutations); will present as young adult with pulmonary hypertension who’s a non-smoker.
- If you know that bosentan treats pulmonary hypertension by increasing the diameter of the vasculature, then you can infer that in pulmonary hypertension, where the vasculature is more constricted, endothelin must be higher.
- Loud P2 means pulmonary hypertension –> pulmonic valve is slamming shut due to increased pressure distal to the valve.
Epoprostenol, iloprost
MOA of epoprostenol and iloprost?
- PGI2 analogues (prostacyclin).
When are they used?
- Pulmonary hypertension.
- Should be noted that dihydropyridine calcium channel blockers, such as nifedipine, are actually first-line for most cases of pulmonary hypertension. Patients non-responsive to calcium channel blockers are trialed on other agents such as bosentan, PGI2 analogues, and sildenafil (yes, Viagra; it’s a phosphodiesterase 5 inhibitor –> increases cGMP –> vasodilation).
Pseudoephedrine, ephedrine
MOA of pseudoephedrine, ephedrine?
- Various; but main one is alpha-adrenergic receptor agonism.
When are they used?
- Nasal congestion
- Prevention of barotrauma in scuba divers (opens Eustachian tubes) –> weird, but a detail that’s associated with these drugs.
Guaifenesin
- Expectorant –> thins bronchial secretions –> facilitates coughing up mucous.
Dextromethorphan
- Mu-opoid receptor agonist
- Used for cough suppression
- Low addictive potential
- Can cause constipation
Dornase alfa (correct, not alpha)
- Recombinant human deoxyribonuclease –> cleaves nucleic acids in bronchial mucous –> thins mucous in patients with cystic fibrosis.
N-acetylcysteine
- Used as the antidote for acetaminophen toxicity.
- Also can be used to thin bronchial secretions by disrupting disulfide bonds.
- Cysteine has a thiol (-SH) side-group that can bind to -S–S- and break open the bonds.
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