SN4 SHORT NOTE 5M

Describe the drugs used in pulmonary arterial hypertension.

Pharmacology · 2nd Professional — Para-Clinical

Definition

Pulmonary arterial hypertension is a mean pulmonary artery pressure above 20 mmHg at rest with a normal wedge pressure, caused by remodelling and vasoconstriction of the pulmonary arterioles.

The Three Pathways and Their Drugs

Pathway	Defect	Drugs	Notes
Nitric oxide – cGMP	Reduced nitric oxide	Phosphodiesterase-5 inhibitors — sildenafil, tadalafil; riociguat (guanylyl cyclase stimulator)	Oral; never with a nitrate; riociguat must not be combined with a PDE-5 inhibitor
Endothelin	Excess endothelin-1, a potent vasoconstrictor and mitogen	Endothelin receptor antagonists — bosentan, ambrisentan, macitentan	Hepatotoxic (bosentan especially) and teratogenic; monthly liver tests and pregnancy prevention are mandatory
Prostacyclin	Reduced prostacyclin	Epoprostenol (continuous intravenous), iloprost (inhaled), treprostinil, selexipag (oral)	Most effective in severe disease; epoprostenol has a half-life of minutes and abrupt interruption can be fatal

CLINICAL PEARL

These drugs treat pulmonary arterial hypertension and are harmful in pulmonary hypertension due to left heart or lung disease. Dilating the pulmonary bed when the problem is a failing left ventricle simply drives more blood into congested lungs; and in lung disease it abolishes hypoxic vasoconstriction, worsening ventilation–perfusion mismatch. The classification decides the treatment.

General Measures and Supportive Treatment

Calcium channel blockers in high dose benefit only the small minority who are vasoreactive on formal testing; given to others they cause harm
Anticoagulation, diuretics for right heart failure, oxygen for hypoxaemia, and treatment of the underlying cause
Avoid pregnancy — maternal mortality is very high, and effective contraception is essential
Digoxin may help right ventricular function and rate control where atrial arrhythmia complicates the picture
Vaccination against influenza and pneumococcus, since respiratory infection is poorly tolerated
Supervised exercise training improves capacity and quality of life, and is no longer discouraged as it once was
Lung or heart–lung transplantation remains the final option for those who progress despite maximal medical treatment

Applied Aspects

In India, rheumatic mitral stenosis and untreated congenital shunts remain major causes, and both are potentially correctable — so the priority is diagnosis rather than vasodilator therapy
Sildenafil is the most accessible and affordable agent, and is widely used where the newer drugs are unaffordable
Never prescribe a nitrate to a patient on a PDE-5 inhibitor; ask directly, since patients often do not mention it
Bosentan requires monthly liver function testing and reliable contraception; it also reduces the efficacy of hormonal contraceptives by enzyme induction, so a second method is needed
Right heart failure, not the pressure itself, determines prognosis, and is what treatment is ultimately aimed at
Combination therapy is now standard in moderate to severe disease, targeting two or three pathways at once rather than escalating a single agent
Six-minute walk distance and functional class are the practical measures of response, and are used to guide escalation
Diagnosis requires right heart catheterisation — echocardiography estimates the pressure but cannot distinguish arterial from post-capillary causes, and treating on echocardiography alone risks giving these drugs to the wrong patient
Chronic thromboembolic pulmonary hypertension is potentially curable by pulmonary endarterectomy, and must be excluded before committing a patient to lifelong drug therapy

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