Eisenmenger Syndrome Medication
- Author: Mikhael F El-Chami, MD; Chief Editor: Park W Willis IV, MD more...
The medical treatment of Eisenmenger syndrome is directed toward the improvement of symptoms related to heart failure and pulmonary hypertension and the prevention and management of complications related to cyanotic congenital heart disease.
A partial list of medications used in the management of Eisenmenger syndrome includes aspirin, to prevent thrombotic complications; allopurinol, for gout; iron supplementation, for microcytosis; and digitalis and diuretics, for symptoms of heart failure.
These agents are useful to remove fluid and reduce preload and afterload in the treatment of heart failure.
Furosemide increases the excretion of water by interfering with the chloride-binding cotransport system; this, in turn, inhibits sodium and chloride reabsorption in the ascending loop of Henle and distal renal tubule.
The dose of furosemide must be individualized to the patient. Depending on response, administer the medication at increments of 20-40 mg, with each dose provided no sooner than 6-8 hours after the previous dose, until the desired diuresis occurs. When treating infants, titrate with 1-mg/kg/dose increments until a satisfactory effect is achieved.
The positive inotropic and negative chronotropic effects of these agents are useful in the setting of left or right heart failure. Cardiac glycosides are used to enhance cardiac contractility as an adjunct to treating congestive heart failure. They are used to augment the function of the failing right ventricle.
Digoxin is a cardiac glycoside with direct inotropic effects, as well as indirect effects, on the cardiovascular system. It acts directly on cardiac muscle, increasing myocardial systolic contractions. Its indirect actions result in increased carotid sinus nerve activity and enhanced sympathetic withdrawal for any given increase in mean arterial pressure.
These drugs can be effective in reversing reactive pulmonary vasoconstriction and can, therefore, lower pulmonary vascular resistance, decrease afterload, reduce the right ventricle, and reduce right-to-left shunting. In some patients, chronic prostacyclin analogue therapy (epoprostenol) can be of benefit, particularly as a bridge to heart-lung transplantation.
Epoprostenol is a strong vasodilator of all vascular beds. It may decrease thrombogenesis and platelet clumping in the lungs by inhibiting platelet aggregation.
Continuous intravenous infusion of the drug can be carried out via a permanent, indwelling central venous catheter, using a small, battery-powered infusion pump worn at the hip or carried in a backpack.
Initiate administration of epoprostenol under close observation in the intensive care unit (ICU), with a right heart flotation catheter in place
Iloprost is a synthetic analogue of prostacyclin PGI2 that dilates systemic and pulmonary arterial vascular beds. It is indicated for pulmonary arterial hypertension (WHO Class I) in patients with NYHA Class III or IV symptoms to improve exercise tolerance and symptoms and to delay deterioration.
Recurrent phlebotomy for erythrocytosis can lead to microcytic anemia. Iron stores should be replaced if the deficiency is symptomatic and the hematocrit is below 65%.
Iron is a nutritionally essential inorganic substance.
These agents are indicated for symptomatic secondary gout.
Colchicine decreases leukocyte motility and phagocytosis in inflammatory responses.
These agents competitively bind to endothelin-1 (ET-1) receptors ETA and ETB in endothelium and vascular smooth muscle, inhibiting vessel constriction and elevation of blood pressure.
Bosentan is an endothelin receptor antagonist indicated for the treatment of pulmonary arterial hypertension (PAH) in patients with WHO class III or IV symptoms. It is used to improve exercise ability and decrease the rate of clinical worsening.
Bosentan inhibits vessel constriction and elevation of blood pressure by competitively binding to ET-1 receptors ETA and ETB in the endothelium and vascular smooth muscle. This leads to a significant increase in the cardiac index associated with a significant reduction in pulmonary artery pressure, pulmonary vascular resistance (PVR), and mean right atrial pressure. Due to its teratogenic potential, bosentan can be prescribed only through the Tracleer Access Program (1-866-228-3546).
Ambrisentan is an endothelin receptor antagonist indicated for PAH in patients with WHO class II or III symptoms. It improves exercise ability and decreases the progression of clinical symptoms.
Ambrisentan inhibits vessel constriction and blood pressure elevation by competitively binding to endothelin-1 receptors ETA and ETB in the endothelium and vascular smooth muscle. This leads to a significant increase in the cardiac index associated with a significant reduction in pulmonary artery pressure, PVR, and mean right atrial pressure.
Because of the risks of hepatic injury and the drug's teratogenic potential, ambrisentan is available only through the Letairis Education and Access Program (LEAP). Prescribers and pharmacies must register with LEAP in order to prescribe and dispense this drug. For more information, see http://www.letairis.com or call (866) 664-LEAP (5327).
Phosphodiesterase-5 Enzyme Inhibitors
The antiproliferative effects of the phosphodiesterase type-5 (PDE5) pathway, which regulates cyclic guanosine monophosphate hydrolysis, may be significant in the chronic treatment of pulmonary hypertension with PDE5 inhibitors such as sildenafil. These agents act synergistically with nitric oxide to promote smooth muscle relaxation.
Sildenafil promotes selective smooth muscle relaxation in the lung vasculature, possibly by inhibiting PDE5. The inhibition of PDE5 increases cyclic guanosine monophosphate (cGMP) activity, which increases the vasodilatory effects of nitric oxide. Nitric oxide is a powerful, naturally produced vasodilator used clinically as an inhaled agent.
Tadalafil is a PDE5 selective inhibitor. Inhibition of PDE5 increases cGMP activity, which increases the vasodilatory effects of nitric oxide. Tadalafil promotes selective smooth muscle relaxation in the lung vasculature, possibly by inhibiting PDE5.
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