Pulmonary+Hypertension

=**The Pharmacologic Treatment of Pulmonary Hypertension**=

__**Pulmonary Arterial Pressure**__ Pulmonary arterial pressure is generated by the right ventricle ejecting blood into the pulmonary circulation, which acts as a resistance to the output from the right ventricle. With each ejection of blood (ventricular systole), the pulmonary artery blood volume increases, which stretches the wall of the artery. As the heart relaxes (ventricular diastole), blood continues to flow from the pulmonary artery into the pulmonary circulation. The smaller arteries and arterioles serve as the chief resistance vessels, and through changes in their diameter, regulate pulmonary vascular resistance. In hemodynamic terms, the mean pulmonary arterial pressure (PAP) can be described by //Equation 1:// **PAP = (CO x PVR) + PVP** where CO =cardiac output, PVR= pulmonary vascular resistance, and PVP = pulmonary venous pressure. The PVP is essentially the same as left atrial pressure. Therefore, increases in CO, PVR or PVP will lead to increases in PAP. Normally, mean pulmonary artery pressure is about 15 mmHg, and the pulmonary artery systolic and diastolic pressures about about 25 and 10 mmHg, respectively. Pulmonary venous pressure is about 8 mmHg. Therefore, the pressure gradient driving flow through the pulmonary circulation is rather small at about 7 mmHg (mean pulmonary arterial minus venous pressures). This is a much lower driving pressure than the systemic circulation where the arterial-venous pressure gradient is about 90 mmHg. Although the blood flow through the pulmonary circulation is essentially the same as the blood flow through the systemic circulation, the pulmonary vascular resistance is ten- to fifteen-fold lower than the systemic vascular resistance, and this explains why the mean pulmonary artery pressure is relatively low.
 * **Pulmonary Arterial Pressure**
 * **Pulmonary Artery Hypertension - Types and Causes**
 * **Rationale for Pharmacologic Treatment**
 * **Drugs Used to Treat Pulmonary Hypertension**

__**Pulmonary Artery Hypertension - Types and Causes**__ Pulmonary artery hypertension (PAH) is defined as a mean pulmonary artery pressure greater than 25 mmHg at rest, or greater than 30 mmHg during exercise. PAH is classified as either primary PAH or secondary PAH. Primary PAH has no known precipitating cause (i.e., it is idiopathic) and appears to be hereditary in some individuals. This is a progressive disease that has a poor prognosis and no known cure. Secondary PAH results from an identifiable cause or condition. The most common cause of secondary PAH is chronic obstructive pulmonary disease. Chronic hypoxia associated with this condition results in pulmonary vasoconstriction (hypoxic vasoconstriction). Other causes include obstructive sleep apnea, congenital heart disease, pulmonary thrombosis (blood clots), or left ventricular failure. Hemodynamically, pulmonary hypertension can be caused by increased right ventricular output, increased pulmonary systemic vascular resistance, or increased pulmonary venous pressure. Because the pulmonary vasculature is normally very compliant, large increases in right ventricular output does not normally cause PAH. However, if the pulmonary vasculature loses its compliance due to disease, then increased right ventricular output can lead to PAH during exercise, for example. Most individuals with primary or secondary PAH have increased pulmonary vascular resistance, which can be caused by structural changes in the vasculature or by increased smooth contraction. Patients who have left ventricular systolic or diastolic failure, or who have severe mitral valve stenosis or regurgitation, can also have secondary pulmonary hypertension because of an increase in pulmonary venous pressure.

__**Rationale for Pharmacologic Treatment**__ If the PAH has an identifiable cause, then measures can be taken to correct the underlying problem. If the diagnosis is primary PAH, or treating the cause of the secondary PAH does not restore normal pulmonary artery pressure, then pharmacologic intervention is required to reduce the pressure. This is done by using vasodilator drugs to decrease pulmonary vascular resistance and thereby lower the pressure. Adjunctive therapy may include **diuretics** to reduce blood volume, which will reduce central venous pressure and right ventricular stroke volume, as well as reduce some of the signs and symptoms of edema and shortness of breath associated with PAH. Anticoagulants are administered to prevent the formation of pulmonary thrombi. Patients with primary hypertension are generally treated with drugs that reduce blood volume (which reduces central venous pressure and cardiac output), reduce systemic vascular resistance, or reduce cardiac output by depressing heart rate and stroke volume. Patients with secondary hypertension are best treated by controlling or removing the underlying disease or pathology, although they may still require antihypertensive drugs.

__**Drugs Used to Treat Pulmonary Hypertension**__ Classes of drugs used in the treatment of PAH are listed below. Clicking on the drug class will link you to the page describing the pharmacology of that drug class. > > - endothelin receptor antagonists > - cGMP phosphodiesterase inhibitors > * under clinical investigation >
 * Diuretics
 * - thiazide diuretics
 * - loop diuretics
 * Vasodilators-
 * calcium-channel blockers
 * - prostaglandins
 * - nitric oxide*