Medical Pharmacology Topics   

Preliminary Outline

Vasodilators (2 of 3)   Angina      Nitrates          Nitroglycerine          Isosorbide Dinitrate          Erythrityl Tetranitrate          Pentaerythritol              Tetranitrate   Angina and Hypertension      Ca+2 Channel  Blockers          Verapamil          Diltiazem          Nifedipine          Nimodipine          Cinnarizine          Bepridil

Ischemic Heart Disease

Ischemic heart disease (angina pectoris) results in pain due to obstruction of coronary arteries. The heart is not getting an adequate supply of oxygen, especially during excretion. Treatment involves three objectives: dilating coronary vessels, redistributing the heart's blood flow  and reducing the heart's oxygen demand. It is difficult to increase blood flow through obstructed arteries even when vasodilating, therefore treatment may concentrate in redistribution of blood flow. Altering the coronary vascular resistance to change blood flow is the only way to increase oxygen supply. By reducing venous return to the heart, ventricular volume and pressure are reduced, and oxygen demand is decreased.

Nitrates are selective venodilatorts (are converted to NO). Veins dilate maximally with very little doses. Arterial dilation begins at low doses and increases with increasing dosage. Resistance vessels require higher doses before they dilate. At higher concentrations, when arterial vasodilation occurs, patients may experience increased heart rate, dizziness and headache. The main drug in this group is nitroglycerine. Nitrates with longer duration of action than nitroglycerine include inscribed Dinitrate, Erythrityl Tetranitrate, and pentaerythritol tetranitrate.

Nitroglycerin is very lipid soluble and may be administered sublingual, oral, IV or transdermal. Sublingual administration prevents the loss to first-pass metabolism that occurs when taken orally, and provides fast absorption (zero order kinetics) for the relief of acute attacks. Dermal application provides sustained release (also zero-order absorption) to prevent attacks during the night. Nitroglycerin is broken down into inactive metabolites. Isosorbide dinitrate is broken down into active metabolites, one of them longer lasting than the parent compound.

Calcium channel blockers prevent the influx of calcium into smooth muscle and its binding to calmodulin. The Ca2+-calmodulin complex alllows phosphorylation of myosin, resulting in muscle contraction. Calcium blockers are classified into four types.

Type I calcium blockers like verapamil and diltiazen have balanced myocardial, electrophysiologic and vascular effects. They also have active metabolites. Verapamil is a nonselective vasodilator which decreases heart rate, contractility and node activity (SA and AV). Diltiazen vasodilates coronary vessels more selectively.

Type II calcium blockers have predominantly vascular effects and include nifedipine, nimodipine, nitrendipine, felidipine and amlodipine. Nifedipine ia a selective vasodilator for peripheral and coronary vessels, and it increases both heart rate and contractility de to reflex. Nimodipine selectively vasodilates cerebral vessels.

Type III are markedly selective for vascular effects (cinnarizine and flunarizine). Type IV have complex pharmacological profiles (bepridil, perhexiline).

Continue to "Cardiac Failure" or take a quiz: [Q1].

Need more practice? Answer the review questions below.

Questions coming soon