Figure 171

Proposed mechanism by which nitroglycerin and the organic nitrates produce relaxation in vascular smooth muscle. Nitrates induce endothelial cells to release NO or a nitrosothiol (endothelium-derived releasing factor, or EDRF). EDRF activates the enzyme guanylate cyclase, which causes the generation of cyclic guanosine monophosphate (GMP), producing a decrease in cytosolic free calcium. The end result is vascular smooth muscle relaxation. SH, sulfhydryl.

sublingually or by spray, is estimated to be 1 to 3 minutes. Isosorbide dinitrate and pentaerythritol tetranitrate also can be administered sublingually or buccally. These compounds have a slower onset and slightly longer duration of action than sublingually or buccally administered nitroglycerin.

Nitroglycerin and other organic nitrate esters undergo first-pass metabolism and are rapidly metabolized in the liver by the enzyme glutathione organic nitrate reductase. Although the metabolites of nitro-glycerin are virtually inactive as vasodilators, two metabolites of isosorbide dinitrate, isosorbide 2-mononitrate and isosorbide 5-mononitrate, do retain some vasodilator and antianginal activity. Isosorbide mononitrate can be administered orally and does not undergo any first-pass metabolism. The latter esters and their metabolites are water soluble and are readily excreted by the kidney.

Relaxation Audio Sounds Autumn In The Forest

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