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.

Coping with Asthma

Coping with Asthma

If you suffer with asthma, you will no doubt be familiar with the uncomfortable sensations as your bronchial tubes begin to narrow and your muscles around them start to tighten. A sticky mucus known as phlegm begins to produce and increase within your bronchial tubes and you begin to wheeze, cough and struggle to breathe.

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