What kinds of nitrate therapy are available?

Nitroglycerin is available as a sublingual tablet or spray, a buccal preparation, long-acting oral tablets, topical preparations (ointment or patch) and intravenous preparations. Isosorbide dinitrate can be used sublingually or orally. 5-Isosorbide mononitrate is available for oral administration only.

What are the mechanisms of action of organic nitrates on the cellular level?

Organic nitrates act as prodrugs which must be converted inside vascular smooth muscle cells to nitric oxide. This conversion is accomplished by a reduction reaction using sulfhydryl groups from cysteine within the cytosol as follows:

N02 + 2 SH – NO + S=S + H20 (nitrate + cysteine ” nitric oxide)

Nitric oxide (NO) directly stimulates guanylate cyclase (GC), resulting in increased levels of intracellular cyclic GMP. GMP acts through phosphorylation of cellular proteins via protein kinases to decrease the availability of calcium to contractile proteins. This results in relaxation.

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