Vasodilators nitrates

Synonym isoamyl nitrite Trade names Amyl Nitrite Nitrit Indications Angina pectoris Category Nitrate Vasodilator Half-life N/A... 

Indications Acute angina Category Nitrate Vasodilator Half-life 1 4 minutes... 

Erectile dysfunction is a frequently encountered problem whose risk factors parallel those of coronary artery disease (CAD). Thus many men desiring therapy for erectile dysfunction already may be receiving (or may require, especially if they increase physical activity) antianginal therapy. The combination of sildenafil and other phosphodiesterase 5 (PDE5) inhibitors with orgaific nitrate vasodilators can cause extreme hypotension. 

The acute adverse effects of the organic nitrates as well as molsidomine are directly related to their therapeutic vasodilation as they can cause orthostatic hypotension, tachycardia and throbbing headache. 

Vasodilators are a group of dtugs, which relax the smooth muscle cells of the blood vessels and lead to an increased local tissue blood flow, a reduced arterial pressure and a reduced central venous pressure. Vasodilators reduce the cardiac pre-load as well as after-load and thereby reduce cardiac work. They are used in a variety of conditions including hypertension, cardiac failure and treatment/prevention of angina pectoris. Major groups are Ca2+-channel blockers (e.g. dihydropyridines), NO-donators (e.g. organic nitrates), K+-channel openers (minoxidil), phosphodiesterase inhibitors (e.g. sildenafil), Rho-kinase inhibitors (e.g. Y27632) or substances with unknown mechanism of action (e.g. hydralazine). Inhibitors of the... 

The toxicity of IPN is evaluated by Ref 6 as follows (a) When inhaled as a vapor or adsorbed thru the skin, IPN acts as a vasodilator and produces a headache in the same manner as other organic nitrates (b) When injected subcutaneously into rats at the rate of 4cc/kg body wt, it was concluded that the max allowable concn is lOOppm and (c) When rats were exposed to different concn levels of IPN in air the following resulted ... 

Nitrates (e.g., ISDN) and hydralazine were combined originally in the treatment of HF because of their complementary hemodynamic actions. Nitrates are primarily venodilators, producing reductions in preload. Hydralazine is a direct vasodilator that acts predominantly on arterial smooth muscle to reduce systemic vascular resistance (SVR) and increase stroke volume and cardiac output. Evidence also suggests that the combination may provide additional benefits by interfering with the biochemical processes associated with HF progression. 

In their studies of the flavoprotein inhibitor, DPI, Bennett and colleagues [91, 120] found that DPI inhibited GTN-induced accumulation of cGMP to the same extent in aortae from naive and from GTN-tolerant animals. They argued that, if inactivation of flavoproteins is a major cause of tolerance, then there should be less scope for further, DPI-induced inactivation in tolerant animals, compared with naive ones. Their conclusion, accordingly, was that, while flavoproteins may participate in biotransformation of organic nitrates and associated vasodilation, their alteration cannot be the basis for nitrate tolerance. 

Needleman, P., Blehm, D J., Rotskoff, K. S., Relationship between glutathione-dependent denitration and the vasodilator effectiveness of organic nitrates. J. Pharmacol. Exp. Then 237 (1969), p. 296-288... 

A number of organic nitrates are potent vasodilators and have been used clinically for over lOOyears, particularly for the relief of the symptoms of angina (Fig. 8.6). The most widely used is glyceryl trinitrate (GTN) but the group includes pentaerythrityl tetranitrate (PETN), isosorbide mononitrate (ISMO) andisosorbide dinitrate (ISDN). 

Because of the high pH required for this process and the poor vasodilator properties of nitrite, this process cannot explain the biological action of organic nitrates. There are two problems in the use of organic nitrates as vasodilators 1. the conditions necessary for the biotransformation that converts an organic nitrate into NO, and 2. the phenomenon of tolerance. The two may be linked. 

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