Nitroglycerin effects

Peng 3, Li Y-3 New insights into nitroglycerin effects and tolerance Role of calcitonin gene-related peptide. Eur 3 Pharmacol 2008 586 9. [PMID 18367169]... 

Therapeutic opportunities for NO synthons include angina, for which nitroglycerin is effectively used, as well as penile erectile dysfunction. NOS inhibitors have demonstrated some protection in cerebral ischemia models and may be potentially beneficial in alleviating cell death associated with cerebral ischemia. l-NMA is under clinical study for treatment of sepsis. 

Isosorbide is rapidly absorbed and undergoes rapid first-pass metaboHsm by the Hver. The bioavaUabUity of the subHngual and chewable tablets is 59% and 22%, respectively, for the regular tablet. Isosorbide is metabolized to isosorbide-2-mononitrate and isosorbide-5-mononitrate, both of which have pharmacologic activity. The elimination half-Hves of subHngual and po isosorbide dinitrate ate 1 and 4 h, respectively. Those of the 2- and 5-mononitrate metaboHtes are 1.5—3.1 h and 4—5.6 h, respectively. The two metaboHtes prolong the elimination half-life of the dinitrate. Adverse effects with isosorbide are similar to those described for nitroglycerin (99). 

Erythrityl is readily absorbed from the GI tract. It undergoes extensive first-pass metaboHsm ia the Hver by glutathione organic nitrate reductase. Time to onset of effect is 5—10 min by subHngual adrninistration and 20—30 min when swallowed. The duration of effects for the two routes ate up to 3 and 6 h, respectively. Adverse effects are similar to those described for nitroglycerin (99). 

Other P"Adrenoceptor Blocking Agents. Carteolol hydrochloride (Table 1) is also a Class II antiarrhythmic agent. In three separate studies in patients having angina pectoris, carteolol was considered effective as evidenced by a reduction in the frequency and severity of anginal episodes, reduction in the amount of nitroglycerin consumed, improvement of ECG parameters, or an increase in the duration of trea dmill exercise (42). 

Each of the transdermal nitroglycerin systems is effective in treating angina pectoris when worn for 12—16 h followed by an off period. The FDA recommends the period without dmg (8—12 h) to mitigate the possibiUty of the patient acquiring a tolerance to the antianginal effects of nitrate therapy. Thus, a noncontinuous dosing schedule of nitrates is recommended even with the transdermal deflvery system (81). 

Nobel invented gelatinous dynamite in 1875 by accident. He investigated the effect of nitroglycerine on the collodion (nitrocellulose in a mixture of ether and alcohol) that he used to treat a cut finger and found that it produced a tough plastic material with adjustable viscosity and high water resistance. 

The nitrates, such as isosorbide (Isordil) and nitroglycerin, have a direct relaxing effect on die smooth muscle layer of blood vessels. The result of diis effect is an increase in the lumen of die artery or arteriole and an increase in the amount of blood flowing through diese vessels. An increased blood flow results in an increase in die oxygen supply to surrounding tissues. 

The nitrates are available in various forms (eg, sublingual, transmucosal, translingual spray, and inhalation). Some adverse reactions are a result of the metiiod of administration. For example, sublingual nitroglycerin may cause a local burning or tingling in the oral cavity. However, die patient must be aware that an absence of this effect does not indicate a decrease in the drug s potency. Contact dermatitis may occur from use of die transdermal delivery system. 

If die nitrates are administered witii the antihypertensives, alcohol, calcium channel blockers, or the phe-notiiiazines, there may be an increased hypotensive effect. When nitroglycerin is administered intravenously (IV), die effects of heparin may be decreased. Increased nitrate serum concentrations may occur when the nitrates are administered witii aspirin. 

Cyclic GMP is made from GTP by the enzyme gua-nylyl cyclase, which exists in soluble and membrane-bound forms. Each of these isozymes has unique physiologic properties. The atriopeptins, a family of peptides produced in cardiac atrial tissues, cause natriuresis, diuresis, vasodilation, and inhibition of aldosterone secretion. These peptides (eg, atrial natriuretic factor) bind to and activate the membrane-bound form of guanylyl cyclase. This results in an increase of cGMP by as much as 50-fold in some cases, and this is thought to mediate the effects mentioned above. Other evidence links cGMP to vasodilation. A series of compounds, including nitroprusside, nitroglycerin, nitric oxide, sodium nitrite, and sodium azide, all cause smooth muscle re-... 

Continuous infusions of nitroglycerin should be initiated at a dose of 5 to 10 mcg/minute and increased every 5 to 10 minutes until symptomatic or hemodynamic improvement. Effective doses range from 35 to 200 mcg/minute. The most common adverse events reported are headache, dose-related hypotension, and tachycardia. A limitation to nitroglycerin s use is the development of tachyphylaxis, or tolerance to its effects,... 

Nitroglycerin should not be stored in the same container as other medications since this may reduce nitroglycerin s effectiveness. 

Repeated use of nitroglycerin is not harmful or addictive and does not result in any long-term side effects. Patients should not hesitate to use nitroglycerin whenever needed. 

Control of exudation depends mainly on the suitable choice of the nitrocellulose used. Some lack of uniformity in this product is certainly desirable. This offers no serious difficulty, although it is necessary to ensure a constant watch on manufacturing processes to see that quality is maintained. In other gelatine explosives, particularly those containing ammonium nitrate, exudation can be induced by slow chemical reaction. The addition of alkalis, for example, can liberate ammonia which in turn can react with nitrocellulose and cause it to lose its power of binding nitroglycerine. Such effects are accelerated at high temperatures and under wet conditions and it is usual practice to test all explosives under such adverse conditions before they are put on the market. 

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