Nitrates long acting

Calcium antagonists or long-acting nitrates for reduction of symptoms when (3-blockers are contraindicated... 

Calcium antagonists or long-acting nitrates in combination with /3-blockers when initial treatment with /3-blockers is unsuccessful... 

Ca2+ channel blocker, long-acting nitrate therapy... 

This hypothesis clearly contradicted a large body of clinical evidence that nitrates were effective. Some years later, using more sensitive and reliable analytical methods, this interpretation was shown to be incorrect, and the clinical utility of long-acting, oral organic nitrate derivatives affirmed. In 1967, one of the pharmacodynamically active metabolites of ISDN, IS-5N, was shown to be formed in vivo, and shortly thereafter it was introduced as a novel long-acting NO donor with improved bioavailability. 

Ml In acute Ml, use nitrates only under close clinical observation and with hemodynamic monitoring. In general, do not use a long-acting form because its effects are difficult to terminate rapidly if excessive hypotension or tachycardia develop. 

Nitrates are required for symptomatic relief of chest pain they are not proven to improve hard outcomes such as MI or death. Nitrates should be given initially sublingually or by spray, followed by oral or transdermal routes if pain is relieved. Lack of pain relief mandates i.v. administration. Beta-blockers such as metoprolol are used and may reduce the risk of subsequent MI. Calcium channel blockers such as dilfiazem, verapamil, or long-acting di-hydropyridines can be added for symptom control if nitrates and beta-blockers do not suffice they do not improve outcomes. In fact, they may worsen outcomes in the presence of left ventricular dysfunction or CHF in acute coronary syndrome. 

Nitroglycerin will be effective for on-going chest pain relief. Ca channel antagonists and long-acting Nitrates can be used when jS-blockers are contraindicated. These drugs may be also used for the initial therapy, additional to -blockers or when jS-blockers treatment failed. However, for the effectiveness of vasodilatation itself is relatively weaker evidence. 

When coronary vasospasm occurs, the balance between oxygen supply and demand can be restored by relieving the spasm, thereby restoring normal coronary blood flow. Acute vasospasm has been successfully aborted through the use of nitroglycerin. In contrast, calcium entry blockers and long-acting nitrates have proved effective in the chronic therapy of coronary vasospasm. 

Traditional long-term anti-ischaemic triple therapy for coronary artery disease consists of a long-acting nitrate, p-adrenoceptor antagonist and a calcium-entry blocker. Most of these agents are also used for the treatment of hypertension. 

The indirect effects of nitroglycerin consist of those compensatory responses evoked by baroreceptors and hormonal mechanisms responding to decreased arterial pressure (see Figure 6-7) this often results in tachycardia and increased cardiac contractility. Retention of salt and water may also be significant, especially with intermediate- and long-acting nitrates. These compensatory responses contribute to the development of tolerance. 

With continuous exposure to nitrates, isolated smooth muscle may develop complete tolerance (tachyphylaxis), and the intact human becomes progressively more tolerant when long-acting preparations (oral, transdermal) or continuous intravenous infusions are used for more than a few hours without interruption. 

Isosorbide Mononitrate This drug is another long-acting nitrate that is similar in structure and function to isosorbide dinitrate. It is typically given orally for prevention of anginal attacks. 

The mechanisms by which tolerance develops are not completely understood. As noted above, diminished release of nitric oxide may be partly responsible for tolerance to nitroglycerin. Systemic compensation also plays a role in tolerance in the intact human. Initially, significant sympathetic discharge occurs and after one or more days of therapy with long-acting nitrates, retention of salt and water may reverse the favorable hemodynamic changes normally caused by nitroglycerin. 

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