Nitrates myocardial infarction

The nitrates are used cautiously in patients witii severe hepatic or renal disease, severe head trauma, acute myocardial infarction (MI), hypotiiyroidism, and during pregnancy (Pregnancy Category C, except for amyl nitrate) or lactation. 

The lack of tolerance has been explained by the fact that the N O-release from these compounds is spontaneous and independent of the presence of thiols [124], that, by contrast, may be an essential cofactor in the action of the nitrate. Martorana et al. [125] showed a marked antiischemic effect of Pirsidomine in a dog model of myocardial infarction. 

Chest pain that is not relieved by two or three tablets within 30 minutes may be due to an acute myocardial infarction. In addition, nitrate administration may result in an increase in intracranial pressure, and therefore, these drugs should be used cautiously in patients with cerebral bleeding and head trauma. 

PHOSPHODIESTERASE TYPE 5 INHIBITORS NITRATES Risk of severe 1 BP and precipitation of myocardial infarction Additive effect Avoid co-administration... 

Sildenafil is contraindicated in patients who are taking organic nitrates, for their metabolism is blocked and severe and acute hypotension result. Patients with recent stroke or myocardial infarction or whose blood pressure is known to be < 90/50 mmHg should not use it. Sildenafil is a substrate for the P450 isoenzyme CYP3A4 (and to a lesser extent CYP2C9) which gives scope for interaction with inhibitors or inducers of this system. The metabolic inhibitors erythromycin, saquinavir and ritonavir (protease inhibitors used for AIDS), and cimetidine, for example, produce substantial rises in the plasma concentration of sildenafil. 

Unstable angma.The chance of myocardial infarction is high and aspirin should be used with other drugs, i.c. a [i-adrcnoceptor antagonist,a nitrate.a calcium channel blocker and possibly heparin i.v. as is judged appropriate. 

A 59-year-old woman with a previous myocardial infarction, hypertension, diabetes, and uterine cancer developed angina. She was treated with nitrates,... 

Nitrates can precipitate myocardial infarction in susceptible patients (32), and occasionally worsen myocardial infarction, producing asystole (33) or ventricular fibrillation (34,35), possibly due to coronary steal or reperfusion of ischemic myocardium. 

It has been convincingly shown that a nitrate-free period reduces nitrate tolerance (72). The modem strategy is to have a nitrate-free period when the patient is asleep, although this results in reduced protection from ischemia in the early morning, the time when many episodes of silent ischemia and myocardial infarction occur. Reports that ACE inhibitors (73) or carvedilol (74) reduce nitrate tolerance are as yet unconfirmed (75). 

The problems that can complicate the use of nitrates in patients with acute myocardial infarction, severe coronary atherosclerosis, and prior cerebrovascular disease have already been stressed. Hypotension, reflex tachycardia, or bradycardia can all be hazardous in individual patients. 

Although meta-analysis of studies in acute myocardial infarction suggested that nitrates protect against death and reinfarction (88), the ISIS-4 study found no such protection for 1 month after infarction (89). However, this study did show that nitrates are relatively safe in suspected myocardial infarction, even though 14% of patients who received nitrates had heart failure. Compared with placebo-treated patients there was an excess of hypotension considered severe enough to withdraw the drug in 15 per 1000 patients in about half the cases it occurred soon after the start of treatment. The excess risk for headache was 18.7 per 1000 and of dizziness 1.6 per 1000, 0.8 per 1000 being associated with profound hypotension. 

Flaherty JT. 1992. Role of nitrates in acute myocardial infarction. Am. J. Cardiol. 70 73B-81... 

M. Hill, H. Takano, X.-L. Tang, E. Kodani, G. Shirk, R. Bolli, Nitroglycerin induces late preconditioning against myocardial infarction in conscious rabbits despite development of nitrate tolerance, Circulation 104, 694-699 (2001). 

Chronic stable angina should be managed initially with /S-blockers because they provide better symptomatic con-trol at least as well as nitrates or calcium channel blockers and decrease the risk of recurrent myocardial infarction (Ml) and CAD mortality. 

Phosphodiesterase 5 (PDE5) is found in blood vessels supplying the corpora cavernosa. Sildenafil inhibits PDE 5 - T cGMP -> vasodilation - T blood flow ->T erectile response. If used concomitantly with nitrates or other potent vasodilators, the excessive fall in blood pressure may lead to death from cardiovascular causes, including myocardial infarct. 

Ishikawa K, Yamamoto T, Kanamasa K, et al Intermittent nitrate therapy for prior myocardial infarction... 

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