Hypotension with nitrates

Isordil is a proprietary (trade name) preparation of isosorbide dinitrate, a nitrate. Sildenafil, the active ingredient of Viagra, interacts with nitrates and the two active ingredients should not be administered concurrently, as a significant hypotensive effect may occur. 

Flypersensitivity to any component of the tablet administration with nitrates (either regularly and/or intermittently) and nitric oxide donors because of the potentiation of hypotension (see Drug Interactions) coadministration with alpha-blockers (vardenafil only) coadministration with alpha-blockers other than 0.4 mg/day tamsulosin (tadalafil only). 

NITRATES ANTI PARKINSON S DRUGS-APOMORPHINE Risk of postural -l BP when apomorphine is given with nitrates Additive effect apomorphine can cause postural 1 BP Monitor BP at least weekly until stable. Warn patients to report symptoms of hypotension (light-headedness, dizziness on standing, etc.)... 

The combination of organic nitrates and sildenafil citrate (Viagra) can precipitate life-threatening hypotension in patients with angina (112). Sildenafil is a selective inhibitor of cyclic GMP-specific phosphodiesterase type 5, which causes smooth muscle relaxation and vasodilatation, and is an effective treatment for male erectile dysfunction. More than 3.6 million prescriptions have been issued as of August 1998, and so far there have been 69 deaths, 12 of which were attributable to the interaction with nitrates, as reported to the FDA. 

Many potential agents of chemical warfare have little to no direct injurious effect on the kidney or urinary system, but instead may cause indirect renal injury and/ or urinary dysfunction. Nitrate esters used as explosives can cause profound hypotension with the potential to result in renal ischemia secondary to decreased renal perfusion (Gahagan and Wismer, 2012). Metabolic acidosis, proteinuria, glucosuria, and myoglobinuria were reported in a survey of five human cases of cydonite... 

Verapamil may cause an additive hypotensive effect when administered with other antihypertensives, alcohol, or the nitrates. Verapamil increases plasma digoxin levels and may cause bradycardia or CHF. 

The nitrate antianginal drug all have the same adverse reactions, although the intensify of some reactions may vary with the drug and the dose. A common adverse reaction seen with diese drug is headache, especially early in therapy. Hypotension, dizziness, vertigo, and weakness may also be associated with headache. Flushing caused by dilatation of small capillaries near the surface of the skin may also be seen. 

The thiazide diuretics are used cautiously in patients with liver or kidney disease, lupus erythematosus (may exacerbate or activate the disease), or diabetes. Additive hypotensive effects occur when the thiazides are given with alcohol, other antihypertensive drugp, or nitrates. 

Common adverse effects of nitrates include postural hypotension, flushing, and headache secondary to venodilation. Headache often resolves with continued therapy and may be treated with acetaminophen. Hypotension is generally... 

The combination of nitrates and hydralazine improves the composite endpoint of mortality, hospitalizations for HF, and quality of life in African Americans who receive standard therapy. A fixed-dose combination product is available that contains ISDN 20 mg and hydralazine 37.5 mg (BiDil). Practice guidelines recommend adding ISDN and hydralazine as part of standard therapy in African Americans with moderately severe to severe HF. The combination may also be reasonable for patients of other ethnicities with persistent symptoms despite optimized therapy with an ACE inhibitor (or ARB) and /Tblocker. The combination is also appropriate as first-line therapy in patients unable to tolerate ACE inhibitors or ARBs because of renal insufficiency, hyperkalemia, or possibly hypotension. 

Sildenafil and vardenafil decrease systolic/diastolic blood pressure by 8 to 10/5 to 6 mm Hg for 1 to 4 hours after a dose. Although most patients are asymptomatic, multiple antihypertensives, nitrates, and baseline hypotension increase the risk of developing adverse effects. Although tadalafil does not decrease blood pressure, it should be used with caution in patients with cardiovascular disease because of the inherent risk associated with sexual activity. 

Many other changes make older adults more vulnerable regarding cardiovascular drugs. There is a decrease in baroreceptor reflex response. This may explain the increased sensitivity to nitrates (Marchionni et al. 1990). With age there is a loss of blood vessel distensibility and enhanced intimal thickness. This can partly explain the increase of systolic blood pressure. Aging is also associated with a reduction in baroreflex-mediated heart rate response to hypotensive stimuli (Verhaeverbeke and Mets 1997, Lakatta and Levy 2003). 

As noted under Mechanisms of Toxicity (Section 4.2), nitrate and nitrite esters are vasodilators with resulting hypotension (Nickerson 1975). Therapeutic doses of nitroglycerin for relief of angina are associated with headaches of vascular origin. Both PGDN and the structurally related ethylene glycol dinitrate produce headaches in humans and methemoglobinemia and hypotension in rats (Andersen and Mehl 1979). 

Anesthetized dogs given 50-250mg/kg intravenously immediately showed hypotension, arrest of gut activity, respiratory paralysis, hyperpnea, and moderate methemoglobinemia. Because death was produced with methe-moglobin levels of only 4%, -propyl nitrate intoxication may be caused in part by a direct action on vascular smooth muscle. (It has been noted that the oral toxicity of -propyl nitrate is very low compared with intravenously administered doses, in which mg/kg doses were lethal versus g/kg orally. )... 

CHF associated with acute Ml treatment of angina pectoris unresponsive to organic nitrates or -blockers production of controlled hypotension during surgical procedures. 

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. 

Severe hypotension Severe hypotension, particularly with upright posture, may occur with small doses of nitrates. 

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