Glyceryl trinitrate adverse effects

In a randomized, open, parallel-group study of the hemodynamic effects of milrinone and glyceryl trinitrate in 119 patients with advanced decompensated heart failure, milrinone was significantly more effective than glyceryl trinitrate (7). Adverse effects caused the withdrawal of milrinone in three of the 58 patients who took it one had ventricular extra beats, one had renal insufficiency, and one had hypokalemia. Headache was the most common adverse effect in both groups, but was less common in those who took milrinone (12 versus 29%). 

Organic nitrates have been in use for over 135 years, and their adverse effects are therefore weU documented. The first compound of this class to be used was amyl nitrite, synthesized in 1844 by Ballard and used to treat angina pectoris by Brunton in 1869. Glyceryl trinitrate was first synthesized by Ascagne Sobrero in 1847 and was used by William Murrell to treat angina pectoris in 1879. 

High-dose transdermal glyceryl trinitrate 50-100 mg given over a period of 12 hours each day for 3 months improved exercise tolerance and left ventricular systolic function in 29 patients with congestive heart failure taking a long-term ACE inhibitor (17). The most frequent adverse effects were skin irritation at the site of patch application and headache, which caused premature glyceryl trinitrate withdrawal in three patients. 

The adverse effects of the nitrates are unaffected by the chemical form or by the route of administration. The spectrum and frequency of adverse effects for the individual drugs, such as glyceryl trinitrate, isosorbide dinitrate, and isosorbide-5-mononitrate, appear to be similar. 

Hypotension is a frequent adverse effect of nitrates (24), resulting from dilatation of arteries and veins. It can be associated with reflex tachycardia and palpitation, and even syncope on assuming an upright posture. Hypotension occurs particularly in old people, especially those with recurrent falls (SEDA-16, 196), and more commonly with glyceryl trinitrate oral spray than with sublingual tablets, because of its faster onset of action (24). It tends to occur more commonly in those who take nitrates infrequently. 

A dramatic rise in plasma glyceryl trinitrate concentrations occurred after exercise in healthy subjects following transdermal administration (92). This altered systemic availability could cause adverse effects. 

Drug formulations Nitrates are often prescribed for Raynaud s phenomenon, but their use is limited by adverse effects such as headache, dizziness, and skin irritation. A new gel formulation of glyceryl trinitrate (MQX-503) has been tested in 219 patients with Raynaud s phenomenon, in a doubleblind, randomized, placebo-controlled trial. MQX-503 was significantly more effective than placebo, and had comparable adverse effects [26 ]. 

---