ASK DIS: Nitrates: Management of Headache

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Headache

most common adverse effects are headache (up to 57%) and dizziness (up to 11%), light-headedness (1% to 10%)
Treatment with isosorbide mononitrate may be associated with light-headedness on standing, especially just after rising from a recumbent or seated position. This effect may be more frequent in patients who have also consumed alcohol
present results therefore suggest that NO may elicit a migraine attack in many healthy subjects if a high enough dose is given for several hours.
A close temporal association between the disappearance of headache and the attenuation of the 5-ISMN induced dilatation of the superficial temporal artery was observed.
In contrast, tolerance in the middle cerebral artery already appeared after 24 h, which was earlier than the development of tolerance to headache.
If vasodilatation is the cause of headache the results point to extracerebral arteries.
However, cytotoxic and pain modulating central nervous system effects of NO, the time courses of which are unknown, may also play a role, involving both intra- and extracranial arteries

Management

In patients who get these headaches, the headaches are a marker of the activity of the drug.
Patients should resist the temptation to avoid headaches by altering the schedule of their treatment with isosorbide mononitrate, since loss of headache may be associated with simultaneous loss of antianginal efficacy.
Aspirin or acetaminophen often successfully relieves isosorbide mononitrate-induced headaches with no deleterious effect on isosorbide mononitrate's antianginal efficacy.
headaches may gradually become less severe as you continue to use isosorbide mononitrate
To reduce the risk of headache, your doctor may suggest starting with one-half tablet (30 mg) once daily each morning for the first 2 to 4 days.

Alternatives

not much evidence available on alternative agents
Calcium channel blockers are an alternative if there are side effects or other conditions that limit the use of beta blockers and nitrates.
Calcium channel blockers may also be used if nitrates and beta blockers do not control angina when used in combination
Diltiazem dilates blood vessels (especially coronary arteries), decreases the heart's force of contraction, and slows the heart's conduction of electrical impulses.
When compared to dihydropyridines and verapamil, diltiazem has a lower frequency of side effects and has a more balanced effect, neither markedly dilating blood vessels nor markedly depressing cardiac function.
dihydropyridine calcium channel blockers and, in some cases, diltiazem can be used in combination with beta blockers for better control of angina. Verapamil, however, is usually not combined with beta blockers because combining the two drugs can markedly slow the heart rate.
Beta blockers are more effective than calcium channel blockers for reducing the frequency of angina, but similar in terms of improving exercise tolerance and decreasing the need for nitroglycerin.

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