Nitrate drugs (nitroglycerin and isosorbide), often used to treat angina, commonly cause headaches. The mechanism of the headaches is believed to be vasodilation of the cerebral arteries.
Nitrate drugs cause direct relaxation of arterial and venous smooth muscle. Venodilation predominates at therapeutic doses, which reduces preload (at higher doses, it reduces afterload). Arteriodilation begins at high doses and can produce hypotension and a reflex tachycardia. Nitrates may be given lingually (spray pump), sublingually, intrabuccally, orally, topically, or by IV infusion.
Pflieger et al. discuss the management of stable coronary artery disease (CAD). CAD is defined as an established pattern of angina pectoris, a history of myocardial infarction, or the presence of plaque documented by catheterization. Anginal symptoms of CAD can be treated with beta blockers, calcium channel blockers, nitrates, or any combination of these.
Heidenreich et al. conducted a meta-analysis comparing the relative efficacy and tolerability of treatment for stable angina with beta-blockers, calcium antagonists, and long-acting nitrates. Beta-blockers provided similar clinical outcomes and were associated with fewer adverse events than calcium antagonists in randomized trials of patients with stable angina. Too few trials compared nitrates with calcium antagonists or beta-blockers to draw firm conclusions about relative efficacy.
Illustration A depicts the mechanism of action of nitroglycerin. Following administration, nitroglycerin may induce vasorelaxation both directly, via the local formation of NO, and indirectly, via its interaction with vasoactive substances released from nerve terminals.
Answer 1: Transient ischemic attacks generally present with aphasia, vision changes, hemiparesis, or parasthesias. Headaches are an unusual presenting sign.
Answer 2: An elevated creatinine kinase is not associated with treatment of angina or headache. It is associated with use of statin therapy.
Answer 3: Beta adrenergic inactivation is not associated with headache.
Answer 4: An acute intracranial hemorrhage may present with headache but this would not be related to treatment of angina.
Pflieger M, Winslow BT, Mills K, Dauber IM. Medical management of stable coronary artery disease. Am Fam Physician. 2011 Apr 1;83(7):819-26. Review. PubMed PMID: 21524048.
PMID:21524048 (Link to Abstract)
Heidenreich PA, McDonald KM, Hastie T, Fadel B, Hagan V, Lee BK, Hlatky MA. Meta-analysis of trials comparing beta-blockers, calcium antagonists, and nitrates for stable angina. JAMA. 1999 May 26;281(20):1927-36. PubMed PMID: 10349897.
PMID:10349897 (Link to Abstract)