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2016 ; 30
(4
): 367-378
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Vasodilator Therapy: Nitrates and Nicorandil
#MMPMID27311574
Tarkin JM
; Kaski JC
Cardiovasc Drugs Ther
2016[Aug]; 30
(4
): 367-378
PMID27311574
show ga
Nitrates have been used to treat symptoms of chronic stable angina for over
135 years. These drugs are known to activate nitric oxide (NO)-cyclic
guanosine-3',-5'-monophasphate (cGMP) signaling pathways underlying vascular
smooth muscle cell relaxation, albeit many questions relating to how nitrates
work at the cellular level remain unanswered. Physiologically, the anti-angina
effects of nitrates are mostly due to peripheral venous dilatation leading to
reduction in preload and therefore left ventricular wall stress, and, to a lesser
extent, epicardial coronary artery dilatation and lowering of systemic blood
pressure. By counteracting ischemic mechanisms, short-acting nitrates offer rapid
relief following an angina attack. Long-acting nitrates, used commonly for angina
prophylaxis are recommended second-line, after beta-blockers and calcium channel
antagonists. Nicorandil is a balanced vasodilator that acts as both NO donor and
arterial K(+) ATP channel opener. Nicorandil might also exhibit cardioprotective
properties via mitochondrial ischemic preconditioning. While nitrates and
nicorandil are effective pharmacological agents for prevention of angina
symptoms, when prescribing these drugs it is important to consider that unwanted
and poorly tolerated hemodynamic side-effects such as headache and orthostatic
hypotension can often occur owing to systemic vasodilatation. It is also
necessary to ensure that a dosing regime is followed that avoids nitrate
tolerance, which not only results in loss of drug efficacy, but might also cause
endothelial dysfunction and increase long-term cardiovascular risk. Here we
provide an update on the pharmacological management of chronic stable angina
using nitrates and nicorandil.