Vasodilators (organic nitrites and nitrates) Flashcards
Organic nitrites and nitrates - 4 drugs
Amyl nitrite
Nitroglycerin (glyceryl trinitrate)
Isosorbide dinitrate.
Isosorbide mononitrate.
Amyl nitrate - administration and onset
Adm inhalation - most rapid onset.
Amyl nitrate - indications
Treatment of acute angina.
Initial management of cyanide poisoning.
Amyl nitrate - MOA in cyanide poisoning
Oxidize hemoglobin to methemoglobin which traps cyanide. Cyanide may then be converted to inactive thiocyanate by administration of thiosulfate.
Nitroglycerin - adm and their indications
Sublingual
Oral - SR - prevent angina attacks (larger doses needed).
Transdermal - prevention of angina attacks.
IV - reduce preload in acute heart failure.
Topical - hospitalized pts with angina or MI.
Isosorbide dinitrate - adm and indicatinos
Oral/sublingual.
Prevention and treatment of angina attacks
Nitrates - MOA
Release of NO in vascular smooth muscle cause vasodilation (mainly venous). Activation of guanylyl cyclase and increased cGMP. Activation of kinases that phosphorylate proteins that decrease intracellular Ca mobilization and decrease phosphorylation of myosin light chains
Nitrates - cardiac effects
No direct cardiac effects.
Venous pooling –> decreased preload –> decreased ventricular volume, pressure and tension –> decreased cardiac output –> decreased BP.
All this reduces cardiac work and oxygen demand.
Nitrates - adverse effects
Dizziness Hypotension Reflex tachycardia Tolerance Headache
Nitrates - interactions
5-PGE inhibitors (sildenafil) - potentiated effect. Both increase cGMP and cause vasodilation.
Mechanism of nitrate tolerance
Free radicals after NO release inactivate aldehyde dehydrogenase.
How can we prevent reflex tachycardia of vasodilators?
Administration of β-blockers.
