Nitrates Flashcards
What is the mechanism of action of nitrovasodilators?
Nitroglycerin, isosorbide mononitrate, and isosorbide dinitrate act as nitric oxide donors, increasing cGMP levels, leading to vascular smooth muscle relaxation and predominant venodilation.
How do nitrates improve angina symptoms?
By decreasing left ventricular preload, nitrovasodilators reduce left ventricular end-diastolic volume. This leads to a decrease in myocardial fiber stretch, resulting in lower contractility as predicted by the Frank-Starling mechanism. The subsequent reduction in left ventricular wall stress decreases myocardial oxygen demand, thereby relieving anginal symptoms.
Why do nitrates primarily affect veins more than arteries?
Veins have a higher compliance, allowing nitrates to preferentially increase venous pooling and reduce preload.
Do nitrates cause arterial dilation?
Yes, but the effect is minimal. The primary effect is on venodilation, which decreases myocardial oxygen demand more significantly than arterial dilation.
Why do nitrates have limited efficacy in dilating atherosclerotic coronary arteries?
Coronary arterioles in severe atherosclerosis are already maximally dilated, limiting further blood flow recruitment.
What are the primary indications for nitrovasodilators?
Used for stable angina, acute coronary syndrome (ACS), hypertensive emergency, heart failure, and pulmonary edema.
Which nitrate is used for acute angina attacks?
Sublingual nitroglycerin, due to its rapid onset of action.
Which nitrate is used for long-term angina prevention?
Isosorbide mononitrate or isosorbide dinitrate.
Why are nitrates beneficial in heart failure?
They reduce preload, decreasing pulmonary congestion and improving symptoms of decompensated heart failure.
What are the common side effects of nitrates?
Reflex tachycardia, flushing, headache, hypotension.
Why do nitrates cause reflex tachycardia?
Systemic vasodilation leads to baroreceptor-mediated activation of the sympathetic nervous system, increasing heart rate.
Why do nitrates cause flushing and headache?
Vasodilation of cerebral and cutaneous blood vessels causes flushing and headaches.
How do nitrates contribute to hypotension?
Vasodilation leads to decreased systemic vascular resistance and reduced venous return, lowering blood pressure.
Which medications are contraindicated with nitrates?
Phosphodiesterase-5 (PDE-5) inhibitors like sildenafil, tadalafil, and vardenafil, due to the risk of severe hypotension.
Why are PDE-5 inhibitors contraindicated with nitrates?
Both increase cGMP levels, leading to excessive vasodilation and life-threatening hypotension.
Why is nitroglycerin contraindicated in right-sided myocardial infarction (MI)?
Right-sided MI is preload-dependent; nitroglycerin reduces preload, leading to severe hypotension and cardiogenic shock.
How is hypotension from right-sided MI managed?
Treated with IV fluids to maintain preload and cardiac output.
Which ECG leads indicate an inferior (right coronary artery) MI?
ST elevations in leads II, III, and aVF.
Which additional leads can help confirm right ventricular involvement in an inferior MI?
ST elevation in right-sided lead V4R indicates right ventricular infarction.
Why is the anti-anginal effect of nitrates primarily due to reduced myocardial oxygen demand?
Decreased preload reduces left ventricular wall stress, lowering myocardial oxygen consumption.
What is the predominant mechanism for pain relief with nitrates in stable angina?
Decreased left ventricular wall stress due to reduced preload.
What is nitrate tolerance and how can it be prevented?
Continuous use leads to reduced effectiveness; a nitrate-free interval (e.g., overnight) is recommended to prevent tolerance.
