NITROGLYCERIN

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Nitroglycerin is a potent vasodilator that acts primarily on venous capacitance vessels, as well as on arterial vessels to a lesser extent. It works by releasing nitric oxide, which in turn leads to smooth muscle relaxation and vasodilation. While nitroglycerin is commonly used in the management of angina and acute coronary syndromes, it also has important roles in the context of anesthesia:

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1. Intraoperative blood pressure control: Nitroglycerin can be used to manage intraoperative hypertension by reducing preload and, to a lesser extent, afterload. This helps to maintain stable blood pressure during surgery and ensures patient safety and optimal surgical outcomes.

2. Coronary perfusion: Nitroglycerin is beneficial in patients with coronary artery disease or those at risk for myocardial ischemia during surgery. By dilating coronary arteries and improving coronary blood flow, nitroglycerin helps maintain adequate myocardial oxygen supply, reducing the risk of ischemic events during the perioperative period.

3. Pulmonary hypertension: Nitroglycerin can be used in the management of acute pulmonary hypertension during surgery, as it reduces both right ventricular preload and afterload, which in turn helps to improve right ventricular function and overall hemodynamic stability.

4. Vasospasm management: In certain cases, such as during neurosurgical procedures, intraoperative vasospasm may occur. Nitroglycerin can help counteract this by promoting vasodilation and improving blood flow.

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Here are the main steps in nitroglycerin's mechanism of action:

 

1. Nitroglycerin bioactivation: After administration, nitroglycerin is metabolized by enzymes called mitochondrial aldehyde dehydrogenase (ALDH2) and organic nitrate reductases in vascular smooth muscle cells and endothelial cells. This process results in the release of nitric oxide (NO).

2. Nitric oxide production: NO diffuses into the smooth muscle cells in the walls of blood vessels, particularly in veins and, to a lesser extent, arteries.

3. Activation of soluble guanylate cyclase (sGC): Inside the smooth muscle cells, NO activates an enzyme called soluble guanylate cyclase (sGC), which catalyzes the conversion of guanosine triphosphate (GTP) to cyclic guanosine monophosphate (cGMP).

4. Increased cGMP levels: The rise in cGMP levels activates protein kinase G (PKG), which in turn phosphorylates several target proteins.

5. Smooth muscle relaxation: The phosphorylation events ultimately lead to a decrease in intracellular calcium levels, causing relaxation of vascular smooth muscle cells. This results in vasodilation, particularly in the venous system.

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                                                                                         Key points about Nitroglycerin

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• Organic nitrate which acts principally on venous capacitance vessels and large coronary arteries.

 

• Produces peripheral pooling of blood and decreases cardiac ventricular wall tension.

 

• Can produce pulmonary vasodilation.

 

• In contrast to Sodium Nitroprusside, which spontaneously produces Nitric Oxide, Nitroglycerin requires the presence of thio-containing compounds.

 

• The nitrate group of Nitroglycerin is biotransformed to Nitric Oxide through a glutathione-dependent pathway.

 

• Elimination half-time of about 1.5 minutes.

 

• The nitrite metabolite is capable of oxidizing the ferrous ion in hemoglobin to the ferric state with the production of methemoglobin.

 

• Used to treat suspected myocardial ischemia as well as volume overload in the setting of heart failure (preload reduction).

 

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