Term
| Outline the general approach to the medical management of angina pectoris. |
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Definition
The three drug classes used to treat angina are organic nitrates, beta-blockers, and calcium-channel blockers. All three work by lowering the oxygen demand of the heart by affecting blood pressure (reducing afterload), venous return (reducing preload), heart rate (slowed), and contractility (reduced).
Organic nitrates: do this by increasing the amount of intravascular nitric oxide which causes smooth muscle relaxation and vasodilation (see answer 18.2). It is also effective in systemic venodilation which decreases preload therefore decreasing the workload on the heart.
Beta-blockers: reduce O2 demand by decreasing the heart rate and the force of contraction by blocking the heart's beta receptors.
Calcium-channel blockers: block the influx of Ca++ into the heart muscle and smooth vasculator muscles, therefore causing vasodilation in the heart muscle as well as systemically, which in turn will reduce afterload. |
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Term
Describe the mechanism of action of nitrates
(see fig 18.2). |
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Definition
Nitrates decrease coronary vasoconstriction by converting to nitrite ions, which will convert to nitric oxide, which activates cGMP (cyclic guanosine monophosphate). An increase in cGMP will lead to dephosphorolization of the myosin light chain, resulting in relaxation of smooth muscle.
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Term
| Know how sildenafil potentiates nitroglycerin and other nitrates. |
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Definition
| (NTG → NO which diffuses into vascular endothelial cell and produces therapeutic action by stimulating guanylyl cyclase which increases intracellular [cGMP] which in turn inactivates the active form of myosin (myosin light chain phosphate) to cause smooth muscle relaxation. cGMP is broken down by phosphodiesterase (PDE). Sildenafil is a PDE inhibitor and thus potentiates the actions of cGMP). |
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Term
| What are key facts to know about nitric oxide (NO)? |
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Definition
Nitric oxide is also known as endothelial derived relaxing factor and has a short half life. Nitric oxide activates guanylate cyclase which in turn works with cGMP. cGMP regulates dephosphorylation of the myosin light chain which causes vasodilation of blood vessels. NO is considered an antianginal, vasodilator, and helps reduce ischemia by decreasing the O2 consumption of the heart and by decreasing the cardiac workload of the heart. NO is the active metabolite of the nitrates (eg, nitroglycerin). In the case of nitroglycerin, as it undergoes dephosphorylation, one of its byproducts is NO which dilates the vessels and reduces acute angina.
The source of endogenous NO = the amino acid arginine. The enzyme that makes NO = NOS (nitric oxide synthase). NO is produced in endothelial cells and very easily diffuses across cell membrane and stimualtes cGMP, which is why smooth muscles relax.
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