Drugs for Angina and Ischemic Heart Disease Flashcards Preview

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Flashcards in Drugs for Angina and Ischemic Heart Disease Deck (48)
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Chronic ischemic heart disease is characterized by`

the partial occlusion of coronary artery


Classic angina

-angina of effort, stable angina

-occlusion of the coronary arteries resulting from the formation of atherosclerotic plaque

-Most common form of angina

-Symptoms occur during exertion or stress


Variant (Prinzmetal) angina:

-episodes of vasoconstriction of coronary arteries


-Genetic in origin

-symptoms at rest

-Less common than classic angina


Angina is the imbalance between

-O2 demand of the heart and oxygen supply via the coronary arteries

-Heart's demand for O2>>O2 supply due to partially blocked coronary artery

-Especially during exertion, stress

-results in chest pain


Approaches to treat Angina

-Reduce O2 demand by decreasing cardiac work OR

-increase O2 supply by increasing blood flow through coronary arteries


Ways to increase coronary blood flow to treat angina--surgical and non-surgical approaches

-Coronary artery bypass grafting (most radical)

-Percutaneous transluminal coronary angioplasty (PTCA)

-Atherectomy--tip of catheter shears off the plaque--risk of reocclusion

-Stent--expandable tube used as scafforlding to keep vessel open (drug eluting stents--antiproliferative drugs--cause cell cycle arrest)


To increase coronary blood flow using vasodilators

-useful in vasospastic (Prinzmetal--variant) angina

-to relieve coronary spasm -to restore blood flow into ischemic area

-NOT useful in atherosclerotic (classic) angina--can make it worse-- due to coronary steal phenomenon


Coronary steal phemomenonen

-redistribution of blood to non-ischemic areas--associated with the dilation of small arterioles

-Ex: potent arteriolar vasodilators like Dipyridamole

-vasodilation prevents adjacent arteries from providing collateral blood flow exacerbating symptoms in classic angina!! But vasodilator useful for variant angina!


Determinants of myocardial oxygen demand (targets for treatment)

-Heart rate





Tachycardia increases HR and can be harmful. Why?

-Tachycardia affects diastole more than systole

-decreased length of diastole so blood flow through coronary artery is impeded

-explains why tachycardia is harmful especially in angina patients


Vasodilator that lacks direct effect on autonomic receptors but may provoke angina attacks


-peripheral vasodilator

-releases NO


Drug classes used in chronic ischemic heart disease

-Nitrates (nitrovasodilators)

-Calcium channel blockers


-Newer agent: Ranolazine




-isosorbide dinitrate

-Isosorbide mononitrate (active metabolite of dinatrate)


Endothelium dependent vascular relaxation

-Release of endothelium-derived relaxing factor (EDRF) by Ach leads to relaxation IF endothelium is present

-endothelial NOS produces NO, an endogenous vasorelaxing agent


Endothelial Nitric Oxide Synthase

-activated by Ca2+-calmodulin complex

-then it activates arginine to make citrilline and NO


NO acts on

-Guanylyl cyclase-->act cGMP-->act Protein kinase G--> causes relaxation by dephosphorylating myosin light chain or by opening potassium channels and causing hyperpolarization and reduced calcium entry


MOA of nitrates in Variant angina

1) Nitrate-->NO via ADH2 (frequently thiols)-->

2) Vascular smooth muscle relaxation-->

3) Coronary artery dilation-->

4) Coronary spasm relief


MOA of nitrates in Classic angina

1)1) Nitrate-->NO via ADH2 (frequently thiols)-->

2) Vascular smooth muscle relaxation-->

3) VENOUS dilation-->

4) Reduced preload-->

5) decreased O2 demand


Multiple effects of NO


-Prevents platelet aggregation

-inhibits interaction of endothelial cells with blood derived cells (leukocytes)--prevents rolling and transmigration and inflammation by leukocytes

-inhibits smooth muscle proliferation (intimal thickening and reocclusion)

-prevents oxidation damage -prevents LDL oxidation (protects against atherosclerosis)


Sensitivity of vasculature to nitrate induced vasodilation

-veins>large arteries>small arteries and arterioles


Nitrovasodilator beneficial action in angina

-decreased myocardial oxygen demand

-relaxation of vascular smooth muscle

-dilation of veins (major effect): increased venous capacitance, reduced ventricular preload

-dilation of arterioles--higher concentrations of nitrates are needed compared to venous dilation


Dilation of arteries leads to

-reduced arterial pressure and after load

-may dilate large epicardial coronary arteries

-no significant increase in coronary blood flow into the ischemic area in atherosclerotic angina


Nitrates in angina of effort

-decreased preload

-decreased oxygen demand


Nitrates in vasospastic angina

-relaxation of coronary artery vascular smooth muscle

-relieving coronary spasm


Nitrate clinical use

-short acting formulations used to relieve the angina attack

-long acting preparations may be used to prevent attacks


Development of nitrate tolerance

-depletion of thiol compounds -increased generation of oxygen radicals

-reflex activation of sympathetic nervous system (tachycardia, decreased coronary blood supply)

-retention of salt and water

-increased generation of superoxide radical depletes tissues of NO


Reason to avoid oral administration of nitrates

-Rapid denitration by the liver enzymes


Adverse effects of nitrates

-headache (meningeal vasodilation)

-orthostatic hypotension -increased sympathetic discharge

-tachycardia, increased cardiac contractility

-increased renal Na+ and H2O reabsorption


Nitrate drug interactions

-interaction of nitrates with drugs used for treatment of erectile dysfunction (sildenafil, vardenafil, tadalafil)

-combination with nitrates causes severe increase in cGMP and a dramatic drop in BP

-acute MI cases have been reported


-Calcium channel blockers

-non-cardioactive (DHP):




-Cardioactive: Diltiazem, Verapamil