Drugs Used In Angina & Chronic Ischemic Heart Disease Flashcards Preview

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Flashcards in Drugs Used In Angina & Chronic Ischemic Heart Disease Deck (31)
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Categories of drugs used in chronic IHD

Nitrates (nitrovasodilators)

Calcium channel blockers




What nitrates are used in chronic IHD?


Isosorbide dinitrate

Isosorbide mononitrate


What calcium channel blockers are used in IHD?

Non-cardioactive (dihydropyridines):



What beta blockers are used in chronic IHD?



Chronic ischmic heart disease is characterized by partial occlusion of a coronary artery. What are the 2 types of IHD?

Classic angina (angina of effort, stable angina): occlusion of coronary aa. resulting from formation of atherosclerotic plaque — MOST COMMON form; symptomatic during exertion or stress

Variant (prinzmetal) angina: episodes of vasoconstriction of coronary aa.; likely genetic in origin, symptoms occur at rest. Much less common than classic


Surgical approaches to treat angina pectoris

Coronary artery bypass grafting

Percutaneous transluminal coronary angioplasty (PTCA)

Atherectomy - tip of catheter shears off plaque (risk of reocclusion)

Stent - expandable tube used as scaffolding to keep vessel open (drug eluting stents may be more effective long term)


In which type of angina are vasodilators useful?

Useful in tx of vasospastic (prinzmetal) angina — to relieve coronary spasm and restore blood flow to ischemic area

Note: vasodilators are NOT useful in atherosclerotic/CLASSIC angina — d/t “coronary steal” phenomenon = redistribution of blood to non-ischemic areas (associated with dilation of small arterioles)


Nitrovasodilators have significant first pass metabolism d/t high nitrate reductase activity in the ____; nitrate reductase activity is saturable.

Bioavailability with oral route is low, so other routes are often used. Partially denitrated metabolites may still have activity and longer half-lives. ______ is a nitrovasodilator that is known to be a poor substrate of nitrate reductase and thus characterized by higher bioavailability


Isosorbide mononitrate


MOA of nitrates in angina

Unknown enzymatic reaction releases NO (or other active metabolite); requires mitochondrial aldehyde dehydrogenase 2 (ADH2)

Thiol compounds are needed to release NO from nitrates. In vascular smooth muscle, NO dilates veins and, at high concentrations, large arteries. Dilation of veins increases capacitance and reduces ventricular preload; dilation of arteries may reduce afterload and dilate large epicardial coronary aa, but there is no substantial increase in blood flow into ischemic area in atherosclerotic angina

Inhibition of platelet aggregation


T/F: there is no “coronary steal” phenomenon with nitrates



Rank the vasculature in terms of sensitivity to nitrate-induced vasodilation

Veins > large arteries > small arteries and arterioles


Describe development of tolerance/limiting factors to use of nitrates

Depletion of thiol compounds

Increased generation of superoxide radicals

Reflex activation of SNS (tachycardia, decreased coronary blood supply)

Retention of salt and water


Clinical use of nitrates

Short-acting formulations are used to relieve acute angina attack [nitroglycerin sublingual or spray, isosorbide dinitrate sublingual or spray]

Long-acting preparations may be used to prevent attacks [nitroglycerin oral or ointment or patch, isosorbide dinitrate oral, isosorbide mononitrate oral—-longest MOA]


Adverse effects of nitrates

Headache (d/t meningeal vasodilation; nitrates are contraindicated with increased ICP)

Orthostatic hypotension

Increased sympathetic dishcarge — tachycardia, increased cardiac contractility

Increased renal Na and H2O reabsorption


Drug interactions with nitrates

Nitrates interact with drugs used to tx ED — sildenafil, vardenafil, tadalafil [severe increases in cGMP with dramatic drop in BP; acute MIs have been reported]


Of the calcium channel blockers used in angina, which is considered long acting?

Amlodipine — t1/2 of 30-50 hours

[Nifedipine and Nicardipine are considered short acting at t1/2 of 4 hr and 2-4 hrs respectively]


Of the calcium channel blockers, which has the greatest effect on decreasing automaticity at SA node and decreasing conduction at AV node?

Verapamil (closely followed by diltiazem


Of the calcium channel blockers used in angina, which one provides the most vasodilation?



Anti-anginal mechanisms of calcium channel blockers

Decreased myocardial O2 demand (helps with atherosclerotic angina) by:

Dilation of peripheral arterioles (decreased PVR and afterload, decreased BP, arterioles > veins so less orthostatic hypotension, dihydropyridines more potent vasodilators)

Decreased cardiac contractility and HR (with cardioactive CCBs)

In addition —
Increases blood supply to help with variant angina via dilation of coronary arteries to relieve local spasm


Adverse effects of CCBs used in angina

Cardioactive CCBs may cause cardiac depression, cardiac arrest, acute heart failure, bradyarrhythmias, atrioventricular block; short acting dihydropyridine CCBs may cause reflex sympathetic activation. Nifedipine increases risk of MI in pts with HTN — slow release and long acting dihydropyridines are better tolerated in those pts

Flushing, HA, anorexia, dizziness, peripheral edema, constipation


MOA of beta blockers used in angina

Decreasing HR —> improved myocardial perfusion and reduced O2 demand at rest and during exercise

Decrease contractility —> decreased O2 demand

Decrease in BP —> reduced afterload


AEs associated with beta blockers used for angina

Reduced cardiac output
Impaired liver glucose mobilization
Increase VLDL, decrease HDL
Sedation, depression
Withdrawal syndrome associated with sympathetic hyperresponsiveness


Contraindications to beta blockers

Peripheral vascular disease
T1D on insulin
Bradyarrhythmias and AV conduction abnormalities
Severe depression of cardiac function


Effects of nitrates alone on HR, arterial pressure, EDV, contractility, and ejection time

HR: reflex increase (undesirable)

Arterial pressure: decrease

EDV: decrease

Contractility: reflex increase (undesirable)

Ejection time: decrease


Effects of beta blockers or CCBs on HR, arterial pressure, EDV, contractility, and ejection time

HR: decrease

Arterial pressure: decrease

EDV: increase (undesirable)

Contractility: decrease

Ejection time: increase (undesirable)


Effects of combined nitrates with beta blockers or CCBs on HR, arterial pressure, EDV, contractility, and ejection time

HR: decrease

Arterial pressure: decrease

EDV: none or decrease

Contractility: none

Ejection time: none


MOA of ranolazine (new agent used in angina)

[ischemic myocardium is often partially depolarized and Na+ channel is voltage gated. Late Na+current is enhanced in ischemic myocardium and brings about Ca++ overload and repolarization abnormalities]

Ranolazine normalizes repolarization of cardiac myocytes and reduces mechanical dysfunction by inhibiting late Na+ current in cardiomyocytes

May reduce diastolic tension and compression of coronary vessels in diastole; may reduce cardiac contractility and oxygen demand


Effect of ranolazine on HR, coronary blood flow, and peripheral hemodynamics

No effect!!


Clinical use of ranolazine

Stable angina which is refractory to standard meds

Decreases angina episodes and improves exercise tolerance in pts taking nitrates, amlodipine, or atenolol


In summary: approaches to tx of variant angina

Management is primarily focused on prevention of episodes

CCBs are first choice drugs; if those are contracindicated d/t low BP, bradycardia, or AV block — Long-acting nitrates are used