Drugs Used in Chronic IHD - Lecture

Question 1

chronic ischemic heart disease

Answer 1

Characterized by partial occlusion of coronary artery

Question 2

Classic angina (angina of effort, stable angina)

Answer 2

occlusion of coronary arteries resulting from formation of atherosclerotic plaque

• most common form of angina
• symptoms occur during exertion or stress

Question 3

Variant (Prinzmetal) angina

Answer 3

episodes of vasoconstriction of coronary arteries

• likely genetic in origin
• symptoms occur at rest
• much less common than classic angina

Question 4

Angina

Answer 4

imbalance between oxygen demand of the heart and oxygen supply via the coronary arteries

balanced at rest - no symptoms

During exertion (exercise or stress): oxygen demand on the heart&raquo_space; supply of oxygen through partially blocked coronary artery –> chest pain

Question 5

Treatments to increase (or restore) coronary blood flow - surgical and non-surgical revascularization approaches

Answer 5

Coronary artery bypass grafting

Percutaneous transluminal coronary angioplasty (PTCA)

Atherectomy - tip of catheter shears off the plaque
-reocclusion

Stent - expandable tube used as scaffolding to keep vessel open
-drug-eluting stents (anti proliferative drugs)

Question 6

Vasodilator clinical use in vasospastic (Prinzmetal) angina

Answer 6

relieve coronary spasm

restore blood flow into ischemic area

Question 7

vasodilators in atherosclerotic (classic) angina

Answer 7

not useful!

Question 8

Coronary Steal Phenomenon

Answer 8

redistribution of blood to non-ischemic areas

associated with dilation of small arterioles (ex. potent arteriolar vasodilators - dipyridamole)

Question 9

Endothelium dependent vascular relaxation

Answer 9

Release of endothelium-derived relaxation factor (EDRF) by ACh

Question 10

Vascular effects of NO

Answer 10

Vasodilation

Inhibits:
Platelet aggregation
monocyte adhesion
smooth muscle cell proliferation
Superoxide radical
LDL oxidation

Question 11

NO mechanism to vasodilation

Answer 11

NO binds to guanylyl cyclase, which converts GTP to cGMP

cGMP activates protein kinase G which

1) leads to Myosin-LC Dephosphorylation and leads to smooth muscle relaxation
2) opens potassium channel which leads to hyper polarization and reduced calcium entry

Question 12

Mechanism of action of nitrates

Answer 12

Nitrates donate NO via ADH2 Thiols

NO –> Vascular smooth muscle relaxation leads to:

1) venous dilations, reduced preload, decreased O2 demand - treats Angina of effort
2) coronary artery dilation, coronary spasm relief - treats variant angina

Question 13

Anti-Anginal mechanisms of CCBs

Answer 13

Decreased myocardial O2 demand - operates in atherosclerotic angina

• Dilation of peripheral arterioles: decreased PVR and after load, decreased BP
• arterioles more affected than veins - less orthostatic hypotension
• Dihydropyridines more potent vasodilator

-Decreased cardiac contractility and HR (observed with cardioactive CCBs)

Increased blood supply (operates in variant angina)
-dilation of coronary arteries relieves local spasm

Question 14

Beta-blocker MOA in angina

Answer 14

decreased myocardial oxygen demand

• Decrease in HR leads to improved myocardial perfusion and reduced oxygen demand at rest and during exercise
• decrease in contractility
• decrease in BP leads to reduced afterload

Question 15

Ischemic myocardium membrane potential abnormalities

Answer 15

Ischemic myocardium often partially depolarized

Na+ channel in cardiomyocytes is voltage-gated

Late Na+ current is enhanced in ischemic myocardium and brings about Ca2+ overload and depolarization abnormalities

Question 16

Ranolazine MOA in angina

Answer 16

normalizes depolarization of cardiac myocytes and reduced mechanical dysfunction

• may reduce diastolic tension and compression of coronary vessel in diastole
• may reduce cardiac contractility and oxygen demand