Lect 6- CAD & Thromboembolic Stroke

Question 1

myocardial ischemia definition

Answer 1

imbalance b/w myocardial oxygen supply and demand

Question 2

contributing factors for myocardial ischemia

Answer 2

1. increased sympathetic outflow= increased myocardial O2 demand
2. decreased coronary blood flow= decreased myocardial O2 supply

Question 3

coronary artery disease (CAD) definition

Answer 3

condition in which the coronary arteries are narrowed by the formation of atherosclerotic plaques (Means there is an atherosclerotic state where blood flow is reduced)

Question 4

2 types of plaques

Answer 4

○ Unstable= fibrous cap is thin and can rupture at any time
○ Stable= outer layer pretty thick
§ Still have narrowing but we will at least avoid having a rupture

Question 5

main symptoms of myocardial ischemia

Answer 5

1. angina pectoris
2. decreased exercise tolerance (since when you are exercising, your symp NS is activated which means heart needs more O2 but if its already getting not a lot, we cannot keep up)

Question 6

2 distinct characteristics of MI

Answer 6

1. sudden interruption of blood supply to myocardium by rupture of an atherosclerotic plaque resulting in thrombosis
2. myocardial function is compromised & tissue can become necrotic

Question 7

myocardial ischemia treatment goals

Answer 7

• short-term goal= prevent/ reduce symptoms of angina

* long-term goals= prevent events of myocardial ischemia (MI, arrhythmias, heart failure) and reduce mortality

Question 8

drugs used in IHD and CAD

Answer 8

• Improve the balance by either increase O2 supply to myocardium or decrease O2 demand by myocardium
○ Some can do both

Question 9

MOA of organic nitrates

Answer 9

PRODRUGS
Upon metabolism release NO (potent vasodilator) → NO is gas → gets to cells and past plasma memb very easily → stim guanylyl cyclase → converts GTP to cGMP → has 2 diff mechanisms that will result in smooth muscle relaxation

Question 10

hemodynamic effects of organic nitrates

Answer 10

1. low doses PREFERENTIALLY dilate veins (dec venous return & preload, dec left & right ventricular chamber size) to need to use less force to pump blood out
2. High dose= will also dilate arteries → creates compensatory tachycardia

Question 11

CV effects of low-mod doses of organic nitrates

Answer 11

1. vasodilate epicardial vessels (>200 um diameter)
2. do NOT impair autoregulation in smaller vessels
3. ) decrease intracavity systolic/ diastolic pressures → increase the blood flow to the subendocardium
4. ) dilate cardiac veins

Question 12

organic nitrates effect on myocardial O2 requirements

Answer 12

inc venous capacitance → dec venous return → dec preload → reduction of O2 demand and inc blood flow to subendocardium

Question 13

antianginal effect of organic nitrates

Answer 13

1. PRIMARY EFFECT= reduction of venous return and myocardial O2 demand
2. dilation of epicardial coronary arteries → improved blood flow/ O2 supply
3. NO in plts → antiplatelet effect (modest but IMPORTANT effect)

Question 14

tolerance in organic nitrates

Answer 14

long term use of high doses may lead to attenuation of their pharmacological effects (potency is being reduced)
TACHYPHYLAXIS

Question 15

side effects of organic nitrates

Answer 15

HEADACHE (due to vasodilation in the brain)

transient dizziness/ weakness, postural/ orthostatic hypotension, drug rash

Question 16

PDE5 inhibitors with nitrates

Answer 16

CAUTION: combo of PDE5 inhibitors (sildenafil, tadalafil, vardenafil) with nitrates may cause severe hypotension!

Question 17

MOA of interaction b/w PDE5 inhibitors and nitrates

Answer 17

• cGMP is inactivated by PDE5 (cyclic molecule converted to linear molecule) → so when we block it cGMP is not inactivated → effect is much more pronounced → severe vasodilation → severe hypotension or maybe even comatose state

Question 18

effects of stimulating the beta-1 receptor in the heart

Answer 18

increase in:

• chrono (heart rate)
• dromo (AV nodal conduction)
• ionotropic (contraction force)

Question 19

effect of beta-adrenoreceptor antagonists

Answer 19

block the beta-1 receptor to decrease O2 demand

Question 20

B1-blockers are effective in treatment of ___

Answer 20

exertional angina= cardioprotective effects

unstable angina & MI= reduce recurrent episodes and improve mortality

Question 21

caution with b1-blockers

Answer 21

in pts with limited cardiac reserve, b-blockers can result in profound decreases in left ventricular function

Question 22

differential effects between CCBs

Answer 22

DHP has more members so it affects blood vessels; non-DHP affects heart (only one heart and a lot of blood vessels)

Question 23

CCBs in treatment of IHD

Answer 23

Non-DHP to decrease contraction of heart so result will be decreased demand
DHP would dilate vessels which would improve supply to the heart

Question 24

heparin parenteral anticoagulants MOA

Answer 24

facilitate binding of thrombin to antithrombin so coagulation factors are not activated

Question 25

warfarin (Coumadin) MOA

Answer 25

vit K antagonist= inhibits vit K epoxide reductase so Vit K is not reduced to activate coagulation factors

Question 26

anticoags use in CAD

Answer 26

usually used w/ other drugs to achieve better therapeutic outcome

Question 27

MOA of aspirin 50-325 mg/day

Answer 27

○ Inhibits COX enzymes → COX converts arachodonic acid to prostaglandins
• Low therapeutic doses= primarily inhibits COX1
○ Stop prod of thromboxane A2 (which usually activates and aggregates plts)
○ Prostaglandin synthesis not affected

Question 28

Aggrenox= aspirin/extended-release dipyridamole

Answer 28

○ Inhibits uptake of adenosine in plts → more adenosine on surface available to activate receptors
○ Inhibits phosphodiesterases (at least 10 subtypes; inhibits mostly ones that prefer cGMP than cAMP) → increased cGMP which causes smooth muscle relaxation and dilation

Question 29

Aggrenox side effect

Answer 29

headache