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Flashcards in lecture 6 Deck (49):
1

myocardial ischemia (IHD)

imbalance between myocardial O2 supply and demand

2

IHD contributing factors

1. increased sympathetic outflow-> incr HR, ventricular wall tension & ventricular contractility-> incr myocardial demand
2. decreased coronary blood flow due to coronary vasospasm &/or coronary atherosclerosis (CAD)-> decreased myocardial O2 supply

3

coronary artery disease

a condition in which coronary arteries are narrowed by the formation of atherosclerotic plaques

4

main symproms of myocardial ischemia

1. angina
2. decreased exercise tolerance

5

myocardial ischemia generally preceds

MI

6

2 distinct characteristics of MI

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

7

IHD short term goal of therapy

prevent/reduce symptoms of angina that limits exercise capability & quality of life

8

IHD long term goals of therapy

prevent events of myocardial ischemia (MI, arrhythmias, HF) & reduce mortality (extend life)

9

IHD treatment

- risk factor modification
- nonpharm therapy: revascularization, coronary artery bypass grafting, percutaneous transluminal coronary angioplasty

10

pharmacological agents used

-nitrates
- beta blcokers
-CCB
- anticoagulants
- antiplatelet agents
- thrombolytic agents
- statins
- ACEI
- pure antianginal drugs
- morphine

11

pharmacological treatments improved the balance between O2 supply & demand by:

- dilating the coronary vasculature (increase O2 supply)
- reducing cardiac workload (decrease demand)

12

organic nitrates MOA

- prodrugs
- upon metabolism release NO
- NO is also biosynthesized in different tissues by NOS
- Potent vasodilator
- NO stimulates guanylyl cyclase-> incr cGMP-> dec intracellular Ca & MLC dephosphorylation-> SM relaxation

13

hemodynamic effects of low dose nitrates

- preferentially dilate veins compared to arterioles-> decreased venous return & preload & decreased left & right ventricular chamber size
-(slight decr. in BP)

14

hemodynamic effects of high dose nitrates

- cause further venous pooling & decrease arteriol resistance
- activation of compensatory sympathetic reflexes (tachycardia)
- cronary blood flow may increase transiently, but it will decrease again if cardiac output & BP are decreased significantly

15

total & regional coronary blood flow (low to moderate doses of nitrates)

1. vasodilate & restore the flow in epicardial vessels
2. do not impair autoregulation in smaller vessels
3. decrease intracavitary systolic & diastolic pressures-> incr blood flow to the subendocardium
4. dilate cardiac veins (may improve cardiac microcirculation)

16

nitrate effects on myocardial O2 requirements

- incr ventous capacitance-> decr venous return-> decr preload-> reduced O2 demand & incr blood flow to subendocardium

17

antianginal effects of nitrates

1. reduction of venous return & myocardial O2 demand- primary effect*
2. dilation of epicardial coronary arteries-> improved blood flow & O2 supply
3. NO in plts-> antiplt effect (modest, but important)

18

tolerance to nitrates

repeated/continuous use of (high) doses of nitrates may lead to marked attenuation of their pharmacological effects (tachyphylaxis)

19

nitrate side effects

1. HA
2. transient dizziness & weakness
3. postural/orthostatic hypotension
4. drug rash

20

caution using nitrates with

PDE5 inhibitors-> severe hypotension!
PDE5I inhibit the conversion of cGMP to GMP-> incr cGMP-> vasodilation

21

PDE5 inhibitors

sildenafil (viagra)
tadalafil (cialis)
vardenafi (levitra)

22

nitrate drugs

nitroglycerin
isosorbide dinitrate
isosorbide mononitrate
nitroglycerin IV
nitroglycerin patch

23

nitrates

- all have a large first pass effects
- all but isosorbine mono have short T1/2 & high clearance rates
- large interindiviual variations in plasma conc.

24

nitroglycerin concentrations are effected by

- route of admin
- IV: highest
- oral: lowerst

25

sublingual NTG

usually taken during anginal attack or in anticipation of exercise or stress-induced attack

26

IV NTG

mainly in clinic for acute coronary syndrome

27

chewable, oral & transdermain Nitrates

long-term prophylaxis of angina

28

what type of beta receptors are in the heart?

beta 1

29

what are the effects of beta 1 stimulation

-tachycardia, contraction force increase, impulses travel in heart faster too, O2 demand is increased
- chrono (inc HR)
- dromo (AV node conduction)
- iono (incr contraction force)

30

with beta-blocker use, are we targeting O2 supply or demand

O2 demand

31

Beta 1 blockers are effective in the treatment of

- exertional angina: reduce severity & frequency of attacks, cardioprotective effects
- UA & MI: reduce recurrent episodes & improve mortality

32

Beta blockers can result in

- profound decreases in LV function
- caution in pts with limited cardiac reserve (critically depend on adrenergic stimulation)

33

DHP CCB act on

arteries/arteriole
- decr. peripheral resistance
- coronary vasodilation
- improved contractility & ventricular function
- improved coronary blood flow
- HR & CO may increase

34

NonDHP CCBs act on

the heart

35

what CCBs would you use in someone suffering from IHD?

NonDHPs
- DHPs can still be useful

36

CCB MOA

block L type Ca channels-> decr influx of Ca-> relaxation

37

nicardipine (DHP) may have selectivity for

coronary vessels

38

parenteral anticoagulants

- UFH & LMWH facilitate binding of thrombin to antithrombin-> several coagulation factors, incl fibrinogen are NOT acivated

39

oral anticoagulants

- warfarin/ vit K antagoinst inhibit vit K epoxide reductase-> vit K is NOT reduced (recovered) to activate coagulation factors (7,9,10,2)

40

anticoagulants

- prevent progression of thrombosis & systemic embolization
- reduce recurrent episodes of UA & MI
- usually are used in combo with other drugs to achieve better therapeutic outcome

41

factors that cause activation & aggregation of plts

TX-A2, thrombin, ADP, collagen, etc
- can serve as targets to inhibit plt activation

42

aggregated plts

form the initial hemostatic plug at sites of vascular injury & are key played in thrombus formation

43

antiplt agents

aspirin

44

aspirin

- NSAID that inactivates COX1 & inhibits TX-A2 formation from arachidontic acid in plts
- 50-320mg/day: complete & permanent inactivation of COX1 w/out clinically sig effect on COX2

45

COX1 ->

- PGs & TX-A2
- plt aggregation & vasoconstriction

46

COX2->

-PGs & prostacyclins
- vasorelaxation & antiplt effect

47

aggrenox

aspirin/ ER dipyridamole

48

common side effect of aggrenox

HA- usually disappears upon continuation of therapy

49

dipyridamole MOA

- inhibits adenosine uptake in plts-> inc adenosine on surface-> A2 stimulation-> incr cAMP in plts-> decr plt activation
- inhibits PDE-> inc cGMP-> SM relaxation & decr plt activation