Pcol Test 4 Angina Part 1

Front 1

what is the most frequent clinical sign of ischemic heart disease

Back 1

angina pectoris

Front 2

what is the leading cause of death in western society

Back 2

ischemic heart disease

Front 3

is angina associated with myocardial necrosis

Back 3

no

Front 4

what are the types of angina

Back 4

chronic stable/classical/typical
atypical/variant
unstable

Front 5

what form of angina is associated with sudden death

Back 5

unstable

Front 6

what are the properties of classic angina

Back 6

relieved at rest
provoked by exertion

Front 7

what are the properties of atypical/variant angina

Back 7

can occur at rest, often at night
often caused by vasospasm of large coronary arteries w/ or w/o coronary artery disease

Front 8

how can we try to fix angina

Back 8

increase O2 supply
decrease O2 demand

Front 9

what is the cause of ischemia

Back 9

stenosis

Front 10

what is the relationship between degree of stenosis and severity of angina

Back 10

there is no correlation

Front 11

what is stenosis

Back 11

how narrow the blood vessel is

Front 12

what will precipitate angina attack

Back 12

anything that increases O2 demand

Front 13

what does O2 supply depend on

Back 13

coronary capillary flow (Q)

Front 14

what is coronary capillary flow regulated by

Back 14

coronary artery vascular tone (how wide arteries are)
coronary perfusion gradient

Front 15

what is coronary perfusion gradient

Back 15

extent of collateral circulation
duration of diastole

Front 16

what is O2 demand regulated by

Back 16

Heart rate
myocardial contractility
myocardial wall tension (LVEDP)

Front 17

in a normal person what happens to their arterioles when they do something like exercise that needs more O2

Back 17

arterioles dilate

Front 18

in someone with angia what happens to their arterioles when they do something that requires more O2 like exersise

Back 18

nothing

reason being that their arterioles are already maximally dilated b/c the heart knows there is an ischemic area and will try to keep blood flow high at that area to keep the arterioles constantly dilated therefore EVENTHOUGH THERE IS AN INCREASED O2 DEMAND THE HEART IS UNABLE TO MEET IT

Front 19

what is the most effective pharmacological treatment for angina

Back 19

decreasing O2 demand

Front 20

what is perfusion pressure determined by

Back 20

coronary artery diastolic pressure - coronary diastolic flow (LVEDP)

Front 21

what will increase LVEDP (wall tension)
what will decrease coronary artery diastolic pressure

Back 21

ischemia
plaque

Front 22

in aortic pressure what happens during systole and diastole

Back 22

blood comes in

Front 23

when does the majority of blood come in during coronary flow

Back 23

diastole

Front 24

what is happening in the coronary arteries during systole

Back 24

while our heart's contracting the coronary arteries are shut

Front 25

what does the PSNS do to the heart

Back 25

release NO through muscarinic Rc on endothelial cells

inhibit SNS activity via prejunctional muscarinic Rc

Front 26

what muscarinic Rc is primarily responsible for NO release

Back 26

M1

Front 27

what muscarinic Rc is primarily responsible for inhibition of SNS activity

Back 27

M2

Front 28

what does the M2 Rc do on sympathetic nerve terminal

Back 28

inhibits NE release

Front 29

what does the SNS have in large coronary arteries

Back 29

alpha 1 - vasoconstrict (on smooth muscle)
alpha 2 - vasodilate via EDRF (NO) release (on endothelial cells)
B1 - vasodilate (on smooth muscle)

Front 30

why do large coronary arteries have B1 instead of B2

Back 30

they have B1 b/c since they are acted upon by the SNS, NE has a higher affinity for B1

Front 31

what Rc are in small resistance vessels

Back 31

alpha 1 - vasoconstrict
alpha 2 - vasoconstrict
B2 - vasodilate

ALL ON SMOOTH MUSCLE

Front 32

in intact endothelial cells what causes vasodilation

Back 32

NO
5HT
PGI2
ACh
histamine
bradykinin

Front 33

in intact endothelial what does 5HT do

Back 33

plateletes release 5Ht producing vasodilation via 5HT1 Rc on endothelial cells releasing NO

Front 34

in intact endothelial what does PGI2 do

Back 34

endothelial cells produce prostacyclin (PGI2) which produces vasodilation and inhibits platelet aggregation

Front 35

what does exercise do in intact endothelial cells

Back 35

increased blood perfusion leads to an increase in NO release

Front 36

in damaged endothelial cells what causes vasoconstriction

Back 36

endothelins
5HT
angiotensin 2
TXA2
NE

Front 37

what does endothelin do in damaged endothelial cells

Back 37

vasoconstriction

in damaged endothelial cells endothelins effect is now greater than NO and PGI2

Front 38

what does exercise do in damaged endothelial

Back 38

exercise increases SNS activity and the alpha effect overides NO and PGI2 since there is no intact endothelial cells to produce those

Front 39

what does 5HT do in damaged endothelial

Back 39

5HT binds to 5HT2 on smooth muscle causing vasoconstriction

Front 40

what are the forms of regulation of coronary blood flow

Back 40

neural
endothelial
metabolic/autoregulation

Front 41

what is the most powerful way coronary blood flow is regulated

Back 41

autoregulation (metabolic regulation)

Front 42

is autoregulation due to SNS or PSNS activity

Back 42

no it can be observed in a denervated heart

Front 43

what does autoregulation primarily effect

Back 43

resistance vessels (areterioles)

Front 44

what does increases SNS activity do to coronary blood flow

Back 44

increases HR and contractility leading to a increase in O2 demand.

the increased O2 demand produces an increase in coronary blood flow.

THIS IS AUTOREGULATION

Front 45

what is the process by which ATP is consumed

Back 45

start w/ normal amounts of ATP
O2 demand goes up
ATP used
ATP converted to ADP
ADP converted to AMP
AMP converted by 5' nucleotidase to ADO (adenosine)
Adenosine carries out vasodilation via A2a Rc
cycle starts over agan

Front 46

under what conditions is ATP use increased

Back 46

conditions of increased O2 demand

Front 47

what happens when there are high levels of ATP

Back 47

low activity of 5' nucleotidase

Front 48

what are the posible fates of Adenosine (ADO)

Back 48

adenosine uptake
adenosine kinase (converts ADO > AMP)
adenosine deaminase (converts ADO to inactive INO)

Front 49

what can happen to ADO when there is chronic hypoxia (chronic IHD) and there is too much ADO

Back 49

shift towards adenosine being deaminated to INO and the failure of autoregulation b/c instead of recycline the ADO it is essentially being terminated

Front 50

what are the most common types of nitrates

Back 50

sublingual pills
patches

Front 51

what are the in vivo mechanism of action of nitrates

Back 51

preload effect
increase coronary perfusion pressure
increase flow through large coronaries via dilation

Front 52

what is the most important in vivo mechanism of action of nitrates

Back 52

preload effects

Front 53

what happens when you lower LVEDP

Back 53

you increase blood flow

Front 54

how do nitrates carry out the preload effect

Back 54

venodilation (veins can now hold more blood and therefore preload decreases)
decrease venous return
decrease wall tension (LVEDP)
decrease work
decrease O2 demand

Front 55

how do nitrates increase coronary perfusion pressure

Back 55

this occurs indirectly as a result of the venodilation which causes a decrease in wall tension (LVEDP) resulting in an indirect increase in coronary perfusion pressure

Front 56

how do nitrates increase flow through large coronaries

Back 56

nitrates directly dilate large coronary arter
increase collateral flow
increase O2 supply

Front 57

on a cellular level how do nitrates treat angina

Back 57

nitrates are NO donors and don't release NO but are instead converted to NO

once converted to NO
NO activates GC (guanylate cyclse)
NO also activates cGMP dependent kinase G which phosphorylate MLCK
phosphorylationg of MLCK resultes in increase in cGMP
increase in cGMP results in VASODILATION

Front 58

what are side effects of angina treatment w/ nitrates

Back 58

due to vasodialtion - may worsen angina due to reflex increase in HR and contractility

Front 59

what is acute prophylasis in relation to nitrates

Back 59

can't take nitrates when doing something that might precipitate angina attack

Front 60

at very high doses what can dipyridamole do

Back 60

inhibit platelet aggregation and inhibit PDE

Front 61

how does dipyridamole increase ADO

Back 61

inhibits adenosine uptake
inhibits adenosine deaminase

Front 62

what is coronary steal

Back 62

you have an arteriole with a blockage due to plaque

to insure ischemia doesn't occur @ rest autoregulation kicks in and releases Adenosine and increases blood flow to make sure it gets to the area of ischemia

when you give dipyridamole since its main function is to release adenosine you won't see an effect in the arteriole w/ the plaque block.

this is due to that arteriole already being maxed out and unable to further dilate.

since the other arterioles are not maxed out, you will see an effect by dipyridamole and as a result there will be increased blood flow to those areas.

this will take away from the blood flow going to the area of ischemia

Front 63

why is coronary steal a negative consequence of dipyridamol

Back 63

you are taking blood flow from an ischemic area and shunting it to areas that don't have ischemia and therefore don't need to extra blood

Front 64

what channels are in the heart and what is the difference

Back 64

voltage operated channels - open and close depending on RMP
receptor operated channels - open and close depending on whether you're activating Rc

Front 65

what type of Rc do calcium channel blockers block

Back 65

L type voltage operated channels

Front 66

how do calcium channel blockers prevent the inactive gate from opening

Back 66

they bind to the inactive state and stabilize that state preventing it from opening

Front 67

what is the mechanism of action of calcium channel blockers

Back 67

decrease O2 demand by heart:

Front 68

how do CCB decrease O2 demand by heart

Back 68

direct negative inotropic effect
decrease afterload - make it easier for the heart to pump/heart doesn't have to work as hard

Front 69

can DHP be used for angina

Back 69

no b/c they have minimal ionotropic effect

Front 70

can calcium channel blockers be used in angina caused by vasospasm

Back 70

yes b/c they dilate coronary arteries

Front 71

what opposes the mechanism of action of Ca

Back 71

anything that increases Ca entry
-Ca supps
-Beta Rc activation

Front 72

how do Beta adrenoceptors agonist? oppose Ca blockers effect

Back 72

Beta agonist bind to Beta Rc and will increase contractility

beta Rc activation leads to activation of PKA
PKA phosphorylate ROC resulting in
increase in # of channels in resting state available for opening
increase in duration of time in open state