Pharm2: Anti-Anginal

Front 1

factors that determine myocardial oxygen demand

Back 1

contactile state, HR, wall tension

Front 2

wall tension is a factor that determines myocardial oxygen demand. What determines wall tension

Back 2

Laplace's law: Tension=(Pressure*Radiu)/wall thickness, systolic wall tension is influenced by afterload diastolic wall tension is determined by preload

Front 3

factors that increase myocardial oxygen demands

Back 3

HR, contactility, arterial pressure, ventricular volume

Front 4

how is the need for increased oxygen met by the myocardium

Back 4

little reserve to extract more, must increase blood flow

Front 5

what is the diastolic crunch

Back 5

perfusion of the endocardium is dependent on the pressure graident  from the blood vesses on top of the heart down to the inside of the heart. During diastolye there is increased pressure inside the heart beause of the increased intraventricular pressure. This decreases the ability to perfuse the endocardium, a problem in stable angina

Front 6

where does the ischemia take place for stable and variant angina

Back 6

stable-subendocardial, variant-transmural (vasospasm)

Front 7

what are the two general pharamcological  approaches to treating angina

Back 7

1. decrease oxygen demands (HR, contractility wall tension (afterload/preload), increase oxygen supply (decrease preload, increase collateral flow, decrease spasm, dilate eccentric stenosis)

Front 8

What class of agents is used to treat acute attacks of both stable and variant angina

Back 8

fast acting nitrates (nitroglycerin, isosorbide dinitrate, isosorbide mononitrate)

Front 9

what class of agents  is used to treat chronic stable angina? Chronic variant angina

Back 9

stable -b blockers nitrates, CC blockers; variant-CC blockers

Front 10

how do nitrates treat angina

Back 10

used for acute episodes and chronic treatment of typical stable angina. They are denitrated by GST and the free nitrate is convered to NO. The NO activates GC which increases cGMP. cGMP diliates the VEINS leading to a decrease in preload thus adecrease in wall tension and myocardial oxygen demand. There is also a small reduction in afterload  due to slight arterial dilation and decrease in BP. Nitrates also dilate the coronary vasculature

Front 11

this class of drugs treats angina by dilating the veins to reduce preload

Back 11

nitrates

Front 12

route of administration for nitrates in acute angina attack

Back 12

sublingual, avoid 1st pass, achieve high blood concentration

Front 13

nitrate that does not undergo 1st pass

Back 13

isosorbide mononitrate

Front 14

nitrate with extended half life

Back 14

isosorbide dinitrate, both di and mono forms are active 1 hr+5 hr

Front 15

side effects of nitrates

Back 15

hypotension, orthostatic hypotension, reflex tachycardia, throbbing headache

Front 16

describe the role of tolerance in nitrate therapy

Back 16

complete tolerance can develop if used for more than a few hours but it is rapidly reversible, for chronic therapy must use smallest effective dose and schedule nitrate free period of at least 8 hours

Front 17

nitrates and PDE5 inhibitors

Back 17

do not use nitrates with PDE5 inhibitors like viagra, can cause extreme hypotension because the nitrates make more cGMP and the viagra prevents it from being broken down

Front 18

how are beta blockers used to treat chronic stable angina

Back 18

propranolol (B1 and B2), metoprolol (B1), block the positive iono/chrono tropic actiof catecholamines on the heart=decrease HR, decreased contractility, decreased blood pressure (afterload)-reduction in oxygen demand and increase in oxygen supply to ischemic areas (because decreased HR) note that decrease in CO may lead to slight increase in preload that can raise wall tension but not significant

Front 19

contraindications to the use of beta blockers for the treatment of chronic stable angina

Back 19

asthma and bronchospastic disease (especial propranolol because it is a non-selective antagonist), severe bradycardia, AV block, pts with coronary spasm (blocking B2 mediated coronary dilation)

Front 20

which type of CCBs would you use for treating chronic stable angina? variant?

Back 20

chronic stable=use dependent=diltiazem, verapamil; vasospastic=voltage dependent=nifedipine

Front 21

describe the use of CCBs for the treatment of chronic stable angina

Back 21

use dependent-verapamil, diltiazem; decrease HR, contractility, and wall stress (secondary to decrease afterlaod sedcondary to decreased systemic BP), = decreased O2 demand. increased O2 supply due to decreased HR, may increase coronary blood flow by dilating colateral vessels or eccentric stenosis

Front 22

describe the use of CCBs for the treatment of vasospastic angina

Back 22

voltage dependent-nifedipine- relieve and help prevent coronary vasospasm, use in combination with a beta blocker to prevent reflex tachycardia and hypotension that will increase oxygen demand

Front 23

how is ranolazine used to treat angina

Back 23

blocks late sodium current in cardiac muscle during ischemia, results in a decrease in Ca overload during ischemia, only used in typical stable angina that is unresponsive to standard therapy

Front 24

used to treat typical stable angina that is unresponsive to Tx with nitrates, beta blockers, or CCBs

Back 24

ranolazine

Front 25

why is it beneficial to use nitrates and beta blockers together to treat chronic stable angina

Back 25

Beta blocker-reduces HR, contractility, BP but can cause vasospasm and increase in wall tension due to compensatory increase in preload. Nitrates block this. Nitrates-dilates the veins, reduce preload but can cause reflex tach. BB's prevent this. Both drugs reduce oxygen consumption and increase subendocardial blood flow but do so by different mechanisms