Angina Pharmacology (L19)

angina is caused by accumulation of _________ resulting from _________ _________

metabolites, myocardial ischemia

in angina the ST segment on an ECG is ___________

depressed

_________ angina happens when plaques reduce the max capacity of the coronary artery

stable (relieved by rest or NG & it’s predictable)

stable angina is relieved by _______ or __________

rest, nitroglycerin

________ angina usually occurs while resting and is due to atherosclerotic plaque ruptures or platelet plug formation (clots) that block blood flow to the heart muscle

unstable (should be treated as an emergency)

___________ angina is due to transient reduction of blood flow caused by coronary artery spasm, with or without atherosclerotic disease

vasospastic (type of unstable angina, also called Prinzmetal’s)

short term goals of angina treatment include reducing _______ or preventing anginal _______ which are limiting the pts exercise capability and impairing their QOL

pain, symptoms

long-term goals of angina treatment are preventing of _______, ________, and _________ to extend the pts life

MI, arrhythmias, HF

____________ nitroglycerin should be used to terminate acute anginal attacks

sublingual (or translingual spray)

_________ nitroglycerin should be used for acute prophylaxis of angina

sublingual (or translingual spray)

____________ nitroglycerin should be used for sustained protection against angina attacks

long-acting (topical ointment, transdermal patches, Ismo, Monoket, Imdur)

___________ nitroglycerin should be used in patients who have failed to respond to other formulations

IV

_____________, loss of hemodynamic and anti-anginal effects after repeated dosing, can occur with nitroglycerin use

tolerance (desensitization)

tolerance, loss of hemodynamic and anti-anginal effects after repeated dosing, can occur with nitroglycerin use

to avoid this we can use ___________ NG dosing

intermittent (to create nitrate-free intervals)

tolerance, loss of hemodynamic and anti-anginal effects after repeated dosing, can occur with nitroglycerin use

to avoid this we can use intermittent NG dosing, which creates ________-______ __________

nitrate-free intervals (12 hours on, 12 hours off)

isosorbide mononitrate has excellent bioavailability after PO administration

intermediate-release tablets, called ___________, are dosed 2x daily and separated by 7 hours

Ismo (Monoket)

isosorbide mononitrate has excellent bioavailability after PO administration

___________-release preparation, called Ismo or Monoket, are dosed 2x daily and separated by 7 hours

intermediate

isosorbide mononitrate has excellent bioavailability after PO administration

intermediate-release tablets, called Ismo or Monoket, are dosed _______ time(s) daily

two (separated by 7 hours)

isosorbide mononitrate has excellent bioavailability after PO administration

intermediate-release tablets, called Ismo or Monoket, are dosed 2x daily and separated by ____________

7 hours

isosorbide mononitrate has excellent bioavailability after PO administration

sustained-release preparation, called ___________, are dosed 1x daily since they have a built-in nitrate-free interval

Imdur

isosorbide mononitrate has excellent bioavailability after PO administration

____________-release preparation, called Imdur, are dosed 1x daily since they have a built-in nitrate-free interval

sustained

isosorbide mononitrate has excellent bioavailability after PO administration

sustained-release preparation, called Imdur, are dosed ________ time(s) daily

one (they have a “built-in” nitrate-free interval)

isosorbide mononitrate has excellent bioavailability after PO administration

sustained-release tablets, called Imdur, are dosed 1x daily since they have a “built-in” __________________

nitrate-free interval

nitroglycerin works by dilating systemic veins

this causes preload (left ventricular end-diastolic pressure) to __________

decrease

nitroglycerin works by dilating systemic veins

this causes ________ (left ventricular end-diastolic pressure) to decrease

preload

nitroglycerin works by dilating systemic veins

this causes ________ ________ stress to be reduced

ventricular wall

nitroglycerin works by dilating systemic veins

this causes CO to ________

decrease (BP= PVR x CO, so BP will also decrease)

nitroglycerin works by dilating systemic veins

this causes O₂ demand to __________

decrease (this is more important than their vasodilator activity)

nitroglycerin works by dilating systemic veins

this causes the workload of the heart to reduce, and in turn reduces myocardial _____ _________

O2 demand (this is more important than their vasodilator activity)

efficacy of nitrates pertains to their ability to decrease ________________, rather than their activity as a coronary vasodilator

O2 demand

MOA: nitroglycerin enter vascular smooth muscle where it is converted to ______ ______

nitrous oxide (NO)

MOA: nitroglycerin enter vascular smooth muscle where it is converted to NO (a potent vasodilator)

NO activates guanylyl cyclase, which increases _______ formation to dephosphorylate myosin

cGMP

MOA: nitroglycerin enter vascular smooth muscle where it is converted to NO (a potent vasodilator)

NO activates guanylyl cyclase, which ___________ cGMP formation to dephosphorylate myosin light-chain phosphate

increases

MOA: nitroglycerin enter vascular smooth muscle where it is converted to NO (a potent vasodilator)

NO activates guanylyl cyclase, which increases cGMP formation to dephosphorylate myosin light-chain phosphate

this causes vascular smooth muscle to __________

relax

MOA: _____________ enter vascular smooth muscle where it is converted to NO (a potent vasodilator)

NO activates guanylyl cyclase, which increases cGMP formation to dephosphorylate myosin light-chain phosphate

this causes vascular smooth muscle to relax

nitroglycerin

nitroglycerin has _______ oral bioavailability

low (<10-20%)

sublingual route is preferred for nitroglycerin and isosorbide dinitrate to avoid _________________

first-pass metabolism

sublingual route is preferred for nitroglycerin and isosorbide dinitrate to avoid first-pass metabolism

this allows it to act fast and the effects usually wear off within ___________

30 minutes

SL nitroglycerin: use 1 dose promptly, then contact EMS is there is no pain relief after _________, or if pain worsens after ________

5 minutes

SL nitroglycerin: use 1 dose promptly, then contact EMS is there is no pain relief after 5 mins, or if pain worsens after 5 mins

continue to take additional SL nitroglycerin, up to _______ doses in ____-minute intervals, while waiting for the ambulance to arrive

3, 5

one common AE of nitroglycerin is __________ caused by meningeal arterial dilation

headache (d/t cerebral vasodilation)

one common AE of nitroglycerin is ______________ caused by arterial dilation in the face

cutaneous flushing

common AEs of nitroglycerin are _________, __________, and/or _________ d/t compensatory effects resulting from baroreceptor reflexes

hypotension, tachycardia, dizziness

nitroglycerin has DDIs and is contraindicated in combination with ___________-inhibitors

phosphodiesterase (sildenafil, tadalafil, or vardenafil)

nitroglycerin has DDIs and is contraindicated in combination with phosphodiesterase-inhibitors like _________. __________, or ___________

Sildenafil, Tadalafil, or Vardenafil

nitroglycerin can only be given with phosphodiesterase inhibitors if it has been 24 hours after taking ________ or ________, or 48 hours after taking ________

Viagra, Levitra (sildenafil, vardenafil)

Cialis (tadalafil)

nitroglycerin has DDIs and is contraindicated in combination with phosphodiesterase-inhibitors like Sildenafil, Tadalafil, or Vardenafil

this is because PIs increase ________ by inhibiting its breakdown, potentiating the action of nitrates

cGMP (makes nitroglycerin act too much —> severe hypotension)

____________ are 1st-line therapy in chronic stable angina (particularity effort-induced)

beta-blockers

beta-blockers reduce myocardial O2 demand by reducing __________, contractility, and ____________

HR, BP (do not use if HR too low or BP too low)

____________ reduce myocardial O2 demand by reducing HR, contractility, and BP

beta-blockers

beta-blockers reduce myocardial O2 demand by reducing HR, contractility, and BP

its also possible they will increase _____________, meaning the heart spends more time in diastole (= decreased HR)

coronary blood flow

beta-blockers reduce myocardial O2 demand by reducing HR, contractility, and BP

its also possible they will increase coronary blood flow, meaning the heart spends more time in _________ (= decreased HR)

diastole

beta-blockers are all equally effective since _____________ may be lost at the high doses needed to treat angina

cardioselectivity

_____________ can be combined with nitrates to prevent reflex tachycardia that can occur with nitrates

beta-blockers (nitrates can increase HR while beta-blockers can decrease HR)

beta-blockers can be combined with ________ (class) to prevent reflex tachycardia that can occur with them

nitrates (nitrates can increase HR while beta-blockers can decrease HR)

beta-blockers are generally well-tolerated, but can cause _____________ d/t beta-2 adrenergic blockade

bronchoconstriction (avoid in pts with asthma)

beta-blockers are generally well-tolerated, but can cause worsening of symptoms of _________ _______ _______ in non-cardioselective drugs

peripheral artery disease (PAD)

CCBs can either be DiHydroPyridines like _________, ___________, or __________, or NON-DiHydroPyridines like ___________ or ________

nifedipine, amlodipine, nicardipine, verapamil, diltiazem

CCBs can either be ___________ like Amlodipine, Nifedipine, or Nicardipine or they can be ___________ like Verapamil or Diltiazem

DHP, NON-DHP

______________ (class) are used in a variety of CV disorders in addition to stable angina like vasospastic angina, HTN, hypertrophic cardiomyopathy, or supraventricular arrhythmias

CCBs

MOA: CCBs can work on the ________ muscles or the __________ msucles

smooth, heart (myocytes)

MOA 1: CCBs block the initial influx of calcium which prevents Ca entry into myocytes, meaning less Ca is around to bind to __________

less of the calcium-_________ complex means less actin—myosin interactions and less myocardial contraction

troponin

MOA 1: CCBs block the initial influx of calcium which prevents Ca entry into myocytes, meaning less Ca is around to bind to troponin

less of the calcium-troponin complex means less _______—_________ interactions and less myocardial contraction

actin, myosin

MOA 1: CCBs block the initial influx of calcium which prevents Ca entry into myocytes, meaning less Ca is around to bind to troponin

less of the calcium-troponin complex means less actin—myosin interactions and less myocardial ____________

contraction

MOA 2: CCBs block the initial influx of calcium which prevents Ca entry into vascular smooth muscle, meaning less Ca is around to bind to _________

less of the calcium-_________ complex means more actin—myosin interactions and more vasodilation

calmodulin

MOA 1: CCBs block the initial influx of calcium which prevents Ca entry into _________, meaning less Ca is around to bind to troponin

less of the calcium-troponin complex means less actin—myosin interactions and less ___________ contraction

myocytes, myocardial

MOA 1: CCBs block the initial influx of calcium which prevents Ca entry into myocytes, meaning less Ca is around to bind to troponin

less of the calcium-troponin complex means ______ actin—myosin interactions and less myocardial contraction

less

MOA 2: CCBs block the initial influx of calcium which prevents Ca entry into vascular smooth muscle, meaning less Ca is around to bind to calmodulin

less of the calcium-calmodulin complex means _____ actin—myosin interactions and more vasodilation

more

MOA 2: CCBs block the initial influx of calcium which prevents Ca entry into vascular smooth muscle, meaning less Ca is around to bind to calmodulin

less of the calcium-calmodulin complex means more ______—________ interactions and more vasodilation

actin, myosin

MOA 2: CCBs block the initial influx of calcium which prevents Ca entry into vascular smooth muscle, meaning less Ca is around to bind to calmodulin

less of the calcium-calmodulin complex means more actin—myosin interactions and more ____________

vasodilation

MOA 2: CCBs block the initial influx of calcium which prevents Ca entry into vascular smooth muscle, meaning less Ca is around to bind to calmodulin

less of the calcium-calmodulin complex means more actin—myosin interactions and more vasodilation

which type of CCBs have greater selectivity for this type of vascular smooth muscle mechanism

DHPs (-dipine)

DHP CCBs have a greater selectivity for __________ muscle and are therefore more potent ________ than Non-DHPs

vascular, vasodilators

________ CCBs have a greater selectivity for vascular smooth muscle and are more potent vasodilators

DHPs (-dipine)

DHP CCBs work by promoting vasodilation —> decreases ________= decreased cardiac workload —> antianginal effects

BP

SEs of DHP CCBs include __________, ________, and/or ________ d/t their potent vasodilation effects

peripheral edema, flushing, headaches (similar to NG)

SEs of _________ (class) include peripheral edema, flushing, and/or headaches

DHP CCBs

Non-DHP CCBs decrease ________ _______ (negative inotrope and negative chornotrope)

myocardial oxygen (less potent vasodilators than DHPs)

________ CCBs decrease myocardial oxygen (negative inotrope and negative chornotrope)

Non-DHP (Verapamil or Diltiazem)

______ CCBs can (and often are) used in combination with beta-blockers

DHP (since they do not lower the BP)

DHP CCBs do not lower BP and therefore can be used in combination with _____________ (class)

beta-blockers (BBs lower the BP already, dont wanna over do it by giving a non-DHP)

______ CCBs cannot be used in combination with beta-blockers

Non-DHP (they decrease myocardial oxygen —> decrease BP)

Non-DHP CCBs cannot be used in combination with _____________ (class)

beta-blockers (both of these classes decrease BP)

____________ antianginal does not reduce HR, BP or vascular resistance

ranolazine

MOA: Ranolazine inhibits late entry of _________ into cardiac myocytes= less ________ inside the cell

sodium

MOA: Ranolazine inhibits late entry of sodium into __________ (cells)

less sodium inside the cell causes an increase in the amount of calcium being pumped OUT of the __________

myocyte

MOA: Ranolazine inhibits late entry of sodium into myocytes

less sodium inside the cell causes a _________ in the amount of calcium being pumped OUT of the myocyte

increase

MOA: Ranolazine inhibits late entry of sodium into myocytes

less sodium inside the cell causes an increase in the amount of _________ being pumped OUT of the myocyte

calcium

MOA: Ranolazine inhibits late entry of sodium into myocytes

less sodium inside the cell causes an increase in the amount of calcium being pumped OUT of the myocyte

reduced accumulation of both Na and Ca in the myocardial cells will decrease __________

contractility (similar to MOA #1 of Non-DHP CCBs)

Ranolazine is used to treat pts with ________ angina who have NOT had adequate responses with other antianginal drugs

stable (chronic)

__________ is used to treat pts with chronic, stable angina who have NOT had adequate responses with other antianginal drugs

Ranolazine

AEs of __________ include QT prolongation and increased BP

Ranolazine

AEs of Ranolazine include __________ and increased _______

QT prolongation, BP

AEs of Ranolazine include QT prolongation and ___________ BP

increased

Ranolazine is contraindicated with patients taking potent inhibitors of _________ (like Diltiazem or Verapamil)

CYP3A4

Ranolazine is contraindicated with patients taking potent inhibitors of CYP3A4, like _______ (antianginal class)

Non-DHP CCBs

______________ is contraindicated with patients taking potent inhibitors of CYP3A4, like Diltiazem or Verapamil

ranolazine

Ranolazine can be used in combination with which class(es) of antianginal drugs

BB, nitrates, DHP CCBs