Anti-Angina

nitrates, beta blockers, CCB

What are the 3 main drug classes used to treat angina?

O2 supply does not meet demand

What causes angina?

plaques, coronary artery spasm

What might cause a decrease O2 supply in the heart?

exertion, stress

What might cause an increased demand in angina?

HR, contractility, afterload, preload

What are the 4 factors that can effect demand?

Arterial oxygen content, coronary blood flow

What are the 2 factors that can effect supply?

pain to arms, neck, jaw, shoulder, back, SOB, sweating, dizziness, syncope, anxiety, nausea, fatigue

What are some classic symptoms of chest pain?

Decrease preload, afterload, MVO2, decrease coronary spasm, increase coronary blood flow

What are the anti-anginal effect of nitrates?

decrease HR, contractility, MVO2

What are the anti-anginal effect of Beta blockers?

increase coronary blood flow (dilate arteries), decrease MVO2

What are the anti-anginal effect of CCBs?

Must be converted to NO

Why is nitrate useless by it self?

dilates veins

What is the primary effect of nitrates?

sulfhydryl donors (only so many of these though)

What converts nitrate to NO?

contractility of the heart

What does nitrate NOT effect?

2-4 min, 1 hour

What is the onset and duration of action for sublingual/buccal glyceryl trinitrate (nitroglycerin (NTG))

decrease intracellular calcium

Why does nitrate lead to the dilation of veins and arteries?

Call EMS (unstable angina)

If chest pain is not relieved in 5 min after 1 NTG what is our game plan?

SL, buccal, IV

What forms of nitroglycerin are available for acute chest pain?

topical ointment, transdermal

What forms of NTG can be used prophylactically?

4-8 hours, 24 hour

What is the duration of action for topical ointment/transdermal glyceryl trinitrate (nitroglycerin (NTG))

Dinitrate (ISDN)

What is the prodrug for mononitrate (ISMN)

Isosorbide (ISDN/ISMN)

What form of nitrate can be given PO in a new formula that overcomes 1st pass effect and is a sustained release?

12 hr gap between doses (normally at night - less activity, less stress on the heart)

Chronic exposure to nitrate leads to the depletion of SH donors, how do we overcome this?

PDE5 inhibitors (viagra, tadalafil, vardenafil)

What is a common DDI for nitrates?

cGMP is not inactivated so we get constant dilation (prolonged hypotension)

What is the MOA for the interaction between PDE5s and nitrates?

postural hypotension, reflex tach, flushing/HA, rash, first pass effect

What are some ADRs associated with nitrates?

avoid sudden positional changes, what to do when symptomatic

Concerning postural hypotension with nitrates, what should you tell your patients?

body is trying to compensate for lower BP caused by vasodilation

Why do you get reflex tach with nitrates?

dilate cerebral arteries (arteries of face/neck)

Why do you get flushing and HA with nitrates?

decrease sympathetic activity, decrease basal HR, decrease contractility

The blockade of the beta receptors in the heart leads to

blocked renin release, decrease angiotensin II, decrease afterload

Blockage of beta 1 receptors on the juxtaglomerular cells in the kidney leads to

HTN, HF

Because we can decrease afterload using beta blockers we can use them to treat?

Mask early hypoglycemia (no tachy, its blocked)

Why are beta blockers scary in the case of diabetics?

bronchoconstriction

Blockage of beta 2 receptors in the lung leads to

carvedilol, labetalol

What beta blockers have alpha blocker activity?

atenolol, bisoprolol, esmolol, metroprolol, nebrivolol, acebutolol (partial agonist)

What beta blockers are B1 selective at a normal dose (hit beta 2s at higher doses)

nadolol, propanolol, timolol, pindolol (partial agonist)

What beta blockers are non-selective?

atenolol, practolol, sotalol

What beta blockers are NOT lipid soluble?

membrane stabilizing activity, intrinsic sympathomimetic activity, liver vs. renal elimination, ADRs

What are some of the differences between the different beta blockers?

bronchospasm

What is an ADR of 1G beta blockers?

maybe peripheral effect on vasodilation

What is the difference between 1G and 2G beta blockers

generation of NO

What is special about nebivolol?

better in BP (block alpha 1), minimal effect on plasma sugar/lipid

What’s so good about 3G beta blockers?

coronary artery spasm, acute termination of exertion-induced angina

Concerning angina, what are beta blockers NOT effective for because they don’t increase oxygen supply?

block sympathetics (no reflex tach)

What is the point of combining beta blockers and nitrates?

may lead to unstable angina and MI

Why do you have to taper a patient off beta blockers?

L-type

What calcium channel is important in the heart because it controls the vasculature in the arterioles, myocardial cells, and AV node

block influx of Ca2+, vasodilation, decrease TPR, decrease MVO2

What is the MOA for CCBs

preload (veins)

What does CCBs have no effect on?

nifedipine

What is the 1st gen DHP CCB?

isradipine, nicardipine, felodipine

What are the gen 2 DHP CCB?

amlodipine

What are the 3rd gen DHP CCB?

verapamil (phenilalkylamines), diltiazem (benzothiazepines)

What are the non-DHP CCBs?

decrease HR, decrease CO, decrease conduction in SA/AV nodes

What is the MOA for the NDHP CCBs?

HF

NDHPs are c/i with

angina, arrhythmias

NDHP is used for

reflex tach

DHP CCBS have more potent peripheral vasodilation which means you have which ADRs?

HTN

DHP CCBs are more commonly used for

CYP3A4 (no grapefruit juice for you)

CCBs are metabolized by

moderate CYP3A4 inhibition (less 1st pass tho)

Why may you need to decrease the dose of NHDP CCBs?

pedal edema, GERD, constipation (verapamil), gingival hyperplasia (nifedipine, isradipine), pain, gingival bleeding

What are the ADRs for CCBs?

inhibit inward sodium current in the heart (decrease intracellular Na, indirectly decrease intracellular Ca2+)

What is the MOA for ranolazine (sodium channel blockers)?

antiarrhythmic, anti-aginal

Ranolazine can be used as a

extensive CYP3A4 metabolism, inhibits CYP2D6

Why does ranolazine have lots of DDI?

HA, dizziness, edema, constipation, QT prolongation

What are some ADRs involved with ranoalzine?

reduces the HR (blocks pacemaker activity)

What is the MOA for ivabradine?

patients with bradycardia

Ivabradine is C/I with

Trimetazidine

What is approved by the european medical agency as a second line anti-anginal when there’s no response to 1st line that is “cytoprotective” since it inhibits fatty acid oxidation but there’s no difference between it and a placebo?

HTN, stress, hyperlipidemia, hyperglycemia, lack of exercise

What are some risk factors for angina