Antianginal Drugs

Front 1

TNG, NitroStat, isosorbine dinitrate

Back 1

nitroglycerin

Front 2

Pharmacologic class of nitroglycerin

Back 2

organic nitrate

Front 3

Therapeutic class of nitroglycerin

Back 3

antianginal, vasodilator, venodilator

Front 4

Pharmacodynamics of nitroglycerin

Back 4

reacts directly with nitrate receptor on SM cell

sulfhydryl groups in or on receptor reduce organic nitrate (R-NO3) to NO2 and then NO

NO crosses into SM cells and activates guanylate cyclase leading to production of cGMP from GTP

cGMP acits to relax SM cells (probably by dephosphorylation of myosin light chains, making them less likely to react with Actin)

then produces venodilation and vasodilation

Front 5

cGMP with regards to NO

Back 5

NO activates guanylate cyclase which produces cGMP from ATP

cGMP acts to relax SM cells (probably by dephosphorylation of myosin light chains, making them less likely to react with actin)

Front 6

Pharmacokinetics of nitroglycerin

Back 6

well absorbed by mouth, BUUUT very high first pass effect

prompt onset (1-2 minutes) when taken as a SL tablet or spray

can also be given transdermally or iv

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Toxicity of Nitroglycerin

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excessive hypotension, especially if the patient is volume depleted

throbbing headache, flushing

Front 8

Interactions of Nitroglycerin with other drugs

Back 8

excessive hypotension with other vasodilators

severe hypotension if taken with Viagra (sildenafil)

Front 9

Special considerations of Nitroglycerin

Back 9

remove transdermal patch BEFORE defibrillation

use only fresh TNG tablets

tolerance can develop quickly (give 8 hrs holiday qday...never take for 24 hours straight)

Tachyphylaxis (less response after repeated dose)

Take when sitting down, not driving (may get syncopic)

Angina goes away in several minutes by reducing preload and lowering afterload by decreasing BP...increased perfusion by coronary arteries by vasodilation of the coronaries

Front 10

atenolol is a longer acting beta blocker

Back 10

atenolol is a longer acting beta blocker

Front 11

what should i NEVER do with beta blockers??

Back 11

never withdrawal beta-blockers abruptly!!!

the abrupt increase in HR, BP, contractility, etc, can lead to abrupt increase in angina or even MI...REBOUND

Front 12

Tenormin, propranolol, metoprolol

Back 12

same class as Atenolol

Front 13

Pharmacologic class of Atenolol (propranolol, metoprolol)

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beta adrenoceptor blocker

beta 1 specific

Front 14

Therapeutic class of Atenolol

Back 14

antihypertensive, antiarrhythmic, primary and secondary prevention of MI, anti-anginal

Front 15

Pharmacodynamics of Atenolol

Back 15

binds directly to beta-receptors, with a preference for beta-1 over beta-2

leads to lower BP via several potential mechanisms

(less CO, less activation of RAA system)

Front 16

Pharmacokinetics of Atenolol

Back 16

available po or iv

variable oral F

onset 1-2 hours

duration: 12-24 hours

can be given once pre day

renally excreted (longer half-life)

Front 17

Toxicity of Atenolol

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excessive hypotension

bradycardia

heart block can worsen severe CHF (but indicated for mild to moderate CHF)

worsen bronchospasm in severe asthmatics

Front 18

Interactions of atenolol with other drugs

Back 18

additive effects with most other antihypertensives

additive AV block with CEB's

Front 19

Special considerations for atenolol

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may be especially useful in HTN patients with exertional angina, MI, atrial fibrillation

watch out for abrupt withdrawal

its generic, so its cheaper

Front 20

Verapamil

Back 20

Isoptin, Calan, similar to nifedipine, amlodipine, and diliazem

Front 21

Pharmacologic class of Verapamil

Back 21

calcium entry blocker

Front 22

Therapeutic class of Verapamil

Back 22

antihypertensive, antianginal, and antiarrythmic

Front 23

Pharmacodynamics of verapamil

Back 23

reduces BP by inhibiting the influx of calcium through "slow channels"

thereby dilating peripheral arterioles

produces negative inotropic effects as well

for angina: reduces afterload, thus decreasing oxygen consumption

inhibits spasm of coronary arteries in vasospastic angina

blocks re-entry paths through AV node in paroxysmal SVT

Front 24

Pharmacokinetics of verapamil

Back 24

absorbed rapidly, but F = 30%

available in SR tablets

cleared by kidney and liver (produces active metabolites)

onset 2 hours po

1-5 minutes iv

half life is 6-12 hours

Front 25

Toxicity of verapamil

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hypotension, AV block, worsening of CHF, and bradycardia

Front 26

Interactions with other drugs and verapamil

Back 26

additive effects with most other antihypertensives

additivie toxic effects on heart when given with beta-blockers

Front 27

Special considerations of verapamil

Back 27

used reduced doses in patients with both renal and hepatic disease

short acting nifedipine (and similar CEB's) can increase risk of MI (unclear why)

pregnancy C

Front 28

For vasospastic angina

Back 28

whether spontaneous or induced, can be dramatically reversed by intracoronary nitroglycerin (observed in cath lab)

BETA BLOCKERS ARE CONTRAINDICATED!!! (because if you give beta-blockers, alpha 1 vasoconstriction will be left unopposed...make it worse)

Use CEB's because of their direct vasodilating action

Front 29

What is vasospastic angina

Back 29

primarily caused by sudden vasospasm of a major coronary artery (which may also be involved with atherosclerosis)

may also be related (or induced) by catecholamines, etc.

Front 30

Do NOT use beta blockers for what?

Back 30

vasospastic angina

Front 31

Unstable angina

Back 31

this is a crescendo angina, preinfarction angina...all phrases that describe angina that is rapidly worsening in terms on intensity of pain, frequency, timing, trigger, duration, response to treatment, etc

most often involves a chronically narrowed artery WITH THE ACUTE DEVELOPMENT OF A RUPTURED PLAQUE

must treat with suppression of platelet adhesion and aggregation

Front 32

Aspirin

(other names)

Back 32

Bayer, Acriptin, Halfprin, many others

Front 33

Pharm class of Aspirin

Back 33

salicylate

Front 34

Therapeutic class of Aspirin

Back 34

analgesic, anti-inflammatory, antiplatelet, antipyretic

Front 35

Pharmacodynamics of Aspirin

Back 35

at low doses (below 325 mg/day) tends to irreversibly inhibit COX in platelets, leading to decreased formation of thromboxane A2 (vasoconstrictor and platelet aggregator) and transiently inhibits COX in endothelium, leading to transient decreased formation of prostacyclin (PGI2...vasodilator, inhibitor of platelet aggregation)

Front 36

Thromboxane A2

Back 36

vasoconstrictor, platelet aggregator

Front 37

Prostacyclin

(PGI2)

Back 37

vasodilator

inhibitor of platelet aggregation

Front 38

Pharmacokinetics of Aspirin

Back 38

F = 60%

T max is variable

Metabolized to salicylate

half life 3-4 hours

duration 4-24 hours

90% excreted as salicylate metabolites in urine

Front 39

Toxicity of aspirin

Back 39

especially at high doses can cause ulceration of GI tract, bleeding disorders, and tinnitus

Front 40

Interactions of aspirin with other drugs

Back 40

inhibits tubular secretion of methotrexate, potentiate bleeding from warfarin

Front 41

Special considerations of Aspirin

Back 41

avoid in patients with nasal polyps and asthma

regular, buffered, enteric coated

Front 42

COX 2 inhibitors

Back 42

selectively inhibits the production of PGI2 (which we said was a vasodilator, inhibitor of platelet aggregation)

this causes worse platelet aggregation

patients had excess strokes and heart attacks

Front 43

Clopidogrel

(common name)

Back 43

Plavix

Front 44

Therapeutic class of clopidogrel

Back 44

platelet aggregation inhibitor

Front 45

Pharmacodynamics of Clopidogrel

Back 45

blocks ADP receptors, which then helps prevent aggregation mediated by ADP released by an activated platelet from recruiting other platelets

useful in primary or secondary prevention of TIA, stroke, angina, MI, PCTA, ACS, stent procedures, etc.

Front 46

Pharmacokinetics of Clopidogrel

Back 46

well absorbed

onset 1-2 hours after oral dose

hepatic metabolism

half life -8 hours

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Toxicity of Clopidogrel

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hemorrhage at virtually any site

Front 48

Interactions of Clopidogrel with other drugs

Back 48

may inhibit CYP 3A4

Front 49

Special considerations of Clopidogrel

Back 49

careful risk/benefit assessment in each patient

ITS QUITE EXPENSIVE

Front 50

Abciximab

(other names)

Back 50

ReoPro

Tirofiban/Aggrastat

Eptifibatide/Integrilin

Front 51

Pharm class of abciximab

Back 51

Fab fragment chimeric monoclonal antibody

Front 52

Therapeutic class of abciximab

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adjuct to PCL to prevent ischemic complications

Treatment of MI

Front 53

Pharmacodynamics of Abciximab

Back 53

noncompetitive inhibitor of the GP IIb/IIIa receptor

prevents binding of fibrinogen, vWF, and other adhesive ligands to the receptor on activated platelets

need to block > 80% of these receptors to maximally inhibit platelet

Front 54

Pharmacokinetics of Abciximab

Back 54

IV bolus followed by IV infusion

half life about 30 minutes

bleeding time declines to <12 minutes with 12 hours of stopping infusion

Front 55

Toxicity of Abciximab

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contraindicated in presence of aneurysm, AV malformation, bleeding, coagulopathy, GI bleed, intracranial mass, retinal bleeding, stroke, surgery, low platelet, trauma, and fasculitis

Front 56

Interactions of Abciximab

Back 56

additive effects with aspirin, clopidogrel heparin, low dose t-PA

Front 57

Special considerations of Abciximab

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exact role is still being defined, and evolves over time

cost is a big factor

Front 58

More about NO...its an EDRF

Back 58

endothelium derived relaxing factor

Front 59

Produce NO directly

Back 59

NO and nitroprusside

Front 60

Drugs that encourage the production of NO from endothelial cells

Back 60

Acetylcholine, histamine, bradykinin, serotonin, substance P

Front 61

Other effects of NO

Back 61

inhibition of platelet aggregation, phagocytosis, excitatory neurotransmission in CNS

Front 62

Propranolol is NOT

Back 62

cardioselective

Thus, other beta-blockers like metoprolol, acebutolol, or atenolol are preferred

important for asthmatics

Front 63

Pindolol has...

Back 63

intrinsic sympathomimetic activity

less effective in anti-angina endeavors and should be avoided

Front 64

Beta blockers have been shown to...

Back 64

prolong survival

Front 65

Beta blockers are contraindicated in...

Back 65

patients with asthma, diabetes, severe bradycardia, peripheral vascular disease, or COPD

Front 66

Make sure to do what with Beta blockers??

Back 66

do NOT discontinue abruptly

gradual tapering of the dose over 5-10 days to avoid rebound angina or hypertension

Front 67

Calcium channel blockers

Back 67

decrease the inward current carried by calcium, resulting in a decreased rate of Phase 4 spontaneous depolarization

slow conduction in tissues that are dependent on calcium currents, such as the AV node

MAJOR EFFECT IS ON VASCULAR SM AND THE HEART

all calcium channel blockers are therefore vasodilators that cause a decrease in SM tone and vascular resistance

used for vasospastic angina: NOT beta blockers (because if beta blockers were used, alpha 1 vasoconstriction would go about unopposed)

Front 68

Verpamil mainly affects:

Nifidepine mainly affects:

Diltiazem mainly affects:

Back 68

Verapamil: myocardium (greater inotropic decreasing effects, but worse vasodilator..greatly metabolized in the liver)

Nifedipine: more effect of SM in peripheral vasculature

Diltiazem: somewhere in between; cardio effects similar to diltiazem, but not as potent...can releive coronary artery spasm...extensively metabolized in the liver)