3-1: 9/6: Pharmacology: Angina And Acute Coronary Syndrome

Front 1

What is stable angina?

Back 1

Chest discomfort due to exertion and relieved by rest

Due to imbalance of O2 supply (inadequate blood flor/oxygenation) and O2 demand (wall tension, HR, contractility)

Need 70% occlusion of artery before get angina (atherosclerosis is main cause)

Front 2

What pathologic changes occur with increasing degree and duration of ischemia?

Back 2

In order:
Ischemia
Diastolic Dysfn
Regional Systolic Dysfn
Electrical Transit Abnrmlts
Chest Pain

Front 3

What is unstable angina?

Back 3

Angina at rest

Front 4

What define a myocardial infarction? Describe subtypes.

Back 4

Myocardial cell necrosis due to reduction in blood supply

ST elevation MI: due to acute, total coronary occlusion-thrombus (almost always component of obstruction)

Non-ST elevation MI: due to partial or transient total coronary occlusion, may be due to thrombos, due to excess in demand

Front 5

What drug categories are used in the treatment of acute coronary syndrome?

Back 5

Acute coronary syndrome is a term used for any condition brought on by sudden, reduced blood flow to the heart.

Treatment includes:
Antithrombins (Heparins, Direct Antithrombins)
Antiplatelet Agents (ASA, Thienopyidines, GP IIbIIIa receptor inhibitors)

Front 6

Unfractionated Heparin:
Mechanism
AEs

Back 6

Indirectly acting, binds antithrombin-3 to inhibit clotting factors (thrombin; Factor XA)
Also activates platelets

Must be delivered IV and continuously

AEs:
Bleeding!
Heparin-induced Thrombocytopenia (platelet drop)--HIT-1 is mild, HIT-2 is serious (due to chronic use of heparin; large risk of thrombus)

Front 7

Low-Molecular Heparin:
Mechanism

Back 7

Anti-Factor Xa effect
Potentially more effective than unfractionated heparin
Less platelet activation than UFH

Inhibits platelet-bound Factor Xa (UFH does not)
Longer half-life
Less likely to cause HIT

Front 8

Enoxeparin:
Drug Class

Back 8

Low-Molecular Heparin
(Lovenox)

Front 9

Direct Thrombin Inhibitors:
Mechanism

Back 9

Inactivate fee thrombin and fibrin-bound thrombin; do not require antithrombin factor

Front 10

Bivalirudin:
Drug Class

Back 10

Direct Acting Thrombin INhibitor
(Angiomax)

Less renal excretion, less bleeding than heparin

Administered IV as substitute for UFH in pts with ACS

Front 11

Fibrinolytic Drugs:
Uses
Mechanism

Back 11

Used in setting of STEMI

Mech: converts plasminogen to plasmin (plasmin degrades fibrin, fibrinogen); acts on circulating factors, so get systemic effect (can't just act on particular thrombus)

Front 12

Aspirin:
Mechanism

Back 12

Acetylates COX-1 (cyclo-oxygenase), causing it to become irreversibly inactivated, thus preventing synthesis of Thromboxane A2, platelet activation is inhibited

Front 13

Thienopyridine Derivates:
Mechanism

Back 13

Inhibit ADP-dependent pathway of platelet activation

Front 14

Clopidogrel:
Drug Class
Use
AEs

Back 14

Thienopyridine Derivative

***This is a pro-drug; has to be metabolized before can exhibit effect

Use: Seconday prevention of CV dz; percutaneous coronary interventions (especially stents), ACS

AE: Mild increases in overall bleeding

Front 15

Ticlopidine:
Drug Class
AEs

Back 15

Thienopyridine Derivative

This is a pro-drug; has to be metabolized before can exhibit effect

AE's: Neutropenia, TTP, serial monitoring required (use is limited because of toxicity)

Front 16

Why are clopidogrel and ticlopidine have variable efficacy in patients?

Back 16

They're pro-drugs and need to be metabolized before become active.

Front 17

Clopidogrel:
Limitations

Back 17

Delayed onset of antiplatelet efects (several hours)
Substantial variability in response (absorption, medication interactions, SNPs)

Front 18

Prasugrel:
Drug Class
Uses
AEs

Back 18

Thienopyridine Derivative

No interactions with inducers/inhibitors of cytochrome p450 system, much more potent than clopidgrel (Plavix)

Used for high risk patients because of bleeding complications (STEMIs)

Front 19

Glycoprotein IIb/IIIa Antagonists:
Mechanism
Uses

Back 19

Monoclonal Ab's against GP IIbIIIa receptor (receptor for fibrinogen which plays role in platelet activation)

Reserves for cath lab (angioplasty)

Front 20

Abciximab:
Drug Class
Uses

Back 20

GP IIbIIIa Receptor Antagonist

Primarily reserved for cath lab (angioplasty)

Front 21

Tirofiban:
Drug Class

Back 21

GP IIbIIIa Receptor Antagonist

Reversible small molecule

Front 22

Eptifibitide:
Drug Class

Back 22

GP IIbIIIa Receptor Antagonist

reversible small molecule; effective for use in ACS pts

Front 23

Real Clinical Practice:
Treating ACS

Back 23

ASA

At least 1 antithrombin (UFH or enoxeparin)

Clopidogrel or prasugrel unless need a CABG

GPIIbIIIa inhibitor for high risk pts going to cat lab (PCI--percutaneous catheterization intervention??)

Front 24

Real Clinical Practice:
Secondary Prevention of CAD

Back 24

ASA or clopidogrel

Front 25

Organic Nitrates:
Mechanism
AEs

Back 25

Supply: selective vasodilation of epicardial coronary arteries to increase supply

Demand: reduction in systemic BP and LV volume to decrease myocardial O2 consumption

AE's:
Tolerance (lack of response; need nitrate free interval of 12-14 hours; usually while asleep)

Headache, hypotn, syncope

Front 26

Nitroglycerin:
Drug Class
Uses
Contraindications

Back 26

Organic Nitrate

Relieves angina

Contra: Hypotn, volume depletion, phosphodiesterase inhibitors (ED drugs), RV infarct

Front 27

Isosorbide:
Drug Class
Uses
Contraindications

Back 27

Organic Nitrate

Relieves angina

Contra: Hypotn, volume depletion, phosphodiesterase inhibitors (ED drugs), RV infarct

Front 28

Propranolol:
Drug Class

Back 28

Non-selective beta-blocker (blocks beta-1, beta-2)

Front 29

Metopolol:
Drug Class

Back 29

Selective beta-blocker (blocks beta-1)

Front 30

Atenolol:
Drug Class

Back 30

Selective beta-blocker (blocks beta-1)

Front 31

Beta-blockers:
Mechanism

Back 31

Reduce heart rate via beta-receptor antagonism
Reduce BP and contractility

Front 32

Verpamil:
Drug Class
Mechanism

Back 32

Calcium channel blocker

Predominantly negative chronotropic/ionotropic effect

Mech: reduce heart rate, reduce contractility

Front 33

Diltiazem:
Drug Class
Mechanism

Back 33

Calcium channel blocker

Balanced negative chronotropic/ionotropic effect and vasodilatory effect

Mech: Reduce heart rate

Front 34

Amlodipine:
Drug Class
Mechanism

Back 34

Calcium channel blocker

Balanced negative chronotropic/ionotropic effect and vasodilatory effect

Mech: Epicardial and arteriolar vasodilation

Front 35

Nifedipine:
Drug Class

Back 35

Calcium Channel Blocker

Predominant vasodilatory effect

Mech: Epicardial and arteriolar vasodilation