CAD Pharmacology

Question 1

Aspirin

Answer 1

Class: NSAID

Mech: Irreversible inhibition of platelet cyclooxygenase which blocks thromboxane A2 formation preventing platelet aggregation.

Thera: Reduction of adverse events (MI, stroke, death) in those with stable angina, unstable angina, MI
Also used as prophylaxis in asymptomatic individuals

Misc: Can cause asthma if allergic

Question 2

Ticlopidine

Answer 2

Class: Thienopyridine derivative

Mech: Inhibits platelet aggregation induced by adenosine diphosphate. It also reduces blood viscosity by decreasing plasma fibrinogen and increases red cell deformity

Thera: Aspirin alternative although has not shown decrease in adverse events in patients with stable angina

Tox: Neutropenia and rarely TTP

Question 3

Clopidogrel

Answer 3

Class: Thienopyridine derivative

Mech: Selectively and irreversibly inhibits the binding of ADP to its platelet receptor (glycoprotein IIb/IIIa) preventing platelet aggregation

Thera: Great antithrombotic (used for new stents)

Tox: Serious bleeding

Misc: Not for chronic use due to serious risk for bleed. Cannot do surgery while patient is on this.

Question 4

Prasugrel

Answer 4

Class: Thienopyridine

Mech: Irreversibly binds to the P2Y12 receptor (GPIIb/IIIa) preventing ADP from binding and platelets from aggregating

Thera: Reduce thrombotic cardiovascular events during an ACS for which patient received PCI (most potent)

Tox: Serious risk of bleed

Misc: Limited to patients less than 75 years old, greater than 60kg and no history of CVA or TIA

Question 5

Ticagrelor

Answer 5

Mech: Similar in structure to ADP so provides reversible block of GPIIb/IIIa

Thera: ACS

Tox: Bleeding greater than clopidogrel

Misc: Does not require hepatic activation
Faster onset of action and eliminated faster requiring bid dosing

Question 6

Dipyridamole

Answer 6

Class: Pyrimido-pyrimidine

Mech: Increases cAMP in platelets which inhibits PDE5, activates adenylate cyclase, inhibits uptake of adenosine from vascular endothelium and RBCs

Thera: Decrease peripheral vascular disease therefore used for stress testing as dilates coronary arteries (increased extracellular adenosine)

Tox: Can lead to coronary stealing (exercise induced ischemia)

Question 7

Cilostazol

Answer 7

Class: Quinolinone derivative

Mech: Inhibits cellular phosphodiesterase increasing cAMP which results in inhibition of platelet aggregation and also causes vasodilation

Thera: Treatment for claudication in people with peripheral vascular disease

Tox: Increased morbidity/mortality in patients with CHF

Question 8

ACE inhibitors

Answer 8

Mech: Blocks endothelial ACE from converting AI to AII and also prevents the breakdown of bradykinin (potent vasodilator)

Thera: Add-on antihypertensive for anyone with chronic kidney disease/proteinuria, CHF, LVH, or post MI (prevents remodeling)
Also reduces risk of future CAD events
May reduce risk for diabetes

Tox: Cough, hypotension, hyperkalemia, angioedema, decreased renal function

Misc: Short-acting, contraindicated in pregnancy, renal artery stenosis, hyperkalemia, and prior angioedema (no ARB either), caution in renal failure

Question 9

Beta Blockers

Metoprolol, Atenolol, Bisoprolol

Answer 9

Mech:  Decrease contractility, HR causing reduced O2 demand
Also a class II antiarrhythmic by inhibiting SNS influence on cardiac electrical activity, increases AP duration and effective refractive period in AV node

Thera: Prevent MIs, prevent sudden cardiac death, increase survival post-MI, reduce angina and ischemia

Tox: Fatigue, worsening claudication, impotence, decreased exercise tolerance, lethargy, insomnia

Misc: Contraindicated in severe brady, high degree AV block, sick sinus syndrome, unstable LV failure, asthma, severe depression, peripheral vascular disease

Question 10

Nitrates

Answer 10

Class: Vasodilator

Mech:  Endothelium independent vasodilator (Activates guanylyl cyclase to form cGMP which inhibits Ca entry into the cell).  Predominately a venodilator (relieves preload and subsequent contractility)
Endothelial effects (inhibits platelet aggregation, inhibits leukocyte endothelial interactions (anti-inflammatory).

Thera: Acute episodes of angina

Tox: Tolerance with chronic use (need nitrate free periods of 8-12 hours), headaches, hypotension, activation of Bezold-Jarisch reflex (causes bradycardia)

Misc: Contraindicated in hypertrophic cardiomyopathy, severe aortic stenosis, significant hypotension, use of PDEi (ED treatments)

Question 11

Dihydropyridines

Nefedipine (1st generation), Amlodipine, Felodipine, Isradipine

Answer 11

Class: Ca Channel blockers

Mech: Interact with L-type VG Ca channels decreasing calcium entry into the vascular smooth muscle cell, preventing contraction, and causing dilation of coronary arteries and arteriolar resistance arteries (Nefedipine is 1st generation and has some negative inotropic effect)

Thera: HTN, Raynauds, angina (3rd choice drug) for Nefedipine and Amlodipine

Tox: Leg edema, HF, AV nodal blockade, bradycardia, flushing, headache, constipation, hypotension

Misc: Contraindicated in overt decompensated HF, bradycardia, sinus node dysfunction, high-degree AV block

Question 12

Nondihydropyridines

Verapamil, Diltiazem

Answer 12

Class: Calcium channel blocker

Mech: Interact with L-type VG Ca channels decreasing calcium entry into the vascular smooth muscle cell, preventing contraction, and causing dilation of coronary arteries and arteriolar resistance arteries
Causes decreased contractility, firing rate of aberrant pacemaker sites, and conduction velocity, prolongs repolarization in SA node and AV node (decreases HR). LESS VASODILATION

Thera: HTN, anti-anginal (chronotropic effects) Arrhythmic

Tox: Leg edema, bradycardia, AV nodal blockade, hypotension, worsening heart failure, constipation, headache, flushing

Misc: Contraindicated in overt decompensated HF, bradycardia, sinus node dysfunction, high-degree AV block