Part 1 of Pharmacology for CAD and Stroke Flashcards
Define MI
Imbalance between myocardial oxygen supply and demand
Contributing factors to MI
Increased sympathetic outflow (increase HR, tensin, contractility)
Decreased coronary blood flow (vasospasm, coronary atherosclerosis)
Define CAD
Coronary arteries are narrowed by formation of atherosclerotic plaque
Reduced blood flow
Unstable angina
Thin fibrous cap
Main symtpoms of MI
Angina pectoris
Decreased exercise tolerance
Characteristics of MI
Sudden interruption of blood supply to myocardium (occlusion) by rupture of plaque resulting in thrombosis
Myocardial function is compromised by tissue and can die
Short term goals of therapy
Prevent/reduce angina
Long-term goals of therapy
Prevent events of myocardial ischemia and reduce mortality
Drugs for treatment of MI do what?
Improve the balance between supply and demand
- Dilate coronary vasculature
Reducing cardiac workload
Organic Nitrates
Produgs
Release NO which is a potentvasodilator
MOA of NO
Stimulates cGMP which stimulates kinase which cause SMC relaxation
Hemodynamic effects of Low dose Nitrates
Dilate veins
Decrease venous return and preload
Decrease chamber size of the heart
Hemodynamic effects of High dose Nitrates
Further venous pooling and decrease arteriolar resistance
- Activate sympathetic reflexes (tachycardia)
- Increase coronary BF but will decrease if BP or CO decrease
Total and regional CV effects of Nitrates
Vasodilate and restore flow in epicardial vessels
Do not impair autoregulation in smaller vessels
Decrease systolic and diastolic pressures (increased BF to subendocardium
Dilate cardiac veins
Anti-anginal effects of Nitrates
Reduce venous return and myocardial oxygen demands (primary)
Dilate epicardial coronary arteries –> improved BF
NO in platelets –> anti-platelet (important)
Nitrates + Tolerance
Potency is decreasing!!!
Side effects of Nitrates
Headache
Rash
Hypotension
Nitrates CAUTION
Not in combo with PDE5 inhibitors because of hypotension
PDE5 inhibitors are
Sildenafil
Tadalafil
Vardenafil
PDE% inhibitors do what?
Inhibit conversion of cGMP to GMP –> MAJOR vasodilation which can cause hypotension and coma!!!
What beta receptors are in the heart?
Beta 1
What beta receptors are in the peripheral
Beta 2
What are effects of stimulating beta 1
Tachycardia
Increased inotropic, dromotropic and chronotropic
Increased oxygen demand
Why are beta-blockers used in IHD?
Target oxygen demand
Beta blockers are used to treat:
Exertional angina (reduce severity and frequency & cardioprotective) UA/MI (reduce recurrent episodes, improved mortality)
Beta blocker CAUTION
In patient with limited cardiac reserve
Can decrease left ventricular function profoundly
DHP work where?
More drugs in the class (more blood vessels than heart) –> work in the periphery
What CCBs can be used in IHD?
DHP and Non-DHP
DHP action
Decrease peripheral resistance and coronary vasodilation
Parenteral anticoagulants
Heparin and LMW heparin facilitate binding of thrombin to anti-thrombin –> several coagulation factors (fibrinogen, etc) are not activated
Oral anticoagulants
Warfarin
Inhibits vitamin K epoxide reductate so vitamin K is not reduced to activate coagulation factors
Anticoagulants are used to:
Prevent progression of thrombus and embolism
Reduce recurrent episodes of UA and MI
Used in combo
TXA2, Thrombin, ADP, Collagen do what?
Activate platelets
Activated platelets do what?
Form the initial hemostatic plug at site of vascular injury –> thrombus
Aspirin
Inactivates COX-1 and inhibits TXA2
Doesn’t effect COX-2
TXA2 is involved in
Platelet aggregation and vasoconstriction
Aggrenox is composed of:
Aspirin
Dipyridamole ER
Dipyridamole MOA to decrease platelet aggregation and activation
Inhibits adenosine uptake –> increase adenosine on the surface –> A2 receptor stimulated –> Increased cAMP in platelets
Dipyridamole MOA for SMC
Inhibit PDE –> Increased cGMP –> NO acts on cGMP –> SMC relaxations
Aggrenox Side effect
Headache
