-plaque is formed in the lumen of the CA, but is not ruptured, narrowing BVs

-causes inappropriate vasoconstriction

-pt will show symptoms upon increased demand of oxygen and cardiac output

-fibrous cap on plaque in vessel ruptures and causes thrombus formation

-thrombus can cause symptoms with or without added oxygen demand

-symptoms are unpredictable

-thrombus size can increase during rest

variant angina

prinzmetal's

-vasopressors compress CA due to vasospasm which causes angina symptoms independant of plaque formation

-these patients still have plaques

1. endothelial cell activation or injury recruits monocytes and T lymphocytes leading to development of a fatty streak

2. continued stress leads to atherosclerotic plaque

3. macrophage apoptosis and cholesterol deposition cause furher plaque organization which may induce further inflammation (fibrous cap is still intact)

4. continued inflammation leads to thinning of fibrous cap and eventually rupture of the cap.  Exposed plaque materials cause thrombus formation and eventually causes CA occlusion

restore balance between myocardial O2 supply (blood flow -> vasodilators, statins, anti-thrombotics) and demand (afterload, preload, HR, contractility)

Nitrites and Nitrates

MOA

- NO in smooth muscle causes Guanylate cyclase to convert GTP to cGMP which causes decreased calcium uptake and increase packaging of calcium into SR storage

-nitrates, nitrites, and nitroprusside directly release NO into the blood

-causes dilation of venous capacitance vessels

-causes arterial dilation

-improves blood flow through collateral vessels which allows for inc. blood supply to ischemic areas of the myocardium

-interacts with PDE5 inhibitors -> severe hypotension

-must be free of these agents for 12-14 hrs per day in order to not develop tolerance

-increasing activity of NO synthase in endothelial cells increases synthesis of NO from L-Arginine which then diffuses into smooth muscle

- factors that increase NO synthase activity:  bradykinin, acetylcholine, some B-blockers (nebivolol)

-cause arterial dilation

-non DHP's depress rate of SA node pacemaker and slow conduction through the AV node

-increase coronary blood flow -> non-DHP's and DHP's (greater)

Ranolazine

-thought to block transcellular late Na+ current

-by altering intracellular Na dependant Ca channels, preventing the Ca overload

-lower Ca causes lower contractility and HR... also reduces Oxygen demand by changing fatty acid oxidation to glycolysis

-interactions:  non-DHP's, grapefruit juice (cyp3a)

PGP inhibitors (amiodarone)

causes: CAD (~70%), arterial HTN, valvular heart disease, extrinsic cardiomyopathy (ischemic, hypertensive, valvular, alcoholic, diabetic), 

intrinsic cardiomyopathy (dilated, hypertrophic, restrictive)

-impaired relaxation of the LV

-raises LV diastolic pressure

-raises left atrial and pulmonary capillary pressure

-causes fluid overload in the lungs

-inhibits Na/K ATPase -> causes increased sodium in the myocytes which activates the sodium calcium exchanger and causes higher calcium in the myocytes.

-causes increased contractility

-indirectly increases parasympathetic tone which decreases HR, and conduction velocity

-is unique in that it can increase contractility while decreasing HR

-AEs: arrhythmias, GI disturbances, Nuronal disturbances, gynecomastia

positively inotropic drug

-a synthetic dopamine analogue

- a racemic mixture (a1- vasoconstriction and b2 vasodilation cancel out) net effect is B1 agonist

positively inotropic drug

non selective B-agonist (B1- inc HR and contractility, B2 - peripheral vasodilation)

positively inotropic drug

-low doses - causes vasodilation by stimulating dopaminergic receptors on smooth muscle and stimulating presynaptic D2 receptors (dec NE release) similar to A2 receptors in effect

-intermediate doses - stimulates B1 receptors in the heart

-high doses - stimulate a1 receptors

positively inotropic drugs

milrinone, enoximone

-inhibits type III PDE (converts cAMP to 5'-AMP)

-inc conc. of cAMP in cardiac and smooth muscle tissue

-inc cardiac contractility and relaxes vascular smooth muscle

-desensitization does not occur

-additive effects with B-blockers

natriuretic peptide

nesiritide, BNP

-synthetic brain natriuretic peptide normally released from brain and ventricles.  Plasma level is elevated in heart failure

-causes arterial and venous dilation

-increases CO and stroke volume w/o inc in HR

-binds to NP receptors, increasing intracellular cGMP causing smooth muscle relaxation

-used for acute decompensated HF