Milane Angina

Pathophysiology of angina

caused by restrictions in blood flow that lead to chest pain

myocardial ischemia

plaque formation → plaque ruptures → blood clot forms

ischemia

low blood flow leading to low O2

reperfusion

regain of blood flow and O2

why is ischemia + reperfusion bad

constant loss and regain of O2 damages cells

stable angina

exertional/exercise-induced

brief (<5 min)

arteriosclerotic plaque buildup

variant/vasospastic/prinzmetal’s angina

spasms in artery of heart

transient vasoconstriction

unstable angina

pain when at rest

emergency situation

thrombus build up

treatment of stable angina

nitrates

CCBs

beta-blockers

treatment of variant angina

nitrates

CCBs

treatment for unstable angina

treat ACS first (anti platelets, ASA, clopidogrel, heparin) + nitrates + beta blockers

for refractory disease: CCBs

exertional angina pathophysiology (in steps)

1. apoB-LPs build up in vessel epithelium & activate inflammatory response

2. monocytes: diapedesis → become macrophages

3. phagocytosis of aggregated apoB-LPs by macrophages

4. macrophages get overloaded w/ apoB-LPs and become foam cells, continue to build up & make artherosclerotic plaque

unstable angina pathophysiology (in steps)

1. foam cell apoptosis

2. macrophage doesn’t eat apoptotic foam cell

3. secondary necrosis: apoptotic foam cell bursts, necrotic core revealed

4. cell debris, cholesterol crystals → impact neighboring cells & fibrous cap

5. fibrous cap weakens & eventually bursts

6. platelet aggregation → thrombus formation

variant angina pathophys

increased contraction b/c of a2-adrenoceptors, increasing oxidative stress

decreased vasodilation b/c decrease of vasodilatory neuropeptides

drug classes that decrease O2 demand

nitrates

beta blockers

CCBs

drug classes that increase O2 delivery

nitrates

CCBs

nitrate prototype

nitroglycerin

nitrate applications

all types of angina

acute coronary syndrome

nitrate MoA

increase cGMP, which decreases Ca2+ which decreases contraction; which dephosphorylates MLC and increases relaxation

beta blocker prototype

propanolol

beta blocker applications

stable, unstable angina

HTN

arrhythmias

migraines

performance anxiety

beta blocker MoA

competitive inhibitors of NE and Epi @ B1 (cardiac) and B2 (smooth muscles, lungs) receptors

decrease HR, BP, contractility, which decreases myocardial O2 requirements at rest and during exercise

beta blocker contraindicated in variant angina why?

blocks b2 receptors, leaves vasoconstriction a1 receptors unopposed, which may worsen angina

CCB prototypes

DHP: nifedipine

non-DHP: verapamil

ranolazine use

used in chronic angina associated w/ ischemic heart disease

ranolazine MoA

inhibits enhanced late Na cannel → prevents Na-Ca exchanger from pumping in Ca and pumping out Na → prevents Ca overload that would trigger arrhythmias

aspirin use

used for unstable angina

aspirin MoA

inhibits COX-1 → prevents cascade that leads to platelet aggregation & activation