Anti-Anginal Flashcards
what is angina
A lack of sufficient oxygen (ischemia) to the heart causes pain, “angina”
why does angina happen
Coronary artery obstruction limits blood supply to part of the myocardium
Atherosclerosis and thrombosis blocks blood flow (unstable angina)
Vasospasm blocks blood flow (variant or Prinzmetal’s angina)
Coronary circulation can meet oxygen demands of myocardium at rest, but not when heart work increased by exercise (exertional angina) due to atherosclerosis.
types of angina
unstable
variant
exertional
what is an unstable angina
Recurrent angina associated with minimal exertion
Prolonged and frequent pain
Thought to be due to fissuring of atherosclerotic plaques and subsequent platelet aggregation
High correlation with myocardial infarction
what is variant angina
a direct result of reduction in coronary flow due to vasospasm, not an increase in myocardial oxygen demand
Normal coronary angiograms
Excellent prognosis
what is exertional angina
usually due to fixed coronary vascular obstruction (surgical revascularization or angioplasty may be beneficial)
approaches for treating angina
Increase coronary blood flow (Nitrates, CCB)
Reduce myocardial oxygen consumption (mvo2) by:
Prevent platelet deposition/aggregation: aspirin
Coronary artery bypass surgery and eluting stents
how do you reduce the myocardial oxygen consumption?
NEGATIVE CHRONOTROPIC EFFECT: decrease heart rate
NEGATIVE INOTROPIC EFFECT: decrease myocardial contractility
Decreased ventricular workload (wall stress): Reduced preload (venodilation) Reduced afterload (vasodilation)
Cellular Mechanism for anti-Anginal action of Nitrates (nitrovasodilators)
denitration to release nitric oxide (NO) which activates guanylate cyclase and elevates intracellular cyclic GMP producing relaxation of vascular (and other) smooth muscle and produces venodilation and coronary vasodilation (endogenous NO produced by nitric oxide synthase)
Cardiovascular Venodilation Effects of Nitrates
results in decreased preload
decreased pressure during diastole in ventricles of heart and reduced wall stress and McO2
Cardiovascular Vasodilation Effects of Nitrates
redistribution of blood flow to areas of ischemia
Selective dilatation of epicardial and collateral coronary vessels
prevents or reverses coronary vasospasm
Overall effect on hemodynamics (nitrates)
(at usual antianginal doses)
BP: unchanged or slight decrease
HR: unchanged or slight increase
Pulmonary Vascular Resistance: decreased
Cardiac Output: reduced (slight)
adverse effects of nitrates
hypotension
headache
drug rash
contraindication of nitrates
Do not take Sildenafil with Nitrates
recommended dose of nitrate
8-12 hour “nitrate free” interval each day, usually at night but in some individuals during day
MOA of non-dihydropyridine
Ca2+ channel blockers
Non-dihydropyridine
Verapamil
Diltiazem
Effects of non-dihydropyridine
decreased heart rate
decreased myocardial contractility
slowed AV conduction
reduces MvO2 by reducing heart rate, contractility, afterload
prevents or reverses vasospasm (coronary vasodilation)
MOA of dihydropyridine
Ca2+ channel blockers
reduced afterload, coronary vasodilation
more potent vasodilators = reflex cardiac stimulation
dihydropyridines
nifedipine
felodipine
dihydropypridine effects
heart rate, myocardial contractility usually unchanged
AV node conduction unaffected
reduces MvO2 by reducing afterload
when to use dihydropyridine-type?
In combination with ß-Blocker for coronary vasodilation, reduced afterload. (avoid Verapamil/Diltiazem + β-Blocker… AV block)
Sinus bradycardia, SA/AV block
Valvular Insufficiency (Aortic, Mitral): reduces afterload
when to use non-dihydropyridine-type?
Asthma/Bronchospastic COPD (cannot use beta-blockers)
Severe Peripheral Vascular Disease with rest painDepression
Labile (variable glucose levels) insulin dependent diabetes
MOA of antianginal effect of B-blockers
Reduce afterload (CNS)
Do not reduce preload (may paradoxically increase short term).
Do not prevent coronary vasospasm
drug of choice of angina
B blockers
Cardiac effects (β1AR) are responsible for therapeutic effects
reduce resting heart rate, myocardial contractility
attenuate increased heart rate, contractility in response to exercise
reduces myocardial oxygen consumption
Non-cardiac effects (β2AR) are responsible for many adverse effects of β-blockers
Bronchospasm
Hypoglycemia
lethargy, confusion, nightmares
alopecia (hair loss)
B Blocker contraindications
Sinus bradycardia
SA/AV block
decompensated CHF
Labile or “brittle”
Diabetes, Asthma
COPD
what does withdraw from B blocker cause
rebound tachycardia, unstable angina or MI
what B-blockers used for unstable angina
nitrates
aspirin
heparin
B-blockers action on exertional angina
reduces HR
myocardial contractility
action of B blocker on vasopastic angina
ineffective
impact of B blocker on myocardial infarction
Reduce chest pain, ST elevation, cardiac enzyme elevation
Reduced Ventricular ectopy and ventricular fibrillation
Reduced reinfarction and ischemic episodes during hospitalization
Reduced mortality during 2-3 years following MI
treatment plan for acute MI/Unstable Angina
ß-blocker IV following by PO therapy provided no CHF, hypotension, or sinus bradycardia/heart block
MOA of Ranolazine (RANEXA®)
Partial fatty acid oxidase inhibitor, increasing glucose oxidation and efficiency of O2 utilization in the heart.
Late sodium current inhibitor with NO effect on HR or BP. It reduces sodium overload and hence ameliorates disturbed ion homeostasis.
what is Ranolazine (RANEXA®)?
Novel metabolic modulator
Ranolazine (RANEXA®) indications
chronic stable angina in combination with amlodipine, ß-blockers or nitrates`
adverse of Ranolazine (RANEXA®)
Dizziness, headache, constipation, nausea
Syncope and asthenia
contraindications Ranolazine (RANEXA®)
Concurrent use of CYP3A4 inhibitors (grape fruit juice, verapamil, diltiazem and others)
Use of tricyclic antidepressants, fluoxetine, Haldol, nefazodone
Digoxin concentrations increase 40-60% through p-glycoprotein inhibition.
Pregnancy category C.
Cost: expensive adjunct therapy with marginal benefit
IC50
Ranolazine has the lowest IC50 in inhibiting late sodium current in the heart
aspirin
provide after unstable angina or MI
reduces reinfarction and CHD death
reduces stroke
warfarin has comparable effect but is costly and has higher morbidity.
T/F: All patients with CHD should receive aspirin therapy unless contraindicated
TRUE
ACE inhibitors
Improve survival Post-MI with LV dysfunction (SAVE, AIRE, GISSI-3)
Reduces MI in high risk patients (HOPE study, Ramipril)
revascularization
Surgical and interventional revascularization is an invaluable adjunct to treatment of medically refractory angina: including: coronary angioplasty, coronary atherectomy, intracoronary laser, coronary artery bypass grafting (CABG)
thrombolytic therapy
results in myocardial salvage, reduction in mortality within first year following MI
LDL reduction with HMG-RI
reduces recurrent MI
may acutely stabilize coronary plaque
HDL raising/Triglyceride Lowering
reduces recurrent MI/CHD death (Helsinki, LRC-CPTT,VA-HIT) (gemfibrozil, niacin)
MOA of nitrates
coronary vasodilation reduced preload (venous) reduced afterload (aterial)
MOA of nifedipine
coronary vasodilation reduced afterload (aterial)
MOA of non-dihydro-P
coronary vasodilation
reduced heart rate
decreased contractile force
reduced afterload (aterial)
MOA beta-blocker
reduced heart rate
reduced contractile force
reduced afterload (aterial)
