B4-050 Treatment of Angina Flashcards
angina occurs when the oxygen need
exceeds the supply
immediate relief of angina
organic nitrates
angina prophylaxis
calcium channel blockers
beta blockers
angina is typically relieved with
rest and/or nitroglycerin
typical location of angina
retrosternal
radiating to left/both arms
classic or variant angina?
atheromatous obstruction of large coronaries, especially with exercise
classic
classic or variant angina?
may require CABG or angioplasty if uncontrolled
classic
classic or variant angina?
spasm or constrication in atherosclerotic coronary vessels
variant
classic or variant angina?
relieved by nitrates and ca channel blockers
variant
oxygen demand is determined by
- contractility
- heart rate
- wall stress
main energy source in heart
fatty acid oxidation
drugs that can shift myocardial metabolism toward glycolysis and reduce oxygen demand without affecting hemodynamics
- trimetazidine
- pFOX inhibitors
oxygen supply depends on
- O2 delivery
- O2 extraction
agents decreasing O2 demand
- beta blockers
- verapamil/dilitiazem
agents that increase o2 supply
- dehydropyridines
- statins
- anti-thrombotics
drugs that can relax vascular smooth muscle work by
- decreasing intracellular Ca (CCB)
- preventing depolarization (nicorandil)
- increasing cGMP (NO)
3 drug groups used to treat angina
- organic nitrates
- CCBs
- beta blockers
organic nitrates, CCBs, beta blockers
decrease myocardial oxygen demand by decreasing:
- HR
- ventricular volume
- blood pressure
- contractility
- reduces intracellular Ca+ concentration, reducing cardiac contractility and work
- recently approved
ranolazine
partially inhibits fatty acid oxidation
trimetazidine
- inhibits xanthine oxidase
- prolongs exercise time in patients with angina
allopurinol
direct bradycardic agent inhibiting the hyperpolarization activated Na+ channel in the SA node
ivabradine
- rho-kinase inhibitor
- reduces coronary vasospasm in experimental animals
fasudil
short acting nitrates
3
- amyl nitrate, inhaled
- nitroglycerin, sublingual
- isosorbide dinitrate
how are different vessel types affected by NO?
- large veins are markedly dilated
- arterioles and precapillary spinchters are dilated less
can potentiate action of NO in angina, causing severe hypotension and MI
sildenafil
can be used to treat cyanide poisoning
NO
effect and result: beneficial nitrate effects
decreased BP and vasodilation
reduced myocardial O2 demand
effect and result: beneficial nitrate effects
reduced ventricular diastolic pressure
improved subendocardial perfusion
effect and result: beneficial nitrate effects
dilation of epicardial arteries
redistribution of coronary flow to ischemic area
effect and result: beneficial nitrate effects
increased collateral flow
improved perfusion to ischemic areas
effect and result: harmful nitrate effects
reflex increases in HR and contractility
increased myocardial O2 demand
effect and result: harmful nitrate effects
reflex tachycardia
reduced perfusion due to shorter diastole
oral nitrates are rapidly metabolized by
hepatic reductase
What two nitrates should be given sublingual for rapid absorption and to avoid hepatic destruction?
- nitroglycerin
- isosorbide dinitrate
what nitrate, if given IV, dilates both arteries and veins equally?
sodium nitroprusside
fastest acting nitrate preparations
amyl nitrate, inhaled
sodium nitroprusside, IV
nitroglycerin, sublingual
acute nitrate toxicity can cause
- orthostatic hypertension
- tachycardia
- throbbing headaches
frequent exposure to nitrates can cause
tolerance
Monday disease
CCBs are orally active drugs that block
L type Ca channels
Ca channels are opened by
stimulation of B receptors
CCBs affects […] more than […]
blood vessels
arteries; veins
- dihydropyridine
- binding site 1A
- vascular selectivity
nifedipine
- benzothiapine
- binding site 1B
- selective for both vascular and myocardium
diltiazem
- phenylalkylamine
- binding site 1C
- selective for myocardial tissue
verapamil
CCB that is the strongest vasodilator, causes reflex tachycardia
nifedipine
CCB with strongest cardiac affects, causes myocardial depression, decreases HR
verapamil
short acting CCBs should be avoided in patients with
hypertension
beneficial effects of dihydropyridines
- coronary vasodilation (increased O2 supply)
- systemic arteriole vasodilation (decreased afterload)
harmful effects of dyhydropyridines
severe hypotension -> reflex tachy -> increased cardiac workload -> increased risk of MI
beneficial effects of verapamil and diltiazem
- reduced SA automaticity and AV conduction
- decreased myocardial contractility and bradycardia –> decreased cardiac work load
harmful effects of verapamil and diltiazem
cardiac depression, resulting in cardiac arrest, AV block, or CHF
may enhance digoxin toxicity
verapamil/diltiazem
should not be used in patients with ventricular dysfunction or SA/AV node disturbances
verapamil/diltiazem
- inhibit insulin secretion
- interfere with platelet aggregation
- relatively minor side affects
CCBs
extremely useful for the mangement of angina associated with effort
beta blockers
do not dilate coronary arteries
beta blockers
beneficial effects of beta blockers
- decreased sympathetic activity (decreased cardiac work)
- direct vasodilation
- bradycardia (increased perfusion time)
may induce or worsen CHF in patients with acute MI or decompensated HF
beta blockers
potentially harmful in variant angina
beta blockers
may increase plasma triglycerides and decrease HDL causing atherosclerosis
beta blockers
most common cause of angina pectoris
atherosclerotic disease of the coronaries
first line therapy: angina
- modify risk factors
- antiplatelets
what drugs are more effective for variant angina?
nitrates and CCBs
most effective drug combinations for angina
- b-blockers and CCBs or,
- 2 CCBs
potentially harmful effects of CCBs or beta blockers can be prevented by
nitrates
and vice versa
relfex tachycardia can be minimized by combining nitrates with
CCBs or beta blockers
result in pronounced dilation of large vessels, reduce preload
nitrates
reduce afterload and/or cardiac function
CCBs
reduce vasocontriction and cardiac function
beta blockers
increase risk for new onset diabetes
beta blockers
acute nitrate toxicity
- headaches
- orthostatic hypertension
- tachycardia
potentiate the action of nitrates and lead to MI
PDE-5 inhibitor
sildenafil
cause decreased oxygen demand
verapamil/dilitiazem
suppress AV and SA nodes
decrease preload via venodilation
nitrates
- decrease afterload by arteriodilation
- decrease TPR
dihydropyridine and nitrates
increase oxygen supply by redistributing blood flow
nitrates
increase oxygen supply by coronary vasodilation
dihydropyridines
reduce sympathetic activity on the heart
beta 1 blockers
decrease peripheral resistance by reducing angiotensin 2
ACE/ARBs
slow down heart rate by depressing SA and AV node
verapamil
short acting nitrate used for acute anginal attacks
sublingual nitroglycerin
short acting nitrate for chronic treatment of angina
oral isosorbide mononitrate
used to treat hypertension and heart failure but can precipitate angina due to reflex cardiac stimulation
hydralazine
result in tolerance or marked reduction of effect upon repeated exposure
nitroglycerin
to reduce nitroglycerin tolerance,
use lowest effective dose with nitrate free intervals of 10-12 hrs daily
preferentially acts as a vasodilator leading to reflex tachy
nefedipine
work as vasodilators without causing relfex tachycardia
a1 blockers
zosins
suppress SA/AV nodes leading to bradycardia
verapamil/diltiazem