093014 ischemic heart disease pharmacology Flashcards
how much of oxygen is extracted from bllod traveling through coronary circulation?
75%, so to increase oxygen supply you won’t get much from increasing the amount extracted of oxygen
myocardial oxygen supply depends on
oxygen content of blood
coronary blood flow (increased demand for oxygen is met by increased coronary flow)
coronary blood flow depends on
diastolic perfusion pressure
coronary vascular resistance (in small arterioles)
intrinsic regulation of coronary vascular resistance is accomplished through?
LOCAL METABOLITES (adenosine, lactate, etc coming from muscle working hard.
endothelial factors
neural innervation
why does perfusion of coronary arteries increase during diastole?
during systole-contraction compresses the coronary arteries
sympathetic intrinsic regulation of coronary vasculture resistance
alpha1 receptors-CONSTRICTION
beta 2 receptors-minor dilation
however, sympathetic nervous system is overriden by metabolic (adnosine, lactate, pH) factors regulating vascular resistance and blood flow
the subencodardial plexus is really dependent on what phase of heart contraction?
diastole
what factors determine oxygen demand of the myocardium?
wall stress (P * r/2h) –h is for wall thickness
contractililty
heart rate
wall stress
tangential force acting on the myofibers tending to pull them apart
energy is used to oppose this force
approximated by Laplace’s law
coronary flow reserve
the maximal increase in blood flow achievable above normal resting flow
why is subendocardium susceptible to ischemia with a limiting stenosis particularly in the case of exertion?
reduced perfusion pressure
elevated LV end diastolic pressure with exertion impedes subendocardial flow
increased HR decreases time during diastole (when the subendocardium receives blood flow)
ECG changes with subendocardial ischemia
ST segment depression
T wave inversion
variant angina
no overt plaques
intense vasospasm
syndrome X
patients with typical signs of angina (related to exertion) who have no evidence of significant atherosclerotic stenoses…likely to due inappropriate constriction of blood vessels
ECG patterns for chronic stable angina
during ischemia, ST segment depression and T wave inversion
what can you do to detect chronic stable angina?
stress testing:
with exercise
or
with pharamcological agents (dobutamine-increases myocardial oxygen demand. adnosine-causes coronary vasodilation)
coronary angiography
lesions visualized radiographically after injecting a radiopaque contrast media into artery
general principles of anti-angina therapy
decrease O2 demand
increase O2 supply
medical therapy of stable angina
acute episodes (goal is fast relief of discomfort)-stop exercise. fast-acting nitrates (nitroglycerin as sublingual tablet or spray)
prevention (goal is to reduce frequency of angina by decreasing cardiac workload and by increasing myocardial perfusion): 3 classes of drugs used for prevention- long acting nitrates beta adrenergic receptor blockers calcium channel blockers
prevention of acute cardiac events:
antiplatelet therapy
lipid regulating therapy
revascularization (in some cases)
nitrates MOA (for use in angina)
in smooth musc, free nitrate is converted to nitric oxide. NO activates guanylyl cyclase, increasing cGMP. cGMP activates cGMP-dependent protein kinase (PKG). PKG phoshphorylates various targets leading to decreased calcium and dephosphorylation of myosin
general vasodilator but much greater effect on venous blood vessels (decreases preload)
is also a coronary dilator–mostly beneficial for vasospasm cases
nitroglycerin bioavailability
low due to extensive first pass metabolism in liver
tolerance of nitrates
complete tolerance can develop if used continually for more than few hours (but also reverses rapidly 24 hours of stopping drug)
therefore, should use smallest effective dose and schedule nitrate-free periods (on-off therapy) of at least 8 hours to prevent tolerance
side effects of nitrates
headache
hypotension
reflex tachycardia
flushing
beta adrenergic receptor blockers MOA (for angina)
reduce oxygen demand by decreasing force of ventricular contraction and heart rate. decreases BP (afterload)
can increase time in diastole to increase coronary perfusion to increase a bit oxygen supply to ischemic areas
decrease in cardiac output can lead to increase in preload that increases wall tension
both non-selective (propranolol, timolol) and beta1 selective antagonists (metoprolol, atenolol) are effective
not effective for angina due exclusively to vasospasm
contraindications of beta blockers
used cautiously or avoided in pts with obstructive airway disease
not used in pts with acutely decompensated heart failure
pts with marked bradycardia or certain heart blocks
pts with insulin treated diabetes
side effects of beta blockers
fatigue, sexual dysfxn
calcium channel blockers MOA
antagonize voltage gated L-type calcium channels
dihydropyridines MOA
potent vasodilators (preferentially dilate arteries)-so decreases afterload and vasodilates coronary arteries
potent for relief of vasospasm
ex of dihydropyridines
nifedipine
amlodipine
non-dihydropyridines MOA
vasodilators but less potent than dihydropyridines (dilate peripheral and coronary arteries)
relieve ischemia primarily by decreasing HR and contractility
examples of non-dihydropyridines
verapamil,diltiazem
side effects of calcium channel blockers
headache, flushing decrease contractility bradycardia edema constipation
ranolazine
decreases frequency of anginal episodes and increases exercise capacity
believed to inhibit late sodium current in cardiac myocytes
medical therapy to prevent acute cardiac events
antiplatelet therapy
lipid regulating therapy
revascularization by can done by
PCI-angioplasty
coronary artery bypass graft surgery
