IHD Pharmacology I - Auchampach Flashcards
What causes ischemic heart disease?
An deficiency in oxygen supply relative to oxygen demand of the heart.
What is the most probable cause of ischemic heart disease?
atherosclerosis of the coronary arteries
How does ischemic heart disease usually present?
variable
pain in the chest, possibly radiating through the arms, jaw, and sternum
What contributes to myocardial oxygen demand?
Wall Stress
Heart Rate
Contractility
What contributes to myocardial oxygen supply? Which factor(s) are stable?
Oxygen content in blood is constant
Coronary blood flow is variable
What is the relationship between coronary blood flow, perfusion pressure, and coronary vascular resistance?
Coronary blood flow= (perfusion pressure)/vascular resistance
What determines the perfusion pressure in the coronary arteries?
the diastolic pressure
When is coronary perfusion the lowest? Why?
Perfusion is lowest during systole; either because the leafs of the valve are blocking it OR because the muscle contraction closes the blood valve… neither makes complete sense
What is an external factor that regulates coronary flow? What is an intrinsic factor?
Sympathetic receptors aplha1 cause constriction.
Adenosine and lactic acid released from the cardiomyocytes cause dialation
What factors related to wall stress increase oxygen demand?
Increased ventricle volume
increase ventricle pressure
What level of coronary obstruction causes a decrease in perfusion during resting flow? What about during increased demand?
90% obstruction is needed to lower resting perfusion
70% obstruction is needed to lower perfusion during increased demand
Why is the subendothelium especially vulnerable to ischemia?
Increased ventricle muscle pressure during systole limits perfusion and during exercise diastole can be shortened, also limiting the perfusion.
What EKG changes can be seen in subendocardial ischemia?
ST segment depression
T wave inversion
What role does endothelial dysfunction play in ischemia?
Incorrect release of endothelial vasodilators
loss of anti-thrombotic properties
What are three forms of chronic ischemic heart disease?
- stable angina (stable plaque that has not burst)
- variant angina/ prinzmetal’s angina (no plaque, vasospasm)
- syndrome X (normal coronary arteries, decreased blood flow)
What is silent ischemia?
Episodes of ischemia that occur without any pain
What is unstable angina?
A coronary artery plaque that has burst and has started a clotting cascade
What disease is seen on an EKG with ST depression? T wave inversion? ST elevation?
ST depression- subendocardial ischemia
T wave inversion-subendocardial ischemia
ST elevation- transmural ischemia
How can stable angina be diagnosed?
cardiovascular stress test, physical or pharmaceutical
OR
coronary angioplasty
What therapies are recommended for acute episodes of ischemia?
Fast-acting nitrates
What three drugs classes are used to prevent ischemia?
Long-acting nitrates
beta-adrenergic receptor blockers
calcium channel blockers
How do long-acting nitrates act to prevent ischemia?
They are potent venous vasodilators, reducing pre-load. They increase production of NO.
What are three nitrates? What are the pharmacokinetics of the each?
Nitroglycerin- low bioavailability, extensive first pass
Isosorbide dinitrate- metabolized to mononitrate
Isosorbide mononitrate-bioactive
Why is nitroglycerin useful if it has an extensive first pass effect?
It is typically used in short-action situations, given sublingually, and has three nitrous groups
What is a problem with using nitrates as a chronic therapy for ischemia?
tolerance
What are adverse effects for nitrates?
Headache
Hypotension
Reflex tachycardia
Flushing
Why are beta-adrenergic receptors useful for treating ischemia?
They decrease oxygen demand by decrease heart rate and pressure.
What are the two classes of beta-adrenergic receptor blockers? What are the drugs in each class?
Non-specific -propanolol -timolol Specific -atenolol -metoprolol
What are some adverse effects of beta-adrenergic receptor blockers?
fatigue
sexual dysfunction
airway constriction
What are some contraindications for beta-blockers?
COPD/asthma
heart failure
bradycardia
What are the two classes of calcium channel blockers? What are the drugs in each class?
Dihydropyridines
- Amlodipine
- Nifedipine
Non-dihydropyridines
- Diltiazem
- Verapamil
Which class of calcium channel blocker treats prinzmetal angina?
Dihydropyridines are potent vasoconstrictors that counter-act the vasospasms seen in prinzmetal angina.
What are some adverse effects of calcium channel blockers?
Headache, flushing • Decrease contractility (V, D) • Bradycardia (V, D) • Edema (especially N, D) • Constipation (especially V)
What is Ranolazine?
a drug that inhibits late sodium current in the cardiomyocytes.
