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Pain caused by ischemia of the heart muscle that results from inadequate or no blood flow and thus inadequate oxygen delivery.
Angina pectoris (or just angina)
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Inadquate blood flow to cardiac muscle due to actual blockage of coronary arteries
Atherosclerotic angina
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Contraction spasms of the coronary arteries
Vasospastic angina
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What type of angina can be associated with other vasospastic disorders such as Raynaud's or migraines?
Prinzmetal/variant/vasospastic angina
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Substance abuse (cocaine, alcohol, marijuana, amphetamines) increase risk of what type of angina?
Prinzmetal's Angina
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Oxygen is delivered to the heart during _____ so with increased _____, time to deliver oxygen to heart is less.
- Diastole
- Systole (heart rate)
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Double product =
Increases (and oxygen requirements of the heart also increase) as intensity of _____________ increases
Systolic BP * HR
exercise
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Therapeutic goal in patients with atherosclerotic angina
Reduce double product w/o reducing exercise capacity/improve exercise capacity
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Drug that selectively targets and reduces heart rate by inhibiting the SA pacemaker current.
Ivabradine
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First line therapy for acute angina symptoms
Sublingual nitroglycerin
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What class of drugs can be used as prophylaxis for episodes of angina?
Nitrates
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Vasodilators (ie. nitrates) are metabolized in their target tissues to their active compound ____ also known as ___
NO= endothelium derived relaxing factor
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In smooth muscle, NO stimulates ______ --> cGMP --> Protein Kingase G -->___________--> Relaxation
- Guanylyl cyclase
- Myosin light chains phosphatase
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What class of drugs relaxes vascular smooth muscle only and what is the rank in which it affects these?
- Nitrates
- Veins >> arteries >> Arterioles
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Nitrates have a major action in reducing _____ on the heart.
preload
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Nitrates have ____ and ____ properties.
When are these seen?
antiplatelet, antithrombotic
Seen w/ IV or transdermal administration of nitroglycerin in treating unstable angina.
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Nitrate stimulation of guanylate cyclase prevents _____ binding to ______ receptors
fibrogen, platelet IIb/IIIa receptors
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Major effect of organic nitrates?
Reduction in myocardial oxygen demand
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How do nitrates decrease the preload and afterolad? This decreases the amnt the heart has to work and thus decreases the oxygen needed to sustain the myocardium.
- Venous dilatation results in pooling of blood in veins --> decreases volume of blood returning to the heart (reducing preload)
- Decrease in blood pressure decreases cardiac afterload.
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Volatile liquid given by inhalation- rapid acting short duration (few minutes); no longer used for angina because it causes methemoglobin at high blood concentrations.
Use for potential antidotal action in cyanide poisoning.
Amyl nitrate
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Which has the greatest first pass effect via the liver: Nitroglycerin, glyceryl dinitrate or glyceryl mononitrate?
- NG > glyceryl dinitrate >>>> glyceryl mononitrate
- Isos are about equal to each other.
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Monday Disease
Workers who are constantly exposed to NG, lose tolerance over weekend and come back on Monday. They get headache, dizziness, tachycardia, etc.
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What are the advantages of sublingual or buccal administration of NG compared to oral?
It avoids hepatic first pass inactivation
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Therapy of choice for acute anginal episodes and prophylactically for activities konwn to elicit angina.
Sublingual NG
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Tolerance is generally not a problem with what form of NG?
Sublingual
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3 contraindications for Nitrates
- Patients on PDE5 inhibitors (sildenafil, viagra, etc) --> dangerous hypotension
- Patients w/ hypertorphic cardiomyopathy (SV already compromised)
- Patients w/ suspected right ventricular infarction --> hypotension
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What ethnic group has a reduced response to nitrates? Why?
- Asians
- NO formation from NG dependant on ALDH2 (mitochondrial aldehyde dehydrogenase) enzyme. There is a polymorphism (ALDH2*2) present in 30-50% of Asians.
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Which class of drugs may result in reflex tachycardia?
Nitrates
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Location of B1 receptors
Heart muscle (increase H$, contractility, AV conduction); Decrease AV node refractoriness
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Location of B2 receptors
Bronchial and peripheral vascular smooth muscle (vasodilation, bronchodilation)
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Location of B3 receptors
adipose tissue and heart (thermogenesis and decreased cardiac contractility)
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Which class of drugs are contraindicated for vasospastic angina?
Beta Blockers
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First line therapyfor chronic stable angina?
These drugs are contraindicated in?
- Beta Blockers
- Vasospastic angina
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Which class of drugs has an effectiveness that is dose-dependent?
Beta-Blockers
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Beta-Blocker Withdrawal
Beta-receptor # is dynamic. Chronic B-blocker thereapy may increase receptor # --> angina, MI, death
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Which Beta blockers are lipid soluble?
Propranolol and metoprolol
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Which beta blockers are water soluble?
Atenolol, Sotalol
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The subclass of clacium channel blockers that targets the blood vessels
- Dihydropyridines
- (Verapamil targets the heart)
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2 drugs used to treat AV nodal arrhythmias
Verapamil, diltiazem
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