Pharm Test 3: Vasodilators & Tx of Angina Pectoris
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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)
Inadquate blood flow to cardiac muscle due to actual blockage of coronary arteries
Contraction spasms of the coronary arteries
What type of angina can be associated with other vasospastic disorders such as Raynaud's or migraines?
Substance abuse (cocaine, alcohol, marijuana, amphetamines) increase risk of what type of angina?
Oxygen is delivered to the heart during _____ so with increased _____, time to deliver oxygen to heart is less.
- Systole (heart rate)
Double product =
Increases (and oxygen requirements of the heart also increase) as intensity of _____________ increases
Systolic BP * HR
Therapeutic goal in patients with atherosclerotic angina
Reduce double product w/o reducing exercise capacity/improve exercise capacity
Drug that selectively targets and reduces heart rate by inhibiting the SA pacemaker current.
First line therapy for acute angina symptoms
What class of drugs can be used as prophylaxis for episodes of angina?
Vasodilators (ie. nitrates) are metabolized in their target tissues to their active compound ____ also known as ___
NO= endothelium derived relaxing factor
In smooth muscle, NO stimulates ______ --> cGMP --> Protein Kingase G -->___________--> Relaxation
- Guanylyl cyclase
- Myosin light chains phosphatase
What class of drugs relaxes vascular smooth muscle only and what is the rank in which it affects these?
- Veins >> arteries >> Arterioles
Nitrates have a major action in reducing _____ on the heart.
Nitrates have ____ and ____ properties.
When are these seen?
Seen w/ IV or transdermal administration of nitroglycerin in treating unstable angina.
Nitrate stimulation of guanylate cyclase prevents _____ binding to ______ receptors
fibrogen, platelet IIb/IIIa receptors
Major effect of organic nitrates?
Reduction in myocardial oxygen demand
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.
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.
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.
Workers who are constantly exposed to NG, lose tolerance over weekend and come back on Monday. They get headache, dizziness, tachycardia, etc.
What are the advantages of sublingual or buccal administration of NG compared to oral?
It avoids hepatic first pass inactivation
Therapy of choice for acute anginal episodes and prophylactically for activities konwn to elicit angina.
Tolerance is generally not a problem with what form of NG?
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
What ethnic group has a reduced response to nitrates? Why?
- NO formation from NG dependant on ALDH2 (mitochondrial aldehyde dehydrogenase) enzyme. There is a polymorphism (ALDH2*2) present in 30-50% of Asians.
Which class of drugs may result in reflex tachycardia?
Location of B1 receptors
Heart muscle (increase H$, contractility, AV conduction); Decrease AV node refractoriness
Location of B2 receptors
Bronchial and peripheral vascular smooth muscle (vasodilation, bronchodilation)
Location of B3 receptors
adipose tissue and heart (thermogenesis and decreased cardiac contractility)
Which class of drugs are contraindicated for vasospastic angina?
First line therapyfor chronic stable angina?
These drugs are contraindicated in?
- Beta Blockers
- Vasospastic angina
Which class of drugs has an effectiveness that is dose-dependent?
Beta-receptor # is dynamic. Chronic B-blocker thereapy may increase receptor # --> angina, MI, death
Which Beta blockers are lipid soluble?
Propranolol and metoprolol
Which beta blockers are water soluble?
The subclass of clacium channel blockers that targets the blood vessels
- (Verapamil targets the heart)
2 drugs used to treat AV nodal arrhythmias
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