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Describe the pathophysiology of ischemic heart disease.
it is best described as a continuum of CAD (risk factors such as smoking, DM, obesity) that leads to ischemia culminating in myocardial infarction. The continuum impairs pumping ability of the heart by depriving the heart muscle of oxygen and nutrients.
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Define unstable angina and acute coronary syndrome
Unstable angina, an acute coronary syndrome, is said to be present when episodes of angina occur at rest and when there is an increase in the severity, frequency, and duration of chest pain in patients with previously stable angina
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Concerning Angina, the three main medications have a predictable benefit because they all reduce this common cardiac parameter?
they all reduce cardiac oxygen demand
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Why is the SL route more ideal for the delivery of nitroglycerin and isosorbide for the treatment of angina?
because their bioavailability is only 10-20%, so in order to bypass 1st pass effect, they are given SL
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Even though lagely theoretic, what is the MOA of the nitrates such as nitroglycerin?
- free nitrate ion release, then converted to NO
- the NO combines with guanylyl cyclase which increases cGMP
- cGMP increases smooth muscle relaxation
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Describe the veinous versus arterial vasolitation effects of nitrates and list 3 effects.
- nitrates relax venous vascular smooth muscle MORE than arterial leading to:
- marked veinous relaxation
- increased venous capacitance
- decreased ventricular load
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According to the Law of Laplace and decreased wall tension, what 2 vascular factors are decreased are decreased with the use of nitrates?
- DEC intraventricular pressure
- DEC ventricular volume
- (the formula is T=(P x R)/M so as radius decreases the tension decreases)
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Describe the mechanism of clinical effect for nitrates in angina of effort.
DEC venous return, DEC intracardiac volume, DEC wall tension = DEC myocardial O2 demand
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Describe the machanism of clinical effect for nitrates in variant angina.
relax smooth m. of epicardial coronary arteries, thus relieving CA spasm
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Describe the mechanism of clinical effect for nitrates in unstable angina.
INC coronary artery diameter and DEC myocardial O2 demand
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Name 3 acute adverse effects of nitrate administration.
- orthostatic hypotension
- tachycardia (autonomic response)
- HA (nitrates contrindicated in increased ICP)
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Name 2 factors thought to contribute to the tachyphylaxis seen with prolonged nitrate admin.
- DEC nitric oxide release
- systemic compensation by sympathetic discharge and salt & water rentention over time
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It is known that nitrosamines from food nitrates are linked to esophageal cancer, is this the same for nitrates?
it unproven for nitrate therapy
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Name 3 potential beneficial effects of nitrate therapy
- DEC ventricular volume
- vasodilation of coronary arteries
- DEC left ventricular diastolic pressure
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Name 3 potenital deleterious effects of nitrate therapy
- reflex tachycardia
- reflex INC contractility
- DEC diastolic perfusion time due to tachycardia
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What cation is necessary for the contraction of smooth muscle and cardiac muscle?
Calcium
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Name 4 general pharmacokinetic characteristics of CCB.
- orally active
- high first pass effect
- high plasma protein binding
- extensive metabolism
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Name the 2 classes of CCBs.
- dihydropyridines
- non-dihydropyridines
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What is the mechanism of action for the CCB?
bind to alpha-1 subunit of L-type Ca++ channels.
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Which calcium channels and where do CCB exert their pharmacodynamic effect?
they bind to the open and inactive channels inside the cell membrane
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What effect would sympathomimetics have on CCB?
they would REDUCE their effect by increasing transmembrane flux of Ca++
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Which class of CCB is more effective on vascular smooth muscle?
dihydropyridines
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Which class of CCB is more effective on cardiac smooth muscle? Name 2 examples.
- non-dihydropyridines
- Verapamil & Diltiazem
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What are the skeletal muscle effects of CCBs?
essentially there are none
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Name 4 toxic effects of CCB.
- bradycardia
- AV block
- heart failure
- arrest
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What would the effect be of someone taking beta blockers and CCB together?
they would be more sensitive to cardiodepressant effect of CCB
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Name the 3 overarching machanisms of clinical effect for CCB administration.
- DEC contractility
- DEC arterial & intra-ventricular pressure
- DEC SA & AV node conduction
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Other than sensitivity, why are non-dihydropyridines a choice agent for control of angina?
they have less reflex tachycardia
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According to Katzung, what are the 3 most important mechanisms for relief of angina and improved exercise tolerance? What class of medication would best facilitate these effects?
- reduced HR
- reduced BP
- DEC myocardial O2 consumption
- Beta blockers
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What is the definition of CHF?
CO not sufficient to maintain tissue oxygen demands
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Name 2 systolic causes and 2 diastolic causes of CHF.
- systolic
- DEC contractility
- DEC EF
- diastolic
- DEC elasticity
- DEC filling
- DEC stroke volume (but can have normal EF)
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Name 4 goals for treatment of CHF.
- prevent further damage
- promote optimal function
- close monitoring and intervention
- minimize acute decompensation
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Name 2 general purposes of cardiac glycoside therapy for CHF.
- provide positve inotropic support
- create negative chronotropic effect
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What is the MOA of digoxin?
- it inhibits sodium pump by altering the Na/K-ATPase transporter which increases intracellular Na+
- it reduces Ca++ expulsion which is then sequestered in the SR
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Describe the electrical effects of digoxin on the heart
- DEC SA nodal rate
- INC AV node conduction velocity
- slight DEC in refractory period period
- so you would see INC PR interval and DEC QT interval
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What is the 1/2 life of digoxin?
about 40 hours
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What is the lower limit for HR with digoxin therapy?
60 bpm
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Name 4 contraindications for cardiac glycoside treatment.
- high K+ (increases toxic effects)
- high Ca++ (increases risk of arrhythmias)
- low Mag (increases digoxin effect)
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What is the formula for CO?
CO=HR X SV
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What is the formula for BP?
BP=CO X SVR
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What are the 3 tenets of treating the acutely failing heart.
- Unload (diuretics)
- Augment (beta agonists)
- Relax (vasodilators)
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What are the intervention classes for treating the chronically failing heart and give an example for each.
- Class A (prefailure --risk factor)
- control obesity, HTN, DM, hyperlipidemia
- Class B (class I-- symptoms with severe exercise)
- Relax: ACEI/ARB
- Augment: B Blocker
- Unload: diurectic
- Class C (II/III- symptoms with marked or mild exercise)
- same as B, add:
- remodel: aldosterone antagonist
- squeeze: digoxin
- more relax: hydralazine, nitrate
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