4/4/2014

   

 


 

 


   

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 4/4/2014

Angina

Factors affecting myocardial oxygen demand

and oxygen supply

Regional
Contractile myocardial
state distribution

Heart Oxygen = Oxygen Coronary

Ventricular rate demand > supply vascular
volume resistance
Wall
tension Coronary
blood flow
LV Aortic
pressure pressure

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 4/4/2014

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Antianginal Agents
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Antianginal Agents

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demand
Angina

supply

Drug Therapy
supply demand

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 4/4/2014

Antianginal Drugs

Drugs used in Angina Pectoris

Vasodilators Cardiac depressants

Nitrates Calcium Blockers Beta-blockers

Long duration

Intermediate

Short Duration

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 4/4/2014

Pharmacokinetics of Nitrate Esters

Onset Duration of Action Metabolites
(min) (min)
Amyl nitrite 0.25 1
Nitroglycerin 2 30
Isosorbide dinitrate 3 60 Active
Erythrityl tetranitrate 15 180
Pentaerythritol tetranitrate 20 330

Nitrate esters act fast! Think about the size of these molecules.
They are rapidly metabolized in the liver (glutathione-nitrate
reductase). Yet, can be used in oral prophylactic therapy, especially
ISDN, ETN and PETN
Nitrate esters and possibility of explosion!
Nitrovasodilators decrease the blood pressure of patients!!

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 4/4/2014

 N ' & )* nitrates   /*

Effect Result
Potential beneficial effects
Decreased ventricular volume Decreased myocardial oxygen
requirement
Decreased arterial pressure
Decreased ejection time
Vasodilation of epicardial coronary Relief of coronary artery spasm
arteries
Increased collateral flow Improved perfusion to ischemic
myocardium
Decreased left ventricular diastolic Improved subendocardial perfusion
pressure
Potential deleterious effects
Reflex tachycardia Increased myocardial oxygen
requirement
Reflex increase in contractility
Decreased diastolic perfusion time due Decreased myocardial perfusion
to tachycardia

15

Nitrates

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sublingual, buccal,

chewable, tablets,
capsules, ointments,
patches, inhalable
sprays, & IVs
_____________________
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 4/4/2014

Nitrates

Nitroglycerin
Prototypical nitrate

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Isordil, Sorbitrate, & Dilatrate SR

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Isosorbide Mononitrate*

Imdur, Monoket, & ISMO

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 4/4/2014

Beta Blockers

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Beta Blockers
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Body System Effects

Cardiovascular bradycardia, hypotension
second- or third-degree heart block
heart failure
Metabolic Altered glucose and lipid
metabolism
CNS dizziness, fatigue,
mental depression, lethargy,
drowsiness, unusual dreams
Other impotence
wheezing, dyspnea

Effects of nitrates alone and with -blockers in angina

pectoris
Nitrates - Combined
alone blockers nitrates with
-blockers
Heart rate Reflex Decrease Decrease
increase
Arterial Decrease Decrease Decrease*
pressure
End-diastolic Decrease Increase None or
volume decrease

Contractility Reflex Decrease None

increase
Ejection time Decrease Increase None

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 4/4/2014

Calcium channel blockers

 Types of Calcium Channel Blockers

Dihydropyridines Nifedipine and others

Phenylalkylamines Verapamil and Bepridil
Benzothiazipines Diltiazem

MWY V&(L

conduction, contractility arterial tone (especially coronary

arteries)

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Calcium Channel Blockers

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 4/4/2014

Protein Binding of Calcium Channels

Blockers
Protein Duration of
Binding Action

Amlodipine >95% 24 h

Nicardipine 95% 3h

Diltiazem ~80% 6 h iv

Bepridil >90% 24 h

Verapamil 90% 8h

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Therapeutic Effects of Antianginal Agents

Therapeutic Nitrates BB CCB

Effect

Supply:
coronary resistance   
Myo Wall Tension   /0
Duration of diastole 0  /0
Demand:
preload   0/
afterload   
contractility 0  
heart rate 0  

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 4/4/2014

Typical Variant MI
Stable Unstable
Organic nitrite and nitrates ++ ++ ++ +
Ca2+-channel blockers ++ 0 to ++ +++ 0
- adrenergic Antagonists ++ ++ 0 +++
Aspirin + +++ 0 +++
Fibrinolytic drugs 0 0 0 +++

Antianginal drugs :
-O2 increase supply and/or lower demand
Myocardial O2 supply: Coronary blood flow, regional flow
distribution
Myocarial O2 demand: amount of energy required to support the
work of the heart
Cardiac work influenced by: heart rate, heart contractility,
myocardial wall tension

Vasodilators- organic compounds containing ONO or ONO2 (prodrugs) all

release NO upon interacting with serum components.

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 4/4/2014

{a

Alcohol consumption and hot baths or spending

time in jacuzzis, hot tubs, or saunas will result in
vasodilation, hypotension, and the possibility of
fainting.

Teach patients to change positions slowly to avoid
postural BP changes.

Encourage patients to keep a record of their anginal
attacks, including precipitating factors, number of pills
taken, and therapeutic effects.

Check Blood Pressure and Heart Rate

BEFORE each dose

Observe for relief of chest pain

Observe for hypotension, dizziness,
tachycardia, headache

Keep in original dark container

Replace every 6 months

Headache and dizziness may occur

Avoid OTC meds

Avoid Alcohol

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