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Flashcards in MI Deck (14):
1

describe the different types of chest pain

- Angina

- rest or unstable angina

- Acute MI

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2

Describe angina pectoris

- chest pain due to inadequate blood flow and therefore inadequate O2 delivery to the heart muscle

- anginal pain is due to RELEASE OF BRADYKININ AND ADENOSINE ONTO NOCICEPTIVE AFFERENTS

3

describe the pharmacological modifications of major determnants of myocardial O2 supply

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4

what factors contribute to oxygen demand and supply

-Oxygen demand

--> heart rate

--> contractility

--> preload

--> afterload

- Oxygen supply

--> Coronary blood flow

--> regional myocardial blood flow

5

define Nitrate Tolerance

- When given acutely, nitrates have potent hemodynamic and theapeutic effects

- these effects were lost rapidly during sustained therapy almost completely when significant plasma concentrations are present throughout the 24 hr period

- tolerance develops early and cannot be overcome with higher dosese

- NITRATE EFFECTS COULD BE MAINTAINED USING DOSING REGIMENTS THAT ALLOW FOR A NITRATE-FREE  or LOW-NITRATE CONC FOR SEVERAL HOURS EACH DAY

6

describe Mech of action of Organic Nitrates

- Prodrug that undergo denitrification by ALDEHYDE REDUCTASE to yeild NO

- NO activates soluble GC --> INCREASE cGMP --> cGK-1 activation

--> increase mitochondrial Ca2+ uptake

--> decrease Ca2+ influx

--> phosphorylates MLCK

--> END RESULT = VASORELAXATION

7

Describe pharmacokinetics of Nitroglycerin

- Nitroglycerin

--> Sublingual or transdermal

--> Hepatic and Intravascular metabolism (1-4 minutes)

8

Describe pharmacokinetics of Isosorbide dinitrate

-isosorbide dinitrate

--> available in phasic, sustained released form --> QD dosing --> AVOID TOLERANCE

--> Given PO or SL

--> Metabolite half life = 2-4 hours

9

Describe pharmacokinetics of Isosorbide monomitrate

isosorbide mononitrate

-- DOES NOT UNDERGO FIRST-PASS HEPATIC METABOLISM

--> Metabolite half life = 2-4 hrs

- Available in sustained, phasic release form --> QD dosing --> avoid tolerance

10

describe pharmacodynamic effects of GTN, ISDN, ISMN

- POTENT VADOILATION IN VEINS --> DECREASE ventricular volume and preload

- NO EFFECT on peripheral vascular resistance

- Little or no effect on the coronary resistance vessels --> AVOID CORONARY STEAL

- in pates with CAD, nitrates can dilate coronary stenoses and collateral vessels --> improve coronary blood flow

11

What are the therapeutic uses of GTN, ISDN, ISMN

- Sublingual

--> ACUTE ATTACKS OF ANGINA

--> GTN and ISDN prophylactic therapy prior to activity leading to angina

- Long-acting nitrates

--> effective in angina, Increase exercise duration, decrease anginal frequency

--> DUE TO NITRATE TOLERANCE, dosing must allow for low or nitrate-free period during the day

--> ISMN is phasic release allowing high conc during day and low during night

12

13

CHF TX

- In acute HF and active ischemia, organic nitrates can be therapy of choice

- ISDN and hydralazine combination can be good in african-americans with CHF

14

What are the side effects for GTN, ISDN, ISMN

- HEADACHES (common

- Hypotension (common with hapid onset of action nitrates)

--> ISDN dose should be up-titrated over several days

- erythema or local edema at site of transdermal application