MI

Question 1

describe the different types of chest pain

• Angina
• rest or unstable angina
• Acute MI

Answer 1

Question 2

Describe angina pectoris

Answer 2

• 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

Question 3

describe the pharmacological modifications of major determnants of myocardial O2 supply

Answer 3

Question 4

what factors contribute to oxygen demand and supply

Answer 4

-Oxygen demand

–> heart rate

–> contractility

–> preload

–> afterload

• Oxygen supply

–> Coronary blood flow

–> regional myocardial blood flow

Question 5

define Nitrate Tolerance

Answer 5

• 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

Question 6

describe Mech of action of Organic Nitrates

Answer 6

• 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

Question 7

Describe pharmacokinetics of Nitroglycerin

Answer 7

• Nitroglycerin

–> Sublingual or transdermal

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

Question 8

Describe pharmacokinetics of Isosorbide dinitrate

Answer 8

-isosorbide dinitrate

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

–> Given PO or SL

–> Metabolite half life = 2-4 hours

Question 9

Describe pharmacokinetics of Isosorbide monomitrate

Answer 9

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

Question 10

describe pharmacodynamic effects of GTN, ISDN, ISMN

Answer 10

- 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

Question 11

What are the therapeutic uses of GTN, ISDN, ISMN

Answer 11

• 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

Question 13

CHF TX

Answer 13

• 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

Question 14

What are the side effects for GTN, ISDN, ISMN

Answer 14

• 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