Drugs for Myocardial Ischemia

Question 1

What is angina pectoris?

Answer 1

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

Question 2

Release of what compounds cause anginal pain?

Answer 2

bradykinin and adenosine onto nociceptive afferents

Question 3

angina clinical description and features:

Answer 3

• retrosternal cehst pressure burning or heavines; radiating occasionally to neck jaw epigastrium shoulders and left arm
• USUALLY WITH exercise cold, emotional stuff from 2-10 min

Question 4

rest/unstable anginal

clinical description and features:

Answer 4

-retrosternal chest pressure burning or heaviness; radiating occasionally to neck jaw epigastrium shoulders and left arm

• pain for less than 20 min
• CAN HAPPEN WITHOUT ANY PHYSICAL ACTIVITY

Question 5

acute MI

clinical description and features:

Answer 5

–retrosternal cehst pressure burning or heavines; radiating occasionally to neck jaw epigastrium shoulders and left arm

-greater than or eequal to 30 min - also get shortness of breath, weakness, nausea, vomiting

Question 6

Agents that decrease heart O2 demand:

Answer 6

• Beta antagonist (decrease HR)
• Ca entry blockers (NDHP-HR and contractility affected)
• organic nitrates

Question 7

Agents that increase heart O2 supply:

Answer 7

• vasodilators -esp Ca entry blockers
• statins - pleotropic effect (activate NO synthase..etc)
• antithrombotics - prevents bloackade

Question 8

increase preload/afterload what happens to contractility? and O2 demand?

Answer 8

increase contractility!

also increase O2 demand

Question 9

organic nitrates -
DRUGS?
MOA?

Answer 9

-mitroglycerin (GTN); Isosorbide dinitrate (ISDN); isosorbide mononitrate (ISMN)

MOA:

• first drug is denitrified by mitochondrial aldehyde reductase to yield NO
• NO activates soluble GC = in cGMP = cGK-1 activation:
  a) inc mitochondrial Ca uptake
  b) dec Ca influx
  c) phosphorylates MLCK (enzyme that causes contraction)
• results in vasorelxation - decrease PRELOAD AND AFTERLOAD

Question 10

Nitrate tolerance:

Answer 10

• if take nitrates throughout the day then the effects will be lost. -higher doses will not overcome tolerance
• NEED TO HAVE NITRATE FREE WINDOW FOR SEVERAL HOURS DURING THE DAY

Question 11

MOA for ntirate tolerance?

Answer 11

biotransformatin (SH groups are depleted) and free radical most popular (endothelium produces many free radicals)

Question 12

Nitroglycerin - pharmacokinetics

Answer 12

**-undergoes hepatic and intravascular metabolism
**-very effective given sublingual (SL) or transdermal (TD) - bypass first pass metabolism
T1/2=~1-4 min but metabolites have T1/2=~40min
-no efficacy for ORAL

Question 13

isisobide dinitrate -pharmacokinetics

Answer 13

• **-available in phasic, sustained release form –> QD dosing –> avoid tolerance
• T1/2= ~40 min
• PO OR SL administration
• Metabolites T1/2=2-4hrs

Question 14

isosorbide mononitrate-pharmacokinetics

Answer 14

• **-does not undergo first pass hepatic metabolism- complete bioavailability
• metabolite halflife 2-4hrs
• **-available in sustained, phasic release form –> QD dosing –> avoid tolerance

Question 15

nitrate effects:

Answer 15

• vary in vascular beds
• *-potent vasodilation in veins = dec ventricular volume and preload
• dilate conduit arteries
• *-no effect on periph vascular resistance
• dilate epicardial corrnary a.
• *- little or no effect on the coronary resistance vessels = AVOID CORONARY STEAL
• if CAD then improve coronary flow via dialation

-HUGE EFFECT ON PRELOAD

Question 16

Coronary steal concept

Answer 16

you have coronary ischemia ongoing and vasodilate the arteries going into that ischemia area then you’re taking blood away from other areas that really need the blood - “stealing the O2”

Question 17

Sublingual nitrates: useful for?

Answer 17

• classic therapy for treatment of acute attacks of angina

- prophylactic SL GTN or ISDN taken before activity that would cause angina

Question 18

long acting nitrates: useful for?

Answer 18

-effective in angina, inc exercise duration and dec anginal frequency

Question 19

WHy is ISMN good treatment for exertional angina?

Answer 19

bc its phasic release formulatin allows for enough drug in the plasma during the day but low concentrations at night =

Question 20

What to give for unstable angina and acute MI?

MOA?

Answer 20

-sublingual GTN
(IV and TD can also be used)
-dilation and prevent constriction of coronary constriction and potential antiplatelet effects

Question 21

What to give for congestive heart failure:

Answer 21

-ACUTE: organic nitrates (SL/IV) significantly lower filling pressure without adverse effects on systemic BP

Question 22

What to give african american with CHF and systolic dysfunction?

Answer 22

ISDN and hydralazne combo

hydralazine (vasodilator) inh oxidation NADPH oxidase so less free radicals

Question 23

organic nitrates side effects:

Answer 23

• headaches** -common early after intiation
• hypotension**- more common with rapid onset GTN (SL) or short acting isisorbide dinitrates
• *-ISDN dose should be titrated over several days
• eryhtema/local edema
• methemoglobinemia is rare