Drugs for Myocardial Ischemia Flashcards
What is angina pectoris?
chest pain due to inadequate blood flow and therefore inadequate O2 delivery to the heart muscle
Release of what compounds cause anginal pain?
bradykinin and adenosine onto nociceptive afferents
angina clinical description and features:
- 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
rest/unstable anginal
clinical description and features:
-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
acute MI
clinical description and features:
–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
Agents that decrease heart O2 demand:
- Beta antagonist (decrease HR)
- Ca entry blockers (NDHP-HR and contractility affected)
- organic nitrates
Agents that increase heart O2 supply:
- vasodilators -esp Ca entry blockers
- statins - pleotropic effect (activate NO synthase..etc)
- antithrombotics - prevents bloackade
increase preload/afterload what happens to contractility? and O2 demand?
increase contractility!
also increase O2 demand
organic nitrates -
DRUGS?
MOA?
-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
Nitrate tolerance:
- 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
MOA for ntirate tolerance?
biotransformatin (SH groups are depleted) and free radical most popular (endothelium produces many free radicals)
Nitroglycerin - pharmacokinetics
**-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
isisobide dinitrate -pharmacokinetics
- **-available in phasic, sustained release form –> QD dosing –> avoid tolerance
- T1/2= ~40 min
- PO OR SL administration
- Metabolites T1/2=2-4hrs
isosorbide mononitrate-pharmacokinetics
- **-does not undergo first pass hepatic metabolism- complete bioavailability
- metabolite halflife 2-4hrs
- **-available in sustained, phasic release form –> QD dosing –> avoid tolerance
nitrate effects:
- 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
Coronary steal concept
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”
Sublingual nitrates: useful for?
- classic therapy for treatment of acute attacks of angina
- prophylactic SL GTN or ISDN taken before activity that would cause angina
long acting nitrates: useful for?
-effective in angina, inc exercise duration and dec anginal frequency
WHy is ISMN good treatment for exertional angina?
bc its phasic release formulatin allows for enough drug in the plasma during the day but low concentrations at night =
What to give for unstable angina and acute MI?
MOA?
-sublingual GTN
(IV and TD can also be used)
-dilation and prevent constriction of coronary constriction and potential antiplatelet effects
What to give for congestive heart failure:
-ACUTE: organic nitrates (SL/IV) significantly lower filling pressure without adverse effects on systemic BP
What to give african american with CHF and systolic dysfunction?
ISDN and hydralazne combo
hydralazine (vasodilator) inh oxidation NADPH oxidase so less free radicals
organic nitrates side effects:
- 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
