Organic Nitrates for Myocardial Ischemia Flashcards
What is the mechanism of action for organic nitrates?
These are prodrugs that must undergo denitrification by mitochondrial aldehyde reductase to yield nitric oxide.
NO activates GTP to cGMP leading to increased calcium influx and vasorelaxation.
What is described by the term nitrate tolerance?
Organic nitrates are subject to tolerance if sustained therapy is given in a 24 hour period.
Tolerance develops early here and cannot be overcome with higher doses.
How can one avoid nitrate tolerance?
Dosing regimens that allow nitrate free or low dose times for hours through the day.
Where is nitroglycerin metabolized and what is its half life?
Metabolized intravascularly and has a half life period of 1-4 minutes.
It does have dinitrate metabolites that have a half life of 40 minutes.
How long is the metabolism rate of Isosorbide Dinitrate and how ong is its half life?
Takes 40 minutes to be metabozed.
Gives rise to isosorbide-2-mononitrate and isosorbide-5-mononitrate with half lives of 2-4 hours.
Can be given as a sustained released form given PO or SL.
How long is the metabolism of isosorbide mononitrate and how long is the drugs half life?
Isosorbide mononitrate does not need to be metabolized for activity!
IT has a 2-4 halflife metabolites.
Can also be given as a sustained release form.
What effect do organic nitrATES have on the veins?
Potent vasodilator of the veins allowing for a decrease in ventricular volume and preload.
What effect do organic nitrates have on peripheral vascular resistance?
Have no effect of the peripheral vascular resistance.
What effect do organic nitrates have on coronary resisistance vessels?
No effect!
Avoid coronary steal.
Best effects are on coronary stenosis!
What are the three indicated uses for Organic Nitrate use?
Acute attacks of angina - Sublingual
Unstable angina and acute myocardial infarction
Congestive heart failure acute and chronic.
Why are organic nitrates the drug of choice for acute HF and active ischemia?
Because Nitric Oxide is able to dramatically lower filling pressure without adverse effects on systemic BP.
What is the best drug combination for african american men with CHF?
ISDN and hydralazine.
What type of drug is Ranolazine?
This is a blocker of late sodium channels used in myocardial ischemia.
What is the indication for the drug Ranolazine?
Ranolazine is indicated for myocardial ischemia it acts to facilitate Ca entry decreasing diastolic tension and cardiac contractility.
What is a side effect of the drug ranolazine?
Ranolazine prolongs the QT interval in patients with coronary artery disease.
