Flashcards in EXAM #2: CV PHARM VIII Deck (22):
What is the physiologic cause of angina?
Release of BRADYKININ and ADENOSINE onto nociceptive afferents
What is angina?
Retrosternal chest pain radiating to the neck, jaw, or back
What is "stable" angina?
Short-duration anginal pain precipitated by:
- Cold weather
What is "unstable" angina?
Longer-standing anginal (~20 min) pain
- Occurs at REST and dissipates with rest
What are the hallmarks of AMI?
- Sudden onset
- Lasts longer than 30 min.
- Associated with dyspnea, weakness, nausea, and vomiting
What are the two general approaches to altering myocardial oxygen consumption to decrease angina?
1) Decrease myocardial oxygen demand
2) Increase myocardial supply
What classes of drugs decrease myocardial oxygen demand?
Ca++ entry blockers
What are the classes of drugs that increase myocardial oxygen supply?
List the organic nitrates that are used for myocardial ischemia.
What enzyme activates organic nitrates?
mitochondiral aldehyde reductase
What is the mechanism of action of the organic nitrates?
1) NO increases cGMP
2 cGMP activates cGK-1, which:
- Increased mitochondrial Ca++ uptake
- Decreases Ca++ influx
- Phosphorylates MLCK
What is the effect of MLCK phosphorylation?
Myosin Light Chain Kinase= MLCK
- Phoshorylation of MLCK inhibits its activity
- When phosphorylated, MLCK cannot activate
Myosin Light Chain, which would cause vasoconstriction
Thus, MLCK phosphorylation causes VASORELAXATION
What is nitrate tolerance? What are the clinical implications?
Sustained organic nitrate therapy reduces the efficacy of the drugs
*****Thus, in patients that need this therapy, a bridge with a different class drug for part of the day is recommended*****
Describe the half life to NTG.
Undergoes hepatic and intravascular metabolism v. quickly
****T1/2 is 1-4 minutes
What is the advantage of Isosorbide Dinitrate?
Available in a sustained release form that allowing for dosing once daily
-->Avoids nitrate tolerance
What are the unique characteristics of Isosorbide Mononitrate?
1) Does not undergo first-pass hepatic metabolism
2) Available in a sustained release form that allowing for dosing once daily
What are the pharmacodynamic effects of the organic nitrates?
Vasodilation of veins DECREASES preload
-->decreases workload of the heart; does NOT dilate the coronary vasculature
What is coronary steal?
Altered coronary blood blow leads to a reduction in coronary blood flow
What are the indications for sublingual nitrates?
1) Acute angina
2) Prophylactic therapy to prevent angina
What are the indications for long-acting nitrates?
- Used in patients with angia to decrease episode frequency and increase exercise duration
What combination therapy is recommended for African Americans with CHF from systolic dysfunction?
ISDN + Hydralazine