Drugs used in Chronic IHD Flashcards
What are the two approaches to treat angina pectoris?
1) Reduce O2 demand by decreasing cardiac work.
2) Increase oxygen supply by increasing blood flow through coronary arteries.
What are ways to increase coronary blood flow?
1) Surgical or non-surgical revascularization approaches
2) Vasodilators
What type of angina are vasodilators useful for? Not useful for?
Useful - Vasospastic (Prinzmetal) angina.
Not useful for atherosclerotic (classic) angina.
What is the significance of coronary steal phenomenon?
Explains why vasodilators are not useful in atherosclerotic angina. Arteriolar dilation (i.e. Dipyridamole) of normal vessels diverts blood away from ischemic/stenotic areas.
What are the determinants of myocardial oxygen demand that are used to reduce O2 demands of heart in tx of angina?
HR, contractility, preload, afterload
What are three nitrovasodilators?
1) Nitroglycerin
2) Isosorbide dinitrate
3) Isosorbide mononitrate
Where is there high nitrate reductase activity?
What else is special about nitrate reductase activity?
Liver - first pass metabolism.
Nitrate reductase activity is saturable.
What is EDRF?
Nitric Oxide: Endothelium-Derived Relaxing Factor - released by ACh when endothelium is PRESENT. NO] relaxes smooth muscle of blood vessels.
What does endothelial NOS produce? And what is the ultimate result?
Produces endogenous NO, resulting in vasorelaxation (of vascular smooth muscle).
What acts as an extracellular NO donor?
An organic nitrate (i.e. Nitroglycerin) that gets metabolically activated to NO.
What physiologically results from NO inside a vascular smooth muscle cell?
NO activates GC, which turns GTP to cGMP, which then activates PKG, which then causes:
1) hyperpolarization of cell and reduced Ca entry (opens K channel) AND 2) smooth muscle relaxation
Sensitivity of vasculature to nitrate-induced vasodilation.
veins > large arteries > small arteries and arterioles
What two things does nitrate-induced relaxation of vascular smooth muscle result in?
What change in coronary blood flow in atherosclerotic angina?
Dilation of veins (major)
Dilation of arteries (needs higher concentration of nitrates). No significant increase in coronary blood flow to ischemic area in atherosclerotic angina.
What effects do nitrates have in angina of effort/atherosclerotic angina (2)?
1) Decreased preload/volume heart has to pump, therefore deceased O2 demand.
What effects do nitrates have in vasospastic angina (2)?
1) Relaxation of coronary artery vascular smooth muscle, relieving coronary artery spasm
Clinical use: short v. long acting nitrovasodilators.
What is the duration of short v. long?
Short acting used to relieve angina attack (10-90min)
Long acting used to prevent attacks (3-10hrs)
Which nitrovasodilators are short acting? Long acting? Formulation?
BOTH:
1) Nitroglycerin - short (subL, spray shortest duration) and long (oral, ointment, patch)
2) Isosorbide dinitrate - short (subL, spray) and long (oral)
ONLY LONG:
3) Isosorbide mononitrate - long (oral longest duration)
How is NO depleted in tissue?
Increased generation of superoxide radicals deplete tissues of NO.