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USMLE - Pharm

Kaplan Section 3 Chapter 5 Anti-Anginal Drugs

Why does a pt get chest pain in ischemic heart disease? Anginal pain happens when O2 delivery to the heart is inadequate for myocardial requirement.
What is classic angina? angina of effort or exercise
What is classic angina due to? coronary atherosclerotic occlusion
What is Prinzmetal angina? vasospastic
What is Prinzmetal angina due to? reversible decrease in coronary blood flow
What is unstable/crescendo angina? Acute coronary syndrome with platelet aggregation
What are the two drug strategies to treat classic and vasospastic angina? 1. inc O2 delivery by dec vasospasm (use nitrates and CCB's); 2. dec O2 requirement by dec TPR, dec CO, or dec both (use nitrates, CCB's, and B blockers)
Name 4 endogenous compounds that can activate the NO pathway Ach, Bradykinin, Serotonin, Histamine ==> vasodilation!
Name 2 nitrates. Nitroglycerin, isosorbide
What is the mechanism of nitrates? NO --> activate guanylyl cyclase --> inc cGMP --> dephosphorylate myosin light chain --> myosin can't interact with actin --> relaxation of vascular sm musc --> venule dilation --> dec preload --> dec cardiac work --> dec O2 requirement
What happens with hi-dose nitrates? In addition to what happens normally, you also get arteriolar dilation --> dec afterload --> dec O2 requirement
What makes using nitrates especially promising for pts? decreases infart size and decreases post-MI mortality
What drugs should be used to treat cyanide poisoning? What is the mechanism? Na-nitrite or Amyl-nitrite --> forms metHb --> MetHB binds CN- ions (prevents CN- from binding to and inhibiting complex IV on the ETC) --> forms cyanometHb ---(add Na-thiosulfate)--->becomes metHb & SCN- (less toxic)
Adverse effects of nitrates 1. MetHbnemia, (more likely with nitrites than with nitrates), 2. tachyphylaxis (require > 12 hr period of "rest"), 3. reflex tachy and fluid retention, 4. effects of vasodilation: flushing, headache, orthostatic hypotension (syncope)
Why shouldn't you use Sildenafil with? Nitrates or other potent vasodilators. Sildenafil causes vasodilation, so combined with another vasodilator --> severe decrease in BP --> can lead to death!
What is the mechanism of CaCB's? block vascular L-type Ca channels --> myosin can't be phosphorylated to interact with actin --> prevention of smooth muscle contraction --> vasodilation --> dec afterload (arterioles most sensitive) --> dec cardiac work
Nifedipine CaCB - vascular selective --> vasodilation in arterioles --> dec afterload --> dec cardiac work. Use for angina or HTN.
Bepridil CaCB - dilates coronary vessels. Also blocks Na and K channels (--> implicated in torsades). Used for angina.
Why would you use B blockers to treat angina? No actions on vascular smooth muscle. With B blockers, you are directly targeting the heart --> dec HR, dec contractility (inotropy), dec CO --> dec O2 requirement.
For what type of angina would B blockers be most effective? Classic (angina of effort) -- not vasospastic. Can also use to offset the reflex tachy caused by use of nitrates (vasodilators).
Compare Carvedilol and Isosorbide Both have been shown to be equally effective vasodilators. (Carvedilol has both a and B blocking actions.)
What is the drug strategy for unstable angina? Nitrates + B blockers + supplemental O2. Prevent thrombosis (and MI) with heparin, warfarin, and antiplatelets (ASA, ticlopidine)
What drugs should you consider for acute coronary syndromes (including unstable angina)? Glycoprotein IIb/IIIa receptor inhibitors (abciximab, eptifibatide, tirofiban)
Created by: christinapham