Flashcards in Cardiovascular pharmacology IX Deck (14):
what is the typical cause of anginal pain?
release of bradykinin and adenosine onto nociceptive efferents
what are agents that decrease oxygen demand?
1. beta blockers
2. some calcium entry blockers
3. organic nitrates
4. calcium entry blockers
what are agents that increase oxygen supply?
1. vasodilators (especially calcium entry blockers)
what are the organic nitrates used to treat myocardial ischemia?
2. isosorbide dinitrate (ISDN)
3. isosorbide mononitrate (ISMN)
what is the MOA of nitrates?
1. prodrugs that must undergo denitrification by mitochondrial aldehyde reductase to yield NO
2. NO activates soluble GC increasing cGMP and cGK-1 activation
3. increased mitochondrial calcium uptake
4. decrease calcium influx
5. phosphorylation of MLCK - vasorelaxation
what are the pharmacokinetics of nitroglycerin?
1. hepatic and intravascular metabolism - very fast half life 1-4 minutes
2. sublingual and transdermal route
what are the pharmacokinetics of isosorbide dinitrate?
phasic, released form - QD dosing to avoid tolerance
what are the pharmacokinetics of isosorbide mononitrate?
1. does not undergo first pass hepatic metabolism - completely bioavailable
2. sustained, phasic release form - QD dosing - avoids tolerance
what are the pharmacodynamic effects of organic nitrates for myocardial ischemia?
1. potent vasodilation in veins - decreased ventricular volume and preload
2. no effect on peripheral vascular resistance
3. little or no effect on coronary resistance vessels - avoids coronary steal (shunting)
4. works to decrease work load rather than vasodilate
why is ISMN effective in the therapy of exertional angina?
phasic release form - effective plasma concentrations during the day
why are nitrates used in acute CHF?
1. dramatically lower filling pressure without adverse effects on systemic BP
2. in acute and chornic ischemia, organic nitrates can be therapy of choice
which drugs are good for African Americans with CHF especially resulting from systolic dysfunction?
ISDN and hydralazine combination
in people with MI and LV failure, why are nitrates a good choice?
decrease in preload due to venous dilation