Cardiovascular pharmacology IX

Question 1

what is the typical cause of anginal pain?

Answer 1

release of bradykinin and adenosine onto nociceptive efferents

Question 2

what are agents that decrease oxygen demand?

Answer 2

1. beta blockers
2. some calcium entry blockers
3. organic nitrates
4. calcium entry blockers

Question 3

what are agents that increase oxygen supply?

Answer 3

1. vasodilators (especially calcium entry blockers)
2. statins
3. antithrombotics

Question 4

what are the organic nitrates used to treat myocardial ischemia?

Answer 4

1. nitroglycerin
2. isosorbide dinitrate (ISDN)
3. isosorbide mononitrate (ISMN)

Question 5

what is the MOA of nitrates?

Answer 5

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

Question 6

what are the pharmacokinetics of nitroglycerin?

Answer 6

1. hepatic and intravascular metabolism - very fast half life 1-4 minutes
2. sublingual and transdermal route

Question 7

what are the pharmacokinetics of isosorbide dinitrate?

Answer 7

phasic, released form - QD dosing to avoid tolerance

Question 8

what are the pharmacokinetics of isosorbide mononitrate?

Answer 8

1. does not undergo first pass hepatic metabolism - completely bioavailable
2. sustained, phasic release form - QD dosing - avoids tolerance

Question 9

what are the pharmacodynamic effects of organic nitrates for myocardial ischemia?

Answer 9

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

Question 10

why is ISMN effective in the therapy of exertional angina?

Answer 10

phasic release form - effective plasma concentrations during the day

Question 11

why are nitrates used in acute CHF?

Answer 11

1. dramatically lower filling pressure without adverse effects on systemic BP
2. in acute and chornic ischemia, organic nitrates can be therapy of choice

Question 12

which drugs are good for African Americans with CHF especially resulting from systolic dysfunction?

Answer 12

ISDN and hydralazine combination

Question 13

in people with MI and LV failure, why are nitrates a good choice?

Answer 13

decrease in preload due to venous dilation

Question 14

what are the side effects of nitrates?

Answer 14

1. headaches

2. hypotension