EXAM #2: CV PHARM VIII

Question 1

What is the physiologic cause of angina?

Answer 1

Release of BRADYKININ and ADENOSINE onto nociceptive afferents

Question 2

What is angina?

Answer 2

Retrosternal chest pain radiating to the neck, jaw, or back

Question 3

What is “stable” angina?

Answer 3

Short-duration anginal pain precipitated by:

• Exercise
• Cold weather
• Stress

Question 4

What is “unstable” angina?

Answer 4

Longer-standing anginal (~20 min) pain

• Occurs at REST and dissipates with rest
• Crescendos

Question 5

What are the hallmarks of AMI?

Answer 5

• Sudden onset
• Lasts longer than 30 min.
• Associated with dyspnea, weakness, nausea, and vomiting

Question 6

What are the two general approaches to altering myocardial oxygen consumption to decrease angina?

Answer 6

1) Decrease myocardial oxygen demand

2) Increase myocardial supply

Question 7

What classes of drugs decrease myocardial oxygen demand?

Answer 7

Beta-blockers
Ca++ blockers
Organic nitrates
Ca++ entry blockers

Question 8

What are the classes of drugs that increase myocardial oxygen supply?

Answer 8

Vasodilators
Statins
Anti-thrombics

Question 9

List the organic nitrates that are used for myocardial ischemia.

Answer 9

Nitroglycerin
Isosorbide Dinitrate
Isosorbide Mononitrate

Question 10

What enzyme activates organic nitrates?

Answer 10

mitochondiral aldehyde reductase

Question 11

What is the mechanism of action of the organic nitrates?

Answer 11

1) NO increases cGMP 
2 cGMP activates cGK-1, which: 
- Increased mitochondrial Ca++ uptake 
- Decreases Ca++ influx
- Phosphorylates MLCK

Question 12

What is the effect of MLCK phosphorylation?

Answer 12

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

Question 13

What is nitrate tolerance? What are the clinical implications?

Answer 13

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

Question 14

Describe the half life to NTG.

Answer 14

Undergoes hepatic and intravascular metabolism v. quickly

**T1/2 is 1-4 minutes

Question 15

What is the advantage of Isosorbide Dinitrate?

Answer 15

Available in a sustained release form that allowing for dosing once daily

–>Avoids nitrate tolerance

Question 16

What are the unique characteristics of Isosorbide Mononitrate?

Answer 16

1) Does not undergo first-pass hepatic metabolism

2) Available in a sustained release form that allowing for dosing once daily

Question 17

What are the pharmacodynamic effects of the organic nitrates?

Answer 17

Vasodilation of veins DECREASES preload

–>decreases workload of the heart; does NOT dilate the coronary vasculature

Question 18

What is coronary steal?

Answer 18

Altered coronary blood blow leads to a reduction in coronary blood flow

Question 19

What are the indications for sublingual nitrates?

Answer 19

1) Acute angina
2) Prophylactic therapy to prevent angina
3) CHF
4) MI

Question 20

What are the indications for long-acting nitrates?

Answer 20

• Used in patients with angia to decrease episode frequency and increase exercise duration

Question 21

What combination therapy is recommended for African Americans with CHF from systolic dysfunction?

Answer 21

ISDN + Hydralazine

Question 22

What are the side effects of organic nitrates for myocardial ischemia?

Answer 22

• Headache

- Hypotension