Katzung 12th ed - Chapter 12 - Antianginal drugs (1)

Question 1

Why are nitrates not given orally?

Answer 1

Because of first-pass hepatic metabolism: the liver contains nitrate reductase, which is a potent inactivator of nitrates.

Question 2

Name an active metabolite of glyceryl trinitrate.

Answer 2

1,2-dinitroglycerin.

Question 3

What is the bioavailability of oral isosorbide mononitrate?

Answer 3

100%

Question 4

What types of vessels are dilated by nitroglycerin?

Answer 4

All types, from the large arteries through to the large veins. Note that the veins dilate with low drug levels, but higher drug levels are required to dilate the arteries.

Question 5

What feature of the coronary arteries may prevent nitroglycerin from dilating the artery?

Answer 5

Concentric atheroma. Note that arteries affected by eccentric atheroma may still dilate asymmetrically in response to nitroglycerin.

Question 6

Explain the steps that lead from nitric oxide to vascular muscle relaxation.

Answer 6

Nitric oxide stimulates guanylyl cyclase, causing increased production of cGMP. cGMP triggers the dephosphorylation of myosin-light-chains, causing muscle relaxation (as the myosin cannot bind with the actin)

Question 7

How do calcium channel blockers cause vasodilation?

Answer 7

Vascular smooth muscle relies on calcium influx from the ECF for contraction. Calcium enters, then binds to calmodulin, which triggers myosin light chain phosphorylation, causing contraction. Calcium channel blockers prevent the entry of calcium into the cell.

Question 8

There are three different groups of drugs that are used to decrease myocardial oxygen requirement in patients with angina. What are they?

Answer 8

Nitrates, Calcium channel blockers, and beta-blockers.

Question 9

How are the nitrates excreted?

Answer 9

Renally.

Question 10

What are two key mechanisms of tolerance of nitrates?

Answer 10

Decrease in the tissue sulfhydryl groups.

Compensatory mechanisms causing salt and water retention.

Question 11

How does the body respond to the fall in TPR and BP caused by nitrates?

Answer 11

Neurohumeral mechanisms (baroreceptor reflex causing tachycardia, increased renin, angiotensin and aldosterone, salt and water retention.)

Question 12

How does sildenafil work?

Answer 12

It reduces the breakdown of cGMP, allowing more cGMP to contribute to vasodilation.

Question 13

What do nitrate drugs do to platelets?

Answer 13

They also increase cGMP, and this causes reduced platelet aggregation.

Question 14

What are the signs / symptoms of nitrate toxicity?

Answer 14

Orthostatic hypotension, tachycardia, throbbbing headache.

Question 15

Why are patients told to take their GTN patch off for 12 hours each day?

Answer 15

To reduce the development of tolerance.

Question 16

Name one important dihydropyridine calcium channel blocker.

Answer 16

Nifedipine.

Question 17

Describe the bioavailability and distribution of calcium channel blockers.

Answer 17

Calcium channel blockers have high first-pass hepatic metabolism. The oral bioavailability of verapamil is 20%. Calcium channel blockers are highly protein-bound.

Question 18

Which tissues do dihydropyridines act on preferentially? Which tissues do non-dihydropyridines act on preferentially?

Answer 18

The ratio of activity on vascular smooth muscle to cardiac tissue is higher in dihydropyridines than in verapamil or diltiazem. Both types block L-type calcium channels.

Question 19

Which calcium channel blocker has the greatest effect on SA nodal tissue and AV nodal tissue?

Answer 19

Verapamil.

Question 20

Verapamil should not be given to patients who are taking __________.

Answer 20

Digoxin (this is because verapamil reduces the clearance of digoxin)

Question 21

What is the relationship between nitrite drugs and methaemoglobin?

Answer 21

Methaemoglobin is formed when the normal ferrous iron (Fe2+) of Hb is converted to ferric iron (Fe3+), which can be caused by nitrites. Methaemoglobin has a poorer affinity for oxygen than normal Hb, and so excessive doses of nitrites can cause pseudocyanosis, tissue hypoxia, and death.