Cardiovascular II - CA++ antagonists

Question 1

Calcium channel antagonists:

1. Selective antagonism of what channel?
2. What are the primary uses of Ca++ channel antagonists?

Answer 1

1. L-type potential operated channel (thus no effect on neural tissue or skeletal muscle)
2. Myocardial ischemia, hypertension, hypertensive emergencies (only DHPs), and cardiac arrythymias (supraventricular tachycardia, atrial fibrillation/flutter - no use of DHPs)

Question 2

What are other potential uses of calcium channel antagonists?

Answer 2

cardioprotection, esophageal spasm, subarachnoid hemorrhage, hypertrophic cardiomyopathy, and migrane (much better migrane drugs)

Question 3

What are the three classes of calcium channel antagonists?

Answer 3

1,4 Dihydropyridines

Phenylalkylamines

Benzothiazepines

Question 4

Example of a 1,4 DHP?

Answer 4

Nifedipine

Question 5

Example of a phenylalkylamine?

Answer 5

Verapamil (the only drug in this class)

Question 6

Example of a benzothiazepine?

Answer 6

Diltiazem (the only drug in its class)

Question 7

Calcium antagonists have four target organ characteristics:

1. Relative population of __ type channels - most prevalent in ___ tissues.
2. Dependence of tissue on ___ ___ (examples of tissues)

Answer 7

1. L, CV
2. external Ca++; heart, arterioles, large coronary arteries, cerebral arteries (therefore NOT skeletal muscle)

Question 8

Calcium antagonists have four target organ characteristics:

3. Theoretical ____ of binding sites.
4. ____ and frequency dependence of binding sites: binding is greater in the ___ state. Thus, different resting membrane potentials may affect drug effectiveness. Increased frequency of stimulation leads to ____ effectiveness. What drug binds best when the channel is inactive? Second best?

Answer 8

3. selectivity
4. voltage; depolarized; increased; verapamil; diltiazem

Question 9

The effects of one type of calcium channel antagonist should never be?

Answer 9

Extrapolated to another type because there is a slight variation in action

Question 10

Nifedipine, Nicardipine, and Nimodipine:

1. Where do the dihydropyridines inhibit L channels?
2. They are more potent ____ than verapamil or diltiazem.

Answer 10

1. Arterial resistance vessels and large coronary/cerebral arteries
2. vasodilators

Question 11

Nifedipine, Nicardipine, and Nimodipine:

These are potent vasodilators because they inhibit?

Answer 11

cyclic nucleotide phosphodiesterase

Question 12

Nifedipine, Nicardipine, and Nimodipine:

The DHPs exhibit little dependence on the ___ of ____ and do NOT inhibit ___ conduction at clinical doses. They are ____ inotropes in vitro but in vivo this is reversed by?

Answer 12

frequency; stimulation; A-V; negative; reflex activation of the SNS

Question 13

Verapamil:

1. Drug class?
2. It is a less potent dilator of arteries than the ____.
3. It produces potent inhibition of?
4. Inotropic and chronotropic effects? Results in?

Answer 13

1. Phenylalkylamine
2. dihydropyridines
3. AV conduction
4. Negative inotrope/chronotrope –> decreased oxygen demand

Question 14

Diltiazem

1. Drug class?
2. As potent as Nefedipine in what function? But?
3. Less potent than Verapimil in what action?

Answer 14

1. Benzothiazepine
2. dilating the coronary arteries but has fewer side effects
3. inhibiting AV conduction

Question 15

Bepridil

1. Treatment of?
2. It significantly prolongs the cardiac ___ ___ and in suceptible patients it may cause?

Answer 15

1. angina
2. action potential; torsade de pointes

Question 16

Bepridil is absolutely contraindicated in what patients?

Answer 16

Those with serious arrhythmias or prolonged QT

Question 17

Therapeutic uses for calcium channel antagonists?

Answer 17

Hypertension, angina, and cardiac arrhythmias

Question 18

Use in hypertension:

1. What drug is a better choice for severe hypertension? Why?
2. These antagonists do not cause what two things associated with other drugs for hypertension?
3. Potential for cardiac depression is potentiated by concurrent administration with?

Answer 18

1. Nifedipine; reflex cardiac effects are less than those seen with other vasodilators
2. Fluid retention or postural hypotension
3. Beta blockers

Question 19

All forms of angina are responsive to Ca++ antagonists; however calcium blockers, especially ____, can ____ angina.

Answer 19

Nifedipine; aggravate

Question 20

Therapeutic uses in cardiac arrhythmias:

Verapamil and Diltiazem are effective for what problems?

Answer 20

supraventricular tachycardias, reentry tachycardia through the AV node, and atrial fibrillation

Question 21

Side effects and contraindications:

Ca++ antagonists are not recommended in patients with?

Answer 21

SA or AV node conduction abnormalities or heart failure

Question 22

Side effects and contraindications:

What side effects are more common with nifedipine?

Answer 22

Hypotension, headache, and peripheral edema

Question 23

Side effects and contraindications:

What side effects are more common in verapamil?

Answer 23

Most common is cardiodepression – also potential hypotension, peripheral edema, or AV block

Question 24

Side effects and contraindications:

What side effects are most common for Diltiazem?

Answer 24

This drug has the least side effects; very minimal likelihood to cause hypotension, AV block, or cardiodepression

Question 25

Pharmacokinetics:

1. The calcium channel antagonist subtypes are all orally active, ____ protein bound, and ____ metabolized.
2. What is much more bioavailable?

Answer 25

1. extensively, highly
2. Nifedipine