Calcium Channel Blockers

Question 1

What is the prototype Phenylalkylamine CCB for this course?

Answer 1

Verapamil

Question 2

What is the prototype benzothIAZEpine CCB for this course?

Answer 2

diltIAZEm

Question 3

What is the prototype 1,4-Dihydropyridine CCB for this course? (2 items)

Answer 3

Nifedipine

Amlodipine

Question 4

What are the therapeutic uses of CCBs? (3 items)

Answer 4

Angina pectoris
HTN
Treatment of supraventricular arrhythmias (A-flutter, A-fib, SVT)

Question 5

What type of CCs do CCBs bind to?

Answer 5

L-type Ca2+ Channel

Question 6

Describe an L-type Ca2+ channel. Which part of the channel do the CCBs bind?

Answer 6

Polymer of 6 transmembrane domains. CCBs bind between the 5th and 6th domains

Question 7

What are the two types of binding to Ca channels?

Answer 7

Use dependent binding

Voltage dependent binding

Question 8

What does use dependent binding mean? What drugs work this way and why?

Answer 8

The channel must be open for drug to bind. More effective at higher rates because channels are open more often. This targets cardiac cells. Diltiazem and Verapamil work this way because of their size.

Question 9

What does voltage dependent binding mean? What does this mean for targeting of drug? What drug works this way?

Answer 9

The greater the depolarization the more effective the drug is. Smooth muscle is more depolarized than cardiac. Nifedipine works this way, and is more effective on vascular smooth muscle.

Question 10

What is the pattern of calcium channel activity?

Answer 10

Closed –> Open –> Inactive. Must return to closed before it can open again.

Question 11

Which channel state do the Phenylalkylamine and Benzothiazepines work?

Answer 11

Open state

Question 12

Which channel state do the Dihydropyridines work?

Answer 12

Inactive state

Question 13

Why aren’t different classes given together?

Answer 13

That have an allosteric binding effect. They don’t have entirely exclusive binding activity. This can either increase or decrease each drugs activity.

Question 14

What are the specific vasodilitory effects of CCBs? (2 items)

Answer 14

1. Relaxation of arterial smooth muscle but not venous smooth muscle
2. Significant reduction in afterload but not preload

Question 15

Why do CCBs act selectively on Cardiac and Vascular Muscle and not on skeletal muscle? (3 items)

Answer 15

They have L-type selectivity.
Neuromuscular channels are N-type and P-type channels.
Skeletal muscle relies on intracellular Ca2+ for contraction not external entry of Ca2+.

Question 16

How do cardiac cells rely on L-type Ca2+ channels? (2 items)

Answer 16

For contraction and for upstroke of the AP in slow response cells.

Question 17

How do smooth muscle cells rely on L-type Ca2+ channels?

Answer 17

For influx of Ca2+ for contraction

Question 18

What primary effects do dihydropyridines like Nifedipine have and why?
What sides effects do they have and what contraindication does this create?

Answer 18

Peripheral vasodilation of arteries due to voltage dependent activity.
Can cause reflex tachycardia, myocardial contractility, and O2 demand. These are contraindicated in tachyarrhythmias as a result.

Question 19

What effect does Verapamil have on Peripheral vasodiltation, coronary vasodilation, preload, afterload, contractility, heart rate, and av conduction

Answer 19

Peripheral Vasodilation +
Coronary Vasodilation ++
Preload none
Afterload - -
Contractility - - -
Heart rate - - -
AV conduction - - -

Question 20

What effect does Diltiazem have on Peripheral vasodiltation, coronary vasodilation, preload, afterload, contractility, heart rate, and av conduction

Answer 20

Peripheral Vasodilation +
Coronary Vasodilation ++
Preload none
Afterload - -
Contractility - - 
Heart rate - - -
AV conduction - -

Question 21

What effect does Nifedipine & Amlodipine have on Peripheral vasodiltation, coronary vasodilation, preload, afterload, contractility, heart rate, and av conduction

Answer 21

Peripheral Vasodilation ++
Coronary Vasodilation +++
Preload none
Afterload - - -
Contractility +/- 
Heart rate +/none
AV conduction none

Question 22

What is the Oral absorption, Bioavailability, Protein binding and Half-life of Verapamil?

Answer 22

Oral absorption - 90%
Bioavailability - 10-35%
Protein binding - 83-92%
Half-life - 2.8-6.3 hours

Question 23

What is the Oral absorption, Bioavailability, Protein binding and Half-life of Diltiazem?

Answer 23

Oral absorption - 90%
Bioavailability - 41-67%
Protein binding - 77-80%
Half-life - 3.5-7 hours

Question 24

What is the Oral absorption, Bioavailability, Protein binding and Half-life of Nifedipine?

Answer 24

Oral absorption - 90%
Bioavailability - 45-86%
Protein binding - 92-98%
Half-life - 1.9-5.8 hours

Question 25

What is the Oral absorption, Bioavailability, Protein binding and Half-life of Amlodipine?

Answer 25

Oral absorption - 90%
Bioavailability - 64-90%
Protein binding - 97-99%
Half-life - 30-50 hours

Question 26

What are the adverse effects of Diltiazem? (5 items)

Answer 26

Moderate hypotension
Moderate peripheral edema
Mild CHF worsening
Mild AV block
Potentiates Beta blockers

Question 27

What are the adverse effects of Verapamil? (7 items)

Answer 27

Moderate hypotension
Mild headaches
Moderate peripheral edema
Moderate constipation
Moderate CHF exacerbation
Moderate AV Block
Moderate caution with Beta blockers

Question 28

What are the adverse effects of Dihydropyridines (Nifedipine, Amlodipine)? (3 items)

Answer 28

Significant hypotension
Significant headaches
Significant Peripheral edema

Question 29

What components need to be monitored when using CCBs? (5 items)

Answer 29

Heart rate
Blood pressure
Anginal symptoms
Signs of CHF
Adverse effects

Question 30

What are contraindications for Diltiazem admin? (4 items)

Answer 30

Hypotension
Bradycardia
AV conduction defects
Severe cardiac failure

Question 31

What are contraindications for Verapamil admin? (4 items)

Answer 31

Hypotension
Bradycardia
AV conduction defects
Severe cardiac failure

Question 32

What are contraindications for Nifedipine & Amlodipine admin? (2 items)

Answer 32

Hypotension

Severe cardiac failure

Question 33

How are CCBs generally metabolized?

Answer 33

Cytochrome p450.