Calcium Channel Blockers

Calcium Channel
Blocking Drugs
Outline
Introduction
Pharmacokinetics
CCB binding sites
Adverse effects
Heterogeneity of action
Contraindications
Cardiac & hemodynamic
Summary
differentiation
Three Classes of CCBs

Chemical Type
Chemical Names
Brand Names
Phenylalkylamines
verapamil
Calan,
Calna SR,
Isoptin SR,
Verelan
Benzothiazepines
diltiazem
Cardizem CD,
Dilacor XR
1,4-Dihydropyridines
Nifedipine
nicardipine
isradipine
felodipine
amlodipine
Adalat CC,
Procardia XL
Cardene
DynaCirc
Plendil
Norvasc
Three Classes of CCBs

H 3C
H 3C
CH3
0
CH3
CH
H 3C
CH3
CH2
CH2
CH2
CH2
CH2
CH3
Verapamil
NO2
CH3
S
H 3C
H 3C
N
H
CH3
Nifedipine
CH2
CH2
N
CH3
CH3
0
0
CH3
CH3
Diltiazem
Widespread use of CCBs
Angina pectoris
Hypertension
Treatment of supraventricular
arrhythmias
- Atrial Flutter
- Atrial Fibrillation
- Paroxysmal SVT
Outline
Introduction
Pharmacokinetics
CCB binding sites
Adverse effects
Contraindications
Summary
differentiation
The 1C subunit of the L-type Ca2+ channel

is the pore-forming subunit
I
II
III
IV
Out
In
III
5
6
IV
III IV
II
The expression and function of the 1C subunit

is modulated by other smaller subunits
2
1C
I
II
III
IV
NH3+
COONH3+
COONH3+
L-Type Ca2+ Channel

NH3+
COO-
COO-
The Three Classes of CCBs Bind to Different Sites
1,4Dihydropyridines
(nifedipine)
Phenylalkylamines
(verapamil)
+
Ca2+
pore
Benzothiazepines
(diltiazem)
CCBs Mechanisms of Action
Increase the time that Ca2+ channels are closed
Relaxation of the arterial smooth muscle but not

much effect on venous smooth muscle
Significant reduction in afterload but not preload
The different binding sites of CCBs result in differing

pharmacological effects
Use-dependent binding (targets cardiac cells)
+20
out
mV
Cell
membrane
-80
in
Diltiazem
Verapamil
Voltage-dependent binding (targets smooth muscle)

+20
-30
-80
mV
out
Cell
membrane
in
Nifedipine
Outline
Introduction
Pharmacokinetics
CCB binding sites
Adverse effects
Contraindications
Summary
differentiation
Why Do CCBs Act Selectively

on Cardiac and Vascular Muscle?
N-type and P-type Ca2+ channels mediate

neurotransmitter release in neurons
Ca2+
Ca2+
Ca2+
Ca2+
Ca2+
postsynaptic cell
Skeletal muscle relies on intracellular

Ca2+ for contraction
Myofibril
Plasma
membrane
Transverse
tubule
Terminal
cisterna of
SR
Tubules of
SR
SR
T Triad
Cardiac cells rely on L-type Ca2+ channels for contraction

and for the upstroke of the AP in slow response cells
Ca2+
Ca2+
L-Type
Ca2+
L-Type
Ca2+
Ca2+
Contractile Cells
(atria, ventricle)
Slow Response Cells

(SA node, AV node)
Vascular smooth muscle relies on Ca2+ influx

through L-type Ca2+ channels for contraction
Ca2+
L-Type
(graded, Ca2+ dependent

contraction)
CCBs Act Selectively on Cardiovascular Tissues
Neurons rely on N-and P-type Ca2+ channels
Skeletal muscle relies primarily on [Ca]i
Cardiac muscle requires Ca2+ influx through

L-type Ca2+ channels
- contraction (fast response cells)
- upstroke of AP (slow response cells)
Vascular smooth muscle requires Ca2+ influx

through L-type Ca2+ channels for contraction
Outline
Introduction
Pharmacokinetics
CCB binding sites
Adverse effects
Contraindications
Summary
differentiation
The different binding sites of CCBs result in differing

pharmacological effects
Use-dependent binding (targets cardiac cells)
+20
out
mV
Cell
membrane
-80
in
Diltiazem
Verapamil
Voltage-dependent binding (targets smooth muscle)

+20
-30
-80
mV
out
Cell
membrane
in
Nifedipine
Differential effects of different CCBs on CV cells

Dihydropyridines: Selective vasodilators
Peripheral
vasodilation
Non -dihydropyridines: equipotent for

cardiac tissue and vasculature
Heart rate
moderating
SN
AV
Potential reflex
increase in
HR, myocardial
contractility
and O2 demand
SN
AV
Coronary
VD
Reduced
inotropism
Peripheral
and coronary
vasodilation
Hemodynamic Effects of CCBs

Effect
Peripheral
vasodilatation
Coronary
vasodilatation
Preload
Afterload
Contractility
Heart rate
AV conduction
Verapamil
Diltiazem
Nifedipine
0/
0/
/ *
0/
/0
Outline
Introduction
Pharmacokinetics
CCB binding sites
Adverse effects
Contraindications
Summary
differentiation
CCBs: Pharmacokinetics
Agent
Oral
Absorption
(%)
BioavailAbility
(%)
Protein
Bound
(%)
Elimination
Half-Life
(h)
Verapamil
>90
10-35
83-92
2.8-6.3*
Diltiazem
>90
41-67
77-80
3.5-7
Nifedipine
>90
45-86
92-98
1.9-5.8
35
>95
2-4
15-24
>95
8-9
20
>99
11-16
64-90
97-99
30-50
Nicardipine
Isradipine
Felodipine
Amlodipine
-100
>90
-100
>90
Outline
Introduction
Pharmacokinetics
CCB binding sites
Adverse effects
Contraindications
Summary
differentiation
Comparative Adverse Effects

Diltiazem
Verapamil
Dihydropyridines
Overall
0-3%
10-14%
9-39%
Hypotension
++
++
+++
Headaches
+++
Peripheral
Edema
++
++
+++
Constipation
++
CHF (Worsen)
AV block
++
Caution w/beta
blockers
++
CCBs - Monitoring
heart rate
blood pressure
anginal symptoms
signs of CHF
adverse effects
Outline
Introduction
Pharmacokinetics
CCB binding sites
Adverse effects
Contraindications
Summary
differentiation
Contradications for CCBs

Contraindication
Verapamil
Nifedipine
Diltiazem
Hypotension
++
Sinus
bradycardia
AV conduction
defects
++
++
Severe cardiac
failure
++
Outline
Introduction
Pharmacokinetics
CCB binding sites
Adverse effects
Contraindications
Summary
differentiation
Which CCB is most likely to cause

hypotension and reflex tachycardia?
A. Diltiazem
B. Nifedipine
C. Verapamil
Contraindications for CCBs include (choose all

appropriate):
A. Supraventricular tachycardias
B. Hypotension
C. AV heart block
D. Hypertension
E. Congestive heart failure
CCBs may improve cardiac function by:

A. Reducing cardiac afterload
B. Increasing O2 supply
C. Decreasing cardiac preload
D. Normalizing heart rate in patients with
supraventricular tachycardias
Thank you!

Calcium Channel Blockers

Uploaded by

Copyright:

Available Formats

Calcium Channel Blockers

Uploaded by

Document Information

Original Description:

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Calcium Channel Blockers

Uploaded by

Copyright:

Available Formats

Calcium Channel

CCB binding sites

Cardiac & hemodynamic

Three Classes of CCBs

Three Classes of CCBs

Widespread use of CCBs

CCB binding sites

Cardiac & hemodynamic

The 1C subunit of the L-type Ca2+ channel

The expression and function of the 1C subunit

L-Type Ca2+ Channel

The Three Classes of CCBs Bind to Different Sites

CCBs Mechanisms of Action

Increase the time that Ca2+ channels are closed

Relaxation of the arterial smooth muscle but not

Significant reduction in afterload but not preload

The different binding sites of CCBs result in differing

Voltage-dependent binding (targets smooth muscle)

CCB binding sites

Cardiac & hemodynamic

Why Do CCBs Act Selectively

N-type and P-type Ca2+ channels mediate

Skeletal muscle relies on intracellular

Cardiac cells rely on L-type Ca2+ channels for contraction

Slow Response Cells

Vascular smooth muscle relies on Ca2+ influx

(graded, Ca2+ dependent

CCBs Act Selectively on Cardiovascular Tissues

Neurons rely on N-and P-type Ca2+ channels

Skeletal muscle relies primarily on [Ca]i

Cardiac muscle requires Ca2+ influx through

Vascular smooth muscle requires Ca2+ influx

CCB binding sites

Cardiac & hemodynamic

The different binding sites of CCBs result in differing

Voltage-dependent binding (targets smooth muscle)

Differential effects of different CCBs on CV cells

Non -dihydropyridines: equipotent for

Hemodynamic Effects of CCBs

CCB binding sites

Cardiac & hemodynamic

CCB binding sites

Cardiac & hemodynamic

Comparative Adverse Effects

CCB binding sites

Cardiac & hemodynamic

Contradications for CCBs

CCB binding sites

Cardiac & hemodynamic

Which CCB is most likely to cause

Contraindications for CCBs include (choose all

CCBs may improve cardiac function by:

You might also like