Calcium channel blockers (CCBs) are medications that lower blood pressure by inhibiting calcium entry into heart and blood vessel cells, easing heart workload and widening blood vessels. They are classified into phenylalkylamines, benzothiazepines, and dihydropyridines, each with specific examples like verapamil, diltiazem, and amlodipine, and used to treat conditions like hypertension and angina. CCBs may cause side effects such as nausea, constipation, and bradycardia, with specific concerns for elderly patients.

1. 1
CALCIUM CHANNEL
BLOCKERS
Mrs. Sandhya Sujeetkumar Ahire
Pharmaceutical Chemistry
8/14/2020
Mrs.SSA(
Pharma'chemistry)
CCB

2. 2
CALCIUM CHANNEL BLOCKERS
• Calcium channel blockers (CCBs) also known as
calcium antagonists. These are several medications
that disrupt the movement of calcium (Ca2
+)
through calcium channels. Calcium channel
blockers are drugs used to lower blood pressure.
• They work by slowing the movement of calcium into
the cells of the heart and blood vessel walls.
Therefore it easier for the heart to pump and
widens blood vessels.
• As a result, the heart doesn't have to work as hard,
and blood pressure lowers. they are first line
antihypertensive drugs. They are also used to treat
angina.
8/14/2020
Mrs.SSA(
Pharma'chemistry)
CCB

3. 3
CALCIUM CHANNELS
Voltage sensitive channel: Activated when
membrane potential drops to around –40
mV or lower.
Receptor operated channel: Activated by
Adrenaline and other agonists—
independent of membrane depolarization
(NA contracts even depolarized aortic
smooth muscle by promoting influx of
Ca2+ through this channel and releasing
Ca2+ from sarcoplasmic reticulum).
Leak channel: Small amounts of Ca2+ leak
into the resting cell and are pumped out by
Ca2+ATPase. Mechanical stretch promotes
inward movement of Ca2+, through the leak
channel or through separate stretch
8/14/2020
Mrs.SSA(
Pharma'chemistry)
CCB

4. 4
CLASSIFICATION
A. Phenyl alkylamine:
EX- Verapamil
B. Benzothiazepine:
EX-Diltiazem
C. Dihydropyridines:
EX- Nifedipine, Felodipine,
Amlodipine, Nitrendipine,
Nimodipine, Lacidipine,
Lercanidipine, Benidipine
8/14/2020
Mrs.SSA(
Pharma'chemistry)
CCB

5. 5
CALCIUM CHANNEL BLOCKERS (CCBS)
MECHANISM OF ACTION
• Calcium is essential for muscular contraction.
• The CCBs protect the tissue by inhibiting the
entrance of Ca+2 into cardiac and smooth
muscle cells of the coronary and systemic
arterial beds.
• All CCBs are therefore arterio dilators that
cause a decrease in vascular resistance.
Cause peripheral arterial vasodilation
• Reduce myocardial contractility (-ve
inotropic action)
• Result: decreased myocardial oxygen
demand
8/14/2020
Mrs.SSA(
Pharma'chemistry)
CCB

6. 6
1,4 –DIHYDROPYRIDINE DERIVATIVES
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7. 7
1. 1,4 dihydro pyridine essential for activity.
2. Substitution at N or oxidation or reduction of the
ring reduces or abolishes activity.
3. A phenyl substitution at 4th
position is optimum
activity.
4. The 3rd
and 5th
position ester gr optimizies
activity.
5. Placement of electron withdrawing substitution
results in agonistic activity.
6. When the ester at c1 and c5 are non identical the
c4 becomes chiral and stereo selectivity is
observed.
7. S enantiomer are found to be effective.
8/14/2020
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Pharma'chemistry)
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8. 8
8. R1 should be unsubstituted or carry a group
which can be readily cleared off
9. The optimal substituents at R2,R6 are lower
alkyl groups.especially methyl replacement of
R2 gr with a basic aminoethyl ether side chain
renders molecule more potent,wheras
replacement by hydrogen or an aryl causes
drop in activity.
10. In the enantiomer of chiral dihydropyridines
the s-enantiomer have proved to be more
effective.
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Pharma'chemistry)
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9. 9
11.Substituent at R4 is phenyl.In
monosubstitutied benzenoid nucleus ,ortho
substituent comp are more active than the
meta substituented compounds.para
substitution comp are inactive .electron
attracting substituent such as NO2 ,cl,CN,CF3
offer advantages over electron donating
substituent. Distribution is possible in
position ortho/meta position.
12.Alkoxy carbonyls are the optimal substituents
in positions R3 and R5. The alcohol
component of the ester gr may be the same
or different,aliphatic or araliphatic vary in
chain length,branching,degree of
8/14/2020
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Pharma'chemistry)
CCB

10. 10
AMLODIPINE
It is a medication used for treatment of
hypertension and coronary artery disease. It is
also used in Stable angina (where chest pain
occurs after physical and emotional stress).
MECHANISM OF ACTION:
Amlodipine relaxes peripheral and coronary
vascular smooth muscles . It produces
coronary vasodilation by inhibiting the entry
of calcium ions into the voltage gated
channels of the vascular smooth muscle and
myocardium during depolarization. It
decreases cardiac work, decrease cardiac
oxygen consumption.
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Pharma'chemistry)
CCB

11. 11
USES
To treat hypertension and chronic stable angina
3-ethyl 5-methyl 2-[(2-aminoethoxy)methyl]-4-
(2-chlorophenyl)-6-methyl-1,4-dihydropyridine-
3,5-dicarboxylate
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12. 12
VERAPAMIL
•It is a calcium channel blockers that is used to
treat hypertension, chest pain from cardiac
ischemia and supraventricular tachycardia.
USES-
 Angina pectoris
 Arrhythmias from ischemic myocardial
syndromes and supraventricular arrhythmias.
 2-(3,4-dimethoxyphenyl)-5-{[2-(3,4-
dimethoxyphenyl)ethyl](methyl)amino}-2-(propan-2-
yl)pentanenitrile
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13. 13
MECHANISM OF ACTION:
 Verapamil inhibits entry of calcium ions into
arterial smooth muscle as well as the myocytes
and conducting tissues.
 These actions lead to reversal and preventions
of coronary artery spasm, reduction in
afterload through peripheral vasodilatation and
reduction in ventricular rate in patients with
chronic atrial flutter or fibrillation and reduction
in the occurrence of paroxysmal
supraventricular tachycardia.
 Verapamil reduces BP, relieves angina and slows
AV conduction
8/14/2020
Mrs.SSA(
Pharma'chemistry)
CCB

14. 14
DILTIAZEM
Diltiazem, a benzothiazepine calcium-channel
blocker, is used alone or with an angiotensin-
converting enzyme inhibitor, to treat
hypertension, chronic stable angina pectoris, and
Prinzmetal's variant angina. Diltiazem is a non-
dihydropyridine (DHP)member of the calcium
channel blocker class, along with Verapamil.
USES-
 Angina pectoris
 Potent calcium channel blocker
 Lower heart rate
(2S,3S)-5-[2-(dimethylamino)ethyl]-2-(4-methoxyphenyl)-4-oxo-
2,3,4,5-tetrahydro-1,5-benzothiazepin-3-yl acetate
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15. 15
MECHANISM OF ACTIONS:
 Slow channel blocker with pharmacologic
actions similar to those of verapamil. Inhibits
calcium ion influx through slow channels
into cell of myocardial and arterial smooth
muscle (both coronary and peripheral blood
vessels).
 As a result, intracellular calcium remains at
sub threshold levels insufficient to stimulate
cell excitation and contraction.
 Slows SA and AV node conduction
(antiarrhythmic effect) without affecting
normal arterial action potential or
Interventricular conduction.
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Pharma'chemistry)
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16. 16
NIFEDIPINE
 A dihydro pyridine derivative.
 Functions mainly as an arteriolar vasodilator.
 This drug has minimal effect on cardiac
conduction or heart rate.
 Used in variant angina caused by
spontaneous coronary spasm
 Other members of this class, amlodipine,
nicardipine, and felodipine, have similar
cardiovascular characteristics except for
amlodipine, which does not affect heart rate
or cardiac output.
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Mrs.SSA(
Pharma'chemistry)
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17. 17
MOA-
• it is prototype DHP with rapid onset and
short duration of action.
• It involves arteriolar dilation, total
peripheral resistance decrease BP fall
USE - hypertension, angina pectoris
8/14/2020
Mrs.SSA(
Pharma'chemistry)
CCB
3,5-dimethyl 2,6-dimethyl-4-(2-
nitrophenyl)-1,4-dihydropyridine-3,5-
dicarboxylate

18. 18
BEPRIDIL HCL
MOA
• It blocks the calcium channel and also
inhibite the sodium flow into the heart
tissue and lengthen cardiac repolarization
USES
• Tratment of stable angina
• Vasodilators
• N-benzyl-N-[3-(2-methylpropoxy)-2-(pyrrolidin-1-
yl)propyl]aniline hydrate hydrochloride
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19. 19
FELODIPINE
MOA
• It act on vascular smooth muscle cell by
stabilizing voltage gated L –type calcium
channel in their inactive conformation.
USES
• Treatment of mild to moderate essential
hypertension.
• 3-ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-
dimethyl-1,4-dihydropyridine-3,5-
dicarboxylate.
8/14/2020
Mrs.SSA(
Pharma'chemistry)
CCB

20. 20
NICARDIPINE
MOA
• It is a potent calcium channel blocker with
marked vasodilators action
USES
• Hypertension
• Angina pectoris
• Asthma
• Cancer
• 3-{2-[benzyl(methyl)amino]ethyl} 5-methyl 2,6-
dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-
dicarboxylate
8/14/2020
Mrs.SSA(
Pharma'chemistry)
CCB

21. 21
NIMODIPINE
MOA
• It acts on vascular smooth muscle cells by
stabilizing voltage gated L-type calcium
channels in their inactive conformation
USES
• haemorrahage from ruptured intracranial
aneurysm
• 3-(2-methoxyethyl) 5-propan-2-yl 2,6-dimethyl-4-(3-
nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate.
8/14/2020
Mrs.SSA(
Pharma'chemistry)
CCB

22. 22
THERAPEUTIC USES OF CCB
 Hypertension: Long acting CCBs are used for
the long term treatment of hypertension.
Amlodipine is the most preferred drug.
 Ischemic heart disease:
 Angina pectoris: DHPs like amlodopine
with beta-blocker are used for long term
management. Verapamil and diltiazem are
used for prophylaxis.
 Vasospastic angina - Verapamil and
amlodopine are the preffered agents.
 Unstable angina - Verapamil is used.
8/14/2020
Mrs.SSA(
Pharma'chemistry)
CCB

23. 23
 Supraventricular arrhythmia: verapamil &
diltiazem are used due to their antiarrythmic
properties.
 Peripheral vascular disease: nifedipine,
felodipine and diltiazem are used for this
purpose. Nifedipine patches are also useful.
 Migraine prophylaxis: verapamil is useful.
 Nocturnal leg cramps: verapamil is useful.
8/14/2020
Mrs.SSA(
Pharma'chemistry)
CCB

24. 24
ADVERSE EFFECTS
1. Verapamil causes Nausea, constipation,
bradycardia, aggravation of
2. conduction defects .
3. Ditiazem also has similar side effect profile
but slightly to lesser extent.
4. DHPs show side effects like nausea, headache,
drowsiness palpitation, hypotension, flushing
and ankle edema.
5. Difficulty in micturation & worsening of
gastroesophageal reflux is seen in elderly
patients.
8/14/2020
Mrs.SSA(
Pharma'chemistry)
CCB

25. 8/14/2020
Mrs.SSA( Pharma'chemistry) CCB
THANK YOU FOR
YOUR
ATTENTION