structures, mechanism of action, uses & marketted formulations of CCBs

1. By
Dr. Kalam Sirisha,
Associate Professor & Head,
Department of Pharmaceutical Chemistry,
Vaagdevi College of Pharmacy, Ramnagar,
Warangal, Telangana
E-mail: ragisirisha@yahoo.com
CALCIUM CHANNEL BLOCKERS

2. VERAPAMIL
Verapamil is a phenylalkylamine calcium channel blocker used in the treatment
of high blood pressure, heart arrhythmias, and angina, and was the first
calcium channel antagonist to be introduced into therapy in the early 1960s. It is
a member of the non-dihydropyridine class of calcium channel blockers, which
includes drugs like diltiazem and flunarizine, but is chemically unrelated to other
cardioactive medications. Verapamil is administered as a racemic mixture
containing equal amounts of the S- and R-enantiomer, each of which is
pharmacologically distinct - the S-enantiomer carries approximately 20-fold
greater potency than the R-enantiomer, but is metabolized at a higher rate.

3. Verapamil uses
•Vasopastic (i.e. Prinzmetal's) angina, unstable angina, and chronic stable
angina.
•Hypertension
•Prophylaxis of repetitive paroxysmal supraventricular tachycardia
• In combination with digoxin to control ventricular rate in patients with
atrial fibrillation or atrial flutter.
•Commonly used for prophylaxis of cluster headaches.
•Studied as MDR inhibitor in chemotherapy

5. BEPRIDIL HYDROCHLORIDE
A long-acting, non selective, calcium channel blocker with significant anti-
anginal activity. The drug produces significant coronary vasodilation and
modest peripheral effects. It has antihypertensive and selective anti-
arrhythmia activities and acts as a calmodulin antagonist. It is no longer
marketed in the United States, as it has been implicated in causing
ventricular arrhythmias.

6. Mechanism of action: Bepridil has inhibitory effects on both the slow calcium
(L-type) and fast sodium inward currents in myocardial and vascular smooth
muscle, interferes with calcium binding to calmodulin, and blocks both
voltage and receptor operated calcium channels. Bepridil inhibits the
transmembrane influx of calcium ions into cardiac and vascular smooth
muscle.
Uses:
Hypertension
Chronic stable angina

8. DILTIAZEM HYDROCHLORIDE
Diltiazem is a calcium channel
blocker. It works by relaxing
the muscles of heart and blood
vessels.
Diltiazem is used to
treat hypertension (high blood
pressure), angina (chest pain),
and certain heart rhythm
disorders.

10. NIFEDIPINE
•Nifedipine, or BAY a 1040, is a first
generation dihydropyridine L-type calcium
channel blocker
•Nifedipine was developed by Bayer in
1972. Since nifedipine's development,
second and third generation
dihydropyridines have been developed
with slower onsets and longer durations
of action. The most popular of the third
generation dihydropyridines
is amlodipine.
•Nifedipine was granted FDA approval on
31 December 1981.

11. Mechanism of action:
Nifedipine blocks voltage gated L-type calcium channels in vascular
smooth muscle and myocardial cells. This blockage prevents the entry
of calcium ions into cells during depolarization, reducing peripheral
arterial vascular resistance and dilating coronary arteries. These actions
reduce blood pressure and increase the supply of oxygen to the heart,
alleviating angina.
Uses:
Nifedipine capsules are indicated to treat vasospastic angina and
chronic stable angina.
Extended release tablets are indicated to treat vasospastic angina,
chronic stable angina, and hypertension.

13. AMLODIPINE
Amlodipine, initially approved by the FDA in 1987, is a popular antihypertensive drug
belonging to the group of drugs called dihydropyridine calcium channel blockers. Due to
their selectivity for the peripheral blood vessels, dihydropyridine calcium channel blockers
are associated with a lower incidence of myocardial depression and cardiac conduction
abnormalities than other calcium channel blockers.
Amlodipine is commonly used in the treatment of high blood pressure and angina.
Amlodipine has antioxidant properties and an ability to enhance the production of nitric
oxide (NO), an important vasodilator that decreases blood pressure. The option for single
daily dosing of amlodipine is an attractive feature of this drug

14. Mechanism of action:
Amlodipine is considered a peripheral arterial vasodilator that exerts its action directly
on vascular smooth muscle to lead to a reduction in peripheral vascular resistance,
causing a decrease in blood pressure. Amlodipine is a dihydropyridine calcium antagonist
(calcium ion antagonist or slow-channel blocker) that inhibits the influx of calcium ions
into both vascular smooth muscle and cardiac muscle. A stronger effect of amlodipine is
exerted on vascular smooth muscle cells than on cardiac muscle cells. Direct actions of
amlodipine on vascular smooth muscle result in reduced blood pressure
Uses:
Amlodipine may be used alone or in combination with other antihypertensive and
antianginal agents for the treatment of the following conditions:
• Hypertension
• Coronary artery disease
• Chronic stable angina
• Vasospastic angina (Prinzmetal’s or Variant angina)
• Angiographically documented coronary artery disease in patients without heart
failure or an ejection fraction < 40%
The terminal elimination half-life of about 30–50 hours

16. FELODIPINE
Felodipine is a long-acting 1,4-dihydropyridine
calcium channel blocker (CCB)b. It acts
primarily on vascular smooth muscle cells by
stabilizing voltage-gated L-type calcium
channels in their inactive conformation. By
inhibiting the influx of calcium in smooth
muscle cells, felodipine prevents calcium-
dependent myocyte contraction and
vasoconstriction. Felodipine is the most potent
CCB in use and is unique in that it exhibits
fluorescent activity. In addition to binding to L-
type calcium channels, felodipine binds to a
number of calcium-binding proteins, exhibits
competitive antagonism of the
mineralcorticoid receptor, inhibits the activity
of calmodulin-dependent cyclic nucleotide
phosphodiesterase, and blocks calcium influx
through voltage-gated T-type calcium
channels. Felodipine is used to treat mild to
moderate essential hypertension
Use: For the
treatment of mild
to moderate
essential
hypertension.

18. NIMODIPINE
Nimodipine is a 1,4-dihydropyridine calcium
channel blocker. It acts primarily on vascular
smooth muscle cells by stabilizing voltage-
gated L-type calcium channels in their inactive
conformation. By inhibiting the influx of
calcium in smooth muscle cells, nimodipine
prevents calcium-dependent smooth muscle
contraction and subsequent vasoconstriction.
Compared to other calcium channel blocking
agents, nimodipine exhibits greater effects on
cerebral circulation than on peripheral
circulation. Nimodipine is used to as an
adjunct to improve the neurologic outcome
following subarachnoid hemorrhage from
ruptured intracranial aneurysm.
Uses: For use as an adjunct to improve neurologic outcome following
subarachnoid hemorrhage (SAH) from ruptured intracranial berry
aneurysms by reducing the incidence and severity of ischemic deficits.

20. NICARDIPINE
Nicardipine (Cardene) is a medication used to
treat high blood pressure and angina. It
belongs to the dihydropyridine class of calcium
channel blockers. It is also used for Raynaud's
phenomenon. It is available in by mouth and
intravenous formulations. It has been used
in percutaneous coronary intervention
Used for the management of patients with
chronic stable angina and for the treatment of
hypertension.