Calcium channel blockers (CCBs) are a class of drugs that inhibit the movement of calcium ions across cell membranes. There are three main classes of CCBs: dihydropyridines like nifedipine, phenylalkylamines like verapamil, and benzothiazepines like diltiazem. CCBs work by blocking L-type calcium channels in cardiac and vascular smooth muscle cells, which decreases calcium entry and inhibits contraction. This leads to vasodilation, reduced peripheral resistance, and decreased blood pressure and workload on the heart. Common uses of CCBs include hypertension, angina, arrhythmias, and migraines. Adverse effects vary between classes but can

1. CCB
Late BRKM GMCJ

2. • Verapamil was developed in Germany in 1962 as a coronary
dilator.
• It had additional cardiodepressant property, but its
mechanism of action was not known.
• Three important classes of calcium channel blockers are
examplified by:
• Verapamil—a phenyl alkylamine, hydrophilic papaverine congener.
• Nifedipine—a dihydropyridine (lipophilic).
• Diltiazem—a hydrophilic benzothiazepine.
• The dihydropyridines (DHPs) are the most potent Ca2+
channel blockers, and this subclass has proliferated
exceptionally

3. Calcium channels
• Voltage sensitive channel: Activated when membrane potential drops
to around –40 mV or lower.
• Receptor operated channel: Activated by Adr 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 sensitive channel.

5. • DHPs are the most commonly used calcium channel blockers
(CCBs).
• The cardiac and smooth muscles cell contraction depends upon
the activation of calcium channels in the cardiac myocytes. For
depolarization of cardiac and other smooth muscles cells, entry
of calcium into the cells occurs through these calcium channels.
• CCBs inhibit the movement of calcium ions across the
membranes of myocardial and arterial muscle cells, altering the
action potential and blocking muscle cell contraction.

6. • A loss of smooth muscle tone, vasodilation, and decreased
peripheral resistance occurs. Subsequently, preload and afterload
are decreased, which in turn decreases cardiac workload and
oxygen consumption.
• Short acting DHPs like nifedipine causes reflex tachycardia and
palpitations, which can be controlled and minimized by addition
of a beta-blocker or giving sustained release preparations.

7. CCB
• Phenyl alkylamine:
• Verapamil
• Benzothiazepine:
• Diltiazem
• Dihydropyridines:
• Nifedipine, Felodipine, Amlodipine, Nitrendipine,
Nimodipine, Lacidipine, Lercanidipine, Benidipine

8. Comparative action of CCBs (DHPs & non-DHPs)

10. MECHANISM OF ACTION OF CCBs
Decrease myocardial contraction, HR & conduction velocity
Causes vacular smooth muscle relaxation
Decrease calcium entry into the cardiac & smooth muscle cells
Block L-type Calcium channels
CALCIUM CHANNEL BLOCKERS

11. Why Do CCBs Act Selectively on Cardiac
and Vascular Muscle?

12. N-type and P-type Ca2+ channels mediate
neurotransmitter release in neurons

13. Skeletal muscle relies on intracellular
Ca2+ for contraction

14. Cardiac cells rely on L-type Ca2+ channels for
contraction and for the upstroke of the AP in slow
response cells

15. Vascular smooth muscle relies on Ca2+ influx
through L-type Ca2+ channels for contraction

16. CCBs Act Selectively on Cardiovascular Tissues
• Neurons rely on N-and P-type Ca2+ channels
• Skeletal muscle relies primarily on [Ca]
• 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

17. Differential effects of different CCBs on CV
cells

18. Hemodynamic Effects of CCBs

19. CCBs: Pharmacokinetics

20. THERAPEUTIC USES OF CCBs
• 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.

21. • 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.

22. ADVERSE EFFECTS
• Verapamil causes Nausea, constipation, bradycardia,
aggravation of
• conduction defects .
• Ditiazem also has similar side effect profile but slightly to
lesser extent.
• DHPs show side effects like nausea, headache, drowsiness
palpitation, hypotension, flushing and ankle edema.
• Difficulty in micturation & worsening of gastroesophageal
reflux is seen in elderly patients.

23. Comparative Adverse Effects

24. Contradication’s for CCBs

25. Drug Dose Special features
Nifedipine 5-20mg BD  Has fast onset of action with short duration.
 Causes reflex tachycardia as a prominent side effects.
 May increase frequency of angina attack.
Amlodipine 5-10mg OD  Has got consistent & good oral bioavailability.
 Diurnal fluctuation of BP are least.
 s-Amlodipine is its enatiomer and equally effective at half the dose with less
ankle oedema.
Felodipine 5-10mg OD  Has higher vascular selectivity.
Nitrendipine 5-20mg OD  Has only 10-30% of bioavailabilty.
 Additionally also releases nitric oxide from the endothelium
 Useful in hypertension with angina.
Nimodipine 30-60mg QID  It is cerebrovascular selective due to high lipid solubility & BBB penetration.
 Used in patients with hemorrhagic stroke & subarachnoid hemorrhage.
Lacidipine 4-6mg OD  Has vasoselective activity and useful in hypertension only.
Lercanidipine 10-20mg OD  Long acting DHP.
 Useful in hypertension.
Benidipine 4-8mg OD  Long acting DHP.
 Has very slow dissociation from DHP receptors.
 Useful in hypertension & angina.