This document discusses calcium channel blockers (CCBs). It outlines three main classes of CCBs: verapamil, nifedipine, and diltiazem. Nifedipine is the most potent as a dihydropyridine. There are three types of calcium channels: voltage-sensitive, receptor-operated, and leak channels. Only the voltage-sensitive L-type calcium channels are blocked by CCBs. CCBs bind to sites on the alpha-1 subunit to restrict calcium entry, with different drugs having varying affinities for channel isoforms. CCBs have negative inotropic effects in the heart by blocking the calcium surge during the action potential plateau phase that

1. CALCIUM CHANNEL BLOCKERS
 Three important classes of calcium channel blockers are:
 Verapamil-–a phenyl alkylamine, hydrophilic papaverine congener
 Nifedipine---a dihydropyridine (lipophilic)
 Diltiazem----a hydrophilic benzothiazepine
 The dihydropyridines are the most potent Ca2+ channel blockers
 Calcium channels
 Three types of calcium channels have been described
 Voltage sensitive channel: activated when membrane potential drop to around -40 mV or
lower
 Receptor operated channel: Activated by Adr & other agonists & independent of membrane
depolarization

2. CALCIUM CHANNEL BLOCKERS
 Calcium channels
 Leak channels: Small amount of Ca2+ leak into resting cell & pumped out by Ca2+ ATPase
 Mechanical stretch promotes inward movement of calcium through the leak channel or
through separate stretch sensitive channels

3. VOLTAGE SENSITIVE CALCIUM CHANNEL

4. VOLTAGE SENSITIVE CALCIUM CHANNEL
 Calcium channels
 Only voltage sensitive L-type Ca2+ channels are blocked by
the CCBs
 The 3 groups of CCBs including verapamil, diltiazem and
nifedipine bind to their own specific sites on the ⍺1 subunit
and all restricting Ca2+ entry
 Further different drugs may have different affinities for
various site specific isoforms of the L-channels
 This may account for the differences in action exhibited by
various CCBs

6. PHARMACOLOGICALACTIONS

7. PHARMACOLOGICALACTIONS
 Heart
 In working atrial and ventricular fibers
Ca2+ moves in during plateau phase of
AP & release more calcium from SR
 This calcium surge causes contraction
through binding to troponin & allowing
interaction of myosin with actin
 The CCBs would thus have negative
inotropic action

8. PHARMACOLOGICALACTIONS
 Heart

9. CALCIUM CHANNEL BLOCKERS
 ADRs
 Nausea, constipation and bradycardia (common)
 Flushing, headache, & ankle edema are less
common

10. CALCIUM CHANNEL BLOCKERS

11. CALCIUM CHANNEL BLOCKERS

12. CALCIUM CHANNEL BLOCKERS
 Pharmacokinetics

13. Pharmacokinetics