Calcium Channel Blockers

Rate limiting calcium channel blockers ( Slow CCB )



A, Dihydropyridine (Lipophilic): These are the most potent calcium channel blockers

• Nifedipine
• Amlodipine
• Nimodipine
• Nitrendipine
• Felodipine

B, Phenylalkylamine (Hydrophilic )

• Verapamil

C, Benzothiazepine

• Diltiazem

Mechanism of Action:

1, Smooth Muscle:

• CCB work by blocking Voltage-gated Calcium channels in blood vessels
• This leads to decreases intracellular Ca+ influx resulting in muscle contraction also decreased. 
• Decreased vascular smooth muscle contraction resulting in increased arterial vascular diameter.
• CCB markedly dilate arterial smooth muscle but have a mild effect venous smooth muscle.
• If vasodilation then decrease peripheral vascular resistance..
• CCB are effective against large vessels stiffness which occurs usually in elder patients where there is increased Sytolic BP

2, Heart:

• CCB blocks Voltage-gated Calcium channels which results in decrease cardiac contractlity.
• Decreases in cardiac contractility leads to decreases in cardiac output.
• The 0 phase depolarization in SA and AV nodes is largely Ca+ mediated.
• Verapamil and diltiazem slows sinus rate and AV conduction due to delayed membrane depolarization. This leads to depression of pacemaker and conduction activity i.e. positive chronotropic and dromotropic action.
• Nifedipine doesn't cause delayed membrane depolarization hence it do not decrease SA and AV conduction that is no negative chronotropic and dromotropic action.

-Dihydropyridine are more selective for smooth vascular muscle and negligible -ve inotropic action.
-Diltiazem causes less depression of contractility than verapamil.

CO= Cardiac Output
PVR= Peripheral Vascular Resistance
 
Hence,
        BP= CO x PVR
If there is Decreased CO and Decreased PVR= Decrease BP.