Calcium - Channel Blockers

Possible Mechanism of Action of Calcium Antagonists: inhibit entrance of calcium ions into cells. Calcium inhibition occurs and through the voltage dependent L-type (slow or long acting) channels in smooth muscle. Their main action is to decrease the amount of intracellular calcium available for contraction to take place.

We’re not required to know the structures, but we must recognize that calcium channel blockers are not all the same, biochemically. Sometimes a national board will ask, for example, what is diltiazem? benzothiazepine, dihydropyridine, or phenylalkylamine… of course we know it is a benzothiazepine!

The calcium channel is a big protein with a few subunits, inserted in the membrane, which allows calcium diffusion down its concentration gradient. The calcium channel is simply the “door” that will be opened or closed, depending if we want calcium diffusion or not. However, this is a complicated door. There is alot of control involved, there are activation gates and inactivation gates, along with places for calcium to bind. It is postulated that the three calcium channel blocker drugs have different shapes, so they bind in different places. They all have certain characteristics that favor the inactive state, to prevent the voltage-gated channel from opening.

The three drugs are acting in different places, this is important because they will have different secondary effects

This is a summary of the calcium activity. Calcium activates the contractile protein, whether these will be contracted depends on the presence of calcium. There are a few systems that can be altered pharmacologically to produce the desired effects.

Calcium Antagonists Increase Myocardial Blood Supply By:

Producing coronary arterial vasodilation

Increasing blood flow

Preventing coronary spasms

So we hope to control the balance between the oxygen supply and the demand.

The beneficial effect is due to several factors. The myocardial contractility is decreased because of less calcium. The heart rate is decreased. The blood pressure is decreased because of the smooth muscle in the systemic arteries—so this creates a better balance where the oxygen demand is decreased, and even if the supply is the same you get a better balance, so there’s a therapeutic benefit.

Category: Pharmacology Notes