8 - Calcium Channel Blockers Flashcards
What are the major roles of calcium in cardiac tissue?
In cardiac muscle, calcium entry is a necessary first step in the contractile process.
Calcium also plays a role in maintaining electrical activity in the SA and AV nodes.
What are the three chemical types of calcium channel blockers? Name the drug in each class.
Phenylalylamines: verapamil
Benzothiazepines: diltiazem
1,4-dihydropyridinesL Nifedipine (first gen) and amlodipine (second gen)
Which CCB is not used for HTN but for vasospasm in the brain and those suffering from subarachnoid hemorrhage?
Amlodipine
What are the main uses of CCBs?
Angina pectoris
HTN
Treatment of supraventricular arrhythmias such as atrial flutter, atrial fibrillation, and paroxysmal SVT.
Which CCB is NOT classified as an anti-arrhythmic drug?
!,4-dihydopyridines: nifedipine and amlodipine
What type of calcium channels do CCBs target? What is the structure of this type of channel?
L-type calcium channels: they form a large barrel and are made up of four transmembrane regions with a central pore where calcium goes through.
What effect do diltiazem and verapamil have on L-type calcium channels?
Use-dependent binding that targets cardiac cells: when the channel opens up, they bind to a site within the pore.
Frequency-dependent effect: The more frequently the channel opens, the more opportunity there is for the drug to get to its binding site.
What effect does Nifedipin have on L-type calcium channels? What type of cells does this effect?
Voltage-dependent binding targets smooth muscles more than cardiac muscles: when the membrane potential is more depolarized (more +) the drug gets attracted to the calcium channel.
Cardiac cells have a resting potential of -90 but smooth muscles have one of -60 so this drug is more selective for smooth muscles.
What confirmation of the calcium channel do Nifedipine and Amlodipine act on?
The inactivated state.
Why are calcium channel blockers not recommended to use together?
There are some similarities in amino acid residues of the binding pockets so allosteric interactions can occur.
One drug may enhance the affinity of the other drug and can cause unpredictable effects.
What is the mechanism of action of CCBs?
Increase the time that Ca2+ channels are non-conducting. by either blocking the pore or keeping it in an inactive state.
These relax arterial smooth muscle but do not have much effect on venous smooth muscle and thus significantly reduce the afterload but not the preload.
Why don’t CCB’s have an effect on neurotransmitter release from neurons?
Because the calcium channels that regulate nt release from the presynaptic membrane are N and P type, so they are not targeted by the drugs.
Why don’t CCBs have an effect on skeletal muscle contraction?
Because Ca2+ entry across the t-tubule is not required for skeletal muscle contraction.
Cardiac cells rely on L-type calcium channels for what two functions?
Contraction and for the upstroke of the AP in slow response cells.
This is important for maintaining cardiac rhythm and the contractile process.
Vascular smooth muscle relies on Ca2+ influx through L-type calcium channels for ________.
Contraction.
