January 27, 2023

Brief instructional video on the indications, mechanism of action of action of amlodipine with a brief description on the use of amlodipine in patients with Raynaud’s phenomenon.

Okay welcome everyone this presentation today will be a brief discussion on amlodipine and its mechanism of actions and some indications and then also one off-label use we have for this medication the classification of m lot of pain is a calcium channel blocker and with calcium channel blockers we have two types we have the dihydropyridine and we have the phenyl

Alkyl amines and a phenyl alkyl amine would be a drugs such as verapamil with m lotta pain this is going to be a dihydropyridine and these are l-type calcium channel blockers and what that means is the l just stands for long lasting and that refers to the length of channel activation and these are going to be voltage-dependent calcium channels so they require an

Electrical stimulus to open up and once they do they will be responsible for excitation contraction coupling and one of the key things we like about the dihedral pyridines is that when compared to the phenyl alcala means they’ve been shown to be relatively selective for vascular smooth muscle tissue so that means we’ll see no significant effect on the sinus node

And the heart rate will seem no significant effect on the electrical conduction velocity and they have no significant effect on cardiac muscle contraction strength and the reason we prescribe this drug is for patients experiencing angina patients with coronary artery disease and patients with hypertension and with these three conditions the main effect that we’re

Concerned with is the vasoconstriction that really constricted blood and that’s going to happen here in the tunica media as the smooth muscle there and strix so we’ll give em a lot of pain as a calcium channel blocker to block that a smooth muscle contraction and so to understand this let’s take a look here at this diagram you see here a our smooth muscle cell

And we see the sarcolemma and if we look a little bit closer there you see the l-type calcium channel right here and what’s going to happen when that channel gets activated calcium is going to rush in from outside the cell it’s going to come and act the activate the ryanodine receptor on the sarcoplasmic reticulum here and in that sarcoplasmic reticulum we have a

Huge storage of calcium so they call that calcium dependent calcium release so the calcium gets released from the sarcoplasmic reticulum comes over here to the myo filament and then it’s going to be involved in stimulating a muscle contraction and again these are the smooth muscles in the blood vessels themselves so before we go on i want to show a quick video just

To show how calcium is involved in signaling that muscle contraction and then we’ll get more into the mechanism of action muscle contractions are controlled by the actions of calcium the thin actin filaments are associated with regulatory proteins called troponin and tropomyosin when the muscle is relaxed tropomyosin blocks the crossbridge binding sites on actin

When calcium ion levels are high enough and atp is present calcium ions bind to the troponin which displaces tropomyosin exposing the myosin binding sites on actin this allows myosin to attach to a binding site on actin forming a crossbridge okay so as the video just showed the cross bridge formation and the muscle contraction is going to be dependent on adequate

Levels of calcium within the cell and so a lot of pain is given to block that l-type calcium channel if you go back to this diagram you can see that blocking that l-type calcium channel will block that calcium dependent calcium release from the sarcoplasmic reticulum and then there just lower levels of calcium with inside the cell it doesn’t bind to the troponin

As much so the tropomyosin stays blocking those myosin binding sites and the smooth muscle in the blood vessel is not able to get that contraction and therefore the blood vessel does not constrict doesn’t contract down it stays nice and wide open and we’ll see the vasodilation just like we see here and that’s going to improve blood flow to the tissue and mainly

We’re concerned with the heart tissue with giving this drug and one of the the off-label uses for em lotta pain is a condition known as raynaud’s phenomenon and raynaud’s phenomenon is a vasospasm of parts of the hand in response to cold or emotional stress so if you see the image on the left that would be a normal blood vessel there in the hand delivering blood

And oxygen to the tissue and with raynaud’s we see it looks more like this picture on the right with that blood vessel constricted down blocking flow and then we’ll notice some reversible discoloration of the fingertips there i will see some pallor cyanosis or ear athena or even a combination of all three and so we can give em a lot of pain and you guys already

Understand the mechanism of action now to block that vasoconstriction and it has been shown to be helpful with these patients with raynaud’s in improving circulation to their fingertips and believing that discomfort so i hope you enjoy this brief presentation i hope it was helpful to you guys and thank you for watching

Transcribed from video
amlodipine (Norvasc) By Chad Cole