Sympathoadrenal System and Catecholamine – Adrenal Medulla

00:01 Adrenal gland pathology, we will dive into the medulla and the important clinical significance and many of those associations that we will see with it, do not underestimate what we have to say about the adrenal medulla.

00:17 First and foremost, understand this is often referred to as being the sympathoadrenal system.

00:22 Why? Because when we have a fight or flight response, sympathetic response from the adrenal medulla wherein the biochemical pathway of forming epi, epinephrine; at the very end on your right is epinephrine.

00:37 You have an enzyme here that you want to be familiar with known as phenylethanolamine-N-methyltransferase, PNMT, the abbreviation that you’ll be oh so comfortable with and familiar when you’re actually forming epi, epi, epi.

00:51 For example, when there is pheochromocytoma, obviously it’s going to be one of the discussions there will be increased activity of this very enzyme.

00:59 It would be nice if you would be able to identify it.

01:02 In the meantime, you have some other enzymes here that you should be familiar with from CNS pharmacology.

01:09 All of these coming from tyrosine, tyrosine hydroxylase, DOPA decarboxylase, Dopamine-beta-hydroxylase… all those enzymes are incredibly important as you know in different parts of your pharmacologic discussions.

01:23 With your epinephrine, it works on every single adrenergic receptor known to man and the pneumonic that’s quite cute that you may want to use is called BLOW.

01:33 What does that even mean? At low doses of epinephrine, it works on beta receptors; at higher doses ,we then work on our alpha receptors therefore then works like your norepinephrine.

01:47 Alpha 2 receptors obviously was going to inhibit centrally the release of your norepinephrine, if you remember [Inaudible 00:01:54] and such, beta-1 receptors and beta-2 receptors at low doses of epinephrine will in fact work on these.

02:03 In the meantime, what you want to pay attention to in the very last column here would be your signal transduction ligand binding is that when you are dealing with alpha-1 receptors, you should be thinking about your blood vessels and undergoing vasoconstriction and here, the second messenger will be GQ.

02:21 Thus, you’re thinking about ip3 phospholipase c and increased calcium, therefore bringing about vasoconstriction.

02:29 All of the others that we’re seeing here will be some form of cyclic AMP.

02:34 If it’s alpha-2, please know this, it’s decreased cyclic AMP because it works through GI.

02:40 Clear? Biochemistry here with some physio and pathology.

02:44 Beta-1 and beta-2 will be increased cyclic AMP... once again, welcome to beta receptors GS.

02:52 Remember that beta-2 will cause smooth muscle relaxation via cyclic AMP because it will then do what? Good, remember that myosin light chain kinase? It will phospholate the myosin light chain kinase rendering it inactive, thus you’re not going to have smooth muscle contraction bringing about smooth muscle vasodilation… from pharmacology here as well.

03:19 You want to be very clear about the influence of beta-2 with smooth muscle vasodilation and relaxation and also with nitric oxide.

03:28 Epinephrine, it is a stress hormone, behaves like your cortisol, glucagon.

03:38 Increased rate and force of contraction, if it’s on the heart beta-1 receptors; increased metabolic rate, dilation of your bronchioles, why? Beta-2, bronchodilation.

03:49 Stimulation of lipolysis in fat cells like it would expect with your glucagon.

03:54 It stimulates an enzyme within adipocyte called? Good, hormone sensitive lipase.

04:02 There will be dilation of the pupil as you can expect with sympathetic activity in the pupil, mydriasis and inhibition of GI secretion… epinephrine.

04:12 Norepinephrine, constriction of blood vessels and for the most part, with that vasoconstriction will bring about increase in systemic vascular resistance.

04:20 You know this physiologically as also being called total peripheral resistance and thus will increase blood pressure.

04:27 Norepinephrine, its primary effect on your blood vessel via alpha-1 receptor; epinephrine just about every single receptor.

04:34 At low dose beta, at high dose alpha behaves like norepi.