Cholinomimetic Activators and Effects

by Pravin Shukle, MD

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    00:01 Hi, welcome to pharmacology by Lecturio.

    00:04 We're going to continue our discovery of the autonomic nervous system and the drugs that we use to control various aspects of it.

    00:12 I'm Dr. Pravin Shukle.

    00:13 Let's start by taking a look at all of the direct activators of the cholinergic system.

    00:19 What we mention before in a previous lecture was that there were two types of cholinergic receptors.

    00:25 The muscarinic receptors and the nicotinic receptors.

    00:29 Now, in order to have activity at the muscarinic or nicotinic receptors, we sometimes use choline esters to activate them.

    00:39 Acetylcholine, methacholine and carbachol will act at both muscarinic and cholinergic receptors.

    00:48 So these three drugs are drugs worth remembering but remember that they're not necessarily specific between the two.

    00:54 The alkaloids, in particular pilocarpine is a very specific muscarinic cholinergic agent.

    01:02 Obviously muscarine, which is a chemical that we use sometimes is a muscarinic agent.

    01:08 And nicotine which is available in any cigarette that you wanna smoke is active at the nicotinic receptor which is where they both got their names.

    01:17 So now, we have acetylcholine in the synaptic cleft.

    01:20 There's one of two things that can happen with acetylcholine.

    01:23 The first thing is that it'll get broken down by acetylcholinesterase into choline and acetate. That's what we call metabolism of acetylcholine.

    01:35 The second thing that can happen is it'll actually act on the cholinergic receptor.

    01:39 Now, if you activate acetylcholinesterase or give it a chance to work the activity of the cholinergic receptor is going to be reduced.

    01:48 So acetylcholinesterase stimulators will actually reduce the effect of that particular choline postsynaptic agent.

    01:59 Let's take a look at indirect activators.

    02:02 So edrophonium is a very short acting acetylcholinesterase inhibitor.

    02:08 Organophosphates are long-acting so they act for about 2 to 8 hours.

    02:14 Malathion, parathion or pesticides and sarin is a terrorist drug if you will, that was used in the 1995 Tokyo attack.

    02:26 So these are acetylcholinesterase inhibitors which means that the amount of acetylcholine is increased in the synaptic cleft because you're inhibiting the breakdown.

    02:36 Carbamates are intermediate-acting acetylcholinesterase inhibitors.

    02:41 They will act anywhere between five and 21 days.

    02:44 So there is neostigmine and physostigmine.

    02:48 And these are often used in the treatment of a disease called myasthenia gravis.

    02:53 We're gonna talk about that in a later lecture.

    02:58 In the eye, what will you see? Well, you will see contraction of the circular or sphincter muscle of the iris, so they will have miosis or contracted pupils, and they will have more near vision, they cannot see far, so they will complain of blurred vision but then when you hold a card in front of them, they can actually read the card.

    03:18 In the heart, you'll often have sinus node suppression.

    03:23 So that means that they have a decreased heart rate.

    03:26 We call that negative chronotropic.

    03:29 And we're gonna use the term chronotropic a lot, remember Cronus was the greek god of time, so negative chronotropic means slower rate.

    03:37 The atria, you have decreased contractile force, that's negative inotropy of the atria.

    03:44 In the AV node, you have decreased conduction velocity.

    03:47 We call that negative dromotropy, Dromos was the patron god of the races in the Olympics.

    03:54 So dromos means how fast you travel down a pathway, decreased conduction velocity is negative dromotropy.

    04:01 In the AV node, you have an increase in the refractory period, and in the ventricles once again we have negative inotropy.

    04:09 So these are the cholinomimetic effects in the heart of something like sarin gas toxicity.

    04:15 In the brain, they will often have an elevated mood, they may look like they're addicted to something.

    04:21 Toxic levels, they will be nauseous, vomiting, they'll often have convulsions, and at the later stages they'll have a coma.

    04:30 What kind of effects are we going to see in the circulatory system? Well, you'll see dilation of peripheral and facial blood vessels.

    04:37 That's because you release EDRF or endothelial derived relaxing factor.

    04:43 So patients will look a little bit red and a little bit like they've been slapped on the cheeks.

    04:49 What kind of effects will you see in the lungs? You'll get quite severe bronchoconstriction, and in fact, this is sometimes the cause of death because people feel like they've asphyxiated and they are intensely wheezing and intensely bronchoconstricted.

    05:04 What kind of effects will you see in the gut? In general with smooth muscle, you'll have increased smooth muscle contraction.

    05:11 So you'll have increase peristalsis, and when you listen to the abdomen, you'll have increased bowel sounds.

    05:17 And in terms of the sphincters, you'll have gastroesophageal sphincter contraction and pyloric sphincter relaxation.

    05:24 So in other words, they're going to have diarrhea and bowel movements.

    05:28 In the urinary tract, the detrusor muscle contracts, the trigone relax, and the sphincter relax, so these patients can go to the bathroom, and that's an important thing to remember because when you're trying to figure out where the toxicity is, if a patient is in urinary retention, it is very unlikely for them to have a cholinomimetic toxicity.

    05:51 Let's move on to skeletal muscle.

    05:54 What kind of activity will you see with cholinomimetic effects with skeletal muscle? First, let me stop and just say that with sarin toxicity, you're not gonna see a lot of skeletal muscle effects but with other drugs you will so let's talk about other drugs.

    06:09 With the neuromuscular end plates in cholinomimetic effects, you will sometimes see activation, and we're gonna talk about this when we talk about anesthetic drugs but succinylcholine is a depolarizing paralytic.

    06:24 So it will depolarize the motor end plate.

    06:27 Once it's depolarized, the patient is paralyzed.

    06:29 Edrophonium is an antidote to these nondepolarizing paralytics.

    06:36 So this is why we have to be aware of not just what's going on with our patients but to be aware of the antidote.

    06:44 Edrophonium is an antidote to a nondepolarizing paralytic and the depolarizing paralytic is succinylcholine, edrophonium will not work with succinylcholine.

    06:56 What is the effect of a cholinomimetic on the exocrine glands? So let's talk about the sweat glands, and earlier I had said that remember that there's a muskiness so it's a muscarinic cholinergic activity.

    07:10 You get excessive sweating in patients who are cholinomimetic.

    07:14 With salivary glands, you get excessive salivation, with tear ducts, you get excessive lacrimation, and with GI and lung mucous glands, you'll have more secretion.

    07:25 So in general there's a lot of fluid secretion.

    07:28 So understanding the pathophysiology and the physiology behind cholinomimetics is important and then you can figure out all of the effects.

    07:40 But if you want to learn using a pneumonic, we also have a pneumonic for you and the pneumonic is DUMBBELSS.

    07:45 One of the problems that I had when I was studying for my exams is I forgot what DUMBBELSS was for.

    07:51 Was it for cholinomimetic or was it for sympathetic.

    07:53 So it's important to remember that DUMBBELSS is a cholinomimetic effect.

    07:57 So D is for diarrhea, U is for urination, M is for miosis or constriction of the pupil, B is for bronchoconstriction, the other B is for bradycardia, E is for excitation of the skeletal muscle and the central nervous system, L is for lacrimation or tear production, S is for salivation, and S is for sweating.

    08:22 There's DUMBBELSS.

    About the Lecture

    The lecture Cholinomimetic Activators and Effects by Pravin Shukle, MD is from the course ANS - Pharmacology.

    Included Quiz Questions

    1. Pilocarpine
    2. Acetylcholine
    3. Carbachol
    4. Methacoline
    1. Neostigmine
    2. Malathion
    3. Parathion
    4. Edrophonium
    5. Sarin
    1. Muscle relaxant
    2. Pesticide
    3. Diagnosis of neuromuscular junction disease
    4. Chemical weapon
    5. Treatment for myasthenia gravis

    Author of lecture Cholinomimetic Activators and Effects

     Pravin Shukle, MD

    Pravin Shukle, MD

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