DIP Episode 25 - Autonomic Pharmacology Part 3

Okay, welcome. My name is Divine. I am a 4th theoretical student. Welcome to the 25th episode of the Divine Intervention Podcasts. In today's episode I'm going to finish up Autonomic Pharmacology and hopefully in a future podcast we can begin on a new section of Pharmacology. So let's get going. So last time we sort of rounded out our Ganofosfit poisoning right and we said we talked about how the path of physiology of organophosphate poisoning involves the inhibition of acetylcholinesteries. And if acetylcholinesteries is inhibited, your levels of acetylcholine build up so you get a cholinergic toxidrone. So you get things like a beam hypotensive or a brain-bedded cardiac because remember your parasympathetic nervous system sort of like cardio depresses the heart. So you get pretty cardio because phase 4 of the pacemaker potential is going much slower. That slope is reduced by colinomematics. You could also get like heart block, you could get like profuse sweating because remember your sweat glands are under the control of the sympathetic nervous system but the under that control with oscarinic acetylcholine receptors. So you get more your inesion, you could get fecal incontinence, again remember your rest and digest it, your pooping and pee and frilly. You can also get lacrimation because remember that's under the purview of cranial nerve 7. And cranial nerve 7 is part of your parasympathetic nervous system.

Remember the parasympathetic nervous system is regarded as cranial sacral outflow. So the cranial part includes cranial nerves like 3, 7, so 3 right, your glomoner of 7, the facial nerve 9, the glossopharyngeal nerve and 10, the vagus nerve. And we said that you treat a gonophosphate poisoning with an acetylcholine receptor antagonist like atropine and then you try to regenerate the acetylcholine esteris with pre-conducting. Okay, so the next set of drugs we'll talk about, let's talk about the moscaryne receptor agonists. The moscaryne receptor agonists, I sort of think of them as being in two classes. We have those that directly attack the receptor. So they directly activate the receptor and then we have those that indirectly activate the receptor. And what do I mean by indirect activation? I mean drugs that inhibit acetylcholine esteris and in so doing increase your levels of acetylcholine. And then if you have increased levels of acetylcholine, you can then activate the moscaryne receptors more. Okay, so one example of an, so let's talk about the first group, the acetylcholine esteris inhibitors. The first group I'll talk about is a nerve gas, right? So sorry, sorry, again works by inhibiting acetylcholine esteris so you can get a collineurgic toxicant from that. Same thing with organophosphates, okay, organophosphates, the acetylcholine esteris inhibitors. So those boost your acetylcholine levels. We've talked about how you treat that.

And then if a patient has my astenia gravins, right, because again, I don't just want to give you drug names, right? I want to show you how you'll be tested. For patient has my astenia gravins, right? You'll want to, the pathophysiology there involves having autoantibodies against the acetylcholine receptor. So you want to try to fix that by creating acetylcholine that can outcompete those aberrant autoantibodies, right? So you do that by giving that acetylcholine esteris inhibitor, like pyridolstigmin. So remember that in my astenia gravins, right, usually you'll see, what's your first step in management or diagnosis? And back in the day was, I gave the tensilent test or whatever. They may still describe it as an experiment or whatever on step one. But in general, right now, the diagnostic test of choice is checking for the antiacetylcholine receptor antibodies. So that's the preferred diagnostic test these days. But you can still go with the tensilent test where you had myastage or phonium, which is an acetylcholine esteris inhibitor. It's a very short acting acetylcholine esteris inhibitor, okay? And your levels of acetylcholine are built up and that transiently improves the symptoms in my astenia gravins. Now, new stigmin and pyridolstigmin, I mean, a new stigmin is another acetylcholine esteris inhibitor. Classically, it's used to treat like post-op elias, right? So after you undergo surgery with anesthetics, your GI tract may be locked up for a bit.

You could try to fix that problem by giving something that encourages your GI tract to go like new stigmin. You build up your acetylcholine levels and remember acetylcholine promotes pooping and pee. Because that's part of the, under the purview of the past and pathetic nervous system. Now, if a person has Alzheimer's disease, right, they have reduced levels of what neurotransmitter? They have reduced levels of acetylcholine, okay? So there are certain things you want to know with acetylcholine in relation to Alzheimer's. So one thing you want to know is that first, the region of the brain, where acetylcholine is produced, okay? The occasionally love to test that that region of the brain is destroyed in Alzheimer's disease, right? So the acetylcholine is actually produced at a structure called the bison nucleus of minor. Okay? So destruction of the bison nucleus of minor is associated with an acetylcholine deficiency, if you may, which is associated with the pathophysiology of Alzheimer's. And another more advanced way they can test the same concept is to say that, oh, Alzheimer's is associated with reduced activity of cooling acetylcholine. Remember, cooling acetylcholine is the real limiting enzyme for acetylcholine synthesis. So in Alzheimer's, if you know that you have an acetylcholine deficiency, you want to try to fix that, right? By doing something that boosts your acetylcholine levels. This is again where an acetylcholine esterase inhibitor comes into play, right?

So the drugs that are approved by the FDA for acetylcholine esterase inhibition in the treatment of my acetylcholine esterase inhibition, okay? Include drugs like d'unepezile. The nepezile is an acetylcholine esterase inhibitor. Galantamine is another acetylcholine esterase inhibitor. Rereverstigme is another acetylcholine esterase inhibitor. And then there is one more that's not so common. Tachran is also an acetylcholine esterase inhibitor that's used to treat Alzheimer's. And remember that patients with Down syndrome add increased risk of early Alzheimer's, right? Because they have three copies of that pre-syniline gene on chromosome 21. Okay, so those are the big things you want to know about your acetylcholine esterase inhibitors. Now let's go to the direct-moscrinic receptor agonist, okay? So these include drugs like Bethanychol, Bethanychol is a muscrinic receptor agonist. You're going to need it for post-op areas. Now what if you get a question about a lady, like in her 30s, that has dental caries? And she feels like a lump in her truth. And she says, oh, I have to get up at night multiple times to drink water because my tongue gets dry. Well, hopefully that helps you think about show greens. Remember show greens is associated with anti-ro, or anti-SSAO, anti-la, or anti-SSB antibodies. You can treat show greens to dryness with a pylocarpin. Pylocarpin is a more of scurrenic receptor agonist that can help you make more saliva.

And remember that pylocarpin can also be used in the treatment of acute anguclujoglocoma, okay? Because you want to try to relieve pressure through those canals of schlim. So you can do that by causing pupillary constriction. And you can use a moscurrenic receptor agonist like pylocarpin for that. And just real quick, while we're on the topic of show greens, don't forget that they had increased risk of a non-hotch. And then we're going to talk about non-hotch.in's B-cell lymph. Excuse me, a non-hotch.in's B-cell lymph from the over activation of lymphoid cells in their salivary glands, for example. Now, the last direct moscurrenic agonist I want to talk about is methacolin, okay? Methacolin is a moscurrenic receptor agonist that is using provocative testing for asthma. So, big things you want to know that if you activate your sympathetic nervous system, you open up your earways, okay? And you can sort of think about that teleologically if you may, because think about it. If you're running from a lion, you want as much energy as possible to make that happen, okay? And to get more energy, more ATP in oxidative phosphorylation, you need oxygen. So, if your earways are open up some more, right? You can get in more oxygen. You can promote electron-transport chain and oxidative phosphorylation that you survive, okay? So, activating your sympathetic nervous system opens up your earway, okay? But, activating your parasympathetic nervous system closes your earway.

That is why I'll be it around, which is a bit of a receptor agonist, is using the treatment of asthma. And, hypertropium or tyotropium, which are moscurrenic receptor and antagonists are used in the treatment of asthma, okay? So, if you want to have a provocative test for asthma, you actually give a moscurrenic receptor agonist like metheculin. In general, you use pretty diluted concentrations. And in most people, when you give them those dilute concentrations, they don't get much in the well of bronchospasin with that. But, in a person that has hypersensitive earways, you give them those dilute concentrations of metheculin, you get bronchoconstriction, the person's FIV1 decreases by some percentage, and there are some codos for the diagnosis of asthma, okay? So, you have like a standardized decrease in FIV1, and you're like, oh, this person has asthma, and then you sort of go from there, okay? So, metheculin can be used in provocative tests for asthma. Now, let's talk about the moscurrenic receptor antagonists. We've sort of talked about these already. Astropine, remember, you can use that for heart block, okay? Because by blocking moscurrenic receptors, they will increase the speed of conduction through the AV node. And for atropine, right, if you're exposed to gymsim weed, you could get an antichoninergic toxic drum from atropine, okay? And the way you treat an atropine overdose, remember, atropine is a moscurrenic receptor antagonist, right?

So, again, you want to try to boost your levels of acyloculin to outcompete atropine at the moscurrenic receptor. So, you do that with a drug known as phyzo-stigmin. Phyzo-stigmin is an acyloculinistries inhibitor that boosts your levels of acyloculin to overcom, to have a common atropine overdose. Scopolamine is another moscurrenic receptor antagonist. You're primarily using fomotion sickness. So, too much acyloculin in your vestibular system causes a lot of like vestibular symptoms, motion sickness symptoms, c-signus symptoms. So, you can treat that by blocking acyloculin receptors. That's why you see many people, they take better drugs or diphenhydramine for motion sickness because diphenhydramine has, yes, it's an antichistamine, but it has very powerful moscurrenic receptor blocking activity. And then, apatropium tootropium, they are also moscurrenic receptor antagonists. Use those more for asthma and COPD. Apatropium is a shorter actin moscurrenic antagonist. The etiotropium is longer actin. And the easy way to remember that is I come before t-in the alphabet. So, I come separately. So, it's short actin. T comes later. So, it's long actin. So, let's round out this discussion by talking about the three types of incontinence. They love to really test this in the context of the parasympathetic nervous system. So, the first one we will talk about is urgent incontinence. It's the one called overactive bladder.

This is something you could potentially find on exams in a patient with multiple sclerosis. So, in this case, the tetrothomeal salts are too active. So, they are working too well. So, these people, they can't get to the restroom before they peel themselves. So, because your tetrothomeal salts are working too well, remember your parasympathetic nervous system makes UP. You can try to reverse that pathology by blocking moscurrenic receptors. So, actually moscurrenic receptor antagonists are very good in the treatment of urge incontinence. And there's a nice nomonic you'll learn as you study for step one. It's called sitting on the darn toilet for the moscurrenic receptor antagonists that are classically used in the treatment of urge incontinence. So, we have drugs like sulafenacin, we have oxybutin, that's the O, we have to teradine, we have daryphenacin and then we have trospial. So, sitting on the darn toilet, those are the moscurrenic receptor antagonists that are used for urge incontinence. Now, if you're dealing with overflowing continents, right, so overflowing continents, the tetrothomeal salts are basically not doing anything because the nerves in your bladder, they can detect when the bladder is full for some reason. And again, this is something that may potentially be found in a patient with a history of multiple sclerosis.

So, for this, because your bladder nerves are not detecting anything, so you're holding onto pee, okay, so these people usually like pee in small spurs when the pressures in the bladder are just too much, where they just have to let out some urine. So, you can try to treat that either with like self-catheterization or you can also give a moscurrenic receptor agonist, okay, to encourage pee because again, you're not sensing anything, so you want to encourage pee by giving a moscurrenic receptor agonist like Bethanico, okay, so notice different kinds of incontinence, but different kinds of treatment, okay, so for urge incontinence, you give a moscurrenic receptor antagonist for overflowing continents, you give a moscurrenic receptor agonist. And then the final one, stressing continents, basically, let's assume you're basically erect a lot of your pelvic floor muscles in the context of multiple childbirths, okay, the classic presentation is a patient that has that pee on themselves when they have an increase in intraptominal pressure, so if they laugh or if they perform any kind of valve-solver-ish maneuver, okay, anything that increases intraptominal pressure increases the loss of urine under those quits. So, the way you treat that, you don't necessarily jump to pharmacology, you can use a kegalexercises, okay, and then you can do surgery if kegalexercises.work. So, this is basically where I'm going to stop with autonomic pharmacology, we're pretty much done.

I'll just do a very quick review of some very high-yield things we talked about along the way. So, remember that in phyocromocytomas, right, you want to use, you want to block alpha receptors first before you block beta receptors. And those alpha receptors, you can block them with like phenoxybenzamine, it's an irreversible alpha one receptor blocker, femtolamine is a reversible alpha one receptor blocker. So, be able to think of those in the context of mechalism and kinetics. And then if a patient has like BPH and Comitant hypertension, right, you want to treat that with an alpha one blocker like Prasocin or Doxazocin, remember, Tamsulocin was the one that was selected for the alpha one 80 receptors that you find in the bladder. And then, clonidin, right, to remember it's an alpha two agonist using the treat hypertension. Remember, alpha two receptors are GI coupled, so they decrease the release of neuropinephrine, so you could use it to treat hypertension. But you want to be wary of a side effect, if you stop the drug, the hypertension comes back in like very full force, okay. So, rebound hypertension is a very big side effect of clonidin. You could actually use clonidin to treat the, you could actually use clonidin in the treatment of Tourette's syndrome. It's just one of those bizarre things you want to know for your exam.

And then, proprylonal law, right, so proprylonal law is a beta one and two receptor blocker, remember, it's used in thyroid storm, because when it helps with the hypoallergenic symptoms, but proprylonal law also inhibits the 5-prem DIO-denies that converts T4 to T3. And in thyroid storm, we said in addition to using proprylonal law, right, you can use steroids, okay. You can use PTU, remember, PTU is a thyroid peroxidis inhibitor, but it also inhibits that 5-prime DIO-denies. And then, my Modepine, just throwing this in here, the person has like a hemorrhagic stroke, like after a subarachnoid hemorrhagin, they say, oh, worst headache of your life, or a thonda-clap headache, or headache that is different in character. From previous headaches, you can give my Modepine, it's a dihydropyridine calcium channel blocker that prevents post-tromatic hemorrhagic stroke, so that they don't get an ischemic stroke after a hemorrhagic stroke. And then, if you want to delete the delivery, right, you want to give a beta to Agnes, because remember, beta to receptors, and in smooth muscle, that causes a relaxation, okay. So, if a patient has, you're trying to delete the delivery for some reason, let's say, for like preterm labor, you can give a beta to Agnes, like terbidolino redogin, they are tocoletics, and they can delete the delivery. Now, for an aphylaxis, right, don't forget that your drug of choice is a penephrase, okay.

Because in an aphylaxis, you want to affect beta to receptors to open up earways, okay. And remember, narypinephrine won't do squat for you in an aphylaxis, right, because it does not necessarily activate beta to receptors. But if a person is in septic shock, narypinephrine, great, okay. Because again, it's a powerful alpha-1 receptor agonist, so that helps you in septic shock, because it sort of increases your systemic vascular resistance to counteract the severe visual dilation. And then, do butamine, right, remember, it's a beta-1 agonist, you can use it in a C-HF and acute C-HF exacerbation, okay. You could also use it in a cardiac stress test. We talked about merino, that is a force for diester, it's 3 inhibitor, so it builds up your levels of cyclic AMP. So, we talked about how that helps your cardiac muscle contract better, so it's a positive inotroup, okay. But that causes smooth muscle relaxation, okay. So, it's also a visual dileter, right. So, it's an I-Nodeileter, if you may. And then, we talked about pylocarpine in the context of synthesis of saliva for chagrin, and also for the treatment of acute anglochlojure, glaucoma. And then, we talked about fixing an atropine overdose with phyzo-stigmin, okay. That's an acetylcholine esterase inhibitor. And then, echothio-fate, it's an acetylcholine esterase inhibitor, it's just one of those weird drugs that just sort of put that in your memory bank.

As another acetylcholine esterase inhibitor, we talked about adrofolio, used it in the tensileant test for the diagnosis of myastiniaegraphis. And then, homotropine cyclopentolytentropicamide, these are all actually most chronic receptor antagonists that I use for diluted eye exams, try because remember, if you activate your parasympathetic system, you get meiosis. So, if you block it, you get my dry asses. Back in the day, people used to use atropine, but atropine sort of ticks forever to wash out of your system. So, the inventive, these are short acting drugs, okay. Homotropine, sort of sounds like atropine, right. Atropicamides and glopentolytia, all short acting, most chronic receptor antagonists. And then, middle drain is a visoactive agent, it causes viso-construction. It turns this up your blood vessels, okay. It's actually used for the treatment of dysautonomia, okay. Where a person has like very libel, I guess, on stable blood pressures based on changes in position. So, I think that's where I'm going to stop. Next time, we'll pick up with another branch of pharmacology or a different subject, but we'll keep matching through pharmacologists, we go along in the coming weeks. So, have a wonderful day and stay blessed. Thank you.

They are acetylcholinesterase inhibitors (e.g., Pyridostigmine), which increase acetylcholine levels at the neuromuscular junction.

Alpha-1 receptor blockers (e.g., Phenoxybenzamine). This prevents uncontrolled hypertension before blocking beta receptors.

"Sitting on the darn toilet" (Solifenacin, Oxybutynin, Tolteradine, Doxepin/Diphenhydramine, Tiotropium).

Acetylcholine. The synthesis is impaired in the nucleus basalis of Meynert.

Pilocarpine (a muscarinic receptor agonist).

A muscarinic receptor agonist (e.g., Bethanechol), to encourage bladder emptying since the nerves are failing to sense fullness.

Checking for anti-acetylcholine receptor antibodies.

Acetylcholinesterase inhibitors (e.g., Donepezil, Rivastigmine).

Urge requires a muscarinic antagonist (to relax detrusor); Overflow requires a muscarinic agonist (to encourage voiding).

Midodrine.

Rebound hypertension upon cessation of the drug.

Ipratropium (short-acting) and Tiotropium (long-acting).

To cause bronchodilation by relaxing smooth muscle in the airways, improving oxygenation.

Checking for anti-acetylcholine receptor antibodies.

Acetylcholinesterase inhibitors (e.g., Donepezil, Rivastigmine).

Urge requires a muscarinic antagonist (to relax detrusor); Overflow requires a muscarinic agonist (to encourage voiding).

Midodrine.

Rebound hypertension upon cessation of the drug.

Ipratropium (short-acting) and Tiotropium (long-acting).

To cause bronchodilation by relaxing smooth muscle in the airways, improving oxygenation.