Muscarinic antagonists

Definitions & Key takeaways

Muscarinic antagonists, also known as antimuscarinic medications, are a class of drugs that block the activation of muscarinic receptors of the parasympathetic nervous system. Examples of muscarinic antagonists include atropine, scopolamine, and ipratropium. These drugs are used to treat a variety of conditions, such as asthma, glaucoma, and urinary incontinence. They can also be used to treat the symptoms of poisoning from organophosphate insecticides.

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Introduction0:00–0:15

Muscarinic antagonists, or antimuscarinic medications, are a class of medications that prevent muscarinic receptors of the parasympathetic nervous system from getting stimulated by acetylcholine.Okay, first things first, the nervous system is divided into the central nervous system, so the brain and spinal cord; and the peripheral nervous system.

Physiology0:15–2:42

The peripheral nervous system can be divided into the somatic nervous system, which controls voluntary movement of our skeletal muscles; and the autonomic nervous system, which is further divided into the sympathetic and parasympathetic nervous systems, and controls the involuntary movement of the smooth muscles, and the glands of our organs.Now, the autonomic nervous system is made up of a relay that includes two neurons.
We’ll focus on just the parasympathetic nervous system. Signals for the parasympathetic nervous system start in the hypothalamus.
These hypothalamic neurons synapse with nuclei in the brainstem or spinal cord, which send out signals to preganglionic neurons that travel to the rest of the body.
Their targets are the parasympathetic ganglion, which consist of many postganglionic neuron cell bodies and are located nearby or directly in the target organs.
The postganglionic neurons extend the rest of the way to the target cell, where they release the neurotransmitter acetylcholine, which is why they are also called cholinergic neurons.
Acetylcholine binds to a type of receptor, known as muscarinic receptors, on the cells of target organs, which allow the parasympathetic nervous system to trigger a ‘rest and digest’ response, meaning that it keeps body-energy use as low as possible to stimulate activities like digestion.It acts in the heart, slowing the heart rate and reducing the cardiac output.
In the gastrointestinal tract, it increases its motility to stimulate digestion and defecation. In the bladder, it causes constriction of the bladder muscle, called the detrusor muscle, which stimulates urination.
In salivary, sweat, and lacrimal glands, it increases their secretions. In the liver, it triggers glucose storage to reduce blood glucose levels.
In the lungs, it causes bronchoconstriction, since in a relaxed state our cells do not consume as much oxygen. In the eyes, it triggers miosis, or constriction of the pupils, to improve close vision and stimulates the contraction of the ciliary muscles, increasing the outflow of aqueous humor, which is the fluid in the anterior chamber of the eye, and this decreases the intraocular pressure.
Finally, its effects on the brain are extremely complicated, but generally, they cause overall stimulation, and they participate in many wanted and unwanted functions, such as movement control and vomiting, respectively.Alright, so medications that block the effects of acetylcholine on muscarinic receptors are called muscarinic antagonists or antimuscarinic medications.

Atropine2:42–3:58

Now, the most famous muscarinic antagonist is atropine. Atropine blocks the “rest and digest” effect from the parasympathetic system, so clinically, it can be used to treat bradycardia, or slowed heart rate.
It decreases bladder smooth muscle contraction so it’s useful for preventing nocturnal enuresis, or bedwetting, in children.
Ophthalmologists can also use atropine to dilate the pupils. Finally, it’s an antidote for poisoning by anticholinesterases like organophosphates found in pesticides.
These agents prolong the effect of acetylcholine by inhibiting their break down, so atropine can help by simply blocking the muscarinic receptors.
Now, for side effects, atropine can produce: tachycardia, or increased heart rate; constipation and urinary retention; dry mouth, skin and eyes; and blurry vision.
The more severe side effects include hyperthermia, dizziness, confusion, and delirium. It’s also contraindicated in individuals suffering from narrow angle glaucoma since it can worsen the obstruction of aqueous humor drainage.Now, other muscarinic antagonists are more effective at targeting certain organs.
Oxybutynin works on muscarinic receptors in the bladder, where they decrease detrusor muscle spasms and prevent urge incontinence, or involuntary urination due to an overactive bladder.Now, ipratropium and tiotropium are well known muscarinic antagonists that work as bronchodilators.

Oxybutynin3:58–4:09

Ipratropium & Tiotropium4:09–4:43

They are usually given via inhalers, where they enter the lungs and bind to muscarinic receptors on the tracheal and bronchial smooth muscles, causing smooth muscle relaxation and dilation of the bronchi.
This makes them effective in relieving chronic obstructive pulmonary disease, COPD for short, and asthma. What sets them apart, mainly, is their duration of action.
Ipratropium is short acting, while tiotropium is long acting. Finally, there are muscarinic antagonists which act primarily in the brain, like scopolamine, benztropine, and trihexyphenidyl.

Scopolamine, Benztropine & Trihexyphenidyl4:43–5:38

Scopolamine prevents the action of acetylcholine on muscarinic receptors in the vomiting center of the brainstem. This makes it effective in preventing motion sickness during travel, or nausea and vomiting after surgery.
On the other hand, benztropine and trihexyphenidyl are mainly active in the striatum, which is a part of the basal ganglia in the brain.
Since usually there’s a balance of signaling between dopamine and acetylcholine in the striatum, a loss of dopamine, like in Parkinson’s disease, increases the relative amount of acetylcholine signalling there.
Therefore they can be given to restore the balance of cholinergic and dopaminergic signaling, and improve the tremors seen in Parkinson’s disease.
However, due to their central nervous system effects, all three of these drugs can produce sedation and mental confusion.
Now, we want to make a simple and fun mnemonic that’ll help you efficiently memorize and retain all these pharm facts! So let’s have an island with a large tropical palm tree for atropine.

Memory Palace5:38–7:35

So under the tree we have a kid who was taking a nap. He peed on the blankets, for nocturnal enuresis, and now he’s staring at the stain with big, dilated pupils.
He put a frozen heart, which represents bradycardia, over the stain to try and cover it up. For side effects, the boy’s mother got a heat stroke, which represents hyperthermia and the CNS side effects like dizziness and confusion.
There’s an empty water bottle next to her to help you remember dryness in the skin, eyes, and mouth. The dad is out of ideas, so he desperately went to a porta potty to see if he can move her to a cooler spot.
The porta potty has a “closed” sign on it to help you remember urinary retention and constipation. The father’s eyes are popping out as he saw the sign, to represent the contraindication for people with glaucoma.
Okay, let’s go over the medications that target specific organs. First, there’s oxybutynin which is represented by an oxygen tank with a large button on it to release oxygen.
It’s connected to a hose that’s inflating a bladder like a balloon to help you remember it’s used for urge incontinence.
Next, let’s have a short palm tree with a rat on top for the short acting ipratropium, and next to it is a tall palm tree with ties on it for tiotropium.
A cop with asthma is sitting between the trees and using his inhaler to help you remember these drugs treat COPD and asthma.
Finally, we have the medications that mainly affect the brain. So by the trees, we have the parking space the cop was checking, which represents Parkinson’s disease.
There’s a Mercedes Benz parked here for benztropine, and there’s three witches inside trying to cast hexes on the cop for trihexyphenidyl.
Getting out of the car is the witch's’ pet, a giant walking scallop for scopolamine. It’s vomiting since the witch’s poor driving skills gave it motion sickness.
##SummaryAll right, as a quick recap, muscarinic antagonists inhibit the effects of acetylcholine on muscarinic receptors.

Review7:35–8:27

This includes the prototypical medication atropine, which can be used to induce pupil dilation, treat bradycardia, nocturnal enuresis, and reverse organophosphate poisoning.
Oxybutynin is given in urge incontinence; and ipratropium and tiotropium are used for COPD and asthma. Scopolamine is given for motion sickness; and benztropine and trihexyphenidyl are used to treat tremors in Parkinson’s disease.
Antimuscarinic side effects are tachycardia, constipation, urinary retention, dry mouth, skin, and eyes, blurry vision, hyperthermia, and confusion.
The main contraindication for these medications is narrow angle glaucoma.But wait, there's more: Here's a mind map with all of the mnemonics from the video.

Mind Map8:27–8:35

Go ahead and pause the video so you can test yourself to see what you remember. Stay tuned for the answers at the end.