in this video I’m going to cover
cholinergic antagonists so let’s get right into it
cholinergic antagonists can be divided into three groups first antimuscarinic agents second ganglionic blockers third neuromuscular blockers so
let’s start with antimuscarinic agents also known as anticholinergic drugs
these agents block primarily muscarinic receptors thus causing inhibition of
muscarinic functions one of the most well known medications that belongs to
this group is Atropine Atropine’s primary sites of actions are
the following eye GI tract heart salivary sweat and lacrimal glands now antimuscarinic activity of Atropine in the eye results in relaxation of ciliary muscle
which causes dilation of the pupil also known as mydriasis inability to focus
visually also known as cycloplegia and unresponsiveness to light so
ophthalmic preparations of Atropine are used before an eye exam or eye
surgery as well as to treat certain inflammatory conditions of the eye
however because of its long duration of action other antimuscarinic
agents such as Cyclopentolate and Tropicamide are preferred over Atropine
while Cyclopentolate and Tropicamide can produce mydriasis that lasts for
hours Atropine’s effects can last for days another feature of Atropine is that
it blocks M3 receptors in GI tract which results in reduction of GI motility from
stomach to colon this translates into prolonged gastric emptying and lengthen
intestinal transit time at higher doses Atropine can also effectively block M2
receptors on the SA node and AV node which produces tachycardia heart rate
may increase by as much as 30 to 40 beats per minute
lastly by blocking muscarinic receptors on
salivary sweat and lacrimal glands Atropine produces dry mouth dry skin and
ultimately causes body temperature to rise the next very well-known medication
in the antimuscarinic group is Scopolamine
so Scopolamine unlike Atropine has a much greater effect on the CNS as well
as longer duration of action for that reason Scopolamine is one of the most
effective medications used for prevention of motion sickness and
post-operative nausea and vomiting it is available in a patch formulation that
provides effects lasting up to three days
another medications in the antimuscarinic group that I want to talk
about are Ipratropium and Tiotropium Ipratropium and Tiotropium block muscarinic acetylcholine receptors without specificity for subtypes this results in
decreased contractility of smooth muscle in the lungs which in turn leads to
bronchodilation and reduction of mucus secretion Tiotropium and Ipratropium
are administered by inhalation for maintenance treatment of bronchospasms
in patients with COPD Ipratropium also comes in a nasal spray formulation
which is often used for treatment of rhinorrhea which is runny nose the main
difference between Ipratropium and Tiotropium is their duration of action
Tiotropium is a long-acting agent that is dosed once daily while Ipratropium is
a short-acting agent that typically requires up to four times daily dosing
another medications that belong to this group are used for treatment of
overreactive bladder these include Tolterodine Darifenacin Solifenacin Oxybutynin Trospium and Fesoterodine these agents have
varying selectivity for the M3 receptor which is the main receptor involved in
bladder function however the overall efficacy among all of these is very similar last but not least I wanted to briefly
mention two muscarinic blockers Benztropine and Trihexyphenidyl which
through their ability to suppress central cholinergic activity were found to
be very beneficial in treatment of Parkinson-like disorders now before we
move on to the next group I wanted to make sure everyone watching this video
remembers their ABCDs which will help us to remember anticholinergic adverse
effects where A stands for agitation B stands for blurred vision
C stands for constipation and confusion D stands for dry mouth and S stands for
stasis of urine and sweating now we can move on to the second group of
cholinergic antagonists which are ganglionic blockers the main agent in
this group is Nicotine which is a main component of cigarette smoke although
Nicotine is a cholinergic agonist it is also considered a functional
antagonist because of its ability to stimulate and then block cholinergic
function so Nicotine acts on the nicotinic receptors of both
parasympathetic and sympathetic autonomic ganglia effects of Nicotine
result from increased release of neurotransmitters such as dopamine
serotonin and norepinephrine just to name a few
Nicotine is a nonselective it stimulates and later depresses autonomic
ganglia for example Nicotine stimulates CNS
which at high enough doses can lead to convulsions and then it depresses CNS
which can lead to respiratory paralysis also by stimulating adrenal medulla and
sympathetic ganglia nicotine increases blood pressure and heart rate but at
higher doses it can cause blood pressure to fall in GI system nicotine increases
the motility which can lead to nausea and vomiting last but not least use of
Nicotine in any form can cause addiction due to CNS stimulation that produces
increased alertness and surge of well-being overall other than to help
people quit smoking Nicotine is not very useful in clinical practice
now let’s switch gears and let’s talk about neuromuscular blockers
neuromuscular blocking agents simply block the cholinergic transmission
between motor nerve endings and nicotinic receptors on the skeletal
muscle so if we zoom in on this part where nerve ending meets the skeletal
muscle fiber you would see these nicotinic receptors to which acetylcholine
can bind and induce their opening opening of these channels let’s sodium ions to
enter the muscle fiber and trigger muscular action potential the potential
travels first along the surface of sarcolemma
which is the excitable membrane that surrounds those cylindrical structures
known as myofibrils then the action potential travels through T-tubule
system which penetrates into the fiber and then the arrival of action potential
causes calcium to be released from the sarcoplasmic reticulum which finally
leads to muscle contraction now let’s see all these steps in action so action
potential causes release of acetylcholine channels open sodium goes
in triggers another action potential calcium gets released and muscle
contracts it’s that easy now neuromuscular blocking agents work
at this junction here by interacting with these nicotinic acetylcholine
receptors we can divide these agents into two groups first nondepolarizing
agents and second depolarizing agents for all of you who need a quick review
of membrane depolarization I strongly encourage you to watch my short
three-minute video about action potential so let’s talk about
nondepolarizing agents first these agents are competitive antagonists they
bind to acetylcholine receptors but they don’t induce ion channel opening what
that means is that they prevent depolarization of the muscle cell
membrane and thus effectively inhibit muscle contraction in clinical practice
these agents are used to facilitate mechanical ventilation and tracheal
intubation as well as to increase muscle relaxation during surgery which
allows for lower doses of general anesthetics
generally speaking nondepolarizing agents are not absorbed from GI and
that’s why must be injected usually intravenously time to onset of action is
rapid usually less than two minutes once administered these agents paralyze small
fast contracting muscle first that is eyes face fingers then larger muscles of
neck trunk and limbs and lastly diaphragm on the other hand these
muscles recover in the reverse manner that is diaphragm first then limbs trunk
and so on and so forth the choice of an agent typically depends on the desired
onset and duration of the muscle relaxation and just a side note a
clinical duration of these agents is a time measured from administration to
recovery of 25% of baseline muscle strength now some of the most widely
used agents in this group are the following Cisatracurium which has
clinical duration of about 90 minutes Pancuronium which also has clinical
duration of about 90 minutes Rocuronium with clinical duration of about 40 minutes
Vecuronium which also has clinical duration of about 40 minutes and lastly
Atracurium with 40 minute clinical duration as well now when it comes to
side-effects Atracurium causes histamine release which results in
fall in blood pressure flushing and bronchoconstriction it also has toxic
metabolite called laudanosine which can provoke seizures especially in
patients with impaired renal function this is why Atracurium has been largely
replaced by its isomer Cisatracurium which fortunately is much less likely to
produce the same adverse effects because its metabolism is independent of hepatic
or renal function therefore Cisatracurium is often used in patients
with multi-organ failure now Vecuronium and Rocuronium are metabolized by liver
so their action may be prolonged in patients with hepatic dysfunction but overall
there are safe and have minimal side effects lastly Pancuronium is excreted unchanged in urine and one of its main side
effects is increase in heart rate now let’s move on to depolarizing agents so
depolarizing agents act as acetylcholine receptor agonists they mimic the
acetylcholine however they are much more resistant to degradation by acetylcholinesterase and therefore produce persistent depolarization now the only depolarizing
agent that’s still used in clinical practice is Succinylcholine so Succinylcholine binds to the nicotinic receptor and unlike the nondepolarizing agents it
actually causes the sodium channel to open which results in membrane
depolarization now because Succinylcholine is resistant to
acetylcholinesterase it causes prolonged depolarization which leads to
a transient fasciculations and finally flaccid paralysis this is referred to as
phase-1 block now eventually sodium channel closes and membrane repolarizes
however due to continued stimulation by Succinylcholine the receptor becomes
desensitized to acetylcholine thus preventing formation of further action
potentials this is referred to as phase-2 block now Succinylcholine has a
rapid onset of action and therefore is commonly used to facilitate rapid
sequence endotracheal intubation in critically ill patients it’s also
sometimes used to provide adequate muscle relaxation during
electroconvulsive therapy following intravenous administration Succinylcholine causes complete muscle relaxation within one minute the effects typically
last up to ten minutes due to rapid redistribution and hydrolysis by plasma
pseudocholinesterase and that brings us to adverse effects in patients deficient
in plasma pseudocholinesterase or patients who have genetic variation of
this enzyme Succinylcholine can lead to
prolonged apnea next prolonged depolarization caused by Succinylcholine
leads to continued flow of potassium into the extracellular fluid which can
result in hyperkalemia now in patients with normal potassium
levels this is usually not a big issue however in those with elevated potassium
levels for example due to burns or large tissue damage Succinylcholine can cause
serious EKG changes and even in severe cases asystole
lastly in genetically susceptible patients Succinylcholine can trigger rare
and potentially fatal condition called malignant hyperthermia symptoms of
malignant hyperthermia include severe muscle contractions and dangerously high
body temperature that can reach as high as 43 degrees Celsius and with that I
wanted to thank you for watching and I hope you enjoyed this video


  1. Another way to remember the effects of anticholinergics is "can't see, can't spit, can't pee, can't shit" (if you don't swear, switch it out for poop, which follows the 1st letter pattern "s-s-p-p")

  2. The only incorrect thing in this lecture is the duration of action of cisatricurium. It's actually around 20-30 minutes.

  3. You're making such light work of what I have to learn in my Clinical Pharmacology course, Great job! Thank you for doing what you do.

  4. nicely presented n all topics covered in short๐Ÿ˜ƒ Thanks a lott๐Ÿ˜Š
    keep making such videos….grtt work๐Ÿ‘

  5. I hv been reading this subject for 2 hrs and i got nth while ur 14 mins video explains everyth.
    Thank you so much ๐Ÿ˜๐Ÿ˜

  6. Bro i just wached a full 2 minute advertisement for you๐Ÿ˜„๐Ÿ˜„

    Keep doing what you are doing bro,you are fantastic in this!๐Ÿ‘

  7. Nondepolarizing agents doesnt "allow for lower doses of general anesthesia" as you indicate around 9:00!!!!!!! These aren't painkillers or sleep medications!!! They make patients cannot move!!!! That doesnt mean that they are well asleep or don't have pain.

  8. โœŒโœŒโœŒโœŒ๐Ÿ˜๐Ÿ˜๐Ÿ˜๐Ÿ˜๐Ÿ˜๐Ÿ˜๐Ÿ˜๐Ÿ˜๐Ÿ˜โคโคโคโคโคโคโคโค

  9. At 0:59
    "Dilation of the pupil…involuntary movement of iris…blush response…we call it Voigh-Kampf, for short."

  10. Really good but heavy accent voice makes it difficult to understand some terms but this was great thanks alot ๐Ÿ’ฏ

  11. People with blonde hair and blue eyes are sensitive to anticholinergics, right? Same goes for Cerebral Palsy. Surprised he didn't mention that.

  12. It literally helped me out seriously you made it so simple and especially I loved the abbreviation like always keep up the excellent work โ™ฅ๏ธ

  13. People older than age 55 who used medication with strong anticholinergic properties daily for 3 years or more had nearly a 50% increased risk of dementia also, dementia persisted up to 2 decades after exposure.

  14. You have told that, unlike atropine scopolamine has loner duration of action ,….. But in books as well as in Google, I have read that scopolamine has short duration of action.
    Which one is right?

  15. I was diagnosed with pseudocholinesterase deficiency 30 years ago because I was gonna have surgery and the anesthesiologists was in the USA at that time from France and he ask about my family history and when I told him my mother has something that she didnโ€™t wake up for 8-10 hours he wanted me tested and I didnโ€™t know the name but he said he did. Before my surgery the next day he came up and talked to me and my family and said I had 1% of the chemical in my body and I could have died and ALWAYS tell the anesthesiologists and request one be in the room and always let the doctor , dentist, eye doctor know. I do that and every time I have to be in recovery longer when they try to take the oxygen Iโ€™m not breathing. Twice I have woke up and heard them saying my name and patting my hand but canโ€™t move and then I am back asleep for hours. What I want to know is by me missing that enzyme will all this not waking us be harmful because I am having heart issues with others also. Also should I be retested since so much has changed to make sure it is not the other enzyme also.
    Thank you in advance for your help.

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