Practice English Speaking&Listening with: Pharmacology - ANTICHOLINERGIC & NEUROMUSCULAR BLOCKING AGENTS (MADE EASY)

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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