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AUTONOMIC NERVOUS SYSTEM

AUTONOMIC NERVOUS SYSTEM -ANATOMY

AUTONOMIC NERVOUS SYSTEM
" Involuntary in Nature.
It isa continuation of Central Nervous System.
S are divided on basis of Anatomy into two types:

2
Parasympathetic Nervous System oharmaMinds
Sympathetic Nervous System

MAK

AUTONOMICNERVOUS SYSTEM -ANATOMY

Parasympathetic Nervous System
Parasympathetic system fibres originates from the sacral ($2,3,4) and cranial (lI, VII, IX, and X) nerves (craniosacral
outflow) of vertebral column.

" In the parasympathetic nervous system (where ganglia are located closer to the organs), preganglionic fibres are
significantly longer than postganglionic fibres.
Il-Oculomotor
Neurotransmitter VIl- Facial
A. Pre-ganglionic Fibre- Acetylcholine X-Glossopharyngeal Nerve
X-Vagal Nerve
B. Post-Ganglionic Fibre -Acetylcholine
(Since Acetylcholine in both fibres, hence parasympatheticsystem is also called cholinergic system)

MAKNG

Ganglion - In the voluntary and autonomic branches of the peripheral nervous system (PNS), ganglions are
collections of neuronal bodies.

AUTONOMIC NERVOUS SYSTEM -ANATOMY

Sympathetic Nervous system
Sympathetic system fibres come from the thoracic and lumbar spinal cord (thoracolumbar outflow) of vertebral column.

" In the sympathetic nervous system, postganglionic fibres are either longer than or
equal to preganglionic fibres.
" Here ganglion is near to the spinal cord.
A. Pre-ganglionic Fibre - Acetylcholine
B. Post-Ganglionic Fibre
AUTONOMIC NERVOUS SYSTEM -ANATOMY
Sympathetic Nervous system
(thoracolumbar outflow) of vertebral column.
" Sympathetic system fibres come from the thoracic and lumbar spinal cord
than or equal to preganglionic fibres.
" In the sympathetic nervous system, postganglionic fibres are elther longer

A. Pre-ganglionic Fibre - Acetylcholine

B. Post- Ganglionic Fibre eharmaMInds
" Here ganglion is near to the spinal cord.

" Neurotransmitters
Nor Adrenaline
Adrenaline (Adrenal Medulla)
Dopamine - Renal Blood Vessels and Mesenteric Vasculature
Acetylcholine - Sweat Glands ( Innervations from Sympathetic Cholinergic Fibres)
( Word -Adre, and hence we called sympathetic nervous system as adrenergic system)

UTONOMIC NERVOUS SYSTEM - ANATOMY

Cvanium

AUTONOMIC NERVOUS SYSTEM

Spinal
Cavd

Canda Phar

Pasn
CThor4co-
lum
br
o u t f o )
Thoracic
Lumba

AUTONOMIC NERVOUS SYSTEM -ANATOMY

AUTONOMIC NERVoUS SYSTEM

Pt.cangieCibve
Pue Gangliae Fibe
Post
AUTONOMIC NERVOUS SYSTEM - ANATOMY
AUTONOMIC NERVOUS SYSTEM
Parameters Cholinergic System Adrenergic Nervous System
Outfiow Craniosacral Thoracolumbar
Preganglionic Fibre Long Short

Postganglionic Fibre Short Long or Equal

Ganglion Close to Organ Away from Organ

Nor- Adrenaline
NTS Acetylcholine Adrenaline
Acetylcholine
Dopamine

HNAPSE AND NEUROTRANSMITTER

Neurotransmitter
" A neuron releases a signaling chemical called a neurotransmitter across a synaptic gap to influence another cell.
" Any
cell.
major body part or target cel that receives the signal may be another neuron, but it could also be agland or muscle
" Example-Acetylcholine, Nor-adrenaline

Synapse
" The places of contact between neurons known as synapses are where information is transferred from one neuron to
the next.
Presynaptic neuron, synaptic cleft, and postsynaptic neuron are the three components of synapses, which most
frequently occur between axons and dendrites.
" Pre-synaptic receptors affect the release of neurotransmitters by
Increasing activity(Nicotinic and Beta)
Decreasing activity (muscarinicand alpha-2)

SYNAPSE AND NEUROTRANSMITTER

Hurotvasmtte)

Recptot

Neeron
 Keeve

BGOLDEN RULE of ANS

BGolden rules says that

Rulel
When you have sympathy for someone, your heart gets very heavy or in other words(stimulated).

Rule 2
Parasympathetic and Sympathetic Nervous System are opposite to each other and balance each other.
5oin Sympathetic Nervous System, Heart Stimulates which leads to
Increase in Heart Rate (Positive Chronotropic Effect)
ncrease in Conduction (Positive Dromotropic effect)
ncrease in Contractility (Positive inotropic Effect)
Whereas in parasympathetic nervous system opposite action occurs,
Decrease in Heart Rate( Negative Chronotropic Effect)
Decrease in Conduction( Negative Dromotropic Effect)
Negligible effect on contractility
Rule 3
Only heart is stimulated in Sympathetic Nervous System, other organs are inhibited or relaxed.

BONCTIONS OF AUTONOMIC NERVOUS SYSTEM

Part Parasympathetic Sympathetic
Heart Heart Rate Decrease Heart Rate Increase
Conduction Decrease Conduction Increase
Contraction Increase
Stomach
Peristalsis Increase Peristalsis Decrease
Acid Production Increase Acid Production Decrease
Diarrhoea Constipation
Bronchus
Bronchoconstriction Bronchodilation
Bronchial secretions increase Bronchial secretions decrease
Bladder
Contraction
Relaxation
(Urination) (Urinary Retention)
Glands
Glands Secretion Increase Glands Secretion Decrease
Pupil
Pupil constriction (Miosis) Pupil Dilation (Mydriasis)
Sexual Function
Erection
Ejaculation
 narmaM
PARASYMPATHETICNERVOUS SYSTEM

CETYLCHOLINE
Acetylcholine is the principal neurotransmitter of the Parasympathetic Nervous System.

The cholinergic neurons synthesize and store Acetylholine (from Acetyl Co-A and choline)
The rate-limiting step in the production of this NT is choline uptake by neurons.

ACh is kept in the vesicles once it has been synthesized.

When a nerve impulse activates the cell, it is discharged (by exocytosis) into the synaptic cleft. During
generation of nerve impulse, there is Ca2+ influx through Ca2+ specific channels.

Afterwards, it stimulate both pre- and post-ganglionic. cholinergic receptors to produce action.

Action of Ach is terminated by Acetylcholinesterase which is present is synapse.

ACETYLCHOLINE
|Choline
Choline Acetyl- CoA

Acetylcholine

ACh

AChE

Ahan

ACETYLCHOLINE
ACETYLCHOLINE

Some Important Drugs

Hemicholinium -Inhibit the uptake of Choline
Vesamicol- Inhibit the storage of ACh in vesicles
Botulinum Toxin - Inhibit the release of Ach
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#All these drugs are responsible for decreasing the levels of ACh in synapse and thus less or no action

-ACETYLCHOLINE Hemicho (iaium

Choline

Choline
Acetyl- CoA

Acetylcholine
Vesamicof
ACh
Btolinurn
Toxin
Ach
AChE

Aion

RECEPTORS

Receptors

Nicotinic Muscarinic

Nm Nn M1 M2 M3
RECEPTORS
Locations
Nn- Ganglia (Both Parasympathetic and Sympathetic) and Adrenal Medulla
Nm-Neuromuscular Junction

M1- Stomach (Pehle Khao)

M2- Heart (Fir Dil Lagao) warmag
M3- Bronchus, Bladder, GIT, Pupil, Glands (Baaki Baad Mai Saare Kaam)

Pre-synaptic Receptors
M1 and M2- They Function to but brakes on Ach release

#Muscarinic Receptors are of 5 types - M1,M2, M3, M4 and M5

M4 Hippocampus and Cerebral cortex
M5-Substantia Nigra and Ventral Tegmental Areas

ETAILED PHARMACOLOGY of Para -System

Heart
" Decrease in Heart Rate( Negative Chronotropic Effect) -Bradycardia
Bradycardia is caused by a decrease in phase 4of the action potential (delay in spontaneous diastolic depolarization).

Decrease in Conduction(Negative Dromotropic Effect)

AV node delay causes a decrease in conduction.

Negligible effect on contractility

MAKING PHA RMACYEAAY

DETAILED PHARMACOLOGY of Para -System

Blood Vessels
Blood vessels lack adirect cholinerglc supply, however thelr endothellum does contain cholinergle
receptors (M3).
" These receptors are stimulated, which results In the release of NO from the endothelium and vasodila
ma
Angther Mechanlsm
The inhibition of nor-adrenaline release from tonlcally actlve vasoconstrlctor nerve endings by ACh lis a
mechanism of vasodilation,

Exceptlon
ACh can activate M3 receptors In the vascular smooth muscle, which can result In vasoconstrictlon If th
endothelium Is damaged.

DETAILED PHARMA COLOGY of Para -System

arPunilel
 DETAILEDPHARMACOLOGY of Para -System
Eyes (Pupils)
" The cholinergic system stimulates the eye's circular muscle (sphincter pupillae), which causes miosis (M3).
Miosis means pupil constriction.
Accommodation is feasible because ACh also causes the ciliary muscle of the eye to contract.Ciliary muscles
functions to change shape of lens in order to accommodate to nearby objects.

Drugs that block cholinergic receptors cause mydriasis and loss of accommodation.

mydriasis miosis

22

ETAILED PHARMACOLOGY of Para -System

Glands
The cholinergic system stimulates glandular secretion, which increases Biadder Anatomy
Salivation
-Ureter

Lacrimation Ph

Perspiration Opening of uretr

Mediated by M3 receptors
Urethra

Bladder
Increased micturition or urination (M3) is the outcome.
Stimulation of the detrusor and relaxation of the trigone (sphincter) of the urine bladder takes place.

DETAILED PHARMACOLOGY of Para -System

GIT
The parasympathetic nervous system stimulates the production of hydrochloric acid in the stomach (NMl and
M3), which raises the chance of developing peptic ulcer disease.
The cholinergic medicines accelerate the GIT's peristalsis and relax the sphincters. This causes diarhea
sometimes.
Bronchus
" Bronchoconstriction is caused by the M3 receptor stlmulation
Tracheobronchial Secretions IncIease

Male Sex Organs

" The cholinergic system cause male organ's erection because It causes vasodilation
 Male Srgans
T alinergic system cause male organ's erection because it causes vasodilation.

DETAILED PHARMACOLOGY of Para -System

Nicotinic Actions
Acetylcholine stimulates both the parasympathetic and sympathetic ganglia and cause complex actions via Nn
receptors

Muscarinic Actions narmaM

ACh acts on the Neuro Muscular Junction or muscle endplate to cause skeletal muscle contraction stimulation
via Nm receptor.

NCNARM AcY EAsY

NTRODUCTIONTO DRUGS

Drugs

Cholinergic Anticholinergic

Direct Indirect

ARMAcY EAsY

Reversible Irreversible

DIRECTACTING CHOLINERGICS
Al cholinergic drugs are known as parasympathomimetic drugs.
They are esters of choline.
Natural - Acetylcholine, Muscarlne, Nicotine, Plocarpine and Arecollne
Semi or Complete Synthetic - Bethanechol, Carbachol and Methacholine
Drugs
Acetylcholine
ItIt ishas meta
no clinical significance as it is metabolsed as soon as It enters the human body.
bolised by two enzymes:
True cholinesterase - Present in Synapse (Also Known as Acetylchollnesterase)
Pseudo cholinesterase - Present in Plasma (Also known as Butrylcholinesterase)
It is terminated very easily by Pseudo enryme and hence rarely used but sometimes used as eyedrops to lnduce mlosis
Bethanechol
Acts on M3 receptor mainly.
Acts on Bladder to treat Atonic Bladder (Urinary Retention)
Methacholine
Acts on M2 receptors that Is myocardium.
For the diagnosis of bronchial f
intravenously. Remember MethacboliC parentsS Without clinlcally obvious asthma, It can be administered
eChallenge Test.
DIRECTACTING CHOLINERGICS
rbachol
stimulates both Nicotinic and Muscarinic receptors.

locarpine
Acts on Pupil via M3 Receptors and causes miosis.
Use-Angle Closure Glaucoma
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Even if one or two doses are missed, intraocular tension may develop due to the drug's extremely brief duration of action.
evimeline
Acts on M3 receptors
Use - Xerostomia (Dry mouth) is Sjogren Syhdrome
Dry Mouth is mostly caused by Radiation Damage of Salivary Glands.

NDIRECT ACTING CHOLINERGICS

These are also known
INDIRECT ACTING
-DRUGS
Anticholinesterase

REVERSIBLE
IRREVERSIBLE

WATER SOLUBLE
LIPID SOLUBLE
Organophosphates Carbamates

Neostigmine
Pyndostigmine
Edrophondum Physostigmine Tacrine
Rivastigmine Galantamlne Donepezl

INDIRECT ACTING CHOLINERGICS

MOA
These are also known as
Anticholinesteraseas they Inhibit the
concentation of Açetyicholine.
chollnesterase enzyme present in synapse and plasma
which leads to increase in the
Reversible AChE Inhibitor
Upldsoluble
1Physostigmine
It is lipid
Anticholnon-ionised.
soluble and
has tertiary
linesterase Drugs(aiy
armine
It is
naturally obtainedstructure.
frarn
It can cross :
Physostigma venenosum.
A Brain
. Corne el
C. GIT Membrarne (cause miosis and therefore used in
Angle Closure
Use (PAD) Glaucoma)
A. Angle
Closure Glaucoma (Doc is
C. Belladonna)(DOC)Poisoning (Acet
Atropine(Polsoning
Datura DOC)azolamide)
Use- (PAD)
A Angle Closure Glaucoma (DOC is Acetazolamide)
B Atropine(Belladonna) Poisoning (DOC)
C Datura Poisoning (DOc)

INDIRECT ACTING CHOLINERGICS

Introduction to Dementia
" Our Brain has an area called Basal Nucleus of Meynert
which has large number of cholinergic neurons.
But with age, no of cholinergic neurons declines. In some people, this
decline is very high.
" Now Acetylcholine functions tocapture and store memory via
Basal Nucleus of Meynert. Since no of cholinergic
neurons decline therefore we can say that Ach level declines which leads to decline in memory called Alzheimer
Dementia.
. It is also called senile dementia as it is observed after 60 years of age.

Another Reason for Alzheimer Disease

Beta-amyloid protein accumulates between neurons. It is created when a bigger protein
protein breaks down. Beta-amyloid 42 is one form that is thought to be known as amyloid precursor
particularly toxic and leads to Alzheimer's.

NDIRECT ACTING CHOLINERGICS

Drugs used for Alzheimer Disease are
Dr Manohar Gobind

D-Donepezil
R-Rivastigmine
M-Memantine
G-Galantamine
#We don't use Physostigmine as it can cause side
effects related to M1, M2 and M3 receptors in periphery such as
ertra urination, hyperacidity. flushing,
Special Points
1 Tacrine -t was used for NGP HAR
Alzheimer disease but banned now due to hepatotoxicity and short duration of
2 Memantine- NMDA receptor action.
3. Rivastigmine is used in both Alzheimer Disease and Parkinsonism Dementia

INDIRECT ACTING CHOLINERGICS

Water soluble Antichollnesterase Drugs

Neostigmine/Pyridostigmine
" It is water soluble and
ionised.
it has quartnery amine
" It is synthetic in structure.
nature.
membrane and GIT, a
" It does not cross BBB,
Corneal
it
directlystimulates Nm receptor and hence it is Nm
"
Pyridostigmine-Longer Acting than Neostigmina Agonist
Uses of Neostigmine (CRAMP)
C- Cobra Bite(it is neurotoxic in nature and it
R- Reversal of Non- blocks Nin and cause Muscle Weakness) (DOC is Anti-venom)
A- Atony of Urinary depolarlzing
Bladder
Neuromuscular Blockers like Pancurpniun
MMyasthenla Gravis (DOC)
P. Post Operative Paralytic ileus/
Post operative urlnary retention
#Of all these conditions, Neostigmine is given in
reversal and myasthenia grovis so that side effeccombination with
ts gssociated withAtropine in Cobra bite, skeletal muscle
relaxants
M3 stimulution does not occur.

INDIRECT ACTING CHOLINERGICS

INDIRECT ACTING CHOLINERGICS
Important Case of Edrophonium
Myasthenia Gravis
It is an autoimmune disorder in antibodies are formed against the Nm receptors. Antibodies bind to the Nm
receptors to inhibit stimulation.
This leads to muscle weakness.
Most common symptom is Ptosis (Drooping of Upper Eyelid)

Important Property of Nm receptor

It requires optimal stimulation of the receptor.
If high stimulation - Muscle Weakness (Cholinergic Crisis)
If Low Stimulation - Muscle Weakness (Myasthenia Gravis)
nds
Therefore, proper diagnosis is required to understand what actual condition is. If high stimulation, then we have to
block the Nm receptor and if low stimulation, then we have to stimulate the receptor.

Solution (Tensilon Test/Edrophonium Test /Ameliorative Test)

We willgive Edrophonium (IV route) which will inhibit the AChE and increase the Acetylcholine. So if the condition
improves, this simplifies that patient was having low stimulation of the Nm receptor and had myasthenia gravis. But in
case, condition of that patient worsened then that patient was having cholinergíc crísis.

NDIRECT ACTING CHOLINERGICS

Important Case of Edrophonium (Why Edrophonium is given not any other drug)
It is a short-acting synthetic anticholinesterase.
1-2 mg intravenous

Drug of Choice for Treatment - Neostigminedihi

DOC for Diagnosis - Edrophonium

MAKINGPH ARMA CY EASY

INDIRECT ACTING CHOLINERGICS

IRREVERSIBLE ANTICHOLINESTERASE
These are the drugs which inhibit the cholinesterase Irreversibly. These are not used clinically except Ecothiopate.

oharm

OGANOPseATES CABAMAIES

INDIRECT ACTING CHOLINERGICS

IRREVERSIRLE
DOC-Atropine (For Both Organophosphate and Carbamate Poisoing)

INDIRECT ACTING CHOLINERGICS

IRREVERSIBLE ANTICHOLINESTERASE

onarmaMp
Which sign of Organophosphate Poisoning cannot be reversed by Atropine?

NDIRECT ACTING CHOLINERGICS

IRREVERSIBLE ANTICHOLINESTERASE
Signs of Atropinisation
1. Mydriasis ( Most Common)
2: Decreased Secretions (Most Reliable)
3. Heart rate > 100

Pinpoint Pupil is seen in OPPO

"
0-Organophosphate and Carbamate Poisoning
"
p-Phenol (Carbolic Acid)
P-Pontine Haemorrhage
0-Opioids
Important Side Efects of
Chronic exposure to someOrganophosphates may
A. Delayed neuropathy organophosphates, result in:
target esterase) (appearing 1-2 weeks after exposure) linked to
axon demyelination. It is caused by NTE
B. Intermediate inhibition, not cholinesterase inhibition. (neuropathy
syndrome, which develops 1-4 days later and is
brought on by cholinesterase Inhibitlon

INDIRECT ACTING CHOLINERGICS

Cholinesterase
IRREVERSIBLE ANTICHOLINESTERASE
Drugs used are Enzyme
here
Reactivators
known as oximes.
These incude
" Pralidoime (PAM)
" Diacetyl
" Obidoxime monoxime (DAM)
Points to remember about
1. them
These are not drug of choiLe.
2. These are not
2. effective in
Oximes are useful in musclecarbamate poisoning
4. Oximes possess weak weakness and respiratory
5. DAM cross BBB Acetylcholinesterase depressiGn.
Inhibiting actlvity
whereas other twa do not crOSs BBB
also
INDIRECT ACTING CHOLINERGICS
IRREVERSIBLE ANTICHOLINESTERASE
Reason Behind the Organophosphate Poisoning and Contraindication of Oximes in Carbamate Poisoning
There are two sites available that is A)Esteratic site and B) AnionicSite
Now, Acetylcholine comes and bind to esteratic site and get metabolized. This process is so fast that it does not bind to the anionic site.

When we give organophosphate, it competes with Acetylcholine and bind with Esteratic site first and this bond is very strong such that it
does not let Acetylcholine bind to esteratic site and hence metabolism stops and due to which level of Acetylcholine increases.

Now when we give oximes, it binds to anionic site and forms bond with Organophosphate molecule. This bond is so strong that bond
between esteratic site and organophosphate breaks. This is how oximes causes reactivation of Acetylcholinesterase.
Now when we give carbamate instead of organophosphate, it binds to both the site at same time. Now we give oximes, they don't work
and are inefficient as no site is there for them to bind.

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Anti - Cholinergics
HARMA

41
OLINERGICS
These drugs work by muscarinicM) receptors and are called anti-chollnerglc drugs or parsympatholytle drugs
These drugs work by inhibiting nicotinic(N)and are called anti-chollnerglc drugs or parasympatholytic drugs and more specificalty
" Drugs blacking Nm are called Neuromuscular blockars
" Drugs blocking the Nn ara called Ganglon blockers

eharm

Anticholinergics

Selective
Miscellaneous Antagonists
Non selective
Special
Agonlsts
CLASSIFICATION
Miscellaneous
Hemicholinium
Vesamicol
Botulinum Toxin

Anti-Cholinergic Drugs

Non-selective Drugs Selective Drugs (Antagonist)

Atropine
M1- Pirenzepine/ Telenzepine
Hyoscine M2-Triptramine
M3- Solifenacin/Darifenacin

ANTICHOLINERGICS
Miscellaneous Drugs
Hemicholinium - Inhibit the uptake of Choline
Vesamicol- Inhibit the storage of ACh in vesicles
Botulinum Toxin Inhibit the release of Ach

" Onabotulinum Toxin A-Useful to prevent Headaches in adult patients with Chronic Migraine.
" Botulinum toxin Type B-cervical dystonia
" Botulinum toxin Type A-strabismus, blepharospasm, glabellar lines (GBS).
" Prabotulinum Toxin -A -Glabellar Lines (Temporary Treatment)

PHARMACOLOGY
M1 Receptor
The parasympatheticnervous system stimulates the productlon of
causes hydrochlorlc acld In the stomach (M1 and M3)., which
Increase in HCL production (Peptic Ulcer)
Increase in GIT's peristalsis
" Diarrhea

Anticholinergic drug willantagonize the M1 receptor and hençe will cause opposite effects
Decrease in HCL production (Indigestion and Achlorhydrla)
Decrease in GIT's peristalsis
Constipation
Drugs
Pirenzeplne and Telenzepine are M1 Selective Antagonsts. These are used in
peptic ulcer.
PHARMACOLOGY

Why Atropine is not used in Peptic Ulcer? Gestie

Ganglig

We don't use Atropine because it inhibits M3

receptor which causes inhibiton of peristalsis.
This leads to decline in gastric emptying. This
means already existing acid will remain in the
stomach and this will cause more damage. So
we give Pirenzipine which only inhibits M1 (not
M3 Receptor)

HARMACOLOGY
M2 Receptor (Cholinergic Drugs)
Decrease in Heart Rate( Negative Chronotropic Effect) -Bradycardia
Decrease in Conduction(Negative Dromotropic Effect)
Negligible effect on contractility

M2 Receptor (Anti -Cholinergic Drugs)

Increase in Heart Rate( Positive Chronotroplc Effect) -Tachycardia
Decrease in Conduction(Positive Dromotropic Effect)
Negligible effect on contractility

Drugs
Atropine is DOC for Bradycardia and AV Block
Atropine is used in ABP International News, A- AV Block B- Bradycardia
RMAC
l -Iridocyclitis<along withsteroids)and P- Poisoning
(Organophosphate and Carbamate)
Special Point about Atropine
Atropine(when started or initial dose) causes bradycardia but later on it causes tachycardia( in later stages or when dose
decrease. Reason is simple. Atropine first block pre-synaptic receptor (M1 and M2) which leads to increase in
Acetylcholine level. This increased ACh stimulates M{ receptor and cause bradycardia. But later on, post-synaptic
receptors are antagonised by atropine which leads to Tachycardia.

PHARMACOLOGY
M3 Receptor

Bronchus (Cholinergic Drugs)

Bronchoconstriction is caused by the M3 receptor stimulation
" Tracheobronchial Secretions increase

Bronchus (Antl -Cholinergic Drugs) warma

Bronchodilation caused by the M3 receptor inhibitlon-Useful in Asthma and COPD
Tracheobronchial Secretlons decrease

Drugs
Tiotropium and Ipratroplum
Ipratropium- Inhibit all M1, M2 and M3
Tiotropium-Inhibit only M1 and M3
Use - Useful in Asthma and COPD

Why Atropine is not used?

Atropine inhibits mucocliary clearance and we don't need It to be inhibited. Tio/lpratroplum does not inhibit the clearance.
Second reason atropine is not avallable in the inhalatlon form whereas Tio/pratropium are available In Inhalation form.

PHARMACOLOGY
Why Atropine is not used?
Atropine inhibits mucociliary clearance and we don't need it to be inhibited. Tio/lpratropium does not
inhibit the clearance.
Second reason atropine is not available in the inhalation form whereas Tio/lpratropium are available in
inhalation form.

PHARMACOLOGY
Bladder (Cholinergic Drugs)
Increased micturition or urination (M3)
Stimulation of the detrusor muscles and relaxation of the trigone (sphincter) of the urine bladder takes place.\

Bladder (Anti-Cholinergic Drugs)

Urinary Retention (M3)- Very Important Side Effect of Anti-cholinergic Drugs
Relaxation of the detrusor muscles and contraction of the trigone (sphincter) of the urine bladder takes place.
Urinary Bladder Capacity increases but urine does not pass.

#Such drugs antagonising the M3 receptor and causing urinary retention are contraindicated in Benign Prostatic
Hyperplasia (BPH)

Indication
These drugs cause urinary retention and therefore can be used in conditions such as
Detrusor Instability (Overactive Bladder)
Urinary Incontinence
Renal Colic

HARMACOLOGY
Drugs (SOFT Bladder of Mira)
S- Solifenacin
As a first line of treatment for an overactive
0-Orybutynin bladder, behavioural therapy (bladder training,
F-Flavoxate, Fesoterodine pelvic floor exercises, and fluid management) is
T-Tolterodine, Trospium used.
Bladder - Darifenacin
Mirabegron - Beta 3 Agonist
Special Points
Trospiurm
All drugs cause CNS side effects which leads to impairment of cognitive abilities and thus unsafe un elderly patients (except
Trospium as it is quartnery in nature)
it is the only drug which can be used with AChE Inhibitors.
Trospium isexcreted in renal secretion and is not metabolized by CYP enzymes therefore can be given in Hepatic failure and
can be given CYP Inhibitors

Solifenocin ond Dorifenocin

Longest acting drug is Solifenacin
Most vesicoselective (M3 - selective)
Can be given in elderny patients if Trospium isno avallable as they are M3 selective.

PHARMACOLOGY
Oxybutynin
" Allthese drugs cause dry mouth as side effect. Maximum is by oxybutynin.
" Oxybutynin and Flavoxate have direct bladder relaxing action.
It is shortest acting drug.

Fesoterodine is prodrug of Tolterodine

eharnmag
 PHARMACOLOGY
Glands (Cholinergic Drugs)
For Organophosphate
The cholinergic system stimulates glandular secretion, which increases Poisoning in Children - You
. Salivation can give Atropine and it is
" Lacrimation dug of choice as there is
Perspiration excessive sweating in
ehar poisoning.
Glands (Anti-Cholinergic Drugs)
Secretions are inhibited here which causes:
Decreased Salivation- Dry Mouth
Decreased Lacrimation -Dry Eyes
Decreased Perspiration - Atropine Fever leads to Hyperthermia (Death can happen) and hence contraindicated in
Children

Indications
To reduce secretions and bronchospasm during general anaesthesia, Glycopyrrolate is administered prior to the
induction of anaesthesia. Glycopyrolate and Atropine are both useful here.
Glycopyrrolate is quartnery ammonium compound so does not enter the CNS.

HARMACOLOGY
Trecha

Bronchus

PHARMACOLOGY
Smooth Musdes (Presence of M3 Receptors)
Smooth Muscles are present Inthe:
A. Bronchus
B. Urinary Bladder
C. GIT
We have covered all of them,
armay
Minds
Ph

Lets tallk GIT and Colicky Pain Here,

GIT
Presence of M3 receptar
M3 stirmulation leads to the increase in
M3 inhibition leads decrease in peristalsis and secretions - (Chances of Diarrhoea are high)
peristalsis and secretions - (Chances of Constipation)
Colicky Paln (Colic)
Colicky Pain is consistent intermittent pain. it is taused due to
contraction can be due ta many reasons. strong contraction of hollow smooth muscles, This

PHARMACOLOGY
CoiCAY of hollow smooth mUSIeS. TIS
pain. It is caused due to strong contraction
Colicky Pain is consistent intermittent
contraction can be due to many reasons.

PHARMACOLOGY
Colicky Pain (Colic)
can be many.
of hollow smooth muscles. Reasons
It is caused due to strong contraction

Colic here:
We have to understand three types of
A. Intestinal Colic e h a rmaM
r
B. Ureteric Colic
C. Biliary Colic

known as Anti-spasmodic Agents)

In all these Colic, D0Care Anticholinergics such as (Also
Dicyclomine
Hyoscine
Propantheline
Oxybutynin
Jab bhiColic dard ho, DHOOP mai jaake khade hojaao.
These drugs willrelax smooth muscles and relieve the pain.

HARMACOLOGY

ParmanMib Hollaa
Colon op
CNade

Musele)

MAKLHHARMACY

PHARMACOLOGY
Eye (Colinergic Drugs)
" The holirerg.c systain sliu'ales the eye's cKular mUscle (sphinter pupillae), which causes mioss (M3).
Aigsis Fitaris pupl Loficun.
Accomodat.on is leosuie Leraue Alhplse causes the ciary mscle of the ey tu cuntiat Cihary muscles
functiars to ctarge shepe uf iens in rder tuaceGnndate to neaby objects
Eye (Anticholinergic Drugs)
Antidolnerg cs relaaes ur black uuntretticn tle eyes cucular auxla (sphneler pupilas), which causes niydiiasis
" Mydriais me atis pupil dilatetiun Pupl Diatat an ts'es a s l on of whule rstng 4nd this ts calied Fundoscogy.
Furdascopy s an Eajtiatiun th et exaniestheluvà ct the eye usirg abght and amagaying glas (baxk of the
inasde ul te eye. includg the rets ed ptk ave) Bug ol (huise is Phanykph ine hus Fundusopy
AuLuudalian is tat teasiue escùay uscle ct tte eye laia to cuntsactisias os pasay) Cilary niu stles
lusctans to tlange sape uf ies ie order tu ascomod ate tu isbyckjvcis Suce, there s luas t
&CiNodeliaf, ti s ts Lel.e das cykpieg
" Cytopkga san be ustdio rstiatio teatug ketactve kedpghsys to yn destwd whit is tha rghactwt iror n the

PHARMACOLOGY
PHARMACOLOGY
Important Points related to EYE
. Anticholinergic cause mydriasis
" Anticholinergic cause cycloplegia (Loss of Accommodation) which means blurred vision.
Mydriasis action of these drugs help in retina examination (Fundoscopy). This is a use of these drugs
Anticholinergics are absolutely contraindicated in the Angle Closure Glaucoma (ACG)
" Anticholinergic cause cycloplegia (Loss of Accommodation) which is useful in two ways
A) Refractive Testing B) Iridocyclitis Paineharm
Drugs
Atropine
Longest Acting Drug (3-7 days)
Strongest Cycloplegic Action (Cycloplegic of Choice in children as it is very difficult to produce cycdoplegia in children as they
are highly functional)
Atropine Ointment is used.

Tropicamide
Shortest Acting Drug and Preferred in Adults (Duration of action - 30-60 mins)
Homatropine
Cyclopentolate

UNDOSCOPYAND GLAUCOMA

Please Watch the

Corne lecture to
understand the
diagram

Ainds
C

CYCLOPLEGIA

Please Wath the

C lecture
understad the
digram
 Marde

PHARMACOLOGY
Atropine and Hyoscine

Hyoscine (Scopolamine)
It is obtained naturally.
Hyoscine has been used as alie detector or truth serum on suspects because it promotes "twilight sleep" and has
amnesic andCNS depressive effects. This use is known as Narco-Analysis. It is not use now as this method is
dangerous and can be fatal. Now, Polygraph Test is used currently to detect lie.
It is used for motion sickness. Motion sickness is induction of vomiting due to motion.
Motion Vestibular System stimulate-- Vomiting centers are activated- ---- Vomiting.
This is prevented by Hyoscine which depresses the vestibular system. Hyoscine is used to prevent motion sickness
but not treat. Hence, Hyoscine is given before the journey.
To avoid motion sickness, scopolamine transdermal patches are administered behind the pinna.
Acetazolamide is the DOC for preventing mountain sickness.

Atropine
It is obtained naturally.
It is CNS Stimulant
It is included in diphenoxylate (an anti-motility medication) to lessen its ability for addiction.

HARMACOLOGY
Special Case of Parkinsonism
For the treatment and prevention of drug-induced Parkinsonism,central
anticholinergic medicines such as
BBB

B-Trihexiphenyl (benzhexol)
B- Benztropine
B-Biperidin
These drugs are DOC for Drugs induced Parkinsonism.

Why are they used?

Anticholinergics help reduce muscle stiffness, sweating, and salivation while also enhancing walking
ability.

PHARMACOLOGY
Atropine Poisoning/Belladonna Polsoning/Datura Polsolng
Drug of Choice - Physostigmine

Mushroom Polsoning
Early (Caused by Inocybe species) - DOC is
Atropine
Delayed (Caused by Amanita species)00C is Thiotic Acid
(Atropine is contraindicated)
PHARMACOLOGY
Special Case of Parkinsonism
For the treatment and prevention of drug-induced Parkinsonism, central anticholinergic medicines such as
BBB
B-Trihexiphenyl (benzhexol)

armaMlnds
B- Benztropine
B- Biperidin
These drugs are DOC for Drugs induced Parkinsonism.

Why are they used?

Anticholinergics help reduce muscle stiffness, sweating, and salivation while also enhancing walking ability.

MAKINGPHARMA

PHARMACOLOGY
Atropine Poisoning/Belladonna Poisoning/Datura Poisoing
Drug of Choice - Physostigmine

Mushroom Poisoning
" Early (Caused by Inocybe species) - DOC is Atropine
Delayed (Caused by Amanitaspecies) -DOC is Thiotic Acid (Atropine is contraindicated)

PHARMACOLOGY
Important Information
Drug of Choice of Open Angle Glauçoma -
Latanoprost
Drug of Choice of Angle Closure Glaucoma - Acetazolamlde

Refraction Testing
" Adults - Tropicamide
" Children - Atropine