Wish you

2011

Autonomic Nervous
System - Autonomic

Pharmacology

Department of Pharmacology

NEIGRIHMS, Shillong

Goal
To Learn about the drugs
affecting the autonomic
nervous system
Be prepared to link mechanism of drug action
with knowledge mainly of cardiovascular anatomy,
physiology and neurobiology
to predict effects of drugs

The autonomic nervous system

maintains the internal environment of
the body clled HOMEOSTASIS
Role of ANS in homeostasis
links to target organs (Cardivascular System , smooth
muscle of GI and glands)

Autonomic Pharmacology is Practical

Mimic or Block transmitters

Nerves to organ Y
release neurotransmitter
X,
and X increases
the activity of organ Y

Drug A blocks
receptors for
neurotransmitte
rX

Drug A decreases
activity of
organ Y

Understanding actions of drugs that

influence the autonomic nervous
system allows prediction of their
effects!
Atropine blocks
muscarinic
cholinergic
receptors
that respond to
ACh

Parasympathetic
nerves
release ACh
and increase
intestinal motility

Atropine blocks muscarinic

receptors
and decreases intestinal motility

Autonomic Drugs are very

much Clinically Relevant

Autonomic drugs are used for th

treatment of Angina

Autonomic drugs are used for th

treatment of Heart

Failure

Autonomic drugs are used for th

treatment of High

Blood
Pressure

Autonomic drugs also used for

treatment of
- Anaphylactic shock
- Septic shock
- Benign prostatic hypertrophy
- Alzheimers disease
- Asthma

Objectives
Review the anatomy of the autonomic
nervous system
Know the neurotransmitters at autonomic
synapses
Understand the mechanism of
neurotransmission in the autonomic
nervous system
Be able to describe the distribution of
adrenergic and cholinergic receptors
Describe general mechanisms by which
drugs interact with the autonomic nervous
system

Autonomic Pharmacology
I. Anatomy of Peripheral Nervous
System

Organization of The Nervous

System
Central Nervous System
Brain and spinal cord

Peripheral Nervous System

Autonomic Nervous System

Afferent Division

Somatic Nervous System

Efferent Division

Sympathetic
thoracolumbar

Parasympathetic
craniosacral

Differences Between
Somatic and ANS

Peripheral Nervous System

Controls
skeletal
muscle

Controls
smooth &
cardiac
muscle &
glands

Somatic
Nervous
System

One
Neuron
Efferent
Limb

Autonomic
Nervous
System

Preganglionic
Postganglionic

Two
Neuron
Efferent
Limb

Peripheral Nervous System

Somatic Nervous
System

Autonomic Nervous
System
Parasympathetic
Nervous System
Selective
Activation

Skeletal
Muscle

Sympathetic
Nervous System
Diffuse
Activation

Glands, Smooth Muscle

& Cardiac Muscle

AUTONOMIC NERVOUS
SYSTEM
SYMPATHETIC
Fight or Flight

PARASYMPATHETIC
Rest and Digest

Parasympathetic Nervous System (Craniosacral Outflow)

SA & AV Node
Sphincter Muscle of Iris
Ciliary Muscle

Bronchi/Bronchial
Glands

Stomach
Small Intestines

Lacrimal Gland
Bile Ducts
Gallbladder
Submaxillary &
Sublingual
Glands

Parotid Gland

Kidney
Large Intestines
Bladder

Genitalia

Sympathetic Nervous System

(Thoracolumbar Outflow)

Pilomotor Muscles
Sweat Glands

Radial Muscle of Iris

Ciliary Muscle

Sublingual/Submaxillary
& Parotid Gland
SA & AV Nodes
His-Purkinje System
Myocardium
Bronchi/Bronchial
Glands

Stomach
Kidneys

Blood Vessels

Intestines

Paravertebral Ganglia
Prevertebral Ganglia

Bladder//Genitalia

ADRENAL
MEDULLA
Chromaffin Cells

Epinephrine
(+) Dilates Airways

(+) Cardiac Output

(+) Muscle Contraction & Efficiency

(+) Fatty Acid Release

(+) Mental Alertness

(+) ACTH & TSH

(+) Glycogenolysis

(-) Intestinal Motility

Sympathetic

Parasympathetic

Origin

Dorso-lumber (T1 to
L2 or 3)

Craniosacral (S2-4)

Distribution

Wide

Head, neck and trunk

Ganglia

Away from Organ

supplied

On or close to the organ

Postganglionic fibers

Long

Short

Pre and post fiber ratio 1:20 to 1:100

1:1 or 1: 2

Transmitter

Noradrenalin

Acetylcholine

Duration

Long and wider

action

Ach rapid destroy

Function

Tackling stress and

emergency

Assimilation of food and

conservation of energy

Enteric Nervous System

Considered 3rd Division of ANS
Auerbach`s plexus or myenteric plexus
Meissner`s plexus or submucous plexus
Stimulation of these neurones causes
release of Ach, NE, VIP, ATP, Substance
P, 5-HT etc.
May be excitatory or inhibitory in Nature

Enteric Nervous System

Neurohumoral
Transmission
Neurohumoral transmission means

the transmission of message across

synapse and neuroeffector junctions
by release of humoral (chemical)
messages
Initially junctional transmission
was thought to be Electrical
But, Dale (1914) and Otto Loewi
(1921) provided direct proof of
humoral transmission vagusstoff
and acceleranstoff
Many Neurohumoral transmitters re
identified: Acetylcholine,
noradrenalin, Dopamine, 5-HT, GABA,
Purines, Peptides etc.

Neurohumoral
Transmission - Steps
1.

Impulse Conduction

Tetrodotoxin and
saxitoxin
2.
Transmitter Release
3.
Transmitter release on
postjunctional
membrane

EPSP and IPSP

4.
Postjunctional activity
5.
Termination of
transmitter action

NET, SERT, DT

What is a synapse?
A synapse is a junction between two neurones across
which electrical signals pass. The human body contains up
to 500 trillion synapses.
presynaptic
cell

postsynaptic
cell

Release of
neurotransmitters
When a nerve impulse arrives at the end of one neurone it triggers the
release of neurotransmitter molecules from synaptic vesicles.

synaptic
vesicle

neurotransmitter
molecules

Continuing the impulse

The neurotransmitters diffuse across the synaptic cleft and
bind with receptors on the next neurone, triggering another
impulse.

synaptic
cleft
nerve
impulse
receptor

Somatic

Sympathetic

Motor Fiber

GanglionPostganglionic Fiber:
Adrenergic

Ach

Sympathetic

Ach

Sweat
Glands

EPI/NE
Ach
Adrenal Gland

Parasympathetic

Smooth Muscle
NE Cardiac Cells
Gland Cells

Ganglion
Ach

Sympathetic

Skeletal
Ach Muscle

Ganglion
Ach

Smooth Muscle
Cardiac Cells
Ach Gland Cells

Cholinergic and
Adrenergic System
Accordingly:
Cholinergic Drugs, i.e., they act by
releasing acetylcholine
But also utilize nitric oxide (NO) or
peptides for transmission

Noradrenergic (commonly called

"adrenergic") Drugs - act by
releasing norepinephrine (NA)

Cotransmission
Peripheral and central Neurones release more than
one active substance when stimulated
In ANS, besides Ach and NA neurones elaborate
Purines (ATP, adenosines), Peptides (VIP) or NPY,
substance P, NO, enkephalins etc.
ACH and VIP, ATP with both Ach and NA
Stored in same neurones, but distinct vesicles
ATP and NA in same vesicle
NANC gut, vas deferens, urinary tract, salivary
glands and certain blood vessels.

Cholinergic System and

Drugs

Cholinergic
Transmission

Acetylcholine (Ach) is major

neurohumoral transmitter at autonomic,
somatic and central nervous system:
The important sites of Acetylcholine as
Neurohumoral transmitters are:

1.
2.
3.
4.

All Postganglionic and few postganglionic

sympathetic to sweat glands and some blood
vessels Muscarinic
All preganglionic (Para and sympathetic) i.e.
ganglia and Adrenal medulla - Nicotinic (NN)
Skeletal Muscle Nicotinic (NM)
Central Nervous System (cortex, basal ganglia
and spinal chord) Muscarinic and Nicotinic

Cholinergic Transmission:
Cholinergic neurons contain large
numbers of small membrane-bound
vesicles (containing ACh) concentrated
near the synaptic portion of the cell
membrane
ACh is synthesized in the cytoplasm
from acetyl-CoA and choline by the
catalytic action of acetyltransferase
(ChAT)
Acetyl-CoA is synthesized in
mitochondria, which are present in large
numbers in the nerve ending
Choline is transported from the
extracellular fluid into the neuron terminal
by a sodium-dependent membrane carrier
(carrier A). This carrier can be blocked by
a group of drugs called hemicholiniums
The action of the choline
transporter is the rate-limiting
step in ACh synthesis

Cholinergic Transmission:
Synthesized, ACh is transported from the
cytoplasm into the vesicles by an antiporter
that removes protons (carrier B). This
transporter can be blocked by vesamicol
Release is dependent on extracellular Ca2+
and occurs when an action potential reaches
the terminal and triggers sufficient influx of
Ca2+ ions
The increased Ca2+ concentration
"destabilizes" the storage vesicles by
interacting with special proteins associated
with the vesicular membrane (VAMPs)
Fusion of the vesicular membranes with the
terminal membrane results in exocytotic
expulsion of ACh into the synaptic cleft
The ACh vesicle release process is blocked
by botulinum toxin through the enzymatic
removal of two amino acids from one or more
of the fusion proteins. Black widow spider

Cholinergic Transmission:
After release - ACh molecules may bind to
and activate an ACh receptor
(cholinoceptor)
Eventually (and usually very rapidly), all of
the ACh released will diffuse within range of
an acetylcholinesterase (AChE) molecule
AChE very efficiently splits ACh into
choline and acetate, neither of which has
significant transmitter effect, and thereby
terminates the action of the transmitter.
Most cholinergic synapses are richly
supplied with AChE; the half-life of ACh in
the synapse is therefore very short. AChE
is also found in other tissues, eg, red blood
cells.
Another cholinesterase with a lower
specificity for ACh, butyrylcholinesterase
[pseudo cholinesterase], is found in blood
plasma, liver, glial, and many other tissues

Differences between 2
AChEs
True AChE

Pseudo AChE

Distribution

All cholinergic
sites, RBCs, gray
matter

Plasma, liver,
Intestine and
white matter

Action on
ACh

Very Fast

Slow

Inhibition

More sensitive to
Physostigmine

More sensitive to
Organophosphates

Function

Termination of
Ach action

Hydrolysis of
Ingested Esters

Cholinergic receptors - 2
types
Muscarinic (M) and Nicotinic (N)

Muscarinic
(M) - GPCR

Nicotinic (N)
ligand gated

Sites of Cholinergic
transmission
Site
1.

All Postganglionic
Parasympathetic
Postganglionic
sympathetic to sweat
gland & BV

Types

Selective
agonist

Selective
antagonist

Muscarinic

Muscarine

Atropine

Ganglia (Both Para and

sympathetic and also
Adrenal Medulla

NN

DMPP

Hexamethoniu
m

Skeletal Muscle

NM

PTMA

Curare

CNS

Muscarinic

Muscarine
Oxotremor
ine

Atropine

2.

Cholinergic receptors
Muscarinic (M) and Nicotinic (N)

Nicotinic receptors:

nicotinic actions of ACh are those

that can be reproduced by the
injection of Nicotine
and also can be blocked by
tubocurarine and hexamethonium
ligand-gated ion channels
activation results in a rapid increase
in cellular permeability to Na+ and
Ca++
results in depolarization and initiation
of action potential

Nicotinic (NM and NN)

Receptor Locations
NM (Muscle type) and NN (Ganglion type)

NM (Muscle type): at neuromuscular junctions of skeletal

muscle:

Postsynaptic and Excitatory (increases Na+ and K+ permeability)

Stimulate skeletal muscle (contraction)
Agonists: ACh, carbachol (CCh), suxamethonium
Selective stimulation by phenyl trimethyl ammonium (PTMA)
Antagonists: tubocurarine, hexamethonium

NN type: In autonomic ganglia of all type (ganglion

type) Sympathetic, Parasympathetic and also Adrenal
Medulla
Depolarization and postganglionic impulse stimulate all
autonomic ganglia
Excitatory Na+, K+ and Ca+ channel opening
Agonists: ACh, CCh, nicotine
Selectively stimulated by phenyl piperazinium (DMPP)
Antagonists: mecamylamine, trimetaphan

Muscarinic (M)
Receptors
Amanita muscaria

Acetylcholine (cholinergic
receptors)

Muscarinic Receptors

Selectively stimulated by Muscarine nd

blocked by Atropine
G-protein coupled receptors
Primarily located in heart, blood vessels,
eye, smooth muscles and glands of GIT
Subsidiary M receptors are also present in
ganglia for modulation
Autoreceptors (M type) are present in
prejunctional cholinergic Nerve endings

Muscarinic Receptors Subtypes

M1, M2, M3, M4 and M5
M1, M2 and M3 are major ones and present
in effector cell and prejunctional nerve
endings in CNS
M4 and M5 are present in certain areas of
Brain and regulate other neurotransmitters
All subtypes have little agonist selectivity
but selective antagonist selectivity

Muscarinic Receptor
Subtypes
M1

M2

M3

Location

Autonomic ganglia, Gastric

glands and CNS

Heart and CNS

SMs of Viscera,
Eye, exocrine
glands and
endothelium

Functions

EPSP & Histamine release &

acid secretion with CNS
learning and motor functions

Less impulse
generation, less
velocity of
conduction,
decreased
contractility,
less Ach release

Visceral SM
contraction,
Constriction of
pupil, contraction
of Cilliary muscle
and vasodilatation

Agonists

Oxotremorine and MCN and

MCN-343A

Methacholine

Bethanechol

Antagonists

Pirenzepine

Methoctramine
& Triptramine

Darifenacin

Acetylcholine (cholinergic
receptors)

Muscarinic Receptors
Selectively stimulated by
Muscarine and blocked by
Atropine

M1

M2

M3

Ganglia

Heart

Glands and SM

Cholinergic Drugs or
Cholinomimetic or
Parasympathomimetics
Drugs producing actions similar
to Ach by interacting with
Cholinergic receptors or by
increasing availability of Ach at
these sites.

Classifiction - Directacting
(receptor
agonists )
Choline Esters
Natural: Acetylcholine
Synthetic: Methacholine,
Carbachol and Bethanechol.

Alkaloids: pilocarpine,
muscarine, arecholine
Synthetic: Oxotremorine

Cholinergic Drugs
Indirect acting
Cholinesterase inhibitors or reversible
anticholinesterases:
Natural: Physostigmine
Synthetic: neostigmine, pyridostigmine, distigmine,
rivastigmine, donepezil, gallantamine, edrophonium,
ambenonium, demecarium

Irreversible anticholinesterases:

Organophosphorous Compounds (OPC) Diisopropyl

fluorophosphate (DFP), Ecothiophate, Parathion,
malathion, diazinon (insecticides and pesticides)
Tabun, sarin, soman (nerve gases in war)
Carbamate Esters Carbaryl and Propoxur (Baygon)

Question
What side effects might you
expect to see in a patient
taking a cholinergic drug?
Hint Cholinergic = ColonUrgent

Ach actions - Muscarinic

1.

Heart: M2

2.

Hyperpolarization of SA node, reuction in impulse

generation and Bradycardia
Slowing of AV conduction and His-purkinje fibres
partial or complete block
Atrial fibrillation and flutter nonuniform vagal
innervations
Decrease in ventricular contractility

Blood Vessels: M3

Cholinergic innervations is limited skin of face and

neck
But, M3 present in all type blood vessel
Vasodilatation by Nitric oxide (NO) release
Penile erection

Muscarinic action
contd.
3.

4.
5.

Smooth Muscles: M3

Abdominal cramps, diarrhoea due to

increased peristalsis and relaxed sphincters
Voiding of Bladder
Bronchial SM contraction dyspnoea, attack
of asthma etc.

Glands: M3

Increased secretions: sweating, salivation,

lacrimation, tracheobronchial tree and gastric
glands

Eye: M3

Contraction of circular fibres of Iris miosis

Contraction of Ciliary muscles spasm of
accommodation, increased outflow and
reduction in IOP

Ach actions - Nicotinic

1.

2.

3.

Autonomic ganglia:

Both Sympathetic and parasympathetic

ganglia are stimulated
After atropine injection Ach causes
tachycardia and rise in BP

Skeletal muscle

IV injection no effect
Application causes contraction of skeletal
muscle

CNS:

Does not penetrate BBB

Local injection in CNS complex actions

(Acetylcholine is not used therapeutically)

Pilocarpine
Alkaloid from leaves of Pilocarpus

microphyllus

Prominent muscarinic actions

Profuse salivation, lacrimation, sweating
Dilates blood vessels, causes hypotension
On Eyes it produces miosis and spasm of
accommodation
Lowers intraocular pressure (IOP) in
Glaucoma when applied as eye drops
Too toxic for systemic use

Pilocarpine contd.
Used as eye drops in treatment of narrow
angle and wide angle glaucoma to reduce
IOP
Used to reverse mydriatic effect of
atropine
To break adhesion between iris and
cornea/lens alternated with mydriatic
Pilocarpine nitrate eye drops ( 1 to 4% )
CNS toxicity after systemic use
Atropine used as antidote in acute
pilocarpine poisoning ( 1-2 mg IV 8hrly )

Pilocarpine Mechanism
in Eye
Causes opening up
of trabecular
pores and
increased
drainage

Muscarine
Alkaloid from mushroom Amanita

muscaria

Only muscarinic actions

No clinical use
Cause mushroom poisoning due to
ingestion of poisonous mushroom
= Early onset mushroom poisoning
= Late onset mushroom poisoning
(neurogenic)

Early Onset Mushroom

Poisoning
Volvariella volvacea

Occurs to 1 hour.
Muscaria cause mild cholinergic symptoms like
nausea, vomiting, salivation, lacrimation,
headache, bronchospasm, diarrhoea
ntidote is Atropine sulphate (0.5-I mg IM twice
daily)
Inocybe or Clitocybe severe cholinergic symptoms
like bradycardia, dyspnoea, hypotension,
weakness, cardiovascular collapse, convulsions
and coma
Antidote is Atropine sulphate ( 2-3 mg IM hrly till
improvement )

Late Onset Mushroom

Poisoning
Occurs within 6-15 hours
Amanita phylloides irritability,
restlessness, nausea, vomiting, ataxia,
hallucination, delirium, sedation,
drowsiness and sleep.
Maintain blood pressure, respiration
Inj. Diazepam 5 mg IM
Atropine contraindicated as it may cause
convulsions and death
Gastric lavage and activated charcoal

Cholinesterase inhibitors:
Reversible anticholinesterases
(Carbamates):

Natural: Physostigmine
Synthetic: Neostigmine, pyridostigmine,
distigmine, rivastigmine, donepezil,
gallantamine, edrophonium, ambenonium,
demecarium

Irreversible anticholinesterases:

Organophosphorous Compounds (OPC)

Diisopropyl fluorophosphate (DFP), Ecothiophate,
Parathion, malathion, diazinon (insecticides and
pesticides)
Tabun, sarin, soman (nerve gases in war)
Carbamate: Carbaryl and Propoxur (Baygon)

AChEs - MOA
Acetylcholinesterase (AchE) is

an enzyme, which hydrolyses

Acetylcholine
The active site of AChE is made
up of two subsites anionic and
esteratic
The anionic site serves to bind a
molecule of ACh to the enzyme
Once the ACh is bound, the
hydrolytic reaction occurs at a
second region of the active site
called the esteratic subsite
The AChE itself gets acetylated
at serine site
Acetylated enzyme reacts with
water to produce acetic acid and
choline
Choline is then immediately
taken up again by the high affinity
choline uptake system on the

Hydrolysis of ACh
-

OH

+C

CH3

+C

O-

CH3

OOH

O
C
O-

CH3

HO

OH

CH3

+
O

Anti-ChEs (MOA)
contd.

Anticholinesterases also react with the enzyme ChEs in

similar fashion like Acetylcholine

Carbamates carbamylates the active site of the enzyme

Phosphates Phosphorylates the enzyme

Carbamylated (reversible inhibitors) reacts with water

slowly and the esteratic site is freed and ready for action
30 minutes (less than synthesis of fresh enzyme)

But, Phosphorylated (irreversible) reacts extremely

slowly or not at all takes more time than synthesis of
fresh enzyme

Sometimes phosphorylated enzyme losses one alkyl group

and become resistant to hydrolysis aging

Edrophonium and tacrine reacts only at anionic site while

Organophosphates reacts only at esteratic site

Cholinesterase inhibitors
contd.

Anticholinesterases
Individual Drugs
2 (two) important clinically used
drugs
Physostigmine lipid soluble,
ganglion acting and less action in
skeletal muscle
Also organophosphates

Neostigmine lipid insoluble,

skeletal muscle acting

Physostigmine

Alkaloid from dried ripe seed (Calabar bean) of African

plant Physostigma venenosum
Tertiary amine, lipid soluble, well absorbed orally and
crosses BBB
Hydrolyzed in liver and plasma by esterases.
Long lasting action (4-8 hours)
Reversible anticholinesterase drug
It indirectly prevents destruction of acetylcholine
released from cholinergic nerve endings and causes ACh
accumulation
Muscarinic action on eye causing miosis and spasm of
accommodation on local application
Antagonises mydriasis and cycloplegia produced by
atropine and anticholinergic drugs
Salivation, lacrimation, sweating and increased
tracheobronchial secretions.
Increased heart rate & causes hypotension

Physostigmine - uses
1. Used as miotic drops to decrease IOP in
Glaucoma
2. To antagonise mydriatic effect of atropine
3. To break adhesions between iris and
cornea alternating with mydriatic drops
4. Belladonna poisoning, TCAs &
Phenothiazine poisoning
5. Alzheimers disease- pre-senile or senile
dementia.
6. Atropine is antidote in physostigmine
poisoning.
7. ADRs CNS stimulation followed by
depression.

Neostigmine

Synthetic reversible anticholinesterase drug.

Quaternary ammonium compound and lipid soluble.
Cannot cross BBB
Hydrolysed by esterases in liver & plasma
Short duration of action (3-5 hours)
Direct action on nicotinic (NM) receptors present in
neuromuscular junction (motor end plate) of
skeletal muscle
Antagonises (reverses) skeletal muscle relaxation
(paralysis) caused by tubocurarine and other
competitive neuromuscular blockers
Stimulates autonomic ganglia in small doses
Large doses block ganglionic transmission
No CNS effects

Neostigmine Uses and

ADRs
Used in the treatment of Myasthenia
Gravis to increase muscle strength
Post-operative reversal of neuromuscular
blockade
Post-operative complications gastric
atony paralytic ileus, urinary bladder atony
Cobra snake bite
Produces twitchings & fasciculations of
muscles leading to weakness
Atropine is the antidote in acute
neostigmine poisoning

Physostigmine and
Neostigmine - Summary
Physostigmine

Neostigmine

Source

Natural

Synthetic

Chemistry

Tertiary amine

Quaternary ammonium
compound

Oral absorption Good

Poor

CNS action

Present

Absent

Eye

Penetrates cornea

Poor penetration

Effect

Ganglia

Muscle

Uses

Miotic

Mysthenia gravis

Dose

0.5-1 mg
oral/parenteral
0.1-1% eye drop

0.5-2.5 mg IM/SC
15-30 mg orally

Duration of
action

4-6 Hrs

3-4 Hrs

Therapeutic Uses
cholinergic drugs
1.

Myasthenia gravis: Edrophonium to

diagnose and Neostigmine,
Pyridostigmine & Distigmine to treat
To stimulate bladder & bowel after
surgery:

2.
3.
4.
5.

Bethanechol, Carbachol, Distigmine.

To lower IOP in chronic simple glaucoma:

Pilocarpine, Physostigmine

To improve cognitive function in

Alzheimers disease: Rivastigmine,
Gallantamine, Donepezil.
Physostigmine in Belladonna poisoning

Myasthenia gravis
Autoimmune disorder affecting 1 in 10,000
population
Causes: Development of antibodies directed to
Nicotinic receptors in muscle end plate reduction
in number by 1/3rd of NM receptors
Structural damage to NM junction
Symptoms: Weakness and easy fatigability
Treatment:
Neostigmine 15 to 30 mg orally every 6 hrly
Adjusted according to the response*
Pyridostigmine less frequency of dosing
Other drugs: Corticosteroids (prednisolone 30-60
mg /day)
Azathioprin and cyclosporin also
Plasmapheresis

Myasthenic crisis
Acute weakness and respiratory
paralysis
Tracheobronchial intubation and
mechnical ventilation
Methylprednisolone IV with
withdrawal of AChE
Gradual reintroduction of AChE
Thymectomy

Snake venom Poisoning

Asian Cobra Bite
Symptoms are similar to
Myasthenia gravis
Atropine sulfate 0.6 mg IV
slowly to counteract
Muscarinic action
Edrophonium chloride (Tensilon)
- 10 mg IV over 2 minutes
reversal of occulomotor and
respiratory paralysis

AChE Poisoning
(Organophopsphorous Poisoning)
Poisoning may be
Occupational, accidental,
Suicidal
Symptoms:
Fall in BP, bradycardia or tachycardia,
cardiac arrhythmia and vascular
collapse
Irrittion of Eye, lacrimation, salivation,
colic, involuntary defection,
breathlessness, blurring of vision
Muscular fasciculations and weakness
Death due to respiratory paralysis

Principles of Treatment
Remove soiled clothes
Wash soiled skin and eyes
Prone Positioning and clear mouth
and throat
Intubation of airway
Gastric lavage
Atropine: All cases of AChE
poisoning, 2mg IV every `10 minutes
continue till atropinization occurs
Cholinesterase reactivators: Oximes

Cholinesterase
Reactivators - Oximes
Pralidoxime (2-PAM), Obidoxime Diacetyl
monoxime (DAM)
Oximes have generic formula R-CH=N-OH
Provides reactive group OH to the enzymes
to reactivate the phosphorylated enzymes
PAM:
Quaternary Nitrogen of PAM gets attaches to
Anionic site of the enzyme and reacts with
Phosphorous atom at esteratic site
Forms Oxime-phosphonate complex making
esteratic site free
Not effective in Carbamate poisoning
Dose: 1-2 gm IV slowly

Khublei Shibun/Thank you