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Autonomic Nervous System -
Autonomic Pharmacology
Department of Pharmacology
NEIGRIHMS, Shillong
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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 neurobiologyto predict effects of drugs
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The autonomic nervous system
maintains the internal environment
of the body called HOMEOSTASISRole of ANS in homeostasis
links to target organs -
(Cardivascular System, smoothmuscle of GI and glands)
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+
Drug A decreases
activity of
organ O
Autonomic Pharmacology is Practical
Nerves to organ
release neurotransmitter ,
and N increases
the activity of organ
Mimic or Blocktransmitters
Drug A blocks
receptors for
neurotransmitter
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+
Understanding actions of drugs that
influence the autonomic nervous
system allows prediction of theireffects!
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For a definite clinical outcome!
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Autonomic drugs are usedfor the
treatment ofAngina
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Autonomic drugs are used
for thetreatment ofHeart
Failure
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Autonomic drugs are used for t
treatment ofHigh Blood
Pressure
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Objectives
Review the anatomy of the autonomic nervous system
Know the neurotransmitters at autonomic synapses
Understand the mechanism of neurotransmission in theautonomic nervous system
Be able to describe the distribution of adrenergic andcholinergic receptors
Describe general mechanisms by which drugs interact withthe autonomic nervous system
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Autonomic Pharmacology
I. Anatomy of Peripheral Nervous System
Recall
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Controlsskeletal
muscle
Controls
cardiac
muscle &
glands
Peripheral Nervous System
SomaticNervousSystem
AutonomicNervous
System
One
NeuronEfferent
Limb
Two
NeuronEfferent
LimbPostganglionic
Preganglionic
smooth &
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Recall Differences - Somatic Vs ANS
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ANS - Organization
Autonomic afferents:
Mixed and nonmyelinated Nerves
Cell bodies are located in the dorsal root ganglion
of Spinal Nerves and the sensory ganglia of
Cranial Nerves
Mainly mediate visceral pain
Also reflexes from CVS, visceral and respiratory
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Organization of ANS
Central Connections
No Exclusive autonomic area in CNS
Intermixing and integration of somatic and ANS occurs
Hypothalamus is the organ to regulate
Sympathetic Lateral and Posterior sympathetic
Parasympathetic Anterior and Medial
Many autonomic centres are located in mid brainmedulla
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Organization of ANS Efferent fibres
Motor limb
Sympatheticand Parasympathetic
Most organs receive bothinnervations
Functionally antagonistic of
each other Overall depends on the tone
at particular moment EXCEPTIONS:
Most Blood vessels, sweatglands and hair folliclesSympathetic
Gastric and pancreatic glands,cilliary muscles -Parasympathetic
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AUTONOMIC NERVOUS SYSTEM
SYMPATHETIC
Fight or Flight
PARASYMPATHETIC
Rest and Digest
Next slide
Distriibution:
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Parasympathetic Nervous System (Craniosacral Outflow)
Genitalia
Bladder
Large Intestines
Kidney
Bile DuctsGallbladder
Small Intestines
Stomach
Bronchi/BronchialGlands
SA & AV Node
Sphincter Muscle of Iris
Ciliary Muscle
Lacrimal Gland
Submaxillary &Sublingual
Glands
Parotid Gland
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Radial Muscle of IrisCiliary Muscle
SA & AV NodesHis-Purkinje System
Myocardium
Bronchi/Bronchial
Glands
Stomach
Kidneys
Intestines
Bladder//Genitalia
Sublingual/Submaxillary& Parotid Gland
Pilomotor MusclesSweat Glands
Blood Vessels
Sympathetic Nervous System(Thoracolumbar Outflow)
Paravertebral Ganglia
Prevertebral Ganglia
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Epinephrine
(+) Fatty Acid Release (-) Intestinal Motility
(+) Glycogenolysis
(+) ACTH & TSH
(+) Mental Alertness
(+) Muscle Contraction & Efficiency
(+) Dilates Airways
(+) Cardiac Output
ADRENAL
MEDULLA
Chromaffin Cells
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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
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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
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Enteric Nervous System
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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 directproof of humoral transmission
vagusstoffand
acceleranstoff
Many Neurohumoral
transmitters identified:Acet lcholine noradrenalin
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Neurohumoral
Transmission - Steps
1. Impulse Conduction
Tetrodotoxin andsaxitoxin
2. Transmitter Release
3. Transmitter release onpostjunctional membrane
EPSP and IPSP
4. Postjunctional activity
5. Termination of transmitter
action
NET, SERT, DT
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Impulse conduction across synapse
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Ach
Ach
Ach
Ach NE
AchEPI/NE
Ach Ach
Somatic
Sympathetic
Sympathetic
Sympathetic
Para-
sympathetic
Postganglionic Fiber:
Adrenergic
Adrenal Gland
MotorFiber
SweatGlands
Smooth Muscle
Cardiac Cells
Gland Cells
Smooth MuscleCardiac Cells
Gland Cells
Skeletal
Muscle
Ganglion
Ganglion
Ganglion
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Cholinergic and Adrenergic System
Accordingly:
Cholinergic Drugs,i.e., they act by releasing
acetylcholine
But also utilize nitric oxide (NO) or peptides fortransmission
Noradrenergic(commonly called "adrenergic")
Drugs- act by releasing norepinephrine (NA)
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Cotransmission
Peripheral and central Neurons release more than one activesubstance 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 insame vesicle
NANC gut, vas deferens, urinary tract, salivary glands andcertain blood vessels.
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Sites of Cholinergic Transmission
Acetylcholine (Ach) is major neurohumoral transmitter at
autonomic, somatic and central nervous system:
1. All preganglionic sites (Both Parasympathetic and
sympathetic)
2. All Postganglionic Parasympathetic sites and sympathetic to
sweat gland and some blood vessels
3. Skeletal Muscles
4. CNS: Cortex Basal ganglia, spinal chord and others
Parasympathetic Stimulation Acetylcholine (Ach) release at neuroeffector junction
- biological effects
Sympathetic stimulation Noradrenaline (NA) at neuroeffector junction - biological
effects
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CholinergicTransmission: Cholinergic neurons contain largenumbers of small membrane-boundvesicles (containing ACh) concentratednear the synaptic portion of the cellmembrane ACh is synthesized in the cytoplasmfrom acetyl-CoA and cholineby the
catalytic action of Cholineacetyltransferase (ChAT)
Acetyl-CoA is synthesized inmitochondria, which are present in largenumbers in the nerve endingCholine is transported from theextracellular fluid into the neuron terminal
by a sodium-dependent membrane carrier(carrier A). This carrier can be blocked bya group of drugs called hemicholiniums
The action of the cholinetransporter is the rate-limitingstep in ACh synthesis
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Cholinergic Transmission:
Synthesized, ACh is transported from the
cytoplasm into the vesicles by an antiporterthat removes protons (carrier B). Thistransporter can be blocked by vesamicol Release is dependent on extracellular Ca2+and occurs when an action potential reachesthe terminal and triggers sufficient influx ofCa2+ ions The increased Ca2+ concentration"destabilizes"the storage vesicles byinteracting with special proteins associatedwith the vesicular membrane (VAMPs)Fusion of the vesicular membranes with theterminal membrane results in exocytotic
expulsion of ACh into the synaptic cleft The ACh vesicle release process is blockedby botulinum toxinthrough the enzymaticremoval of two amino acids from one or moreof the fusion proteins. Black widow spider??
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Cholinergic Transmission:
After release - ACh molecules may bind to
and activate an ACh receptor(cholinoceptor) Eventually (and usually very rapidly), all ofthe ACh released will diffuse within range ofanacetylcholinesterase (AChE)molecule AChE very efficiently splits ACh intocholineandacetate, neither of which hassignificant transmitter effect, and therebyterminates the action of the transmitter. Most cholinergic synapses are richlysupplied with AChE; the half-life of ACh inthe synapse is therefore very short. AChEis also found in other tissues, eg, red blood
cells. Another cholinesterase with a lowerspecificity for ACh, butyrylcholinesterase[pseudo cholinesterase], is found in bloodplasma, liver, glial, and many other tissues
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Differences between 2 AChEs
True AChE Pseudo AChE
Distribution All cholinergic
sites, RBCs,
gray matter
Plasma, liver,
Intestine and
white matter
Action on:
Acetycholine
Methacholine
Very Fast
Slower
Slow
Not hydrolyzed
Inhibition More sensitiveto
Physostigmine
More sensitive toOrganophosphates
Function Termination of
Ach action
Hydrolysis of
Ingested Esters
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Cholinergic receptors - 2 types
Muscarinic (M) and Nicotinic (N):
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Acetylcholine (cholinergic receptors)
Muscarinic Receptors
1. Selectively stimulated by Muscarineand blocked by Atropineall are G-
protein coupled receptors2. Primarily located in heart, eye, smooth muscles and glands of GIT
3. Subsidiary M receptors are also present in ganglia for modulation
4. Autoreceptors (M type) are present in prejunctional cholinergic Nerveendings also in adrenergic nerve terminals leading to vasodilatation
when Ach is injected5. Blood vessels: All blood vessels have muscarninc receptors although no
cholinergic innervations
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Muscarinic Receptors - Subtypes
Pharmacologically - M1, M2, M3, M4 and M5
M4 and M5 are present in certain areas of Brain and regulate
other neurotransmitters
M1, M3 and M5 fall in one class, while M2 and M4 in another
class
However till today, M1, M2 and M3 are major ones and
present in effector cell and prejunctional nerve endings in CNS
All subtypes have little agonist selectivity but selective
antagonist selectivity
Most organs usually have more than one subtype but one
subtype predominates in a tissue
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Muscarinic Receptors - Location
M1:Ganglion Cells and Central Neurons (cortex,
hippocampus, corpus striatum)
Physiological Role: Mediation of Gastric acid secretion and
relaxation of LES
Learning, memory and motor functions
M2: Cardiac Muscarinic receptors
Mediate vagal bradycardia
Also auto receptors in cholinergic nerve endings M3:Visceral smooth muscles, glands and vascular
endothelium. Also Iris and Ciliary muscles
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Location Autonomic ganglia,
Gastric glands and CNS
Heart and CNS SMs of Viscera,
Eye, exocrine
glands and
endothelium
Functions EPSP & Histaminerelease & acid
secretion with CNS
learning and motor
functions
Less impulsegeneration, less
velocity of
conduction,
decreased
contractility,
less Achrelease
Visceral SMcontraction,
Constriction of
pupil,
contraction of
Cilliary muscle
andvasodilatation
Agonists Oxotremorine and MCN
and MCN-343A
Methacholine Bethanechol
Antagonis
ts
Pirenzepine Methoctramine
& Triptramine
Darifenacin
Muscarinic Receptor
Subtypes
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Acetylcholine (cholinergic receptors)
Muscarinic Receptors
Selectively stimulated by Muscarine and
blocked by Atropine
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Nicotinic (N) Receptors
Nicotinic receptors: nicotinic actions of ACh arethose that can be reproduced by the injection ofNicotine (Nicotiana tabacum)
Can be blocked by tubocurarine andhexamethonium
ligand-gated ion channels
activation results in a rapid increase in cellularpermeability to Na+ and Ca++ resulting -depolarization and initiation of action potential
Ni ti i (N d N ) R t
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Nicotinic (NM and NN) Receptor -
comparison
NM (Muscle type)
1. Location: Skeletal Muscleend plates
2. Function:Stimulate skeletal
muscle (contraction)3. MOA: Postsynaptic and
Excitatory (increases Na+ andK+ permeability)
4. Agonists:ACh, carbachol(CCh), suxamethonium
Selective stimulation by phenyltrimethyl ammonium (PTMA)
5. Antagonists: tubocurarine,hexamethonium
NN (Ganglion type)
1. Location: In autonomic ganglia ofall type (ganglion type) Sympathetic, Parasympathetic andalso Adrenal Medulla
2. Function: Depolarization andpostganglionic impulse stimulateall autonomic ganglia
3. MOA: Excitatory Na+, K+ andCa+ channel opening
4. Agonists: ACh, CCh, nicotine
Selectively stimulated by
phenyl piperazinium (DMPP)
5. Antagonists: mecamylamine,trimetaphan
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Sites of Cholinergic transmission
and types of Receptors
All Postganglionic
Parasympathetic
Postganglionic sympathetic to
sweat gland & BV
Muscarini
c
Muscarine Atropine
Ganglia (Both Para and
sympathetic and also
Adrenal Medulla
NN DMPP Hexamethoniu
m
Skeletal Muscle NM PTMA Curare
CNS Muscarini
c
Muscarine
Oxotremorin
e
Atropine
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Ganglia Concept - summary
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Cholinergic Drugs or Cholinomimetic
or ParasympathomimeticsDrugs producing actions similar to Achby interacting with Cholinergic receptors
or by increasing availability of Ach at thesesites.
l f (
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Classifiction - Direct-acting (receptor
agonists )
Choline Esters
Natural: Acetylcholine
Synthetic: Methacholine, Carbachol and
Bethanechol
Alkaloids:Pilocarpine, Muscarine, Arecholine
Synthetic: Oxotremorine
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Cholinergic Drugs Indirect acting
Cholinesterase inhibitors or reversibleanticholinesterases:
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 EstersCarbaryl and Propoxur (Baygon)
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Question
What side effects might you expect to
see in a patient taking a cholinergic drug?
Hint Cholinergic = Colon-Urgent
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Ach actions - Muscarinic
1. Heart: M2
Hyperpolarization of SA node, reduction in impulse generation andBradycardia
RP in SAN and PF increased but atrial muscles fibers abbreviated
Slowing of AV conduction and His-purkinje fibres partial or
complete block
Atrial fibrillation and flutter nonuniform vagal innervations
Decrease in ventricular contractility
2. Blood Vessels: M3
Cholinergic innervations is limited skin of face and neck
But, M3 present in all type blood vessel Vasodilatation by Nitricoxide (NO) release
Penile erection
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Muscarinic action contd.
3. Smooth Muscles: M3 Abdominal cramps, diarrhoea due to increased peristalsis and
relaxed sphincters
Voiding of Bladder
Bronchial SM contraction dyspnoea, attack of asthma etc.
4. Glands: M3 Increased secretions: sweating, salivation, lacrimation,
tracheobronchial tree and gastric glands
5. Eye: M3 Contraction of circular fibres of Irismiosis
Contraction of Ciliary muscles spasm of accommodation,increased outflow and reduction in IOP
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Ach actions - Nicotinic
1. Autonomic ganglia: Both Sympathetic and parasympathetic ganglia are stimulated
After atropine injection Ach causes tachycardia and rise in BP
2. Skeletal muscle IV injection no effect
Application causes contraction of skeletal muscle
3. CNS: Does not penetrate BBB
Local injection in CNS complex actions
(Acetylcholine is not used therapeutically)
Bethanecol Uses: Postoperative and postpartum urinaryobstruction, neurogenic bladder and GERD (10-40 mg oral)
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Pilocarpine
Alkaloid from leaves ofPilocarpus 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
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Pilocarpine contd.
Used as eye drops in treatment of narrow angle and wideangle glaucoma to reduce IOP
Used to reverse mydriatic effect of atropine
To break adhesion between iris and cornea/lens alternatedwith 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 )
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Pilocarpine Mechanism in Eye
Causes opening up
of trabecular
pores and
increased
drainage
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Muscarine
Alkaloid from mushroomAmanita muscaria
Only muscarinic actions
No clinical use
Mushroom poisoning due to ingestion of poisonousmushroom
= Early onset mushroom poisoning (Muscarine type)
= Late onset mushroom poisoning (neurogenic)
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Early Onset Mushroom Poisoning
Occurs to 1 hour
Symptoms are characteristic of Muscarinic actions
Inocybe or Clitocybe severe cholinergic symptoms likevomiting, salivation, lacrimation, headache, bronchospasm,
diarrhoea bradycardia, dyspnoea, hypotension, weakness,cardiovascular collapse, convulsions and coma
Antidote is Atropine sulphate ( 2-3 mg IM every hrly tillimprovement)
Hallucinogenic type: due to Muscimol or ibotenic acid presentin A. muscria. Blocks muscarinic receptors in brain andactivate mio acid receptors. No specific treatmentAtropineis contraindicated.
Volvariella volvacea
L t O t M h
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Late Onset Mushroom
Poisoning
Occurs within 6-15 hours
Amanita phylloides due to peptide toxins Inhibit RNA andprotein synthesis
Irritability, restlessness, nausea, vomiting, bloody diarrhoeaataxia, hallucination, delirium, sedation, drowsiness and sleepKidney, liver and GIT mucosal damage
Maintain blood pressure, respiration
Inj. Diazepam 5 mg IM Atropine contraindicated as it may cause convulsions and
death
Gastric lavage and activated charcoal
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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)
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AChEs - MOA
Acetylcholinesterase (AchE) isan enzyme, which hydrolyses
The active site of AChE is made
up of
The 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
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
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Hydrolysis of ACh
N
O
C
CH3
O
+
-
+ NO
CCH
3
O
+
-
+
OH-
NO
CCH3
O
+
-
OH
NOH CH3
O
+
HO
+
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Anti-ChEs (MOA) contd.
Anticholinesterases also react with the enzyme ChEs in similar fashion likeAcetylcholine
Carbamates carbamylates the active site of the enzyme
Phosphates Phosphorylates the enzyme
Carbamylated (reversible inhibitors) reacts with water slowly and the esteratic siteis freed and ready for action 30 minutes (less than synthesis of fresh enzyme)
But, Phosphorylated (irreversible) reacts extremely slowly or not at all takesmore time than synthesis of fresh enzyme Sometimes phosphorylated enzyme losses one alkyl group and become resistant to
hydrolysisaging
Edrophonium and tacrine reacts only at anionic site while Organophosphatesreacts only at esteratic site
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Cholinesterase inhibitors contd.
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Anticholinesterases Individual Drugs
2 (two) important clinically used drugs
Physostigminelipid soluble, ganglion acting and
less action in skeletal muscle
Also organophosphates
Neostigminelipid insoluble,skeletal muscle
acting
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Physostigmine
Alkaloid from dried ripe seed (Calabar bean) of African plant Physostigmavenenosum
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 nerveendings and causes ACh accumulation
Muscarinic action on eye causing miosis and spasm of accommodation on localapplication
Antagonises mydriasis and cycloplegia produced by atropine and anticholinergicdrugs
Salivation, lacrimation, sweating and increased tracheobronchial secretions.
Increased heart rate & causes hypotension
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Physostigmine - uses
1. Used as miotic drops to decrease IOP in Glaucoma2. To antagonise mydriatic effect of atropine
3. To break adhesions between iris and cornea alternating withmydriatic drops
4. Belladonna poisoning, TCAs & Phenothiazine poisoning5. Alzheimers disease- pre-senile or senile dementia.
6. Atropine is antidote in physostigmine poisoning.
7. ADRs CNS stimulation followed by depression.
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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 neuromuscularjunction (motor end plate) of skeletal muscle
Antagonises (reverses) skeletal muscle relaxation (paralysis) caused bytubocurarine and other competitive neuromuscular blockers
Stimulates autonomic ganglia in small doses
Large doses block ganglionic transmission
No CNS effects
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Neostigmine Uses and ADRs
Used in the treatment of Myasthenia Gravis to increasemuscle 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 toweakness
Atropine is the antidote in acute neostigmine poisoning
Ph ti i d N ti i
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Physostigmine and Neostigmine -
Summary
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 gravisDose 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
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Therapeutic Uses cholinergic drugs
1. Myasthenia gravis: Edrophonium to diagnose andNeostigmine, Pyridostigmine & Distigmine to treat
2. To stimulate bladder & bowel after surgery:
Bethanechol, Carbachol, Distigmine.
3. To lower IOP in chronic simple glaucoma: Pilocarpine, Physostigmine
4. To improve cognitive function in Alzheimers disease:Rivastigmine, Gallantamine, Donepezil.
5. Physostigmine in Belladonna poisoning
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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
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Myasthenic crisis
Acute weakness and respiratory paralysis
Tracheobronchial intubation and mechnical
ventilation
Methylprednisolone IV with withdrawal of AChE Gradual reintroduction of AChE
Thymectomy
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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
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AChE Poisoning (Organophopsphorous
Poisoning)
Poisoning may be
Occupational, accidental,Suicidal
Symptoms:
Fall in BP, bradycardia or tachycardia, cardiac arrhythmiaand vascular collapse
Irrittion of Eye, lacrimation, salivation, colic, involuntarydefection, breathlessness, blurring of vision
Muscular fasciculations and weakness
Death due to respiratory paralysis peripheral and central
l f
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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
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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 thephosphorylated 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
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Khublei Shibun/Thank you
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Peripheral Nervous System
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SkeletalMuscle
Peripheral Nervous System
Somatic NervousSystem
Autonomic NervousSystem
Parasympathetic
Nervous System
Sympathetic
Nervous System
SelectiveActivation
DiffuseActivation
Glands, Smooth Muscle& Cardiac Muscle
Ch li i T i i
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Cholinergic Transmission
Acetylcholine (Ach) is major neurohumoraltransmitter at autonomic, somatic andcentral nervous system:
The important sites of Acetylcholine as Neurohumoral
transmitters are:1. All Postganglionic and few postganglionic sympathetic to sweat
glands and some blood vesselsMuscarinic
2. All preganglionic (Para and sympathetic) i.e. ganglia and Adrenalmedulla - Nicotinic (NN)
3. Skeletal MuscleNicotinic (NM)
4. Central Nervous System (cortex, basal ganglia and spinal chord)Muscarinic and Nicotinic
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