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A SEMINAR ON
Presented By: Ms. Kirti Vadi
Guided By: Dr. Jalpa Suthar
Dept. Of Pharmacology &
Organization of nervous system
Acetycholine drug profile
Types of cholinergic receptors
Classification of drugs
Directly acting cholinergic drugs
Indirectly acting cholinergic drugs
Therapeutic uses of cholinergic drugs
AchE Poisoning (organophosphorous poisoning)
Side effects of cholinergic drugs
ORGANIZATION OF NERVOUS SYSTEM
The chief neurotransmitter in the parasymphathetic nervous system is
acetylcholine. Hence it is also known as cholinergic system. The drugs that
produce effect similar to that of acetylcholine are termed as cholinergic agents
or parasympathomimetic agents.
TYPES OF CHOLINERGIC RECEPTORS
Features NM NN
Location and function
depolarization of muscle end
plate -contraction of skeletal
CNS: site specific excitation or
Nature Has intrinsic ion channel,
pentamer of only α2 β Ɛ or
and subunits, each subunit
Has intrinsic ion channel,
pentamer of only αβ subunits,
each subunit has 4TM
Opening of cation (Na+, K+)
Opening of cation (Na+, K+,
Agonist PTMA, Nicotine DMPP, Nicotine
Antagonist Tubocurarine Hexamethonium,
CLASSIFICATION OF DRUGS
agents are classified into the
drugs-These drugs mimic the
actions of ACh at muscarinic
and nicotinic receptors by
binding directly to these
•Indirectly acting cholinergic
drugs-These drugs act by
inhibiting the activity of
enzyme which degrades ACh to
inactive products: choline and
DIRECTLYACTING CHOLINERGIC DRUGS
A. CHOLINE ESTERS
B. NATURAL ALKALOID
It is chief alkaloid obtain from the leaves of shrub Pilocarpus jaborandi. It
It has muscarinic action and also mild nicotinic action.
1. Ophthalmic use:
For initial treatment of open angle glaucoma (0.5% to 4% solution),
reduction in intraocular pressure occur within few min and lasts for 4-8 hrs.
To counteract mydriasis produce by atropine
To break the adhesion between the iris and lens
2. As sialagogue – used to stimulate salivary secretion in patients after laryngeal
surgery. (5-10 mg orally)
C. MISCELLANEOUS AGENTS
TREMORINE and OXOTREMORINE are not used therapeutically, but used
only as investigated research tool to stimulate Parkinsonism like symptoms in
Which results from activation of muscarinic receptors in basal ganglia and
elsewhere in CNS.
INDIRECTLYACTING CHOLINERGIC DRUGS
Acetylcholinesterase (AchE) is an enzyme which degrades acetylcholine to inactive
products: choline and acetic acid.
These agents act by inhibiting the AchE, by reversible or irreversible binding
which indirectly increase the concentration of acetylcholine in the synaptic cleft
and ultimately at the respective cholinergic receptors.
A. REVERSIBLE (COMPETITIVE) INHIBITORS OF AChE
• The reversible anticholinesterase
drugs have a similar structure to ACh.
• They combine with the anionic and
their esteric site of AChE.
• This complex is less readily
hydrolysed than AChE-ACh complex.
• It results in a temporary inhibition of
• This inhibition prolong the duration of
action of ACh released in the synaptic
Its an alkaloid obtain from the dried ripe seeds of Physostigma venenosum.
It is highly lipid soluble and shows better absorption in the all the body
compartments including CNS and can crosses BBB.
It has marked muscarinic effects and also stimulate ganglia but negligible
nicotinic effects at neuromuscular junction.
It is highly toxic and so has only limited use.
It is having intermediate duration of action. (30min-2hr)
To counteract the effects of mydriatics
To prevent the adhesion between iris and the lens
for the treatment of glaucoma
Belladonna (atropine) poisoning
This drugs are least absorb and do not cross BBB.
This drugs have important therapeutic effects on skeletal muscle neuromuscular
Low doses moderately prolong and intensify the action of released ACh at motor
endplate, this results in strengthening of muscle weakness.
A quaternary ammonium compound that binds to the anionic site of the enzyme
The ionic bond formed is readily reversible, and the action of the drug is very brief.
It is used mainly for diagnostic purposes, because improvement of muscle strength
by an anticholinesterase is characteristic of myasthenia gravis but does not occur
when muscle weakness is due to other causes.
Duration of action: 5-15 min
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
Antagonizes (reverses) skeletal muscle relaxation (paralysis) caused by tubocurarine
and other competitive neuromuscular blockers
Stimulates autonomic ganglia in small doses but Large doses block ganglionic
No CNS side effects.
COMPARATIVE FEATURES OF
PHYSOSTIGMINE AND NEOSTIGMINE
Source Natural Synthetic
Chemistry Tertiary amine Quaternary ammonium
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
B. IRREVERSIBLE INHIBITORS OF AChE
These agents are called irreversible blockers because they phosphorylated the esteratic site of
AChE irreversibly by forming a covalent bond.
Pentavalent organo-phosphorous compounds containing fluoride or organic group.
During the process, this group is released leaving the remaining part of drug molecule attached
covalently with the esteratic site of AChE through its phosphorous atom.
After phosphorylation, AChE becomes inactive and very stable due to covalent bonding.
Recovery depends on new synthesis (few weeks)
Ecothiophate (exception) : is having a quaternary nitrogen which can bind also to the anionic
site of the enzyme slow hydrolysis (few days) not strictly irreversible
Sometimes phosphorylated enzyme losses one alkyl group and become resistant to hydrolysis
THERAPEUTIC USES OF CHOLINERGIC
Edrophonium to diagnose
Neostigmine, Pyridostigmine & Distigmine to treat
To stimulate bladder & bowel after surgery:
Bethanechol, Carbachol, Distigmine
To lower IOP in chronic simple glaucoma:
To improve cognitive function in Alzheimer’s disease:
Rivastigmine, Gallantamine, Donepezil
Physostigmine in Belladonna poisoning
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 of muscle and fatigue which worsens after the exrecise but goes
off after the rest, slurring speech, diplopia, difficulty in swallowing
Neostigmine – 15 to 30 mg, orally, every 6 hrly
Dose requirement may fluctuate time to time – adjustment required according to
Pyridostigmine – 60-120mg, 4-6hrly, orally
Acute weakness and respiratory paralysis
Tracheobronchial intubation and mechanical ventilation
Methylprednisolone IV with withdrawal of AChE
Gradual reintroduction of AChE
Edrophonium is used for diagnosis of Myasthenic crisis (disease itself) and
cholinergic crisis (overdose of Anti-ChE)
Improvement of symptoms – myasthenic crisis
Worsening – Cholinergic crisis
AChE POISONING (ORGANOPHOSPHOROUS
Organophosphate poisoning is poisoning due to organophosphates(OPs).
The underlying mechanism involves the inhibition of acetylcholinesterase ,
leading to the buildup of acetylcholine in the body.
Diagnosis is typically based on the symptoms and can be confirmed by
measuring butyryl-cholinesterase activity in the blood.
Poisoning may be – Occupational, accidental, Suicidal
Fall in BP, bradycardia or tachycardia, cardiac arrhythmia and vascular
Irritation of Eye, lacrimation, salivation, involuntary defection,
breathlessness, blurring of vision
Muscular fasciculations and weakness
Death due to respiratory paralysis – peripheral and central
The treatment consist of specific antidote or Cholinesterase Reactivators
1. Specific antidotes
Atropine-All cases of AChE poisoning, 2mg IV every `10 minutes – till
muscarinic symptoms disappears
2. Cholinesterase Reactivators – Oximes
Oximes have generic formula R-CH=N-OH
Provides reactive group OH to the enzymes to reactivate the phosphorylated
enzymes eg. Pralidoxime (2-PAM), Obidoxime Diacetyl monoxime (DAM)
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