Autonomic Nervous System
Dr. Karun Kumar
Assistant Professor
Dept. of Pharmacology

Parasympathetic
nervous system

Working of ANS
• Efferent neurons  The ANS carries nerve impulses
from the CNS to the effector organs by way of two
types of efferent neurons: the preganglionic
neurons and the postganglionic neurons
• The cell body of the first nerve cell, the
preganglionic neuron, is located within the CNS

• The preganglionic neurons emerge from the
brainstem or spinal cord and make a synaptic
connection in ganglia (an aggregation of nerve cell
bodies located in the peripheral nervous system)
• The ganglia function as relay stations between the
preganglionic neuron and the second nerve cell,
the postganglionic neuron
• The cell body of the postganglionic neuron
terminates on effector organs, such as smooth
muscles of the viscera, cardiac muscle, and the
exocrine glands

Cholinergic transmission
• Acetylcholine  Neurotransmitter at
1. Neuromuscular junction (NMJ)
2. All preganglionic neurons
3. All postganglionic parasympathetic neurons
4. Postganglionic sympathetic neurons in sweat
glands

Synthesis, storage and destruction
of ACh
• Synthesized locally in the cholinergic nerve endings

Cholinesterase
• 2 types:-
1. Acetylcholinesterase—AChE or true
cholinesterase
2. Butyrylcholinesterase—BuChE or pseudochE

Location of cholinergic receptors
1. M1  Autonomic ganglia, gastric glands, CNS
2. M2  Heart (SA node, AV node, atrium)
3. M3  Visceral smooth muscle, ciliary muscle,
Exocrine glands, vascular endothelium
4. NM  Neuromuscular junction
5. NN  Autonomic ganglia, adrenal medulla

Pehle khao (M1)phir dil lagao (M2)
baaki kaam baad mein (M3)

Cholinergic agonists
1. Direct acting agonists  Bind & activate Ach rec.
a) Choline esters  Ach, Bethanechol, Carbachol
b) Plant alkaloids  Muscarine, Nicotine,
Pilocarpine, Arecoline
2. Indirectly acting agonists (anti-chE)
a) Reversible  Carbamates, Non-carbamates
b) Irreversible  Carbamates, Organophosphates

Indirectly acting agonists

Pilocarpine
• Obtained from the leaves of Pilocarpus microphyllus
and other species
• Prominent muscarinic action (M3) & mild nicotinic
action at ganglia (NN)
• Applied to the eye, it penetrates cornea and
promptly causes miosis, ciliary muscle contraction
and fall in intraocular tension lasting 4–8 hours.
• Uses  Open angle glaucoma, xerostomia
• S/E  Initial stinging sensation in the eye and painful
spasm of accommodation, marked sweating,
salivation and ↑ in other secretions

Edrophonium
• Resembles Neostigmine in action
• Has a brief duration of action (10–30 min)
• Diagnostic agent for myasthenia gravis
• Dose: 2–10 mg i.v.

Myasthenic vs Cholinergic crisis
• Myasthenic crisis  Ach ↓↓
• Cholinergic crisis  Ach ↑↑
• Edroph. (Rev. inhib. of AchE)  ↑ Ach at NMJ
↓ ↓
Dramatic improvement Worsened condition
(Myasthenic crisis) (Cholinergic crisis)
• Short duration of action (desirable for pts.
presenting with cholinergic crisis as the worsening
in their condition would be for short lasting)

Uses of anti-cholinesterases
1. Glaucoma
2. To reverse the effect of mydriatic  After
refraction error testing
3. To prevent and break adhesions between iris and
lens/cornea  Miotic is altered with mydriatic
4. Myasthenia gravis  Neostigmine is used
5. Postoperative decurarization  To reverse effect
of muscle relaxants
6. Postoperative paralytic ileus/urinary retention

Why neostigmine is used in
myasthenia gravis ?

7. Cobra bite  To antagonize the curare-like action
of cobra neurotoxin
8. Belladonna poisoning  Physostigmine is drug of
choice for atropine poisoning
9. Alzheimer’s disease  Rivastigmine, Donepezil
and Galantamine afford some symptomatic
improvement

Signs and symptoms of OP
poisoning (Muscarinic)
M  Miosis
U  Urination
S  Secretions↑ (Salivation, lacrimation & sweating)
C  Cardiac contraction & conduction slows
A  Abdominal cramps
R  Reduction in i.o.t. (esp. in glaucoma)
I  Increased GI motility
N  NO (Nitric oxide) dependent vasodilatation
I  Inc. sec. from GIT & tracheobronchial tract
C  Constriction of tracheobronchial tract

Toxic manifestations
• Nicotinic  Fasciculations of skeletal muscles
leading to paralysis
1. Monday = Mydriasis
2. Tuesday = Tachycardia
3. Wednesday = Weakness
4. Thursday = Hypertension
5. Friday = Fasciculations

Toxic manifestations
• CNS
1. Restlessness
2. Tremors
3. Convulsions
4. Ataxia
5. Respiratory arrest

Treatment
1. Termination of further exposure to the poison—
fresh air, wash the skin and mucous membranes
with soap and water, gastric lavage according to
need
2. Maintain patent airway, positive pressure
respiration if it is failing
3. Supportive measures—maintain BP, hydration,
control of convulsions with judicious use of
diazepam

Specific antidotes
1. Atropine  All cases of anti-ChE (carbamate or
organophosphate) poisoning must be promptly
given atropine 2 mg i.v. repeated every 10 min till
dryness of mouth or other signs of atropinization
appear (upto 200 mg has been administered in a
day). Continued treatment with maintenance
doses may be required for 1–2 weeks
2. Cholinesterase reactivators Pralidoxime is
injected i.v. slowly in a dose of 1–2 g (children
20–40 mg/kg) [Only in OP poisoning]

Atropine
Uses (ATROPA)
1. As mydriatic-cycloplegic in refraction error
testing, fundoscopy, iridocyclitis
2. Traveller’s diarrhea
3. Rapid onset mushroom poisoning
4. Organophosphorus poisoning
5. Preanaesthetic medication
6. Arrhythmias (brady-arrhythmias)

Adverse effects of Atropine
(DHATURA)
1. Dry mouth, difficulty in swallowing & speaking
2. Hot dry skin & hypotension
3. Accommodation paralysis (blurring of near vision)
4. Tachycardia
5. Urinary Retention & fecal retention (constipation)
6. Ataxia & acute congestive glaucoma may
precipitate
• “Dry as a bone, blind as a bat, red as a beet, and
mad as a hatter”

Dental implication of atropine
• Xerostomia caused by atropinic drugs can promote
dental caries and oral candidiasis

Treatment of atropine poisoning
1. If poison has been ingested, gastric lavage should
be done with tannic acid
2. Patient should be kept in a dark quiet room
3. Cold sponging or ice bags are applied to reduce
body temperature
4. Physostigmine 1–3 mg s.c. or i.v. antagonises
both central and peripheral effects
5. Other general measures (maintenance of blood
volume, assisted respiration, diazepam to control
convulsions) should be taken as appropriate

Contraindications of atropine
1. Individuals with a narrow iridocorneal angle—
may precipitate acute congestive glaucoma
2. Caution is advocated in elderly males with
prostatic hypertrophy—urinary retention can
occur

Interactions
1. Absorption of most drugs is slowed because
atropine delays gastric emptying. Extent of
digoxin and tetracycline absorption may be
increased
2. Antihistaminics, tricyclic antidepressants,
phenothiazines, disopyramide, pethidine have
anticholinergic property—additive side effects
occur with atropinic drugs

Uses of other anti-cholinergics
1. To relieve urinary frequency and urgency,
enuresis in children (Vasicoselective)
2. Bronchial asthma and COPD  Ipratropium
bromide and Tiotropium bromide
3. Parkinsonism  Central anticholinergics reduce
tremor and rigidity
4. Motion sickness  Hyoscine (severe case),
Dicyclomine (mild cases)