This document provides an introduction to autonomic pharmacology and discusses cholinergic and anticholinergic drugs. It describes the autonomic nervous system, including its sympathetic and parasympathetic divisions. Cholinergic transmission is mediated by acetylcholine and hydrolyzed by cholinesterase. Cholinergic drugs such as acetylcholine act on muscarinic and nicotinic receptors to affect various organs. Anticholinesterases inhibit cholinesterase and amplify the effects of endogenous acetylcholine. They are used to treat conditions like glaucoma, myasthenia gravis, and postoperative ileus. Their overdose requires supportive care and antidotes like atropine.

1. Introduction to autonomic
pharmacology, Cholinergics and
anticholinergics
Dr. S. Parasuraman
Associate Professor, Faculty of Pharmacy,
AIMST University, Malaysia.
Introduction to Pharmacology - for allied health sciences

2. Nervous System
Central nervous
system
Peripheral
nervous system
Afferent division Efferent division
Somatic system Autonomic nervous
systemSympathetic
(thorcolumbar outflow)
Come from the thoracic
and lumbar regions (T1
to L2/3) of the spinal
cord
Parasympathetic
(craniosacral outflow)
Come from brainstem
(Cranial Nerves III, VII, IX, X)
or the sacral spinal cord (S2,
S3, S4)
Enteric nervous
system

3. Spinal nerves
• There are 31 pairs of
spinal nerves
– 8 cervical
– 12 thoracic
– 5 lumbar
– 5 sacral
– 1 coccygeal
The human spinal column is made
up of 33 bones.
• 7 - cervical region
• 12 - thoracic region
• 5 - lumbar region
• 5 - sacral region
• 4 - coccygeal region

4. Autonomic Nervous System
• The autonomic nervous system (ANS) is a complex set
of neurons that mediate internal homeostasis
without conscious intervention or voluntary control.
• The ANS maintains blood pressure, regulates the rate
of breathing, influences digestion, urination, and
modulates sexual arousal.
• There are two main branches to the ANS – the
sympathetic nervous system and the
parasympathetic nervous system.
The effects of autonomic control are rapid and essential for homeostasis

5. Motor neuron pathways in the (a) somatic nervous system and (b) autonomic
nervous system

6. Structure of the sympathetic division of the autonomic nervous system
Trachea and bronchi: Bronchodilation
Liver: Glycogen glucose conversion increased
Iris muscle: Pupil dilated
Blood vessels in heart : Vasoconstriction
Heart: Rate and force of contraction
increased
Salivary glands: Secretion inhibited
Stomach: Peristalsis reduced
Sphincters closed
Intestines: Peristalsis and tone decreased
Vasoconstriction
Kidney: Urine secretion decreased
Bladder: Smooth muscle wall relaxed
Sphincter closed
Sex organs: Generally Vasoconstriction

7. Structure of the parasympathetic division of the autonomic nervous system
Trachea and bronchi: Bronchoconstriction
Liver: Blood vessels dilated
Secretion of bile increased
Iris muscle: Pupil constricted
Heart: Rate and force of contraction
decreased
Salivary glands: Secretion increased
Stomach: Secretion of gastric juice and
peristalsis increased
Intestines: Digestion and absorption
increased
Kidney: Urine secretion increased
Bladder: Muscle of wall contracted
Sphincters relaxed
Sex organs: Male: erection;
Female: variable

8. Summary of the neurotransmitters released

9. Autonomic Motor Pathways
Preganglionic Neurons
• Autonomic Ganglia
– There are two major groups of autonomic ganglia
• sympathetic ganglia
• parasympathetic ganglia
• Sympathetic Ganglia:
– The sympathetic ganglia are the sites of synapses between
sympathetic preganglionic and postganglionic neurons.
– There are two major types of sympathetic ganglia:
• sympathetic trunk ganglia
• prevertebral ganglia

10. Autonomic Motor Pathways
Preganglionic Neurons
• Autonomic Ganglia
– There are two major groups of autonomic ganglia
• sympathetic ganglia
• parasympathetic ganglia
• parasympathetic ganglia:
– Preganglionic axons of the parasympathetic division
synapse with postganglionic neurons in terminal
(intramural) ganglia. They are the ciliary ganglion,
pterygopalatine ganglion, submandibular ganglion, and otic
ganglion

11. Autonomic Motor Pathways
Postganglionic Neurons
• A single sympathetic preganglionic fiber has
many axon collaterals (branches) and may
synapse with 20 or more postganglionic
neurons.

12. Autonomic Motor Pathways
Relative lengths of neurons

13. ANS Neurotransmitters and Receptors
ANS Receptor Receptor Sub-type
Parasympathetic
nervous system
Nicotinic cholinergic
receptors
Nn, Nm
Muscarinic cholinergic
receptors
M1, M2, M3
Sympathetic
nervous system
α adrenergic receptor α1, α2
β adrenergic receptor β1, β2, β3
Sympathetic nervous system Parasympathetic nervous system

14. Functions of the autonomic nervous system
• Sympathetic stimulation prepares the body to
deal with exciting and stressful situations, e.g.
strengthening its defences in danger.
sympathetic stimulation mobilises the body for
'fight or flight'.
• Parasympathetic stimulation has a tendency
to slow down body processes except digestion
and absorption of food and the functions of
the genitourinary systems. Its general effect is
that of a 'peace maker' allowing restoration
processes to occur quietly and peacefully.

15. Cholinergic System and Drugs

16. Cholinergic System
• Cholinergic transmission
– Acetylcholine (ACh) is a major neurohumoral transmitter at
autonomic, somatic as well as central sites.
• Synthesis, storage and destruction of Ach
Ach is synthesized locally in the cholinergic nerve endings by the following pathway

17. Cholinergic System
• Cholinesterase
Immediately after release, Ach is hydrolyzed by the
enzyme cholinesterase and choline is recycled.

18. Cholinergic System
• Sites of cholinergic transmission and type of
receptor involved

19. Cholinergic Drugs
(Cholinomimetic, Parasympathomimetic)
• These are drugs which produce actions similar to that
of ACh, either by directly interacting with cholinergic
receptors (cholinergic agonists) or by increasing
availability of ACh at these sites
(anticholinesterases).

20. Cholinergic Drugs
(Cholinomimetic, Parasympathomimetic)
Cholinergic
drugs
Cholinergic
agonists
Choline esters
E.g.: Acetylcholine, Methacholine,
Carbachol, Bethanechol
Alkaloids
E.g.: Muscarine, Pilocarpine, Arecoline
Anticholinest
erases
Reversible
Carbamates
E.g.: Physostigmine,
Neostigmine
Acridine
E.g.: Tacrine
Irreversible
Organophosphates
E.g.: Dyflos (DFP),
Malathion
Carbamates
E.g.: Carbaryl,
Propoxur

21. Pharmacological actions of Cholinergic Drugs
• ACh as prototype
Organ/ System Muscarinic actions
Heart • Cardiac muscarinic receptors are of the M2 subtype
• ACh hyperpolarizes the SA nodal Cells - decreases
heart rate -bradycardia
Blood vessels • Muscarinic (M3) receptors are present on vascular
endothelial cells
• All blood vessels are dilated, Fall in BP and flushing
Smooth
muscle
• Smooth muscle in most organs is contracted (mainly
through M3 receptors)
• Bronchial muscles constrict
Glands • Secretion from all parasympathetically innervated
glands is increased via M3 and some M2 receptors
Eye • Contraction of circular muscle of iris - miosis

22. Pharmacological actions of Cholinergic Drugs
• ACh as prototype
Organ/ System Nicotinic actions
Autonomic ganglia • Both sympathetic and parasympathetic ganglia
are stimulated
Skeletal muscles • i.v. injection – no effect
• Intra-arterial injection - can cause twitching and
fasciculations
• Iontophoretic application causes contraction of
the fibre
CNS actions • ACh injected i.v. does not penetrate blood-
brain barrier and no central effects
• direct injection into the brain produces arousal
response followed by depression

23. Pharmacological actions of Cholinergic Drugs
• ACh as prototype

24. Uses Cholinergic Drugs
• ACh is not used because of evanescent and
nonselective action.
• Methacholine was occasionally used to terminate
paroxysmal supraventricular tachycardia but is
obsolete now.
• Bethanechol has been used in postoperative/
postpartum nonobstructive urinary retention,
neurogenic bladder to promote urination.
• Pilocarpine: a third-line drug in open angle glaucoma.
• Muscarine, Arecoline: Not used therapeutically

25. Pharmacological actions of anticholinesterases
• P’cological actions of anticholinesterases
• The actions of anti-ChEs are due to amplification of
endogenous ACh.
• Lipid-soluble agents (physostigmine) have more
marked muscarinic and CNS effects.
• Lipid-insoluble agents (neostigmine) produce more
marked effect on the skeletal muscles.

26. Pharmacological actions of anticholinesterases
• P’cological actions of anticholinesterases
Organ/ System Pharmacological actions
Ganglia • Anti-ChEs stimulate ganglia primarily through
muscarinic receptors present there.
• High dose: depolarization of the ganglionic nicotinic
receptors and blockade of transmission
CVS • Cardiovascular effects are complex. Whereas
muscarinic action would produce bradycardia and
hypotension, ganglionic stimulation would tend to
increase heart rate and BP.
• overall effects are often unpredictable and depend
on the agent and its dose.

27. Pharmacological actions of anticholinesterases
• P’cological actions of anticholinesterases
Organ/ System Pharmacological actions
Skeletal muscles • Force of contraction in partially curarized and
myasthenic muscles is increased.
• Higher doses cause persistent depolarization of
endplates resulting in blockade of neuromuscular
transmission weakness and paralysis.
CNS actions • Cognitive function may be improved in Alzheimer’s
disease.
• higher doses produce excitement, mental
confusion, disorientation, tremors and convulsions
followed by coma.
Other effects • Stimulation of smooth muscles and glands of the
gastrointestinal, respiratory & urinary tracts

28. Uses Cholinergic Drugs (anticholinesterases)
• As miotic: In glaucoma, anticholinesterases
(pilocarpine) reduce the intro ocular tension (i.o.t.)
by increase the tone of ciliary muscle and sphincter
pupillae.
• Myasthenia gravis: Neostigmine and its congeners
improve muscle contraction by allowing Ach released
from prejunctional endings to accumulate and act on
the receptors.
• Postoperative paralytic ileus/urinary retention: This
may be relieved by 0.5–1 mg s.c. neostigmine.

29. Uses Cholinergic Drugs (anticholinesterases)
• Postoperative decurarization: Neostigmine 0.5–2.0
mg (30–50 µg/kg) i.v., preceded by atropine or
glycopyrrolate 10µg/kg to block muscarinic effects.
• Cobra bite: Neostigmine + atropine prevent
respiratory paralysis induced by cobra venom.
• Belladonna poisoning: Physostigmine 0.5–2 mg i.v.
repeated as required is the specific antidote for
poisoning with belladonna or other anticholinergics.
• Alzheimer’s disease: The relatively cerebroselective
anti-ChEs, rivastigmine, donepezil and galantamine
are now commonly used.

30. Treatment for anticholinesterase poisoning
• Anticholinesterases are easily available and
extensively used as agricultural and household
insecticides; accidental as well as suicidal and
homicidal poisoning is common.
• Treatment
– Maintain patent airway
– Supportive measures—maintain BP, hydration, control of
convulsions
– Specific antidotes: Atropine, Cholinesterase reactivators
(Pralidoxime)

31. Thank you