1) The document discusses various cholinergic agonists including natural alkaloids like muscarine, pilocarpine, and arecholine as well as synthetic alkaloids like oxotramorine and nicotine. 2) It also discusses various types of anticholinesterases that can be reversible like physostigmine or irreversible like organophosphorus compounds. 3) The effects of acetylcholine are discussed in various organ systems mediated through muscarinic and nicotinic receptors.

1. Dr. RAGHU PRASADA M S
MBBS,MD
ASSISTANT PROFESSOR
DEPT. OF PHARMACOLOGY
SSIMS & RC.
1

2. Muscarinic Agonists
Natural Alkaloids:
Muscarine
Pilocarpine
Arecholine
Synthetic Alkaloid:
Oxotramorine
Mainly Nicotinic Agonists
Natural Alkaloids:
Nicotine
Synthetic Alkaloids:
Dimethylphenylpiperazinium(DMPP)

3. Reversible
Tertiary amines
Physostigmine
Quaternary Ammonium compounds
Neostigmine
Pyridostigmine
Distigmine
Ambenonium
Demecarium
Tacrine
Miscelloneous Donepezil
Galantamine
Rivastigmine

4. Irreversible Anticholinesterases
(Organophosphorus Compounds)
Ecothiophate
2) War Gases:
Sarin
Tuban,
Soman
3) Insecticides:-
Parathion
Malathion
Diisopropyl Flurophosphate (DFP)
Tetramethyl Pyrophosphate (TMPP)
Octamethyl Pyrophosphotetra amide (OMPA)

6.  Central Nervous System (CNS) - Brain and spinal
cord
 Peripheral Nervous System (PNS) - Located outside
the brain & spinal cord Autonomic Nervous
System (ANS) & the somatic
 The PNS receives stimuli from the CNS & initiates
responses to the stimuli after it’s interpreted by the
brain

10. HEMICHOLIUM
VESAMICOL
BOTULINUM

14. Sites of Cholinergic Activity
-Preganglionic synapses of both sympathetic and parasympathetic ganglia
- Parasympathetic postganglionic neuroeffector junctions
- All somatic motor end plates on skeletal muscles
M2 M4 M5M3M1
Gi Go
Adenylyl cyclase
cAMP
Hyperpolarization (heart)
Cardiac inhibition
Antagonism of smooth
muscle relaxation
RECEPTOR
INTRACELLULAR
TRANSDUCER
ELECTRICAL
MECHANICAL
PHYSIOLOGICAL
RESPONSES
Gq
Phospholipase C
Diacyl-glycerol IP3
Depolarization
Smooth muscle contraction
Glandular secretion

15. Eyes: contraction of ciliary muscle and smooth muscle of the iris
sphincter (miosis) – aqueous humor outflow, drainage of the
anterior chamber
Cardiovascular: Bradycardia (possibly preceded by tachycardia),
vasodilation (all vascular beds including pulmonary and
coronary – M3) and hypotension, reduction of the
contraction strength (atrial and ventricular cells) diastolic
depolarization ,
Negative chronotropic effect (inhibition of adrenergic activation)
Negetive ionotropic effect-activation of SA node M2 receptor

16. GI - increases in tone, amplitude of contractions, and
peristaltic activity of the stomach and intestines,
enhances secretory activity of the gastrointestinal tract.
Urinary bladder - increase ureteral peristalsis, contract the
detrusor muscle of the urinary bladder, increase the
maximal voluntary voiding pressure, and decrease the
capacity of the bladder.
Respiratory system-brochoconstriction and increased
bronchial secretions
Other effects – Increased secretion from all glands that
receive parasympathetic innervation (salivary, lacrimal,
tracheobronchial, digestive and exocrine sweat glands)

17. CNS-there are complex stimulatory effects-ataxia,
behavioral disturbances and restlessness with tremors
and convulsions
Blood vessels-arteries have M3 receptors but no
innervationexagenous cholinomimetic  transient
but marked fall in blood pressuredue to
vasodilationendothelium release EDRF-Endothelium
Derived Relaxing Factors-NO
Other effects – Increased secretion from all glands that
receive parasympathetic innervation (salivary, lacrimal,
tracheobronchial, digestive and exocrine sweat glands)

18.  Homotropic receptor interaction
 Heterotropic receptor interaction

19. Is the neurotransmitter of the parasympathetic N.S and
cholinergic nerves, it is therapeutically of no importance
due to:
1. Multiplicity of actions.
2. Rapid inactivation by acetyl-cholinesterase.
3. Has both muscarinic and nicotinic activity.

20. Structurally related to ACH, has strong muscarinic
activity but no nicotinic actions.
It directly stimulates muscarinic receptors of the GIT
causing increase intestinal motility and tone,
It also stimulates detrusor muscle of the bladder
causing urine expulsion.
Clinical uses: Atonic bladder stimulation such as in
postpartum and post operative non obstructive
urine retention.
Side effects: Sweating, salivation, flushing,
hypotension, nausea, abdominal pain, diarrhea, and
bronchospasm.

21. Has both muscarinic and nicotinic actions, has
strong effect on CVS and GIT, it causes release of
epinephrine from adrenal medulla by its nicotinic
action, using it locally on the eye cause Miosis.
Clinical uses: Rarely used because of high potency
and long duration of action except in the eye to
cause Miosis and to decrease intraocular pressure.

22. Mainly used in ophthalmology, it exhibit muscarinic
activity, it produces rapid miosis and contraction of the
ciliary muscle.
Clinical uses; It is the drug of choice in the emergency
lowering of inrtra-ocular pressure in case of glaucoma.
Side effects:
It can enter the brain and cause CNS disturbances, it
stimulate profuse sweating and salivation.
painful spasm of accommodation for near vision.

23. - sol. 1%, 2%, 4%
- in open angle glаucoma
Applied to the eye, it
penetrates cornea and
promptly causes
miosis, ciliary muscle contra-
ction, and fall in intraoccular
tension (< 22 mm) lasting 4-8 h.
Systemic effects:
sweating, salivation
Cardiovascular effects: in small doses – fall in BP, but in high
doses elicits rise in BP and tachycardia, probably due to
ganglionic stimulation (through muscarinic receptors

25. 50
100
150
200
A B C D1 min
M- и N-effects of ACh
Bloodpressure[mmHg]
ACh
2 mcg i.v.
ACh
50 mcg
ACh
50 mcg
ACh
5 mg
M-
effect
M-
effect
N-
effect
Atropine
2 mg i.v.