CHOLINERGIC DRUGS

Parasympathomimetic /
cholinomimetic drugs (s):
 Parasympathomimetic /
cholinomimetic drugs (s)
•Neuron with acetylcholine (Ach) as neurotransmitter.
•Drug that mimic the action of acetylcholine.
•Also called cholinomimetic, cholinergic agonist or
cholinergic drugs.
Produce actions similar to that of Ach, either by-
1. Binding directly to chlolinoreceptors. e.g. Cholinesters,
cholinomimetic alkaloids.
OR
2. Increasing availability of Ach at these sites. e.g.
Anticholinesterase
 5 sites of action
Synthesis
1. Synthesis of
Ach
2. Storage
3. Release
4. Receptor
interaction
5. Inactivation
6. Recycling
 Acetylcholine actions
Acetylcholine produce actions, either by-

Binding directly to chlolinoreceptors. e.g.

· Muscarinic - M1 M2 M3 M4 M5.
· Nicotinic – NM NN.
or
Increasing availability of Ach at these sites.
e.g. Cholinoreceptive tissue
 Effector response
Ach (neurotransmitter) binding to receptor, translate
the extracellular signal into a response that may be
further propagated or amplified within the cell.
Cholinoreceptor >> receptor responsive to
neurotransmitter Ach.
· Muscarinic - M1 M2 M3 M4 M5.
· Nicotinic – NM NN.
Cholinoreceptive tissue >> Tissue responsive to
neurotransmitter Ach.
 CHOLINERGIC DRUGS
These are the drugs which produce actions similar to
that of Ach, either by-
Binding directly to chlolinireceptors. e.g.
Cholinesters, cholinomimetic alkaloids.
or
Increasing availability of Ach at these sites. e.g.
Cholinoreceptive tissue.
Anticholinesterase
 Muscarinic –
Receptor type, location and action
Rec Location Action

M1 –gastric parietal cell,

Gastric HCL acid secretion
- autonomic ganglia CNS

M2 – heart, Bradicardia
--autoreceptor in nerve endings. Decrease Ach secretion
– visceral smooth muscle
-visceral smooth muscle contraction
M3 - exocrine gland - exocrine gland secretion
-endothelium - NO > EDRF mediated
vasodilatation

M 4 M5 . – not well defined.

 Nicotinic –
Receptor type, location and action
Receptr Location Action
nomenc

NM – neuromuscular Skeletal muscle

junction contraction

NN - autonomic Transmission in
ganglia ganglia
 Classification of Cholinomimetics
1. DIRECT-ACTING 2. INDIRECT-ACTING
(receptor agonists) (cholinesterase inhibitors)

Choline Cholinomim Reversible Irreversible

esters etic alkaloids Carbamyl Organophosp
inhibitorshates (OPC)
Acetylcholin Nicotine* PhysostigminEchothiophat
e* Pilocarpine* e* e (N+)
Methacholin Muscarine Neostigmine* Sarin*
e* (N )
+ Malathion +

Diazinon+
Bethanechol Pyridostigmi
* ne (N+)
Carbachol *
 Actions of acetylcholine (prototype) A.
Muscarinic –
1. Visceral smooth muscle: Contraction of-
• GIT- peristalsis increased >> abdominal cramp and
diarrhoea.
• Urinary bladder- voiding of bladder > urination
2. Exocrine gland : increased secretion of all gland
•Lacrimation, salivation, increased HCL secretion,
•Sweating, increased Tracheobronchial secretion.
3. Eye >> miosis, increased outflow, reduction of IOP.
4. Heart: bradycardia
Muscarinic action
SLUDGE
Salivation
Lacrimation
Urination
Gastrointestinalmotility
Diaphoresis
Emesis
 Actions of acetylcholine (prototype)
Nicotinic
1. Skeletal muscle – contraction, twitching and
fasciculation.

2. Autonomic ganglia – stimulates both the

sympathetic and parasympathetic autonomic
ganglia
 Anticholinesterase drugs
Indirect-acting
Drugs: Carbonyl inhibitors and Organophosphates
(OPC). .
Inhibitors of ACh metabolism: Inhibit
acetylcholinesterase enzyme.
Accumulation of acetylcholine in synaptic cleft --
Mechanism of
Anticholinesterase
action
->> increases local
concentrations of
Ach. effect of ACh is
amplified,
- Leading to
muscarinic or
nicotinic effects,
- effect can be
therapeutic or life
threatening
 OPC (Anticholinesterase) poisoning
DUMBELS:
D –Diarrhoea
U – Urination
M –Miosis
B –Bronchoconstriction
E – Excitation (sk muscle, CNS)
L - Lacrimation
S – Salivation, sweating
CNS effects: anxiety, Headache,
- Tremor, seizures, depression, -death
Treatment of OPC poisoning
The effects of acetylcholine can be blocked
by
Atropine, in part, to counteract the
muscarinic action as a treatment for SLUDGE

AND
Pralidoxime- reactivates AchE. In some
cases, by the use of pyridinium oximes.
 Major uses of Cholinomimetic Drugs
1. Pilocarpine in treatment of open or narrow angle glaucoma as
miotic.
2. Physostigmine in treatment of
• Glaucoma- reduce intraocular pressure
• An antidote in atropine poisoning.
3. Neostigmine in treatment of
• reversal of neuromuscular blockade as antidote for
tubocurarine, and Myasthenia gravis.
4. Bethanicol/ in treatment of postoperative paralytic ileus/ urinary
retention
5. Tacrine, rivastigmine (cerebro-selective anti-ChEs) in Alzheimer’s
disease.
6. Isoflurophate in treatment of open angle glaucoma.