CHOLINERGIC
AGONISTS
WHAT ARE
CHOLINERGIC AGONIST
Cholinergic agonists are drugs that
mimic or potentiate the actions of
acethycholine
WHAT ARE THE TWO MAJOR
FAMILIES OF CHOLINERGIC
RECEPTORS
1. Muscarinic- this receptor family
earned its name because it was first
identified using muscarine, an
alkaloid found in certain poisonous
mushroom.
2. Nicotine
The muscarinic receptors, namely, M1 to M5.
They are found in ganglia, smooth muscle,
myocardium, secretory glands and the CNS.
The nicotinic receptors.
1. Neuronal nicotinic (Nn) located in autonomic
ganglia
2. Muscular nicotinic(NM), located in the
neuromuscular junction
WHAT TYPES OF CHOLINERGIC
AGONISTS ARE AVAILABLE FOR
CLINICAL USE?
Cholinergic agonists can be divided into
two major groups:
1. Direct-acting agonists chemically bind with
and activate muscarinic and nicotinic receptors in the
body.
2. Indirect-acting agonists inhibit the enzyme
acethycholinesterase and therefore increase the
concentration of acethylcholine within the
synapse
DIRECT ACTING
Acetyl choline
Bethanecol
Carbachol
methacholine
pilocarpine
Nicotine
INDIRECT ACTING ( reversible)
Ambenomium
Donepezil
Edrophonium
Galantamine
Neostigmine
Physostigmine
Pyridostigmine
Rivastigmine
tacrine
INDIRECT ACTING (irreversible)
Ecothiophate
Isoflurophate
PARATHION
MALATHION
REACTIVATION OF
ACETYLCHOLINEESTERASE
pralidoxime ( PAM )
CHOLINERGIC AGONISTS
Neurotransmission at cholinergic neurons
Synthesis, storage, release, and binding of
acetyl choline.
Synthesis—choline cotransport system
involving sodium.
Storage in vesicles.—contains ach & ATP.
Release—opening of ca channels.
Binding—ach binds to either of two
receptors muscarinic or nicotinic.
Degradation-acetylcholine esterace
cleaves acetyl choline to choline and
acetate in synaptic cleft.
Recycling- choline recaptured by
sodium and gets transported back to the
neuron.
Muscarinic receptors – decreased HR,
increased glandular secretory activity,
stimulation of smooth muscle
contractions.M1,M2,M3,M4 & M5
Nicotinic receptors – increased B.P
(peripheral vasoconstriction),
contraction of skeletal muscle. NM, NN.
Location of muscarinic receptors
Ganglia of pns
Autonomic effector organs—heart, smooth
muscle, brain and exocrine glands.
Location of nicotinic receptors
Cns, adrenal medulla, neuro muscular
junction.
Cholinergic agonists
Direct acting
Indirect acting
Direct acting
Choline esters
Acetylcholine
Bethanechol
Carbachol
Methacholine
Alkaloids
Muscarine
Pilocarpine
Acetyl choline —both muscarinic and
nicotinic activities.
Actions---CVS: decrease in heart rate &
cardiac output. Mimics effects of vagal
stimulation.
Decrease in blood pressure—due to
vasodilatation.---rise in intracellular
calcium.
GIT: INCREASES MOTILITY OF THE GI
AND BLADDER
PULMONARY SYSTEM: INCREASES
SECRETION OF THE BRONCHIOLES
THE EYE- IT CAUSES CONSTICTION OF
THE PUPILLARY SPHICTER MUSCLE,
WHICH CAUSES MIOSIS AND
ACCOMODATION.
PNS: contraction of skeletal muscle
CNS it affects neurotransmission
Endocrine: release epinephrine from the
adrenal medulla and it stimulates sweat gland
secretions
ACH – both muscarinic (M) and nicotinic
(N) receptors
Bethanechol – strong M and low or no
N
Carbachol – both (Strong N)
Pilocarpine – more M
What are the clinical
indications
Acetylcholine is used to achieve miosis
during ophthalmic surgery. In general, it is
rarely used because it has widespread
effects and is so rapidly hydrolyzed by
acetylcholinesterase.
WHAT ARE THE
ADVERSE REACTIONS
The adverse effects result from excessive generalized
cholinergic stimulation. They include:
Diarrhea and decreased blood pressure
Urination
Miosis
Bronchoconstriction
Excitation of skeletal muscle
Lacrimation
Salivation and sweating
DUMBELS
THERAPEUTIC USES
Bethanechol increases intestinal
motility, especially after surgery.
Because this drug also stimulates the
detrusor muscle of the bladder, it is also used
to treat urinary retention.
BBB- Bethanechol stimulates the
Bladder and Bowel.
Carbachol
This drug is rarely used in the clinics, but it can
be used for GLAUCOMA and to stimulate miosis
during ophthalmic surgery
Pilocarpine
An alkaloid.
Its physiologic actions
cause miosis and contraction of the ciliary
muscle,
decreases heart rate,
causes bronchial smooth muscle contraction,
increases secretions from salivary , lacrimal
and sweat glands.
Clinical use
Pilocarpine is good miosis and opening the
trabecular meshwork around the canal of schlemm.
Therefore is used treatment of glaucoma
Adverse effects? Pilocarpine is able to enter the
brain and causes CNS disturbances such as
hallucinations and convulsions, along with
generalized cholinergic stimulation
Methacholine
Methacholine used for diagnostic
purposes.
testing for bronchial hyper reactivity and
asthma
Major contraindication to the use of
muscarinic agonists
Asthma
Choline esters (muscarinic agonists) can
produce bronchoconstriction. In the
predisposed patient, an asthmatic attack may
be induced.
Hyperthyroidism
Choline esters (muscarinic agonists) can
induce atrial fibrillation in hyperthyroid
patients.
Peptic ulcer
Choline esters (muscarinic agonists), by increasing gastric
acid secretion, may exacerbate ulcer symptoms.
Coronary vascular disease
Choline esters (muscarinic agonists), as a result of their
hypotensive effects, can further compromise coronary blood
flow.
Adverse Effects:
Muscarinic Agonists
salivation
diaphoresis
colic
GI hyperactivity
headache
loss of accommodation
Indirect acting
thru enzyme
Reversible inhibitors
Irreversible
inhibitors
1. Isoflurophate
2. Echothiophate
3. Parathion
4. Edrophonium
5. Physostigmine
6. Neostigmine
How do they work?
By inhibiting the enzyme acetylcholinesterase which
is responsible for the hydrolysis of
acetylcholine.
Neuronal response to acetylcholine is therefore
enhanced.
Which indirect- acting cholinergic agonists have the
ability to irreversibly inhibit acetylcholinesterase?
Only the organophosphates
( isoflurophate, echothiophate and parathion)
irreversibly inhibit acetylcholinesterase
Reversible" Anticholinesterases Used
Clinically
Edrophonium
Diagnosis test for myasthenia gravis
Physostigmine - Used in treatment of
glaucoma, antidote in atropine overdose
Neostigmine
Pyridostigmine: use for treatment of ileus,
urinary retention, myastenia gravis
Demecarium
Ambenonium - Used in treatment of
myasthenia gravis
Physostigmine
Actions – muscarinic and nicotinic
actions.
Miosis and spasm of accomodation.
Decreases intraocular pressure
High doses can cause convulsions
Neostigmine
Has a quarternary nitrogen. there fore it
does not enter the cns.
Use – antidote for tubocurarine &
treatment of myasthenia gravis.
Acetylcholinesterase Inhibitors
("Irreversible")
Soman
Parathion
Malathion
Isoflurophate
Echothiophate
treatment of glaucoma.
Note used as insecticides
Organo phosphate
poisoning
Reactivation of acetylcholine
esterase
Pralidoxime (PAM)
(Pyridine – 2 aldoxime chloride)
Drugs affecting the release:
· Drugs which increase Ach release (mainly venom
toxins)
· b bungarotoxin
· Banded krait venom
· Black widow spider venom
· These toxins cause a massive release of Ach which
results in fasciculations of muscle
followed by paralysis as all of the Ach is drained from
the nerve terminal
Drugs which decrease Ach
release
· Botulinum toxin
· Produced by the Clostridium botulinum
· This bacterium lives in unsterilised canned
foods.
Drug that interfere with the synthesis
Choline uptake inhibition
· Hemicholinium
Prepare botox
Trigeminal neuralgia
Bio weapon—1 pound---entire human population
Glaucoma

a disease of the eye marked by increased
pressure within the eyeball that can result in
damage to the optic disk and gradual loss of
vision.
Myasthenia gravis

a disease characterized by progressive weakness
and exhaustibility of voluntary muscles without
atrophy or sensory disturbance and caused by an
autoimmune attack on acetylcholine receptors at
neuromuscular junctions.