Cholinergic
Drugs
Content
ANS
•
Cholinergic
drugs
•
Pharmacology
of acetylcholine
•
Organophosphorous
poisoning and its treatment
Intended Learning Outcomes
At the
end of this lecture, student will be able to
•
List the
cholinergic drugs
•
Explain
the pharmacology of acetylcholine
•
Describe
pharmacokinetic of Ach
•
Explain
organophophorous poisoning
•
Describe
treatment of poisoning
Cholinergic Drugs (Parasympathomimetics)
•
+
effector cells innervated by cholinergic nerves
•
Ester of choline
–
Acetylcholine,
methacholine, carbachol, bethanechol
•
Cholinomimetic alkaloids
–
Pilocarpine,
muscarine, arecholine
•
Choline esterase inhibitors (Anticholine
esterase)
–
Physostigmine,
neostigmine, organophosphorous compounds
Pharmacological Actions of Acetylcholine
CVS
•
Heart
–
+ vagus
nerve
–
Depress
SA Node: negative chronotropic
–
Decrease
FOC: negative Inotropic
–
May
cause AV block
–
Increase
CV
•
Blood vessels
–
Dilate
skin, mucous membrane blood vessels
–
M3 – R:
release NO
–
Dilates
coronary arteries
–
Doubtful
effect: cerebral, pulmonary vessels
–
IV: transient
flushing, sense of warmth in skin, throbbing headache
–
Decrease
PR – BP Falls
Smooth muscle
• GIT:
increase tone and peristalsis
• Gall
bladder: Contraction
• Bladder:
Detrusor muscle contraction, trigonal sphincter relaxation
• Bronchial
smooth muscle: constriction, bronchospasm
• Ureter:
usually contraction
• Uterus:
inconsistent response
Secretions
• Increase
gastric, intestinal, pancreatic, bronchial, salivary, lacrimal, nasopharyngeal
• Increase
bronchial secretion: accompanied by bronchospasm
• May
result in cough and dyspnea
• Salivary:
profuse and watery
• Sweat
glands: increase sweating
Eye
• Instillation
– no effect
• Intracarotid
injection: miosis
• Contraction
of circular muscle fibers
• Decrease
IOP
• Increase
the drainage of ocular fluid through canal of Schlemm
• Contraction
of ciliary muscle
• Relaxation
of suspensory ligaments
• Lens
bulge into anterior chamber
• Increase
thickness, decrease focal length
• Vision
fixed for short distance
• Spasm
of accomodation
Autonomic ganglia
• Ach
+ ganglia
• Post
ganglionic site: Increase NA/ Ach
• NA: BP- Peripheral vasoconstriction
• Large
dose: Adrenal medulla +
• Sustained
increase in BP
Myoneural Junction
• Contraction
of skeletal muscle
• High
conc: paralysis by persistent depolarisation
Miscellaneous
• Essential
for normal behaviour and cognition
• Does
not cross BBB
Uses
• Extreme
transient action
• Not
used in clinical practice
• Substitutes
: Effective orally
• More
selective in actions
Cholinergic Drugs
Cholinomimetic alkaloids
• Pilocarpine
(P. microphyllus, P. jaborandi)
• Muscarine
(Amanita muscaria)
• Arecholine
(Areca catechu)
• Cevimeline
– M3
agonist
– Incerase
salivary and lacrimal secretion
– Used
in dry mouth
Choline esterase inhibitors (Anticholine esterases)
• Inhibits
true and peudo choline esterase
• Prevent
inactivation of Ach
Reversible choline esterase inhibitors
• Natural:
Physostigmine
• Synthetic:
Neostigmine, pyridostigmine, ambenonium, demecaium, edrophonium, tacrine,
rivastigmine
Irreversible choline esterase inhibitors
• OPC
• Useful:
Di isopropyl fluorophosphate, metrifonate, echothiophate
• Insecticides:
Fenthion, malathion, sumithion, monocrotophos, octamethyl pyrophosphotetramide
Uses of reversible Anti ChE
• Glaucoma
• For
decurarisation, Curare poisoning
• MG
• GIT:
Post-operative paralytic ileus
• Urinary
retention (Rare)
• AD
• Snake
venom poisoning
Irreversible Anti ChE
• Absorbed
by all the routes
• Cross
BBB
• Glaucoma:
echothiophate
• Worm
infestation: dichlorovos, dichlorofos (Not used)
• Toxicological
importance
OPC Poisoning
Muscarinic effects
• Eyes:
Miosis, spasm of accomodation, head ache, conjunctival hyperemia
• inhalation: bronchospasm, cough, increases
secretions, tightness in chest
• Ingestion:
anorexia, nausea, vomitting, abdominal cramps, tenesmus and diarrhoea
• Severe
bronchospasm, pulm. edema – fatal
Nicotinic effects
• Fasciculations,
twitching, generalised weakness, depolarisation type paralysis
Central effects
• Giddiness,
anxiety, confusion, ataxia, hypotension, respiratory depression, convulsion,
coma
• Death
– due to respiratory paralysis
Neurotoxic effects
• Demyelination
of nerve tracts in CNS & PNS
• Permanent
functional derrangements
• Not
related to ChE inhibition
• Weakness,
fatiguability, twitching, loss of tendon reflexes
Treatment
of acute OPC Poisoning
• Remove
soiled clothes
• Wash
soiled skin/ eyes
• Nurse
in prone position
• Clear
mouth, throat
• Insert
airway/ intubate
• Gastric
lavage
• Atropine
in sufficient qty.
• ChE
activator: Pralidoxime (1-2 g)
• Supportive
measures: Oxygen, shock treatment
• Convulsion:
Diazepam
• Vigilance
for delayed toxicity
• Note:
Mouth to mouth respiration to be avoided
Summary
• Cholinergic
drugs stimulate effector cells innervated by cholinergic nerves
• Cholinergic
drugs: Ester of choline, Cholinomimetic alkaloids, Choline esterase inhibitors
(Anticholine esterase)
• Acetylcholine
actions – mostly inhibitory; stimulatory on digestion and exocrine glands
• Pralidoxime
is the antidote for OPC poisoning
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