Cholinergic Drugs – Pharmacology B. Pharma 5th Semester PDF Notes

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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