This document discusses various cholinomimetic drugs that act directly or indirectly on acetylcholine receptors. Direct acting drugs such as carbachol, methacholine and pilocarpine mimic acetylcholine, while indirect acting drugs like neostigmine and pyridostigmine inhibit the acetylcholinesterase enzyme. The document also summarizes the pharmacological effects, therapeutic uses, and side effects of specific cholinomimetic drugs including atropine, homatropine, propantheline, neostigmine and pilocarpine.
introduction ,classification of cholinergic receptor ,and its function ,anti cholinergic agents -atropine and its pharmacology ,semi synthetic and synthetic atropine substitutes
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introduction ,classification of cholinergic receptor ,and its function ,anti cholinergic agents -atropine and its pharmacology ,semi synthetic and synthetic atropine substitutes
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TESDA TM1 REVIEWER FOR NATIONAL ASSESSMENT WRITTEN AND ORAL QUESTIONS WITH A...
Cholinergic_agonist_antagonist
1. Two types
•Direct acting Cholinomimetics: Mimics the function
of acetylcholine
•Indirect acting cholinomimetics : Inhibits the acetyl
cholinesterase enzyme
3. Pharmacological Effect Pharmacokinetics Adverse effect
•Muscarinic action
predominates
•Profound effect on CVS
and GIT
•Cause miosis
•Sufficiently absorbed from
GIT
•Early onset of action
•Purgation occurs within 20
minutes
•Duration of action : 4-8 hrs
after topical administration.
24 hrs for intraocular
administration
Salivation ,sweating
and abdominal pain
Hypotension
Bronchoconstriction
Purgation
Urination
Tremors
Carbachol
4. Therapeutic use Antidote Contraindication Dose rate
•To treat colic in
horse
•Ruminal stasis or
impaction in cattle
•Post-operative
intestinal atony
•Retention of urine or
uterine disorder
•Used as miotic agent
Atropine ,
epinephrine
Pregnant animals
Should not used by IM
or IV
•Cattle and horses:
1-2 mg ,S/C , May
be repeated at 30-60
min
•Sheep: 0.1-0.2 mg
S/c
5. Pharmacological Effect Pharmacokinetics Adverse Effect
•Pure Muscarinic agent with no
or negligible nicotinic action
•More prominent action on CVS
than GIT and other system
•Cause negative inotropic and
chronotropic effect and
generalised vasodilation
•Administered orally but
is poorly absorbed
•Slowly metabolized by
acetylcholinesterase at the
rate of 1/3 rd of Ach
•Hypotension
•Loss of
consciousness
•Nausea
•Vomiting
Methacoline
6. Therapeutic use Antidote Contraindication Dose rate
•To diagnose bronchial
hyperreactivity in condition
like Asthma and Chronic
obstructive Pulmonary
disease.
•To stimulate paroxysmal
atrial tachycardia
•Rarely used in veterinary
practice
Atropine Contradicted in stomach
ulcers,high blood
pressure,liver disease
7. Pharmacological Effect Pharmacokinetics Adverse effect
•More selective action on
muscarinic receptors on
exocrine gland than other
tissues
•Produces rapid miosis and
contraction of ciliary m/s
•Small dose cause fall in
BP
•High dose elicit rise in BP
•Augments GI motility
•Enhances tone and
motility of uterus ,UB ,gall
bladder and biliary ducts
•Systemic
administration is not
available in animals
•Produces miosis within
15 minute
•After IV administration
can enter Brain and
cause CNS
disturbances.
At high doses causes
muscarinic sign such as colic
,dairrhoea ,sweating
,salivation
,bronchoconstriction hypo-
tension and bradycardia
Local irritation may occur
Pilocarpine
8. Therapeutic uses Antidote Contraindication Dose rate
•Choice in emergency
lowering of intraocular
pressure of both narrow
and wide angle glaucoma
•To improve tear secretion
•To treat Xerostomia
•To control mydriasis and
cycloplegia
•Atropine •Contraindicated in
heart failure
,spasmodic colic ,d/s
of respiratory tract
and during gestation
•For glaucoma:
All species: 0.5-2%
sol^n , 3-4 times
daily for instillation
into conjuctival sac
•To improve tear
secretion: 1 or 2
drops of 1%
9. Pharmacological Effects Pharmacokinetics Adverse Effect
•Cholinomimetics activities
similar to Pilocarpine but is more
potent and possesses nicotinic
and CNS stimulation as well
•Stimulates exocrine secretions
of salivary ,digestive and
respiratory gland
•Depress heart rate ,BP and may
produces bronchoconstriction
•Contracts UB and increase
peristaltic movement of GIT
Activates muscarinic
receptors of
cholinergically
innervated effector cells
Contraction of urinary
bladder
Depress heart rate and
blood pressure
•Similar to Pilocarpine
•Stimulation of CNS and
m/s fasciculation
Arecoline
10. Therapeutic use Antidote Contraindication Dose rate
•Used as taeniafuge (anticestodal)
when administered at fasting
•Purgative effect in horse (but
now infrequently used)
•To slow down the Alzheimer’s
d/s in human
•Atropine Same as
Pilocarpine
1 mg/kg body
weight used as
teniacide in dogs
I.e. administered
orally
11. Pharmacological Effect Adverse Effect
•Profound activation of peripheral
parasympathetic NS
•Produces hypotension and slowing of
heart
•Stimulation of smooth m/s in GIT
,bronchioles ,ureter ,urinary bladdder and
gall bladder
•Hypotension ,slowing of heart
•Muscarine is a potent poison
Muscarine
12. Therapeutic uses Antidote Dose rate
•Used as experimental agent
•Has no other therapeutic use
•Atropine Has no therapeutic use
14. Pharmacological Effect Pharmacokinetics Adverse Effect
•Increase tone of intestine
•Stimulation of salivary and
sweat gland secretions
•Bronchoconstriction
•Ureter constriction
•Bradycardia
•At neuromuscular junction
produces contraction of the
skeletal muscles
•Powerful anticurare action
and reverse the
neuromuscular blockade
produced by curare and its
denervation
•Not well absorbed orally
•After IV administration :
acts within 2 minute
•Duration of action : 30
minute
•After IM administration :
acts within 20-30 minute
•Duration of action : 2-4
hrs
•Does not penetrate blood
brain barrier so minimizes
its central effect
•Metabolized in liver
•Also hydrolyzed by
plasma cholinesterase
•Nausea and vomiting
•Hypersalivation
•Sweating
•Miosis
•Lachrymation
•Dairrhoea
•Abdominal cramps
•Bronchoconstriction
•Hypotension and
bradycardia
Neostigmine
15. Therapeutic Use Antidote Contraindication Dose rate
•To reverse effect of
competitive
neuromuscular blocking
agents such as d-
tubocurarine and
vecuronium
•Treatment and
management of paralytic
ileus ,atony of rumen and
urinary bladder
•Stimulation of skeletal
muscle contraction
Atropine •Mechanical intestinal
or urinary tract
obstruction
•In late pregnancy
•Should be used with
care in patient with :
Bronchial asthma
,Arrhythmia , Epilepsy
and peptic ulcer
disease
•For reversal of M/S
relaxant effect:
Dogs and cats:
0.025-0.04mg/kg ,
IM or S/C
Horse ,cattle and
sheep :0.02-
0.04mg/Kg ,S/C
Swine:0.04-
0.06mg/Kg ,IM
•For diagnosis of
Myasthenia gravis:
Pets:0.04mg/Kg ,IM
0.02mg/kg IV
16. Pharmacological Effect Pharmacokinetics Adverse Effect
Similar to Neostigmine Slower onset of action
(15-30 minute) and
longer duration of
action than
Neostigmine
Fewer than Neostigmine but
the effect persist for longer
duration than Neostigmine
Pyridostigmine
17. Therapeutic Use Antidote Contraindication Dose Rate
•Primarily in treatment
of myasthenia gravis in
dog
•Preferred over
Neostigmine
•Antidote to poisoniong
by anticholinergic (eg:
atropine) and
neuromuscular blocking
agent (eg:d-tubocurarine)
Atropine,
Pralidoxi-
me
•Mechanical
intestinal or urinary
obstruction.
•Cautiously used in
patients with
bronchial asthma
•For reversal of muscle
relaxant effect(curare
toxicity)
Dogs/Cats: 0.15-
0.3mg/Kg ,IM or IV as
needed
•For treatment of
Myasthenia Gravis
Dogs/Cats: 0.5-3mg/Kg
, Po ,3 times daily
18. Pharmacological Effects Pharmacokinetics Adverse effect
Reversible inhibition of
cholinesterase enzyme.
•Well absorbed orally and
from conjuctiva.
•Crosses blood brain
barrier
Peripheral toxicity
characterized by nausea
,vomiting and dairrhoea.
Physostigmine
19. Therapeutic Use Contraindication Dose Rate
Topically applied to
conjuctiva, glaucoma,
severe anticholinergic
toxicity.
Contraindicated to GI
obstruction, asthma,
diabetes mellitus
Solution of 0.5-1%
physostigmine salicylate
used topically 3 times a
day.
20. drugs which block action of neurotransmitter acetylcholine.
Whether CNS OR PNS, it acts on all effector sites innervated by
cholinergic nerves.
Divided into three types; 1. Antimuscarinic agents
2. Ganglionic blockers
3. Neuromuscular blocker
23. Some major drugs(elaborated)
Atropine
Also called as dl-Hyoscyamine.
Alkaloid obtained from Atropa belladonna and
Datura stramonium.
Chemically is an ester of tropic acid with a
complex organic base tropine.
The intact ester of tropic acid and tropine is
considered essential for antimuscarinic
receptor action of atropine.
24.
25. Mechanism of action Commence its action by acting as competitive
antagonist of acetycholine and other agonist
at muscarinic receptor.
High dose may also block nicotinic receptors
at the automatic ganglia and at
neuromuscular junction.
Action is reversible as its action can be
surmounted by using by increasing
concentration of ach or choline esters.
Question?
Atropine does its work effectively for which
exogenous or endogenous receptor.
26. Pharmacological Effect At low does or in initial dose produces transient
bradycardia due to blockade of M1
At normal dose it produces tachycardia due to
blockade of M2
Create vasodilation, consequence, attenuation
of BP.
Reduces tone and motility of gut, closure of
sphincter, prolong gastric emptying, decrease
peristalsis.
27. All non- vascular smooth muscles are relaxed
due to blockade of M3
Relaxes ureter and urinary bladder, so urine
retention.
Dilate pupil( mydriasis), induces cyclopegia.
Induces bronchodilation .
28. Dampens the secretion of ducted gland.
Stimulatory effect in the CNS but over abuse
lead to hallucination and disorientation. The
eventuality is paranormal condition.
29. PHARMAC0KINETICS-
Lipid soluble so well absorbed through
enteral or parenteral or topical.
Crosses placenta, CNS and can reach
milk ducts.
Metabolized in liver and bounded to
plasma protein
30. the medicine.
,
SIDE EFFECTS/ ADVERSE
EFFECT
Dry mouth, dysphagia, constipation,
restlessness, tachypnoea, urine retention.
May also lead to seizures, convulsion, coma
and death.
Overdose leads to disaster in dogs, humans,
cats while rabbit is resistant due to atropinase.
31. Contraindication and Precaution
Patient suffering from glaucoma, congestive
heart failure, intestinal hypomotility, obstructive
uropathy, tachycardia, heart failure.
32. DOSE
Dog and cat- 0.03- 0.1 mg/kg, IM or SC
Cattle and Horses- 0.03-0.06mg/kg, SC or IM
Sheep- 0.08-0.16mg/kg, SC or IM
Swine- 0.02-0.04mg/kg, IM or SC
Birds- 0.04-0.1mg/kg
33. Homatropine
It is prepared from atropine.
Similar to atropine except that it is an ester of
mandelic acid rather than of tropic acid.
Almost pharmacologically similar to atropine,
but 10 times less potent.
Mostly used in cycloplegic to temporarily
paralyze accomodation and as mydraitic to
dilate the pupil.
34.
35. PROPANTHELINE Similar to atropine but have high level of
ganglionic blocking activity.
In GI tracts it reduces spasms and gastric
secretions at doses which produce only mild side
effects.
The ganglionic blocking activity is believed to aid
antisecretory effect propantheline.