Autonomic nervous system

1. A- CHOLIN ESTERASEA- CHOLIN ESTERASE
‫الملح‬ ‫فاضل‬ ‫محمد‬ ‫ثامر‬ ‫حسان‬‫الملح‬ ‫فاضل‬ ‫محمد‬ ‫ثامر‬ ‫حسان‬
Group – B -Group – B -

2. 2- carbachol2- carbachol
 PotentPotent agonist activity.agonist activity.
 direct act :Nonselective (Muscarinic /direct act :Nonselective (Muscarinic /
Nicotinic)Nicotinic)
 ..

3.  USES:USES:
 1. Topically for glaucoma;1. Topically for glaucoma;
 2. intraocular for miosis in surgery.2. intraocular for miosis in surgery.
 3. expel gases3. expel gases
 4. stimulate intestinal motility.4. stimulate intestinal motility.
 5.relive urinary retention5.relive urinary retention
 Side Effects:Side Effects: Corneal edema; decreased visionCorneal edema; decreased vision..

4. 33--bethanecholbethanechol
 ActionAction::
 Potent muscarinic agonist (directlyPotent muscarinic agonist (directly
stimulate Muscarinic receptors)stimulate Muscarinic receptors)
 Orally effective, also administered byOrally effective, also administered by
subcutaneous injection.subcutaneous injection.
 Increased hydrolytic stabilityIncreased hydrolytic stability

5.  Therapeutic applicationsTherapeutic applications::
 For the relief of post-surgical urinaryFor the relief of post-surgical urinary
retention and abdominal distention Andretention and abdominal distention And
stimulate atonic bladderstimulate atonic bladder
 ((Stimulant of GI tract smooth muscle andStimulant of GI tract smooth muscle and
urinary bladder).urinary bladder).
 Adverse effectsAdverse effects::
 Low toxicity, no serious side effects.Low toxicity, no serious side effects.
 Should be used with caution in asthmaticShould be used with caution in asthmatic
patients.patients.

6. 4-Methacholine -----4-Methacholine -----
More stable than acetylcholine.More stable than acetylcholine.
 More selective action (muscarinic nicotinic).More selective action (muscarinic nicotinic).

7. B- Natural alkaloid :B- Natural alkaloid :
muscarine , arecolin ,muscarine , arecolin ,
pilocarpinepilocarpine

8. PilocarpinePilocarpine
 Natural product. Isolated from the leaves ofNatural product. Isolated from the leaves of
Pilocarpus jaborandiPilocarpus jaborandi..
 Actions :Actions :
 decrease in IOP , miosisdecrease in IOP , miosis
 stimulator of secretions.stimulator of secretions.
 Available as ophthalmicAvailable as ophthalmic
solution, gel, tablet .solution, gel, tablet .

9.  Systemic effects:Systemic effects: include copious sweating,include copious sweating,
salivation and gastric secretion.salivation and gastric secretion.
 Uses:Uses:
 lowering of IOP therefore Used in the treatmentlowering of IOP therefore Used in the treatment
of glaucomaof glaucoma
 treatment of xerostomia (dry mouth).treatment of xerostomia (dry mouth).
 Adverse effects:Adverse effects:
 1-blurred vision1-blurred vision
 2- lacrimation2- lacrimation
 3- sever sweating3- sever sweating
4-bronchospsm4-bronchospsm

10. GlaucomaGlaucoma
disease characterized by increase of intradisease characterized by increase of intra
ocular pressure, atrophy of optic disc ,lossocular pressure, atrophy of optic disc ,loss
in the field of vision.in the field of vision.
Glaucoma :Glaucoma : divided into 2 typesdivided into 2 types
1-open wide angle Glaucoma (chronic)1-open wide angle Glaucoma (chronic)
2-narrow closed angle Glaucoma (acute)2-narrow closed angle Glaucoma (acute)

11. Figure 14-5
Forms of primary adult glaucoma. (A) In open-angle (chronic) glaucoma, the
anterior chamber angle remains open, but drainage of aqueous humor
through the canal of Schlemm is impaired; (B) in closed-angle (acute)
glaucoma, the angle of the iris and anterior chamber narrows, obstructing
the outflow of aqueous humor.

13. Parasymathomimetic drug:Parasymathomimetic drug:
1- direct acting cholinergic1- direct acting cholinergic
agent (Natural and cholineagent (Natural and choline
esterase )esterase )
2- Indirect acting cholinergic2- Indirect acting cholinergic
agent:agent: Divided intoDivided into
reversible irreversiblereversible irreversible

14. 2- Indirect acting cholinergic2- Indirect acting cholinergic
agent:agent: Divided intoDivided into
reversible irreversiblereversible irreversible

15. reversiblereversible
 Acetylcholinesterase Inhibitors (AChEI)Acetylcholinesterase Inhibitors (AChEI)
(cholinesterase enzyme inhibitors (ChEI)(cholinesterase enzyme inhibitors (ChEI)
 Inhibition of acetylcholinesterase (AChE)Inhibition of acetylcholinesterase (AChE)
lead to increases the concentration oflead to increases the concentration of
acetylcholine (ACh) in the synapse.acetylcholine (ACh) in the synapse.
 This results inThis results in prolonging the actionprolonging the action ofof
ACh, producing both muscarinic andACh, producing both muscarinic and
nicotinic responses.nicotinic responses.

16. AnticholinestrasesAnticholinestrases
(reversible(reversible))
Acetylcholinestrase is an enzyme thatAcetylcholinestrase is an enzyme that
cleavescleaves Ach toAch to acetate and choline.acetate and choline.
Drugs thatDrugs that inhibit this enzymeinhibit this enzyme provideprovide
cholinergic action.cholinergic action.

17. AGENTS AFFECTINGAGENTS AFFECTING
CHOLINERGIC TRANSMISSIONCHOLINERGIC TRANSMISSION
HemicholiniumHemicholinium
LatrotoxinLatrotoxin
VesamicolVesamicol
Botulinus toxinBotulinus toxin
CalciumCalcium
PhysostigminePhysostigmine
AtropineAtropine
d-Tubocurarined-Tubocurarine

18. 11--physostigminephysostigmine
 Natural product, isolated from the seeds ofNatural product, isolated from the seeds of
Physostigma venenosumPhysostigma venenosum
 Physostigmine : Sensitive to heat, light,Physostigmine : Sensitive to heat, light,
moisture etc.moisture etc.
 Diffuses into the CNSDiffuses into the CNS

19. physostigminephysostigmine
Actions:Actions:
 Stimulate Muscarinic Nicotinic sits .Stimulate Muscarinic Nicotinic sits .
 StimulateStimulate NicotinicNicotinic receptors ofreceptors of
neuromuscular junctions.neuromuscular junctions.
 Duration of action about 2-3 hr.Duration of action about 2-3 hr.
 Stimulate CNSStimulate CNS

20. physostigminephysostigmine
Therapeutics uses:Therapeutics uses:
 Topically in eye.Topically in eye.
 Anti doteAnti dote forfor atropine (atropine (treat over dose oftreat over dose of
anticholinergic drugs.anticholinergic drugs.
 Treatment of myasthenia gravies.Treatment of myasthenia gravies.
 increase intestinal bladder motilityincrease intestinal bladder motility
 Terminate the effect ofTerminate the effect of tubocurarine.tubocurarine.
 Topical application in the treatment ofTopical application in the treatment of
glaucomaglaucoma

21. physostigminephysostigmine
Adverse effects:Adverse effects:
-convulsions-convulsions
-Bradycardia-Bradycardia
-paralysis of skeletal muscles-paralysis of skeletal muscles

22. 22--neostigmineneostigmine
 Chemically more stable than physostigmineChemically more stable than physostigmine
 Longer duration of action (2-4 hr)Longer duration of action (2-4 hr)
 Neostigmine administered orally or ivNeostigmine administered orally or iv
*adverse effects:*adverse effects:
generalized cholinergic stimulation.generalized cholinergic stimulation.

23. **Therapeutics uses:Therapeutics uses:
1-1- stimulate bladder GIT.stimulate bladder GIT.
2- antidote of tubocurarine.2- antidote of tubocurarine.
3- treat of myasthenia gravis.3- treat of myasthenia gravis.
4-4- The most frequent use of neostigmine isThe most frequent use of neostigmine is
to prevent atony of the intestinal, skeletal,to prevent atony of the intestinal, skeletal,
and bladder musculature.and bladder musculature.
 5- Also used as urinary stimulant.5- Also used as urinary stimulant.

24. Myasthenia gravisMyasthenia gravis
Autoimmune diseaseAutoimmune disease
Ab againstAb against Ach receptorsAch receptors at neuromuscular junctionat neuromuscular junction
Weakness of skeletal musclesWeakness of skeletal muscles
Edrophonium used for diagnosisEdrophonium used for diagnosis
Neostigmine , pyridostigmine used for treatmentNeostigmine , pyridostigmine used for treatment

25. 33--pyridostigminepyridostigmine
** treatment of myasthenia gravis** treatment of myasthenia gravis
**duration of action 3-6hr.**duration of action 3-6hr.
 PyridostigminePyridostigmine is the most widelyis the most widely
used for the treatment of myastheniaused for the treatment of myasthenia
gravisgravis

26. 44--EdrophoniumEdrophonium
 Administered parenterallyAdministered parenterally
 Rapid onsetRapid onset
 short duration of actionshort duration of action 10-20 min( short10-20 min( short
acting )acting )
 Also exhibits direct cholinomimetic effect onAlso exhibits direct cholinomimetic effect on
skeletal muscleskeletal muscle
 Used in the Diagnosis of myasthenia gravis.Used in the Diagnosis of myasthenia gravis.
 Over dose cause cholinergic crisisOver dose cause cholinergic crisis
 Atropine is the antidoteAtropine is the antidote

27. Irreversible cholinestraseIrreversible cholinestrase
inhibitorsinhibitors
1- organophosphorus ;;1- organophosphorus ;;
((malathion parathionmalathion parathion)) :used in:used in
insecticideinsecticide
2- Tabun Sarin : nerve gas (chemical war2- Tabun Sarin : nerve gas (chemical war
agent )agent )

28.  Irreversible InhibitorsIrreversible Inhibitors
 Compounds containingCompounds containing phosphoryl orphosphoryl or
phosphonic groupphosphonic group that can react with ChEthat can react with ChE
to form ChE-phosphate complexes stable toto form ChE-phosphate complexes stable to
hydrolytic cleavage.hydrolytic cleavage.
 Mainly used as agricultural insecticides andMainly used as agricultural insecticides and
nerve gas agents.nerve gas agents.

29. Mechanism of actionMechanism of action
 Combined of o.p.c with choline esteraseCombined of o.p.c with choline esterase
enzyme irreversible formation anewenzyme irreversible formation anew
compoundcompound
 O.p.c + chE -------------- o.pO.p.c + chE -------------- o.p——chEchE
 O.p.c highly lipid solubleO.p.c highly lipid soluble

30. Adverse effects ofAdverse effects of
organophosphate compoundsorganophosphate compounds::
 Miosis , RhinorrheaMiosis , Rhinorrhea
 Frontal headache , BronchoconstrictionFrontal headache , Bronchoconstriction
 Laryngospasm , SalivationLaryngospasm , Salivation
 GIT disturbances , BradycardiaGIT disturbances , Bradycardia
 Sweating , LacrimationSweating , Lacrimation
 Involuntary micturition , Muscle weaknessInvoluntary micturition , Muscle weakness
 Ataxia, confusion ,Ataxia, confusion ,
 DeathDeath

31. treatmenttreatment
 1- stop exposure1- stop exposure
 2-wash skin2-wash skin
 3-oxygen supply .3-oxygen supply .
 4 replace fluid .4 replace fluid .
 5-atropine5-atropine
 6- 2-PAM(Pralidoxime)6- 2-PAM(Pralidoxime)

32. Reactivation of acetylecholinestraseReactivation of acetylecholinestrase
 PralidoximePralidoxime
synthetic compound that cansynthetic compound that can reactivatereactivate thethe
acetylcholinestrase if its given beforeacetylcholinestrase if its given before agingaging ofof
enzyme ((aging mean: loss of an alkyl gp fromenzyme ((aging mean: loss of an alkyl gp from
the structure of enzyme)).the structure of enzyme)).
PralidoximePralidoxime :Effective antidote for poisoning:Effective antidote for poisoning
byby parathion and related pesticidesparathion and related pesticides
•• Most effective by intramuscular, intravenous, orMost effective by intramuscular, intravenous, or
subcutaneous administrationsubcutaneous administration
•• Treatment is effective if initiated within fewTreatment is effective if initiated within few
hourshours