1. DRUG ACTING ON A.N.S 1- cholinergic drugs A- Parasympathomimetic D
د. جوناء lec 2
DRUG ACTING ON A.N.S
1- cholinergic drugs
A- Parasympathomimetic D
B- Parasympathlytic D
2- adrenergic drugs
A- sympathomimetic D
B- sympatholytic D

2. Parasympathetic drugs :
A- Parasympathomimetic D Cholinergic agonist: Agents that bind to acetylcholine receptors and stimulates the
parasympathetic system (“parasympathomimetic”).
B- parasympathlytic D Cholinergic antagonist: Agents that bind to acetylcholine receptors but exhibit no intrinsic activity (“parasympatholytic” – competitive to endogenous Ach)

3. Parasympathomimetic drug: These are the group of drugs which produce effects resembling those produced by the stimulation of parasympathetic autonomic nervous system on the target organs

4. cholinergic Drugs (Muscarinic Agonists):
Pharmacological responses to the interaction of cholinergic agonists with muscarinic receptors include:
Contraction of smooth muscles
Vasodilation of vascular system
Increased secretion from exocrine glands
Decrease in heart rate and force of contraction
Constriction of pupil

5. Parasympathomimetic drug:
1- direct acting cholinergic agent
2- Indirect acting cholinergic agent: divided
into reversible & irreversible

6. (parasympathomemtic)
Cholinergic drugs
agonist
Muscarinic agonist
(parasympathomemtic)
Nicotinic agonist
antagonist

7. Parasymathomimetic drug

8. A. Directly Acting Cholinergic Drugs : I. Choline Esters
Acetylcholine
Carbachol
Methacholine
Bethanechol

9. A- cholin esterase 1-Acetylcholine
Effect of ACH :
1.on the intestine : Increase S.M contraction
2.on the urinary tract : Increase in muscle
tone and contraction
3. on blood vessels : vasodilatation

10. 4.on the secretary gland :increase secretion
5. on the S.M of trachea :contract , increase
bronchial secretion, bronchoconstriction ,
6.on the skeletal Muscle : increase Muscle tone
7. On the heart : bradycardia
8. On the eye : miosis , decrease in I.O.P
9 .On the adrenal gland

11. Prototypical muscarinic (and nicotinic) agonist, Nonselective action.
but a poor therapeutic agent.
Chemical/enzymatic instability; Low bioavailability (poorly absorbed); Quick onset and short duration of action.
Use: In ocular surgery, causes complete miosis in seconds.

12. 2- carbachol direct act :Nonselective (Muscarinic / Nicotinic)
Potent agonist activity.
direct act :Nonselective (Muscarinic / Nicotinic)
Also acts indirectly by promoting ACh release and anticholinesterase (weak) activity.

13. USES:
1. Topically for glaucoma(main use)
2. intraocular for miosis in surgery.
3. expel gases
4. stimulate intestinal motility.
5.relive urinary retention
Side Effects: Corneal edema; decreased vision.

14. 3- bethanechol
Action:
Potent muscarinic agonist (directly stimulate Muscarinic receptors)
Orally effective, also administered by subcutaneous injection.

15. Therapeutic applications:
1. post-surgical urinary retention.
stimulate atonic bladder
In urologic treatment, bethanechol is used to stimulate the atonic bladder, particularly retention.
2.Postoperative non-obstructive GITdisorder to preventconstipation.

16. Adverse effects:
Bethanechol causes the effects of generalized cholinergic stimulation These include
1.sweating, salivation, flushing.
2.Decreased blood pressure
3.nausea, abdominal pain,diarrhea. 4.bronchospasm

17. 4-Methacholine -----
More stable than acetylcholine.
Has methyl group in its structure
More selective action (muscarinic > nicotinic).
Has both muscarinic and nicotinic actions (very mild nicotinic actions )

18. METHACHOLINE
Therapeutic uses: given as inhalation for diagnostic of asthma.
Muscarinic actions are prominent on CVS
Cause brady cardia and hypotention.

19. B- Natural alkaloid
muscarine arecolin pilocarpine

20. Pilocarpine
Natural product. Isolated from the leaves of Pilocarpus jaborandi.
less potent than ACH but is uncharged and can penetrate the CNS at therapeutic doses.
Pilocarpine exhibits muscarinic activity and is used primarily in ophthalmology

21. Pilocarpine

22. on eye:decrease in IOP , miosis
Actions :
on eye:decrease in IOP , miosis
it experiences a spasm
of accommodation. The vision
becomes fixed at some particular distance
. Systemic effects: include copious sweating, salivation and gastric
secretion

23. USES
1. is the drug of choice for emergency lowering of intraocular pressure of both open-angle and angle-closure glaucoma.
This action occurs within a few minutes, lasts 4 to 8 hours, and can be repeated.Available as ophthalmic
solution, gel, tablet
2. treatment of xerostomia (dry mouth).

24. 3.The miotic action of pilocarpine is also useful in reversing mydriasis due to atropine

25. Adverse effects: 1-blurred vision 2- lacrimation 3- sever sweating
4-bronchospasm
5-CNS effect(cross BBB)
Cevimeline and pilocarpine used in treatment of sjogrens syndrome(lack of tear and dry mouth)to increase salivation.

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

27. Figure 14-5 Forms of primary adult glaucoma
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.

29. Parasymathomimetic drug:
1- direct acting cholinergic
agent (Natural and choline
esterase )
2- Indirect acting cholinergic
agent: Divided into
reversible & irreversible

30. 2- Indirect acting cholinergic
agent: Divided into
reversible & irreversible

31. Anticholinestrases (reversible)
Acetylcholinestrase is an enzyme that cleaves Ach to acetate and choline.
Drugs that inhibit this enzyme provide cholinergic action.

32. AGENTS AFFECTING CHOLINERGIC TRANSMISSION
Hemicholinium
Latrotoxin
Vesamicol
Botulinus toxin
Calcium
Physostigmine
Atropine
d-Tubocurarine

33. reversible
Acetylcholinesterase Inhibitors (AChEI) (cholinesterase enzyme inhibitors (ChEI)
Inhibition of acetylcholinesterase (AChE) lead to increases the concentration of acetylcholine (ACh) in the synapse.
This results in prolonging the action of ACh, producing both muscarinic and nicotinic responses.

35. 1- physostigmine Actions: Stimulate Muscarinic & Nicotinic sits .
Stimulate Nicotinic receptors of neuromuscular junctions.
Duration of action about 2-4 hr.
Stimulate CNS

36. Natural product, isolated from the seeds of Physostigma venenosum
Physostigmine : Sensitive to heat, light, moisture etc.
Diffuses into the CNS
Antidote for atropine poisoning
Topical application in the treatment of glaucoma

37. Therapeutics uses: physostigmine Topically in eye.
Anti dote for atropine (treat over dose of anticholinergic drugs.(central and peripheral).
Treatment of myasthenia gravies.
increase intestinal & bladder motility
Terminate the effect of tubocurarine.

38. physostigmine Adverse effects: -convulsions -Bradycardia
-paralysis of skeletal muscles

39. Myasthenia gravis Autoimmune disease
Ab against Ach receptors at neuromuscular junction
Weakness of skeletal muscles
Edrophonium used for diagnosis
Neostigmine , pyridostigmine used for treatment

40. 2- neostigmine Chemically more stable than physostigmine
Longer duration of action (2-4 hr)
Neostigmine administered orally or iv
Not cross CNS.
*adverse effects:
generalized cholinergic stimulation.

41. 2- antidote of tubocurarine. 3- treat of myasthenia gravis.
*Therapeutics uses:
1- stimulate bladder & GIT.
2- antidote of tubocurarine.
3- treat of myasthenia gravis.
4- The most frequent use of neostigmine is to prevent atony of the intestinal, skeletal,
and bladder musculature.(After surgery)
5- Also used as urinary stimulant.

43. 3-pyridostigmine
** treatment of myasthenia gravis
**duration of action 3-6hr.
Pyridostigmine is the most widely used for the chronic treatment of myasthenia gravis.

44. 4-Edrophonium Administered parenterally Rapid onset I.V.
short duration of action min( short acting )
Also exhibits direct cholinomimetic effect on skeletal muscle
Used in the Diagnosis of myasthenia gravis.
Over dose cause cholinergic crisis
Atropine is the antidote

45. Indirect Acting Agents used to treat Alzheimer’s disease
Anticholinesterase with specific CNS.
Donepezil (Aricept)—said to delay progression of the disease by up to 55 weeks. Does not cause liver toxicity.
Galantamine
Rivastigmine long acting. Twice a day dosing.
Tacrine (Cognex)—hepatoxic. Elevated liver enzymes usu. Within 18 wks. > in women.

46. Irreversible cholinestrase inhibitors
1- organophosphorus ;;
(malathion & parathion) :used in insecticide
2- Tabun & Sarin : nerve gas (chemical war agent )

47. Irreversible Inhibitors
Compounds containing phosphoryl or phosphonic group that can react with ChE to form ChE-phosphate complexes stable to hydrolytic cleavage.
Mainly used as agricultural insecticides and nerve gas agents.

48. Mechanism of action
Combined of o.p.c with choline esterase enzyme irreversible & formation anew compound
O.p.c + chE o.p—chE
O.p.c highly lipid soluble

49. Adverse effects of organophosphate compounds:
Miosis , Rhinorrhea
Frontal headache , Bronchoconstriction
Laryngospasm , Salivation
GIT disturbances , Bradycardia
Sweating , Lacrimation
Involuntary micturition , Muscle weakness
Ataxia, confusion ,
Death

50. treatment 1- stop exposure 2-wash skin 3-oxygen supply .
4 replace fluid .
5-atropine
6- 2-PAM(Pralidoxime)

51. Reactivation of acetylecholinestrase
Pralidoxime
synthetic compound that can reactivate the acetylcholinestrase if its given before aging of enzyme ((aging mean: loss of an alkyl gp from the structure of enzyme)).
Pralidoxime :Effective antidote for poisoning by parathion and related pesticides
• Most effective by intramuscular, intravenous, or subcutaneous administration
• Treatment is effective if initiated within few hours