Cholinergic Drugs and anticholinesterases play an important role in optometry, ophthalmology as well as medicine.

2. • Cholinergic drugs/agents
• Parasympathomimetic drugs/agent
• Drugs that enhance the parasympathetic
activity

3. • Drugs – stimulate Parasympathetic Nervous
System
• Called cholinerigics
– Because ACh is a neurotransmitter in PNS
– Those drugs resemble the effects produced by
stimulation of PNS (cholinergic nervous system).

5. • Acetylcholine
• Muscarinic receptors
• Nicotinic receptors

8. • Iris
– In the front of the eye, the muscles of the iris (colored
portion of the eye) control the amount of light
entering the eye. Pigments in the iris give it color.
– The iris is made up of smooth muscle fibers that
adjust pupil size.
• Pupil (black aperture of the eye)
– is not a structure at all; rather,
– it is an opening created by the circular iris.
– Its blackness is due to the lack of reflection of light
from within the eye.
– The pupil allows light into the eye.

9. Iris and pupil

10. Control
• Control of the Iris
– The iris is composed of a pigmented epithelium, the anterior sphincter
muscle, and the dilator muscle.
– The sphincter and dilator are both smooth muscles.
• The sphincter muscle contracts in response to parasympathetic
stimulation,
• while the dilator contracts in response to sympathetic
stimulation.
• Changes in the amount of light falling on the retina stimulate or
inhibit each pathway

14. • It is the pressure inside the eye needed to maintain the shape of the globe, as well
as the normal function of the eyeball.
• It is maintained by the balance between formation and drainage of an intraocular
fluid called aqueous humor.
• It is formed by the ciliary processes in the posterior chamber, passes between the
iris and lens to enter the anterior chamber, and leaves the eye through the
trabecular meshwork and Schlemm’s canal.
• Normal IOP About 10-21 mm of Hg, but varies considerably from individual to
individual. Glaucoma may occur with IOP within the so called normal range or
persons with high IOP may not have glaucoma (ocular hypertension).

16. • Generally,
– Parasympathetic nervous system activation
causes
– decrease in IOP ***
– Sympathetic nervous system activation causes
– Increase in IOP ***

17. Increased IOP

21. • Directly by stimulating the
nicotinic or muscarinic
receptors
Or
• Indirectly by inhibiting
cholinesterase, promoting
acetylcholine release, or
through other mechanisms

24. Direct acting on
receptors

26. Parasympathomimetic drugs
Direct acting
C holine ester Alkaloid
Acetylcholine
Methacholine
Carbachol
Bethanechol
Pilocarpine
Others
Aceclidine
Indirect acting
Reversible ChE
inhibitors
Irreversible
ChE inhibitors
Physostigmine
Neostigmine
Edrophonium
Ecothiophate

27. (eg. Acetylcholine, carbachol,
methacholine, bethanechol)
(eg. Pilocarpine)
(eg. Aceclidine)

29. • Direct acting
– Choline ester
• Acetylcholine
• Carbachol
• Methacholine
• Bethanechol
– Alkaloids
• Pilocarpine
– Aceclinide

30. • Direct acting parasympathetic agent
• Has very short half life (rapidly destroyed by
cholinesterase enzyme)
• Is not used as antiglaucoma agent
• Is used as intraoperative miotic agent

31. • More stable than acetylcholine
• Is not easily destroyed by cholinesterase
• Is used as antiglaucoma agent
• More powerful than pilocarpine both miotic
and an IOP lowering agent
• Instillation into the eye as well as
intracamerally
intracameral : within a chamber, such as the anterior or posterior chamber of the eye. i.e.
anaesthesia injection of an anaesthetic agent into the anterior chamber of the eye, usually
during surgery.

32. • According to BPC (British Pharmaceutical Codex)
– Eyedrops contains up to 3% of carbachol but
– As an alternative miotic for pilocarpine allergic
patients, optometrists should find 0.5% adequate to
reverse sympathomimetic mydriatics.
• It is poorly absorbed through the cornea and it
includes a wetting agent, such as benzalkonium
chloride, which has additional role of bactericide.

33. • That is not easily inactivated by cholinesterase
• 1% solution is used as a miotic
• Also needs wetting agent to help it to
penetrate the cornea

34. • Carbachol is more effective for GIT and
bladder
• Methacholine is more effective for CVS (Atrial
paroxysmal tachycardia when other measures
are failed)
• Methacholine requires 10-20% solution for
miosis and
• This strength is also use for glaucoma

35. • Direct acting parasympathomimetic drug
• Action similar to release of acetylcholine acting on
autonomic effector cells
• Acts primarily on muscarinic effector organs and cells
• Most popular anti-glaucoma drug
• Topical route
• Anti-glaucoma action by facilitating aqueous outflow by
stimulating longitudinal muscle fibres of ciliary body

36. • Systemic
– Increased salivation, sweating, nausea, vomiting,
diarrhoea,
lacrimation
– Bronchiolar constriction (serious)
• Eye
– Decreased vision
– Supra-orbital and temporal headache
– Drug allergy
– Retinal detachment
– May have cataractogenic effect

37. • Local application to eye – 0.5-4%
• 1% is mostly recommended by practitioners
• Miosis starts after commencing in about 10 mins
• Maximal in half an hour
• Gradually decrease over 6 hours with 1% solution

38. • Symthetic cholinergic drug
• Resemble to pilocarpine
• Less ciliary spasm

39. • Reversible anticholinesterases
– Physostigmine
– Neostigmine
– Edrophonium
• Irreversible anticholinesterases
– Echothiophate
– DFP

40. • Cholinesterase is a non-specific type of enzyme which is present at all
cholinergic sites
• It acts of acetylcholine to divide into acetyl CoA and choline
• And terminates its action
• Anticholinesterases – competitively inhibits action of cholinesterases
• Cause sustained action of ACh on its receptor
• Prolongs the action of ACh

41. • Uses
– Miotic agent
– Antiglaucoma agent
– Anticholinergic drug poisoning

42. • The action of Anti-AChE on ACh is being inhibited by
physostigmine
• Allows the ACh to accumulate at sites of cholinergic
transmission
• Effects will similar to continuous stimulation of
cholinergic fibres

43. • Inhibition is temporary (hence – reversible)
• Effects limited to about 12 hours
• Then dissociates

44. • Little use today as miotic
• On instillation, pupil constriction starts between 5 and 10 minutes ,
maximal in about 30 min and last up to 12 hours (with 0.5%
solution)
• Physostigmine 1% should not be used - Even for emergency by
sudden attack of acute glaucoma
• Marked pupillary constriction, normal size will not be regained for a
few days
• Reserved for medical treatment for the later stage of simple
glaucoma where weaker miotic agents cannot control any longer

45. • Uses- similar to physostigmine
• Neostigmine is more effective for the
treatment and diagnosis of myasthenia gravis
– Improves diplopia, ptosis, general muscular
weakness, other features of myasthenia gravis

46. • Lacrimation
• Vomiting, diarrhoea
• Abdominal cramp
• Bradycardia
• Respiratory depression
• Pulmonay oedema
• Convulsions

48. • Both anticholinesterase and direct neuromuscular
stimulating effects
• Use
– Diagnosis of myasthenia gravis
– Post op decurarisation

49. • Chemically related to organophosphorous
compounds
• Originally developed as nerve gas and
insecticides but some found to be used for
medical purposes (ecothiophate)

50. • Irreversible anticholinesterase compound
• Facility of outflow is increased
• Peak action is after 24 hrs
• May persist up to approximately 4 days
• Therapeutic uses
– Open angle glaucoma (0.06%-0.25% solution)
– Accomodative estropia

51. • Is not without side effects
• Systemic side effects in some persons (frequency of
dosage)
– Diarrhoea, nausea, vomiting, abdominal cramps,
– General weakness and fatigue
• Locally
– Iris cysts (disappear when discontinued) can be prevented
by simultaneous use of phenylepherine (which does not
impair the therapeutic effect of ecothiophate)

52. • Must be freshly prepared by the pharmacist in
a diluent supplied by the manufacturers
• The drops only remaining stable if the solution
is kept refrigerated

53. • Di-isopropyl fluorophosphate (DFP) is
dispensed as 0.01-0.1% oily solution since
water rapidly inactivates it.
• Now unavailable

56. • The following precautions should be observed
in the use of miotics following mydriatics
– Explain to the patient or parent the reason for
using a miotic.
– Ask whether the patient has previously had a
miotic instilled and whether there was any
adverse reaction to the drug used.
– Issue a note which identifies the miotic used and
provides advice on what action the patient should
take in the event of an adverse reaction.

57. • Brunton, L. Chabner, B. Knollman, B. Goodman & Gilman’s
Pharmacological Basis of Therapeutics. 12th Edition. United
States: The McGraw-Hill Companies, Inc.
• Hopkins, G, Pearson, R (2007). Ophthalmic Drugs Diagnostic
and Therapeutic Uses. 5th ed. USA: Elsevier . 85-278.
• Sengupta, KK, Mukherji, R (2006). Essentials of Ocular
Pharmacology and Therapeutics . UK: Anshan Limited. 148-
174.

58. References for figures
• http://pharmacologycorner.com/acetylcholine-
receptors-muscarinic-and-nicotinic/
• http://www.susrut.org/kolkata-eye-
hospital/Glaucoma
• http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1323
919/pdf/brjopthal01153-0038.pdf