Cholinergic Drugs and Anticholinesterases in Optometry
• Cholinergic drugs/agents
• Parasympathomimetic drugs/agent
• Drugs that enhance the parasympathetic
• Drugs – stimulate Parasympathetic Nervous
• Called cholinerigics
– Because ACh is a neurotransmitter in PNS
– Those drugs resemble the effects produced by
stimulation of PNS (cholinergic nervous system).
– 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.
• 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
• while the dilator contracts in response to sympathetic
• Changes in the amount of light falling on the retina stimulate or
inhibit each pathway
• 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).
– Parasympathetic nervous system activation
– decrease in IOP ***
– Sympathetic nervous system activation causes
– Increase in IOP ***
• Direct acting parasympathetic agent
• Has very short half life (rapidly destroyed by
• Is not used as antiglaucoma agent
• Is used as intraoperative miotic agent
• 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
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
• 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.
• 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
• Carbachol is more effective for GIT and
• Methacholine is more effective for CVS (Atrial
paroxysmal tachycardia when other measures
• Methacholine requires 10-20% solution for
• This strength is also use for glaucoma
• 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
– Increased salivation, sweating, nausea, vomiting,
– Bronchiolar constriction (serious)
– Decreased vision
– Supra-orbital and temporal headache
– Drug allergy
– Retinal detachment
– May have cataractogenic effect
• 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
• Symthetic cholinergic drug
• Resemble to pilocarpine
• Less ciliary spasm
• Cholinesterase is a non-specific type of enzyme which is present at all
• 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
• The action of Anti-AChE on ACh is being inhibited by
• Allows the ACh to accumulate at sites of cholinergic
• Effects will similar to continuous stimulation of
• Inhibition is temporary (hence – reversible)
• Effects limited to about 12 hours
• Then dissociates
• 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%
• 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
• Reserved for medical treatment for the later stage of simple
glaucoma where weaker miotic agents cannot control any longer
• 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
• Both anticholinesterase and direct neuromuscular
– Diagnosis of myasthenia gravis
– Post op decurarisation
• Chemically related to organophosphorous
• Originally developed as nerve gas and
insecticides but some found to be used for
medical purposes (ecothiophate)
• 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
• Is not without side effects
• Systemic side effects in some persons (frequency of
– Diarrhoea, nausea, vomiting, abdominal cramps,
– General weakness and fatigue
– Iris cysts (disappear when discontinued) can be prevented
by simultaneous use of phenylepherine (which does not
impair the therapeutic effect of ecothiophate)
• 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
• Di-isopropyl fluorophosphate (DFP) is
dispensed as 0.01-0.1% oily solution since
water rapidly inactivates it.
• Now unavailable
• 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.
• 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-