Cholinergic Drugs and Anticholinesterases in Optometry

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

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Cholinergic Drugs and Anticholinesterases in Optometry

  1. 1. • Cholinergic drugs/agents • Parasympathomimetic drugs/agent • Drugs that enhance the parasympathetic activity
  2. 2. • 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).
  3. 3. • Acetylcholine • Muscarinic receptors • Nicotinic receptors
  4. 4. • 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.
  5. 5. Iris and pupil
  6. 6. 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
  7. 7. • 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).
  8. 8. • Generally, – Parasympathetic nervous system activation causes – decrease in IOP *** – Sympathetic nervous system activation causes – Increase in IOP ***
  9. 9. Increased IOP
  10. 10. • Directly by stimulating the nicotinic or muscarinic receptors Or • Indirectly by inhibiting cholinesterase, promoting acetylcholine release, or through other mechanisms
  11. 11. Direct acting on receptors
  12. 12. 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
  13. 13. (eg. Acetylcholine, carbachol, methacholine, bethanechol) (eg. Pilocarpine) (eg. Aceclidine)
  14. 14. • Direct acting – Choline ester • Acetylcholine • Carbachol • Methacholine • Bethanechol – Alkaloids • Pilocarpine – Aceclinide
  15. 15. • 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
  16. 16. • 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.
  17. 17. • 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.
  18. 18. • 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
  19. 19. • 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
  20. 20. • 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
  21. 21. • 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
  22. 22. • 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
  23. 23. • Symthetic cholinergic drug • Resemble to pilocarpine • Less ciliary spasm
  24. 24. • Reversible anticholinesterases – Physostigmine – Neostigmine – Edrophonium • Irreversible anticholinesterases – Echothiophate – DFP
  25. 25. • 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
  26. 26. • Uses – Miotic agent – Antiglaucoma agent – Anticholinergic drug poisoning
  27. 27. • 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
  28. 28. • Inhibition is temporary (hence – reversible) • Effects limited to about 12 hours • Then dissociates
  29. 29. • 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
  30. 30. • 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
  31. 31. • Lacrimation • Vomiting, diarrhoea • Abdominal cramp • Bradycardia • Respiratory depression • Pulmonay oedema • Convulsions
  32. 32. • Both anticholinesterase and direct neuromuscular stimulating effects • Use – Diagnosis of myasthenia gravis – Post op decurarisation
  33. 33. • Chemically related to organophosphorous compounds • Originally developed as nerve gas and insecticides but some found to be used for medical purposes (ecothiophate)
  34. 34. • 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
  35. 35. • 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)
  36. 36. • 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
  37. 37. • Di-isopropyl fluorophosphate (DFP) is dispensed as 0.01-0.1% oily solution since water rapidly inactivates it. • Now unavailable
  38. 38. • 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.
  39. 39. • 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.
  40. 40. 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

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