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Understanding Glaucoma and Pilocarpine Treatment

Learn about glaucoma and how pilocarpine can be used as a treatment for open-angle glaucoma. Discover the types, effects, and risk factors of glaucoma, as well as the mechanism of action of pilocarpine.

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Understanding Glaucoma and Pilocarpine Treatment

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  1. It is estimated 2 out of every 100 people over the age of 65 have glaucoma and half of these people don’t know it. From Cassel, Billig, Randall

  2. Pilocarpine as a Treatment for Open Angle Glaucoma By Tom Zurakowski

  3. Objective: Inform my audience about glaucoma and the use of pilocarpine as a treatment for open angle glaucoma.

  4. The Eye

  5. MajorPartsoftheEye Sclera Ciliarybody Choroid Retina Cornea Iris Pupil OpticNerve AnteriorSegment Lens CanalofSchlemm PosteriorSegment (containsvitreoushumor) Marieb Fig16-6

  6. Eye Fluid Production and Pressure Cornea Anteriorchamberangle Iris Trabecularmeshwork Schlemm’scanal (out) Pupil Posteriorchamber Ciliarybody (in) Lens Vitreous Zonule Cassel, Billig, Randall Fig 8-2

  7. Intraocular Pressure (IOP) • Eye is like a balloon • “Normal Pressure” (16 - 21)mm Hg • Continuous replacement of aqueous humor • Measurement of Pressure (tonometry) • 1) Goldmann contact tonometer • 2) “air puff” tonometer

  8. Glaucoma - What is it? - Types of Glaucoma 1) Closed-Angle Glaucoma 2) Open-Angle Glaucoma 3) Normotensive (Low Tension) Glaucoma - Who’s at risk 1) > age 55 2) family history 3) having diabetes 4) being very nearsighted 5) African American - Effects of Glaucoma 1) Tunnel Vision 2) Blindness

  9. Types of Glaucoma Closed-Angle Glaucoma Open-AngleGlaucoma Blocked drainage of aqueous Blocked drainage of aqueous Anterior chamber open Anterior Chamber angle closure Blockage at trabecular meshwork Cassel, Billig, Randall Fig 8-4 Cassel, Billig, Randall Fig 8-3

  10. Effect of Glaucoma

  11. Cause of Blindness - Cupping of Optic Nerve Cassel, Billig, Randall

  12. Pilocarpine -Origin of the Drug -South American Shrub - Pilocarpus jaborandi -Isolated in 1875 -Chemical Structure + - Cholinergic Parasympathomimetic agent

  13. Reaction Mechanism - Pilocarpine binds to muscarinic receptor - Activates receptor binds G-protein - Removal of GDP and addition of GTP to G-protein - Dissociation of G-protein from muscarinic receptor - Separation of G-protein into alpha and beta-gamma subunits - Alpha subunit interacts with and activates Phospholipase C - Phosphatidyl inositol biphosphate (PIP) complex - Phospholipase breaks down PIP into inositol 1,4,5-triphosphate (IP3)and diacylglycerol (both 2o) - IP3 interacts with ER membrane which releases Ca2+

  14. Muscle Action - Ca2+ binds to calmodulin forming a complex - This complex binds to caldesmon - When caldesmon is bound by Ca2+/calmodulin complex this allows myosin-actin interactions to occur -The muscle (pupil)contracts Marieb Fig 16-7

  15. Reaction Sequence Phospholipase C Phosphatidyl inositol biphosphate (PIP) complex G- Protein subunits , ,  GDP\ Inositol 1,4,5 - triphosphate (IP3) + diacylglycerol Myosin-actin interaction (Muscle Contraction) GTP Muscarinic Receptor caldesmon Ca2+ Calmodulin/ Ca2 Endoplasmic Reticulum

  16. The End Result - Contraction of pupil and stimulation of ciliary muscle - Tension on scleral spur opening trabecular meshwork - Increased out flow, lowering of pressure

  17. Bibliography 1. Cassel, Gary, H., Michael D.Billig, and Harry G.Randall The Eye Book. The Johns Hopkins University Press. Baltimore, Maryland. 1998. 2. Finn, Paul, Registered Pharmacist Luther Hospital, Eau Claire, WI. Personal Interview. 17 Feb. 1999. 3. Nybakken, Craig, Registered Pharmacist Luther Hospital, Eau Claire, WI Pesonal Interview. 17 Feb. 1999. 4. Hardman, Joel, G., Lee E. Limbird, (et.al.) Goodman's and Gilman's Pharmacological Basis of Therapeutics. 9th ed. R.R. Donnelly and Sons Co. New York, NY. 1996. 5. Riley, Michael, R., Steven, K Hebel, (et.al) Drug Facts and Comparisons. Wolters Kluwer Co. St. Louis, MO 1999. 6. MBC 3320: Lecture 3 (January 19,1999) [Online] Available World Wide Web http://www.neurosci.pharm.utoledo.edu/MBC3320/lecture03.html 7. Allen, James, H. May's Diseases of the Eye. Robert E. Krieger Publishing Co. Huntington, NY. 1976. 8. Occular Pharmacology [Onlilne] Available World Wide Web http://www.eye.ttu.edu/lectures/Crosson_OcPharm.html 9. Cholinergic receptors [Online] Available World Wide Web http://www.kumc.edu/research/medicine/pharmacology/mgordon/Autonomics/Introduction/enrich3.htm. 10. ANS neurotransmitters [Online] Available World Wide Web http://www.kumc.edu/research/medicine/pharmacology/mgordon/Autonomics/Cholinergics/ans_trans1.htm#Eye 11. Marieb, Elaine, N. Human Anatomy & Physiology. 4th ed. Addison Wesley Longman, Inc. Menlo Park, CA. 1998. 12. Randall, David, Warren Burggren, Kathleen French. Animal Physiology Mechanisms and Adaptations. 4th ed. W.H. Freeman and Co. New York, NY 1997. 13. Stryer, Lubert. Biochemistry. 2nd Ed. W.H. Freeman and Co. SanFransico, CA 1981. 14. Waschke, Kevin A. (1996) New Perspectivies in the Pharmacologic Treatment of Primary Open-Angle Glaucoma: Pathogenesis and Patient Factors. [Online] Available World Wide Web: http://www.mjm.mcgill.ca/back_issues/V2n1/glaucoma.html

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