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Transcript
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
Pilocarpine as a Treatment for
Open Angle Glaucoma
By Tom Zurakowski
Objective: Inform my audience
about glaucoma and the use of
pilocarpine as a treatment for
open angle glaucoma.
The Eye
Major Parts of the Eye
Ciliary body
Cornea
Iris
Pupil
Sclera
Choroid
Retina
Optic Nerve
Anterior Segment
Lens
Canal of Schlemm
Posterior Segment
(contains vitreous humor)
Marieb Fig16-6
Eye Fluid Production and Pressure
Cornea
Iris
Anterior chamber angle
Trabecular meshwork
Schlemm’s canal
(out)
Pupil
Posterior chamber
Ciliary body
(in)
Lens
Vitreous
Zonule
Cassel, Billig, Randall Fig 8-2
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
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
Types of Glaucoma
Open-Angle Glaucoma
Blocked drainage of aqueous
Blocked drainage of aqueous
Anterior chamber open
Blockage at trabecular
meshwork
Cassel, Billig, Randall
Closed-Angle Glaucoma
Fig 8-4
Anterior Chamber
angle closure
Cassel, Billig, Randall
Fig 8-3
Effect of Glaucoma
Cause of Blindness
- Cupping of Optic Nerve
Cassel, Billig, Randall
Pilocarpine
-Origin of the Drug
-South American Shrub
- Pilocarpus jaborandi
-Isolated in 1875
-Chemical Structure
+
- Cholinergic Parasympathomimetic agent
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+
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
Reaction Sequence
Phospholipase C
Phosphatidyl inositol
biphosphate (PIP) complex
G- Protein
subunits , , 
GDP\
Inositol 1,4,5 - triphosphate (IP3) + diacylglycerol
GTP
Myosin-actin interactio
(Muscle Contraction)
Muscarinic Receptor
caldesmon
Endoplasmic Reticulum
Ca2+
Calmodulin/ Ca2
The End Result
- Contraction of pupil and stimulation of ciliary muscle
- Tension on scleral spur opening trabecular meshwork
- Increased out flow, lowering of pressure
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