9/26/2017

Disclosure Statement

 “I have no relevant financial relationships with the manufacturer(s) of any commercial product(s) and/or Joseph Bergmann, MD provider(s) of commercial services discussed in this CME activity.”

Medical Treatment Medical Treatment

 Is it effective / How does it work?  Oral  Is it safe / What are the side effects?  Methazolamide  Acetazolamide  Is it expensive?  Topical  How do I take my drops  Prostaglandins  Do I need to do this my whole life?  Beta-blockers  Alpha-adrenergic  Carbonic Anhydrase Inhibitors  Cholinergic Agonists  Rho Kinase Inhibitors

Oral Carbonic Anhydrase Oral Carbonic Anhydrase Inhibitors Inhibitors  Preparations/ Dosing  Anatomy/ Physiology/ Pharmacokinetics  Side Effects  Cost

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Oral CAIs Oral CAI’s: Side Effects

 How is it available?  Allergy  Methazolamide ○ 25-50mg 2-3 times daily  Rare  Acetazolamide ○ 250-500 mg standard release dosed 4-6 hours  Aplastic anemia, Thrombocytopenia, ○ 500 mg Sequels (standard release) dosed 12 hours Agranulocytosis  How it works  Decrease aqueous humor formation by direct antagonist activity on  Hypokalemia ciliary epithelial carbonic anhydrase  Create systemic acidosis  Common  90% of enzyme must be inhibited for it to be effective  Methazolamide is liver metabolized, acetazolamide is kidney  GI: nausea, diarrhea, weight loss, metallic taste metabolized  Nervous: Lethargy, depression, parathesias,  Action  Onset within 1 hour decreased libido  Peak 2-4 hours (sustained release  Renal: Kidney stones  duration  “Hangover”

Oral CAI’s: Cost Prostaglandin  Acetazolamide  Regular and Sustained Release (Diamox Analogs Sequels) ○ $$$  Methazolamide  $$$

Prostaglandin Analogs Prostaglandin Analogs

 How is it available?  How it works  Prostamides  Improves aqueous outflow  Bimatoprost, Latanoprost, Travaprost  Pressure dependent and independent ○ Xalatan introduced in 1996  Elevated presence of metalloproteinases--- ○ Once daily dosing breaking down the collagen matrix within the uveoscleral region that surround the ciliary  Decosanoid muscle bundles.  Unoprostone isopropyl (Rescula)  Increases uveoscleral outflow to >50%  BID dosing

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Prostaglandin Analogs Prostaglandin Side Effects

 Effect of Prostaglandins  Hyperemia  Latanoprost / Travaprost 25-32% reduction in  ? Cystoid Macular Edema IOP ○ Prodrugs metabolized in cornea  Anterior Iritis  Bimatoprost 27-33% reduction in IOP  ? exacerbation of underlying herpes  Unoprostone isopropyl 13-18% reduction in IOP keratitis  Duration  Dry eye  Onset: slow  Peak: 10-14 hours  Duration: near 24 hours

Prostaglandin Side Effects Cosmesis

 Eyelash changes  Periorbital fat atrophy  Periorbital Pigmentation  Iris color changes

Prostaglandin Analogs: Cost Beta-Blockers

 Latanoprost  Travaprost  Travatan Z  Lumigan  Rescula

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Beta-Blockers Beta-Blockers

 Timolol was intro in 1978  How it Works  Nonselective  Aqueous suppressant  Timolol, levobunolol, carteolol, metipranilol  inhibits synthesis of cyclic adenosine  Selective monophosphate in the ciliary epithelium  Betaxolol—preferentially binds beta-1  hepatic metabolism with renal excretion adrenergic receptors thus being cardio-selective Effect  Multiple studies now support once daily  20% reduction in pressure dosing vs. BID  Onset: 20 minutes  AM dosing  Peak: 1-2 hours  ? Tachyphylaxisis  Duration: nearly 24 hours

Timolol: Side Effects Timolol: Cost

 Cardiac  Cheap  bradycardia, syncope, decreased BP, arrhythmia  decrease HDL and increase total cholesterol  Respiratory  bronchospasm  Central Nervous  depression, hallucination, fatigue  Ocular  burning, dryness  Other  impotence, mask hypoglycemic sign

Alpha-adrenergics Alpha-adrenergics

 Brimonidine (Alphagan/Alphagan-P)  Dosed BID  multiple concentrations ○ higher concentration = more hypersensitivity  Apraclonidine (Iopidine)  Epinephrine and Dipivefrin HCL ○ nonselective, not used any longer

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Alpha-adrenergics Brimonidine: Side Effect

 How it works  Ocular  aqueous suppressant I  improves uveoscleral outflow  allergy (peak onset 12-18 months),  alpha-2 adrenergic agonist activating g-coupled protein conjunctival blanching, dryness, mydriasis, receptors inhibiting adenylate cyclase thereby decreasing c-AMP eyelid retraction  vasoconstriction also can cause acute lowering of IOP  Systemic  prolonged use leads to buildup of prostaglandins in eye thereby explaining improved uveoscleral outflow  headache, dry mouth, fatigue, bradycardia,  Effect hypotension  Up to 26% reduction in IOP  Children: NO! NO! NO!  Onset: rapid  Peak: 2 hours  somnolence, apnea, hypotension, seizure  Duration: up to 12 hours  Tachyphylaxis

Alpha-adrenergic Cost Topical CAIs

 Alphagan P  Brimonidine (Generic)  Iopidine

Topical Carbonic Anhydrase Topical CAIs Inhibitors  • Dorzolamide 2% (Trusopt) and  How it works Brinzolomide 1% (Azopt)  Aqueous suppressant  inhibits carbonic anhydrase in ciliary body  Both are now generic epithelium  Both are BID or TID dosing  90%+ of enzyme must be inhibited for effective IOP control Effect  15-20% reduction in IOP  Onset: relatively rapid  Peak: 2 hours  Duration: 8-12 hours

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Topical CAIs: Side Effects Topical CAIs Cost

 Sulfa Allergy?  Azopt  Ocular  Trusopt  blurred vision(myopic shift), irritation,  Brinzolomide burning, pain, dermatitis  Dorzolamide  Systemic  rhinitis, taste disturbance, fatigue  Renal  kidney stones

Cholinergics Pilocarpine Cost

Direct Acting Pilocarpine 1-6% solutions BID-to-QID dosing Indirect Acting (never seen these used) Echothiophate Iodide Demercarium Iodide Physostigmine Isoflurophate

Cholinergics Pilocarpine Side Effects

 How it works  Ocular  increase trabecular outflow  miosis (decrease vision)  causes contraction of the longitudinal  brow ache muscle in ciliary body thereby pulling on the scleral spur and stretching the trabecular  myopic shift meshwork  shallow anterior chamber  Effect : 15-25% reduction in IOP  retinal detachment  Onset: 10-30 minutes  inflammation  Peak: 1.5-2 hours  Systemic  Duration: 4-8 hours  essentially none...very safe

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Rho -Kinase Inhibitors Combinations

 The next revolution in medical glaucoma -  • Cosopt Kinase Inhibitors care?  Dorzolomide/timolol  Increased outflow through trabecular meshwork  Combigan  How: reduces cellular stiffness  Brimonidine/timolol  May also be neuro-protective, anti-  Simbrinza inflammatory and improve bloodflow to the  Brimonidine/Brinzolomide optic nerve  Not available yet: 2 US companies are in early clinical research--likely be years

Combinations Preserative free

 Occudse  Beta-blocker  Cosopt-PF  Combination timolol and dorzolamide  Zioptan  prostaglandin

Medical Tx in Children Medical Tx in Pregnancy

 1st Trimester  NO Alphagan/Brimonidine  Brimonidine is Class B (preferred)  Caution with beta-blocker  ? teratogenicity of all others  2nd Trimester  CAIsoften acceptable  Brimonidine and Beta-blockers are generallyOK  Prostaglandins--premature labor  Prostaglandinssafety  CAI--fetal growth monitoring  3rd Trimester  Brimonidine, beta-blockers, CAIs ok at least early  Brimonidine not near labor--CNS depression  Prostaglandin not recommended  Post-partum  CAIs and Beta-blockers rec by American Academy of Peds with breast feeding

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The Green Stuff Lifestyle Modification

 “Doc is there something I shouldn’t eat or that I should avoid?”  “Doc is there an exercise that will help?”  “I saw an advertisement for these supplements that treats/cures glaucoma”

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