glaucoma medications l.
Download
Skip this Video
Loading SlideShow in 5 Seconds..
GLAUCOMA MEDICATIONS PowerPoint Presentation
Download Presentation
GLAUCOMA MEDICATIONS

Loading in 2 Seconds...

play fullscreen
1 / 65

GLAUCOMA MEDICATIONS - PowerPoint PPT Presentation


  • 906 Views
  • Uploaded on

GLAUCOMA MEDICATIONS. WHAT WE HAVE, WHERE WE’RE GOING… Jill Autry, OD, RPh Eye Center of Texas, Houston drjillautry@tropicalce.com. THE HISTORY OF GLAUCOMA. The terms “glaucosis” and “hypochyma” were used synonymously Vague terminology meaning “greenish/bluish” discoloration

loader
I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
capcha
Download Presentation

PowerPoint Slideshow about 'GLAUCOMA MEDICATIONS' - Patman


An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript
glaucoma medications
GLAUCOMA MEDICATIONS

WHAT WE HAVE, WHERE WE’RE GOING…

Jill Autry, OD, RPh

Eye Center of Texas, Houston

drjillautry@tropicalce.com

the history of glaucoma
THE HISTORY OF GLAUCOMA
  • The terms “glaucosis” and “hypochyma” were used synonymously
  • Vague terminology meaning “greenish/bluish” discoloration
  • Used indiscriminately in discussions of blindness until 1800s
  • “Hypochyma” linked later to cataract and considered treatable
  • “Glaucosis” was the incurable association
the history of glucoma
THE HISTORY OF GLUCOMA
  • In 1622, linked to firmness of globe
    • “humour settled in hollow nerves…the eye grown more solid and hard than natural…”
    • Thought to be disorder of vitreous or choroid
  • In 1820, glaucoma and cataract were differentiated
  • In 1840, the term glaucoma was linked to increased IOP but only in regards to acute or absolute glaucoma
  • In 1857, the ophthalmoscope was invented allowing for view of optic nerve damage
the history of glaucoma treatment
THE HISTORY OF GLAUCOMA TREATMENT
  • In 1857, iridectomy was introduced for acute glaucoma
  • In 1875, the use of a miotic for acute glaucoma
  • In 1935, used medications for the treatment of a less acute form of increased IOP which can lead to same end result
  • In 1957, oral CAI for use in glaucoma treatment
diagnosis
DIAGNOSIS
  • Gonioscopy
  • Optic nerve examination
  • Intraocular pressure
  • Pachymetry
  • Visual field
  • Nerve fiber layer analysis
aqueous and anatomy
AQUEOUS AND ANATOMY
  • Aqueous is continuously produced by the ciliary body
    • 2-3 µl/minute produced on a diurnal curve
    • Turnover every 1.5-3 hours
  • Aqueous flows from the posterior chamber through the pupil into the anterior chamber
  • Aqueous filters largely through the trabecular meshwork (90%)
  • Aqueous also exits to a smaller extent through the ocular venous system (10%)
    • Uveoscleral outflow (ciliary body, choroid, scleral vessels)
autonomic nervous system
AUTONOMIC NERVOUS SYSTEM
  • Sympathetic regulation
    • Fight and flight
    • 2 main classes of receptors
      • Beta receptors (ß1 and ß2)
      • Alpha receptors (α1 and α2)
  • Parasympathetic regulation
    • Lay down on the couch and go to sleep
autonomic nervous system8
AUTONOMIC NERVOUS SYSTEM
  • Pupil is controlled by both
    • Sympathetic system dilates the pupil by stimulating the contraction of dilator muscle
    • Parasympathetic system constricts the pupil by causing contraction of the sphincter muscle.
  • Ciliary body is controlled by both
    • Sympathetic system for aqueous production
    • Parasympathetic system causing ciliary body muscle movement
pilocarpine
PILOCARPINE
  • Cholinergic, parasympathomimetic agent
  • Mechanisms of action are completely mechanical
  • Causes miosis of pupil by contraction of iris sphincter muscle
    • Constricts the pupil pulling the peripheral iris away from the trabecular meshwork
  • Pulls scleral spur posteriorly and internally
    • Produces alterations in ciliary body mediated configuration of the outflow apparatus
pilocarpine10
PILOCARPINE

Max of 10-20% IOP reduction

Available in 0.5%, 1%, 2%, 3%, 4%, 6%

Pilopine HS 4% gel

1% or 2% is most widely used

Chronic use limited by efficacy, compliance factors, and side effects

pilocarpine11
PILOCARPINE
  • Adverse effects and limitations
    • Pupil constriction
      • Permanent after long term use
    • Induced myopia
    • Headache
      • Accommodative spasm
    • Blurred vision
      • Accommodative spasm
    • Retinal detachment
    • Frequency of use
when to use pilo
WHEN TO USE PILO
  • Acute angle closure
    • Verify with gonioscopy
      • Other eye should be narrow, too
    • Usually hyperopic, older patients with increasing lens size
    • Can be precipitated by certain medications
    • ??? Wait until IOP is below 40mmHG????
  • Prophylaxis against angle closure
why not use pilo more
WHY NOT USE PILO MORE?
  • Miosis
  • Young patients
    • Increased headache
    • Blurred vision secondary to fluctuating myopia
  • Inflammatory conditions
    • Increases flare in the anterior chamber
  • Myopic patients
    • More at risk for retinal detachment
  • Patients with cataracts
    • Pupil constriction limits vision
    • Small pupil can complicate cataract extraction
prostaglandins
Prostaglandins
  • Prostaglandin F2α analogues
    • Xalatan (latanoprost)
    • Lumigan (bimatoprost)
    • Travatan (travoprost); Travatan Z (BAK free)
  • Increase fluid outflow through ocular venous system (uveoscleral outflow)
  • Max IOP reduction of 33-40%
  • Once daily (qhs) meds
    • Twice daily yields less IOP reduction
prostaglandins15
Prostaglandins
  • Systemic side effects are extremely rare
  • Allergy is extremely rare
  • Most side effects are local and cosmetic
    • Conjunctival hyperemia
    • Iris pigmentation
    • Periorbital darkening
    • Eyelash growth/thickening/darkening
when prostaglandins are your first choice
WHEN PROSTAGLANDINS ARE YOUR FIRST CHOICE
  • Primary Open Angle Glaucoma
  • Ocular Hypertension
  • Pigmentary Glaucoma
  • Pseudoexfoliative glaucoma
  • Angle recession glaucoma
    • Not during acute episode if possible
when prostaglandins are your last choice
WHEN PROSTAGLANDINS ARE YOUR LAST CHOICE
  • Elevated IOP secondary to trauma
  • Inflammatory glaucoma
    • Glacomatocyclitic iritis (aka Possner-Schlossman)
    • Fuch’s Heterochromic iridocyclitis
    • IOP increases due to herpetic disease
  • History of/concern of inducing macular edema
    • Diabetic with macular edema, epiretinal membrane
  • Steroid induced glaucoma
  • Post-surgical IOP spike
  • Neovascular glaucoma
  • Unilateral treatment
comparison of prostaglandins
Comparison of Prostaglandins
  • Similar in ability to lower pressure
    • Lumigan 0.03% is lower across more time points
    • Xalatan has highest non-responder rate
  • All are associated with hyperemia
    • Structure mediated, not preservative mediated
    • Lumigan 0.03%=Travatan Z>Xalatan
    • Less severe hyperemia (66%) with new Lumigan 0.01% compared with Lumigan 0.03%
  • All may cause iris color and eyelash growth
    • Iris color changes permanent
      • Least with Lumigan; most with Xalatan
    • Eyelash changes impermanent; most with Lumigan
when adding agents
WHEN ADDING AGENTS
  • Think mechanism of action
  • Best chance of additivity by combining medications with different mechanisms
  • PGAs lower IOP by increasing aqueous outflow (uveoscleral/trabecular)
  • Complement a PGA by adding a drug that inhibits aqueous production
    • Brimonidine (also has uveoscleral MOA)
    • CAI
    • Beta-blocker
ciliary body and autonomic nervous system
CILIARY BODY AND AUTONOMIC NERVOUS SYSTEM
  • Sympathetic system increases aqueous production
    • Through stimulation of ß receptors
    • ß blockade decreases aqueous production
  • Sympathetic system decrease aqueous production
    • Through activation of α2 receptors
    • α2 agonists decrease aqueous production
alpha 2 agonists
ALPHA-2 AGONISTS
  • 2-adrenergic agonist
  • Apraclonidine (Iopidine)
  • Brimonidine (Alphagan)
    • Enhanced α2 selectivity due to double ring structure
brimonidine
BRIMONIDINE
  • Primary mechanism of action is decreased aqueous production
    • Great additive agent to PGA
  • Secondary mechanism of action is enhanced uveoscleral outflow
    • Great combination agent with timolol
  • Max IOP reduction of 20-30%
  • Bid to tid dosing
alphagan p 0 1
ALPHAGAN P 0.1%
  • Purite preservative
  • Higher pH
    • Neutral, nonionized form is better absorbed
  • Decreased drug concentration
    • 50% decrease
  • Unaltered efficacy
  • Less chance for local allergy
  • Less chance for systemic side effects
    • Dry mouth, fatigue, hypotension
ocular allergy
OCULAR ALLERGY
  • Ocular allergies in up to 30% of patients
    • Original Alphagan 0.2% and generic brimonidine 0.2%
      • 30% allergy rate
    • Alphagan P 0.15%
      • 20% allergy
    • Alphagan P 0.1%
      • 10% allergy
when to use brimonidine
WHEN TO USE BRIMONIDINE
  • Additive agent to a PGA
    • First or second line addition
  • Monotherapy with PGA is contraindicated
  • Post-op IOP spikes
  • Concerns for preservative toxicity
  • Only category B glaucoma drop for pregnancy
when not to use brimonidine
WHEN NOT TO USE BRIMONIDINE
  • History of allergy to brimonidine in any concentration
  • Eyelid swelling, tenderness, itching, follicular reaction
    • Can develop within weeks/months of initiation or even years later
  • Patients prone to hypotension
  • Patients with complaints of somnolence
ciliary body and autonomic nervous system28
CILIARY BODY AND AUTONOMIC NERVOUS SYSTEM
  • Sympathetic system increases aqueous production
    • Through stimulation of ß receptors
    • Beta blockade decreases aqueous production
  • Sympathetic system decrease aqueous production
    • Through activation of α2 receptors
    • α2 agonists decrease aqueous production
beta blockers
BETA BLOCKERS
  • Decrease aqueous production
  • No effect on outflow
  • Max IOP reduction of 20-30%
  • Once to twice daily (qd to bid) dosing
    • qd dosing equivalent to bid dosing
  • May be less effective if on oral beta blocker
beta blockers30
Beta Blockers

Timoptic (timolol)

Timoptic XE (timolol gel)

Betimol (timolol)

Betagan (levobunolol)

OptiPranolol (metipranolol)

Ocupress (carteolol)

Betoptic S (betaxolol)

concerns with treatment
CONCERNS WITH TREATMENT
  • Elderly
  • Lung Disease
    • Contraindicated in asthma, COPD, etc.
  • Heart disease
    • Contraindicated in CHF (heart failure)
  • Diabetes
  • Impotence
selective beta blocker
Selective Beta Blocker
  • May cause less side effects
  • Still use cautiously
  • Betoptic S (betaxolol suspension)
    • Fewer side effects on the lung
    • Decreased efficacy vs. other beta blockers
long term efficacy
LONG TERM EFFICACY
  • Effect diminishes with time
  • First few weeks is “short-term” escape
    • Up-regulation of beta receptor numbers
  • Long-term drift
    • A receptor or intracellular tolerance develops
what about combigan
WHAT ABOUT COMBIGAN?
  • Alphagan 0.2% with timolol 0.5%
  • Complementary mechanism of actions
  • Dosed BID
  • Less allergy than any of the other Alphagan products (5% vs 20% allergy rate)
    • 50% less than 0.2 brimonidine
  • Advantages of combination therapy
combigan in adjunctive therapy with a pga mean iop
COMBIGAN™ in Adjunctive Therapy With a PGA: Mean IOP

Added to a PGA baseline

-6.9 mm Hg(29%)

*

*

Mean IOP (mm Hg)

COMBIGAN™(brimonidine tartrate/timolol maleate

ophthalmic solution) 0.2%/0.5% + PGA (n = 37)

*P < .0001 vs baseline

Month

1Nixon and Hollander. 2AAO, 2007. Data on file, Allergan, Inc.

carbonic anhydrase
CARBONIC ANHYDRASE
  • Carbonic anhydrase is an enzyme present in the biochemical production of aqueous
    • Causes bicarbonate and hydrogen movement
  • Inhibition of carbonic anhydrase
    • Blocks active transport needed for aqueous production
  • End result is reduction of aqueous humor formation
  • Subsequent decrease in intraocular pressure
topical cai
TOPICAL CAI

Reduce aqueous humor production

Max IOP reduction of 15-20%

bid to tid dosing

Dorzolamide (Trusopt®)

Brinzolamide (Azopt®)

Dorzolamide + Timolol

Cosopt®

adverse effects concerns
ADVERSE EFFECTS/CONCERNS
  • Bitter taste
  • Stinging
  • Conjunctival hyperemia
  • Tachyphylaxis
  • Concerns with history of sulfa allergies
  • Corneal concerns
sulfa allergy
SULFA ALLERGY
  • Sulfa allergy not sulfur allergy
  • Rash is common sign; usually seen in the antibiotic class of sulfonamides (like Septra or sulfacetamide ointment)
  • Less likely to see in non-antibiotic meds
  • Diamox, Neptazane, Azopt, Trusopt, Cosopt
  • Even less likely to see with topical medications
  • Sulfites and sulfates are chemically different-no cross reactivity with sulfa allergies
cornea and cai
CORNEA AND CAI
  • Invest Ophthalmol Vis Sci, 2008 Mar;49(3):1048-55.
    • Role of carbonic anhydrase in corneal endothelial HCO3-transport.
  • Arch Ophthalmol. 2007 Oct;125(10):1345-50.
    • Effect of dorzolamide on central corneal thickness in humans with cornea guttata.
  • Arch Ophthalmol. 204 Jul;122(7):1089.
    • Short-term effect of dorzolamide on central corneal thickness in humans with cornea guttata.
indigent programs
INDIGENT PROGRAMS
  • Allergan (Lumigan, Alphagan P, Combigan)
    • 1-800-553-6783
  • Alcon (Azopt, Travatan Z, Betoptic S)
    • 1-800-222-8103
diamox acetazolamide
DIAMOX(Acetazolamide)
  • Nonbacteriostatic sulfonamide
  • Decreases carbonic anhydrase
    • Decreases hydrogen and bicarbonate formation
  • Results in decreased aqueous production in the ciliary body by producing a systemic acidosis
  • Results in alkaline diuresis in the kidney but tolerance develops quickly
  • Contraindicated in renal, hepatic, or respiratory disease
diamox acetazolamide43
DIAMOX (Acetazolamide)
  • Decreases carbonic anhydrase in the ciliary body which decreases aqueous humor formation
  • Decreases IOP by 40-60%
  • Starts to work in 1 hour, peak effect at 4 hours
  • Comes in 125mg, 250mg, 500mg sequels
  • Angle closure dose: (2) 250mg tablets initially—needs PI
adverse effects
ADVERSE EFFECTS

Metallic taste

Paresthesias (“pins and needles”)

Used mostly in emergencies because of side effects with chronic use

Kidney stones

Acute respiratory failure

Acid-base imbalances

Blood dyscrasias (aplastic anemia)

Induced myopia

use in lowering iop
USE IN LOWERING IOP
  • Treatment of acute angle closure glaucoma
  • Treatment of less acute increased IOP
  • Treatment of post-surgical IOP spikes
oral cai uses
ORAL CAI USES
  • Treatment of pseudotumor cerebri
  • Treatment of other causes of increased intracranial pressure
  • Controversial treatment of serous retinal detachments
  • Treatment/prevention of “altitude sickness”
other uses for glaucoma drops
OTHER USES FOR GLAUCOMA DROPS
  • May be helpful with Fuch’s patients
    • Avoid CAIs
  • Stabilizing visual acuity/Rx in RK patients
    • Especially prostaglandins given duration of action
  • Brimonidine can
    • Decrease pupil size to eliminate glare
    • Decrease hyperemia
    • Lacks side effects of pilocarpine
other uses for glaucoma drops48
OTHER USES FOR GLAUCOMA DROPS
  • Iopidine® to diagnose Horner’s?
    • Has been demonstrated to have same sensitivity as cocaine test for diagnosis of Horner’s
    • Alphagan less likely to give reliable results secondary to increased alpha-2 selectivity
  • Pilocarpine for diagnosis of Adie’s pupil
    • 1% dilute 1:10 to make 0.1% solution
    • 2% dilute 1:20 to make 0.1% solution
adie s tonic pupil
ADIE’S TONIC PUPIL

Usually young female

Poor reaction to light

Slow constriction to near

Slow redilation following near constriction

Vermiform movement

Constricts to 0.125% pilocarpine

May not constrict in initial stage

Long standing can result in small pupil

oral pilocarpine
Oral Pilocarpine
  • Salagen® (oral pilocarpine)
    • 5 mg qid for dry mouth
  • Approved for dry mouth with Sjogren’s patients
  • Approved for dry mouth associated with head/neck radiation
  • Also used Evoxac®
    • 30 mg tid
novel pharmaceuticals
Novel Pharmaceuticals
  • Adenosine A1 receptor antagonist
  • TGF-beta2 growth factor inhibition
  • Wnt antagonist sFRP1
  • Decreasing neuronal toxicity
    • Glutamate inhibition
    • Nitrous oxide inhibition
    • Capsase enzyme antagonists
  • Decrease matrix metalloproteinases
topical application and glaucoma
TOPICAL APPLICATION AND GLAUCOMA

Corneal permeability

Less than 5% of drop is absorbed through cornea

Conjunctival vasculature loss of drug

Tear wash out

Drug solution drainage through nasolacrimal system

Spillover out of the eye

High concentrations inducing local reactions

Preservative toxicity

systemic treatment and glaucoma
SYSTEMIC TREATMENT AND GLAUCOMA

Blood-Aqueous Barrier

prevents systemically administered substances from entering into the aqueous humor

Blood-Retinal Barrier

severely limits drug entry into the extravascular space of the retina and into the vitreous

Need high systemic doses to overcome

Results in higher side effects/toxicity

current ocular drug delivery
Current Ocular Drug Delivery

Drops

Less than 5% of drop is absorbed into cornea or anterior chamber

Ocular toxicity of preservatives

Subconjunctival injections

Periocular injections

Intravitreal injections

Risk of infection/IOP spikes/RD

Sustained release implants

Systemic-oral and intravenous

Exposes whole body to potential toxicity

advances in ocular drug delivery
Advances in Ocular Drug Delivery

Formulation factors

Surfactants-dispersion of solutes

Viscolyzers-retention and bioavailability

Instilled volume

Reduced with thicker agents

Administration technique

Non-preserved buffering techniques

Minimizes toxicity

More natural pH

advances in ocular delivery
Advances in Ocular Delivery

Increased ocular contact time

Ointments

Gels

Liposome formulations

Nanoemulsions

Colloidal systems

Disperse and encapsulate meds

glaucoma and drug delivery
GLAUCOMA AND DRUG DELIVERY

Controlled release

Sustained pharmaceutical levels

Sustained IOP control

Decreased frequency of dosing

Compliance

Reduced drug concentration

Decreased local side effects

Avoid systemic side effects

drug releasing contact lens
DRUG RELEASING CONTACT LENS
  • Concerns
    • Ability to load total drug mass onto contact lens
    • Ability to release drug at therapeutic doses
    • Avoid creating ocular toxicity
    • Maintaining optical clarity
    • Maintaining refractive properties
    • Amenability to storage
    • Biocompatibility
drug releasing contact lens59
DRUG RELEASING CONTACT LENS
  • Advantages
    • Increase compliance
    • Increase contact time
    • Decrease medication concentration
    • Up to 50% absorption through cornea
drug releasing contact lens60
DRUG RELEASING CONTACT LENS
  • Hydrogel contact lens trial
    • Timolol and Brimonidine
    • Maximum uptake of drug and release was limited
    • Silicon-hydrogels were similar
  • Molecularly imprinted hydrogel CL
    • Better retention of drug and slower release
    • Smaller molecules load better
drug releasing contact lens61
DRUG RELEASING CONTACT LENS
  • Liposomal coated hydrogel contact lenses
    • Lidocaine and levofloxacin trials
  • Drug entrapped contact lenses
    • Polymer technology
    • Drug containing surfactants
    • Drug polymer film coated in a hydrogel lens
      • Proven linear release kinetics
plug based delivery system
PLUG BASED DELIVERY SYSTEM
  • Drug core inside punctal plug
  • Sustained drug release over time
  • Phase II clinical trial
    • Latanoprost was used
    • L-PPDS
      • Latanoprost punctal plug delivery system
subconjunctival route
Subconjunctival Route
  • Safer and less invasive than the intravitreal route
  • Systemic absorption is low
  • Lower systemic side effects while providing a localized drug effect
  • Substantial evidence indicating that drugs administered subconjunctivally can reach the vitreous effectively
  • Injectable microspheres have already been tested
    • Timolol with continual release up to 107 days
intravitreal delivery
INTRAVITREAL DELIVERY
  • Vitrasert
    • Ganciclovir implant for AIDS associated CMV
  • Retisert
    • Fluocinolone implant for posterior uveitis
  • Ozurdex
    • Dexamethasone injectable, biodegradable pellets for RVO
  • Medidur
    • Fluocinolone injectable implant for diabetic macular edema
in conclusion

IN CONCLUSION…

Jill Autry, OD, RPH

drjillautry@tropicalce.com