Download Ocular Pharmacology

Ocular Pharmacology
Erica Tolar DVM, DACVO
Drug Delivery
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Topical-most common route for ophthalmic medications
o Solution-the drug is completely dissolved in a solvent
o Suspension-particles of a drug in a saturated aqueous vehicle
 Topical steroids-prednisone acetate; must shake well prior to use
o The palpebral fissure holds approximately 25-30uL of fluid
o The average eye drop contains 25-70uL of fluid
o The eye can only hold one drop at a time!
o Must wait 5 minutes between eye medications
o Administering one drop right after another drug will reduce the availability of the
first drug
o Topical medications read the aqueous, iris, ciliary body, penetration past the lens
is minimal
o Melanin binding can influence the pharmacologic effect of drugs
 Atropine
o Ointments or gels improve precorneal retention of the drug
o Ointments can be administered at the same time, however you must give solutions
prior to ointments
o No delay in wound healing if you use ointments vs. solutions
o Avoid ointments in corneal perforations or an impending corneal perforation
o Soft contact lenses or collagen shields are another way to deliver medications
Subconjunctival
o Therapeutic drug levels for 8-12 hours after an injection with a water soluble
medication and up to 2-3 weeks with a drug in suspension
o Don’t inject through the sclera!
Retrobulbar
o Most often used for regional anesthesia
o Potential complications: globe perforation, optic nerve injury, orbital hemorrhage,
central anesthesia
o Used in horses to perform standing procedures
Intracameral
o Used during intraocular surgery
Intravitreal injection
o Vitreous is resistant to medication penetration due to lack of blood supply
o Complications: retinal detachment, lens trauma, hemorrhage
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Systemic penetration
o Some medications can be stopped by the blood ocular barrier unless there is
ocular inflammation, infection or trauma to promote penetration
o Eyelids need to be treated with systemic therapy
Anti-infectious Agents
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Indiscriminate use encourages the development of drug resistant bacteria
Bacteriostatic or bactericidal
Cephaloporins-cefazolin, first generation, gram positive cocci
Aminoglycosides-gentamicin, tobramycin, neomycin
o Gram positive and negative
o Synergistic with cephalosporins
o Available in an ointment preparation
o Neomycin can cause irritation and some animals can have an allergic reaction
o Gentamicin can delay epithelial healing
Tetracycline-doxycycline
o Mycoplasma and chlamydia
o Decreases matrix metalloproteinases
Chloramphenicol
o Readily diffuses into the anterior chamber
o Good for stromal abscesses
o Aplastic anemia is a side effect in people so recommend glove use when applying
Polypeptide antibiotics-polymyxin B, bacitracin, gramicidin, vancomycin
o No penetration into the anterior segment
Fluoroquinolones-ofloxacin, ciprofloxacin, moxifloxacin, gatifloxacin, levofloxacin
o Gram positive and negative
o Ciprofloxacin is available as an ointment
o Minimal toxicity
o Ofloxacin has higher corneal penetration and can exceed MIC better than
ciprofloxacin
o Retinal toxicity with oral baytril in cats
Lincosamides and Macrolides-clindamycin, erythromycin, azithromycin
o Toxoplasma, chlamydia, mycoplasma
o Azithromycin has more gram negative spectrum-bartonella species
Sulfonamides
o Toxic to the lacrimal gland
o 4% of dogs on TMS develop dry eye
o Measure STT before starting medication and have the owner monitor STT every
couple days in at least 1 eye
Anti-viral
o All are virostatic and don’t eliminate latent infection
o Pyrimidine nucleoside analogues
 Idoxuridine, trifluridine
o Purine nucleoside analogues
 Acyclovir, vidarabine, cidofovir, famcyclovir
 Cidofovir is BID dosing
o L-Lysine
 Exchange arginine for lysine which decreases viral replication
 500mg PO q12h
o Interferon
 Unsure about stability out of a subzero freezer
Glucocorticoids
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Block cyclooxygenase and lipooxygenase pathways
Decrease cellular exudation
Inhibit fibroblastic/collagen formation
Slow epithelial migration
Decrease post-inflammatory neovascularization
Stabilize inflamed capillary permeability
Dexamethasone sodium phosphate
o 5-7 times more anti-inflammatory effect than prednisone acetate
o Very poor corneal penetration
o Not indicated for uveitis
o Used for keratitis, conjunctivitis
Don’t use steroids in the face of ulcerative keratitis
May potentiate infectious keratitis and result in malacia
Oral steroids have good intraocular penetration
Hydrocortisone is an incredibly weak anti-inflammatory
Nonsteriodal Anti-inflammatories
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Flurbiprofen, diclofenac, suprofen, ketorolac
Diclofenac is better at stabilizing the blood ocular barrier
Can worsen infectious keratitis especially herpetic keratitis in cats
Rimadyl, meloxicam, previcoxx are good for ocular inflammation
Calcineurin inhibitors
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Tacrolimus, cyclosporine, pimecrolimus
Doesn’t penetrate into the aqueous
Penetrates well into the lacrimal gland increasing lacrimation
Good for inflammatory diseases of the cornea
Medications can take up to 2 months to work
Cytotoxic agents
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Azathioprine
Activated in the liver
Uveitis, scleritis, VKH, optic neuritis, GME
Monitor CBC, liver values
Megesterol Acetate
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Eosinophilic keratitis in cats
Side effects: polyphagia, polydipsia, pyometra, diabetes, behavior changes
Anti-glaucoma medications
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Reduce aqueous humor secretion
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Increase aqueous humor outflow
o Direct-acting parasympathomimetics
 Pilocarpine-very acidic
 Causes miosis
 Minimal pressure lowering ability
 Carbachol-used after intraocular surgery to decrease post operative
pressure spikes
 Avoid in secondary glaucoma
o Indirect-acting parasympathomimetics
 Demecarium bromide
 Used for miosis to manage lens subluxations
 Optic nerve sparing effect
 Systemic toxicity can result (vomiting, diarrhea)
 Avoid in secondary glaucoma
o Nonspecific adrenergic agonist
 Epinephrine and dipivefrin
 Decrease aqueous formation by decreasing blood flow and increase
outflow
 Minimal pressure lowering ability alone
o Alpha 2-Adrenergic Agonists
 Apraclonidine-decreases aqueous production but toxic
o Beta blockers
 Nonspecific beta blocker-timolol, carteolol, levobunolol
 Decrease aqueous production
 Maximum reduction in 2-4 hours
 Decreases heart rate, can exacerbate asthma in cats
o Carbonic Anhydrase Inhibitors
 Decreases aqueous production, 98% of carbonic anhydrase must be
inhibited to achieve full IOP reduction
 Aqueous production is suppressed by 40-60%
 Dorzolamide, brinzolamide, methazolamide
 Systemic administration is comparable to topical administration BID-TID
 Using oral and topical together don’t have an additive effect
 Methazolamide causes systemic acidosis and $$$
 Dorzolamide is acidic and can cause blepharitis
o Prostaglandin Analogues
 Travaprost, latanoprost, unoprostone, bimatoprost
 Prodrug is enzymatically hydrolyzed during its passage through the
corneal epithelilum and the active form is released in the anterior chamber
 Cats have different receptors and are not able to metabolize these drugs
like dogs or humans
 Increases uveoscleral outflow as well as decrease aqueous production
 Latanoprost can decrease IOP in glaucomatous dogs 50%
 Dosing 1-2 times daily
 Used in primary glaucoma
o Osmostic Agents
 IV or oral administration
 Distributed in the extracellular fluids causing an increase in their
osmolality which causes a gradient from the aqueous and vitreous humor
into the plasma
 NOT to be used in uveitis cases
 Mannitol, glycerin
o Neuroprotectants
 Calcium channel blockers, nitric oxide inhibitors, free radical scavengers
 Demecarium bromide
Mydriatics/Cycloplegics
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Cholinergic antagonists-paralyze the pupillary sphincter
Sympathomimetics-stimulate the iris dilator muscle, no cycloplegia
Not indicated in glaucoma
Decreases STT
Salivation, especially in cats
Tropicamide
o Minimal cycloplegia
o Dilation in 30 minutes
o Short acting
Atropine
o Potent mydriatic and cycloplegia
o Maximum dilation in 30-60 minutes
o Melanin binding
Phenylephrine
o Sympathomimetic
o Use in combination with atropine to dilate the pupil
o Vasoconstriction
o Dilute formulation used in identifying location of lesion in Horner’s syndrome
Epinephrine
o Sympathomimetic
o Used intracamerally during intraocular surgery
Local anesthetics
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Impede sodium ion entrance to the axon interior preventing nerve depolarization
Repeated application is toxic to the corneal epithelium and should NEVER be used as a
therapeutic agent for pain
Proparacaine
o Needs to be refrigerated
o Single application lasts 45 minutes, maximum effect lasts 15 minutes in dogs, 25
minutes in cats
Tetracaine
o Shorter duration of anesthesia compared to proparacaine
o More irritating
Lidocaine
o Rapid onset, lasts 45 minutes to 1 hour
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o Used in local blocks
Bupivacaine
o 4 times more potent than lidocaine
o Lasts 5-10 hours with the 0.5% solution
o Use in combination with lidocaine
Topical Disinfectants
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Dilute betadine solution
1:10 to 1:50
Tissue Adhesives
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Cyanoacrylate
Antibacterial properties
Reported to stop melting
Surface must be dry when applying, use 30g needle to apply
Produces heat when curing, can rupture a descemetocele
Anticollagenase Agents
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Matrix metalloproteinases and serine proteinases maintain normal corneal health,
dysregulation of these will result in corneal stromal degradation
These agents decrease matrix metalloproteinase activity
Acetylcysteine
EDTA-binds zinc and calcium
Tetracyclines-chelates cations needed for enzyme activity preventing degradation
Serum
o Antiproteolytic activity
o Epithelialtrophic properties that promote corneal healing
o Good for 1 week in the fridge
o Must have aseptic preparation
Galardin, Ilomostate-synthetic MMP inhibitors
Hyaluronate
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Aquify-over the counter
Remend/Equitrix-similar product, has not been compared to other HA products
The Future
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Nanoparticle technology
o Increases surface area dramatically which increases tissue exposure and
absorption
Iontophoresis
o Propels charged compounds into ocular tissues
o Uses a small electrical current to drive the drug into the tissue
o Fungal keratitis, uveitis, retinoblastoma
Drug eluting contact lenses
o Deliver times up to 4 weeks rather than just hours
Eye misters and microdroplets
o Improve compliance-mean dogs!
Implants
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o Controlled sustained drug release
o Biodegradable and nonbiodegradable
o Episcleral implants, intrascleral, suprachoroidal and intravitreal implants
o Biodegradable inserts for the lower conjunctival sac
Intraocular lenses
o Make the lens a drug reservoir or “coat” the lens in a drug such as an antiinflammatory or antibiotic