Ocular Pharmacology

Erica Tolar DVM, DACVO

Drug Delivery
 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

infection or trauma to promote penetration o Eyelids need to be treated with systemic therapy Anti-infectious Agents  Indiscriminate use encourages the development of drug resistant bacteria  Bacteriostatic or bactericidal  Cephaloporins-cefazolin. cidofovir. famcyclovir . erythromycin. moxifloxacin.  Systemic penetration o Some medications can be stopped by the blood ocular barrier unless there is ocular inflammation. 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. chlamydia. 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. 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. vancomycin o No penetration into the anterior segment  Fluoroquinolones-ofloxacin. trifluridine o Purine nucleoside analogues  Acyclovir. azithromycin o Toxoplasma. gram positive cocci  Aminoglycosides-gentamicin. vidarabine. first generation. tobramycin. bacitracin. ciprofloxacin. gramicidin. gatifloxacin.

diabetes. meloxicam. liver values Megesterol Acetate  Eosinophilic keratitis in cats  Side effects: polyphagia. ketorolac  Diclofenac is better at stabilizing the blood ocular barrier  Can worsen infectious keratitis especially herpetic keratitis in cats  Rimadyl. optic neuritis. GME  Monitor CBC. pyometra. polydipsia. 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  Azathioprine  Activated in the liver  Uveitis. VKH. suprofen. diclofenac.  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  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  Flurbiprofen. cyclosporine. previcoxx are good for ocular inflammation Calcineurin inhibitors  Tacrolimus. scleritis. behavior changes Anti-glaucoma medications  Reduce aqueous humor secretion .

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 . 98% of carbonic anhydrase must be inhibited to achieve full IOP reduction  Aqueous production is suppressed by 40-60%  Dorzolamide. unoprostone. can exacerbate asthma in cats o Carbonic Anhydrase Inhibitors  Decreases aqueous production. brinzolamide. 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. 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. carteolol. latanoprost. levobunolol  Decrease aqueous production  Maximum reduction in 2-4 hours  Decreases heart rate. 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.

lasts 45 minutes to 1 hour . glycerin o Neuroprotectants  Calcium channel blockers. 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. 25 minutes in cats  Tetracaine o Shorter duration of anesthesia compared to proparacaine o More irritating  Lidocaine o Rapid onset. free radical scavengers  Demecarium bromide Mydriatics/Cycloplegics  Cholinergic antagonists-paralyze the pupillary sphincter  Sympathomimetics-stimulate the iris dilator muscle. 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  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. nitric oxide inhibitors. maximum effect lasts 15 minutes in dogs. no cycloplegia  Not indicated in glaucoma  Decreases STT  Salivation.

Ilomostate-synthetic MMP inhibitors Hyaluronate  Aquify-over the counter  Remend/Equitrix-similar product. 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 . 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. has not been compared to other HA products The Future  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. o Used in local blocks  Bupivacaine o 4 times more potent than lidocaine o Lasts 5-10 hours with the 0. use 30g needle to apply  Produces heat when curing.5% solution o Use in combination with lidocaine Topical Disinfectants  Dilute betadine solution  1:10 to 1:50 Tissue Adhesives  Cyanoacrylate  Antibacterial properties  Reported to stop melting  Surface must be dry when applying. can rupture a descemetocele Anticollagenase Agents  Matrix metalloproteinases and serine proteinases maintain normal corneal health.

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 anti- inflammatory or antibiotic . o Controlled sustained drug release o Biodegradable and nonbiodegradable o Episcleral implants. intrascleral.