Ocular Pharmacology Flashcards
Categories of drugs in the eye
Glucocorticoids
NSAIDs
Immunomodulators - cyclosporine A
Topical glucocorticoids
Cause transactivation of anti-inflammatory genes and trans repression of pro-inflammatory genes
◦ Block the arachidonic acid pathway (phospholipase A 2)
Glucocorticoid receptors in the
◦ Cornea
◦ Lens
◦ Retina
Indications for topical glucocorticoids
Anterior segment inflammation
◦Conjunctivitis, keratitis, anterior uveitis ◦WITHOUT ULCERATION!!!
◦Systemic
Eyelid, posterior segment, orbital, optic nerve, CNS
Formulations for topical glucocorticoids
Topical prednisolone acetate (1%)
Prednisolone sodium succinate or phosphate
Dexamethasone sodium phosphate
Hydrocortisone formulation …
Topical prednisolone acetate 1% a
Topical prednisolone acetate (1%)
◦ Acetate increases ocular penetration (lipophilicity)
◦ Increases potency
◦ Appropriate for intraocular diseases (ie anterior uveitis)
Prednisolone sodium succinate or phosphate
Prednisolone sodium (water soluble) succinate or phosphate
◦ Ophthalmic formulations also available
◦ Do not cross an intact cornea
◦ Appropriate for corneal surface diseases (ie IMMK?)
Dexamethasone sodium phosphate (0.1%)
Penetrates an intact cornea
◦ Also available in an inexpensive ointment formulation
◦ Also available in formulations combined with antimicrobials
◦ Neo/poly/dex
Hydrocortisone formulations
◦ Less potent
◦Do not penetrate intact cornea
◦Often combined with Abs Potency/penetration
◦ Prednisolone acetate ≈ dexamethasone SP > pred SS or SP»_space;>hydrocortisone
Adverse effects of topical glucocorticoids
◦ Potentiate infection
◦ Fungus!!!
◦ Delay re-epithelialization of corneal ulcers
◦ Calcific band keratopathy - calcium deposition in cornea
Long term topical use may cause endocrine issues
◦ Still safer than systemic steroids
Mechanism of action for topical NSAIDs
◦ Inhibition of COX enzymes
◦ Decreased PG production
Currently available topical formulations non-selective
◦Inhibit both COX-1 and COX-2
Adverse effects of topical NSAIDs
◦ Less concern for potentiating infection compared to GCs
◦Decreased corneal epithelialization, ulcer/wound healing
◦ Particularly products containing thimersol
◦Still safer than systemic NSAIDs
◦ No reported GI or renal effects
Formulations for topical NSAIDs
◦ Flurbiprofen (0.03%)*
**Currently in pharmacy
◦Diclofenac sodium (0.1%) **
◦Ketorolac (0.5%) **
◦Nepafenac (0.1%)
◦Bromfenac sodium (0.09%)
◦ Bromfenac is considered the most potent but $$$
◦ NSAIDs are still less potent than topical corticosteroids
Systemic GCs and NSAIDs
Steroids sometimes used in severe cases
NSAIDs used more frequently
◦ Non-selective drugs are more effective
◦ Flunixin meglumine vs firocoxib in the horse
◦ Firocoxib reaches higher intraocular concentrations
◦ Does not work well clinically
Cyclosporine A
Immunomodulators
◦ Binds calcineurin
◦Blocks IL-2 production which prevents activation of T cells
Useful in lymphocyte mediated diseases
◦ Anterior uveitis
Cyclosporine A formation
T opical formulations do not penetrate an intact cornea
◦ Better efficacy for surface diseases
◦Immune-mediated keratitis
◦Eosinophilic keratitis
Systemic administration is costly
Carries a small risk of renal, hepatic and neurologic toxicity
Cyclosporine A implant
◦ For anterior uveitis
◦ Placed during a time when the eye is quiescent
◦ Therapeutic concentrations achieved in w - m
◦ Can deliver drug for months to years
◦ Effects may last even after the drug is gone
◦ $$$ (Sx plus ophthalmologist)
Autonomic NS and the eye
Controls pupil size
Sympathetic activation - mydriasis - dilation
Parasympathetic activation - miosis
Drugs that cause mydriasis
Sympathomimetic
Parasympatholytic
Drugs for miosis
Sympatholytic
Parasympathomimetic
Sympathomimetic drugs
Alpha 1 receptor agonists - phenylephrine
Parasympatholytics
Cholinergic antagonisms (anticholinergic drugs)
Tropicamide
Atropine
Phenylephrine
Effective in dogs
Not as effective in cats & horses
Can be combo therapy w anticholinergic drugs - maximum dilation
Tropicamide
Short acting
More appropriate for diagnosis than treatment
Atropine
Common w treatment
Very potent and very long acting
Can over come mydriasis in the presence of inflammation, relieves pain from ciliary spams
Prevents synechiae and 2ndary glaucoma
Adverse effects of atropine
Decreased tear production
◦Treated and untreated eye ◦May cause ileus
Frequent admin
Inflammation makes drugs less effective
Concern for colic - taper asap
Eye color that’s most effected by atropine
Blue eyes
Dilated pupils for longer effects**
Drugs that cause miosis
Parasympathomimetics
Cholinergic agonists
Pilocarpine - direct agonist
Demecarium bromide - Indirect agonists, acetylcholinesterase inhibitor
Use of parasympathomimetics
Used to treat glaucoma (sometimes)
◦ Actually increase IOP in normal horses
Used to treat dry eye = Dogs, neurogenic
ADEs limit use
◦ Vomiting, anorexia, diarrhea, lethargy and weakness
use for pilocarpine
Local irritation and dilator muscle atrophy
Carbachol
◦ Headaches, muscle spasm
Demecarium bromide
◦ Carbamate
◦ Irritation, V/D
Timolol
Sympatholytic
Non selective beta blocker
Reduces IOP by decreasing aqueous humor production
Use w caution in patients w cardiovascular disease**
Timolol n dogs and cats
Poor efficiency
Bradycardia, mild bilateral miosis
Timolol in horses
Better efficiency
Fewer adverse effects
Drugs for glaucoma
Dorzolamide - Carbonic anhydride inhibitors
Inhibition of carbonic anhydrase in the ciliary processes
◦Decreases aqueous humor secretion
◦Slows the formation of bicarbonate ions
◦Reduction in sodium and fluid transport
◦ Doses which inhibit CA 90% decreased aqueous humor production by 50%
Prostaglandin analogues
Latanoprost (PGF 2 alpha)
Lowers IOP by increasing outflow of aqueous humor
Prostaglandins increased the sclera’s permeability to aqueous fluid
Dogs and horses - not effective in cats
Topical /local anesthetics mechanism
Sodium channel blockers
Prevent depolarization of nerves
Block propagation of nerve signals
Topical admin of anesthetics
Provides anesthesia to corneal and conjunctival surfaces
◦Diagnostic procedures
Tonometry, collection of cytology/culture samples
◦ Have antibacterial properties! May affect culture results
◦Surgical procedures
Sole agent for minor procedures (grid keratotomy) Adjunctive agent for major procedures (conjunctival graft)
Adverse effects of topical anesthetics
◦ CONTRAINDICATED AS THERAPY FOR ULCERATIVE
KERATITIS!!!
◦ Toxic to epithelium ◦May destabilize tear film ◦Inhibit normal corneal blink reflex
Topical Admin anesthetic drugs
Proparacaine - fast acting, lasts 25 cats 45 dogs min
Tetracaine - shorter duration w more pain on instillation
Cocaine - don’t use anymore
Local admin for anesthetics
Blockage of sensory and motor innervation
Sensory - local line block - eyelid procedures
Frontal nerve block - ocular surface procedures
Motor - Auriculopalpebral nerve block - eyelid muscle function
◦ Retrobulbar nerve block - extraocular and intraocular muscle function
Drugs for local admin anesthetics
Lidocaine - rapid onset, 45-60 minutes
Bupivacaine - longer duration 5-10 hours. Some animals could be allergic
Topical antiproteases
Elevated levels of proteases on corneal surface involved in pathogenesis of disease
- matrix metalloproteinase - 9
- can cause corneal melting
Use of antiproteases
Topical
Autologous serum ◦ N-acetylcysteine
Systemic
◦ Tetracyclines ◦ Doxycycline in tears
Autologous serum - topical antiproteases
Contains α2 -macroglobulins and α1-antitrypsin
◦Inhibits serine proteases as well as MMPs
◦Cheap!
◦Need to collect aseptically
◦Maintain sterility
Names for topical glucocorticoids
Prednisolone acetate (1%)
Prednisolone sodium succinate or phosphate
Dexamethasone sodium phosphate
Hydrocortisone formulations
Names for topical NSAIDs
Flurbiprofen (0.3%)
Diclofenac sodium (0.1%)
Ketorolac (0.5%)
Nepafenac (0.1%)
Bromfenac sodium (0.09%)
Drug classes & names for mydriasis
Sympathomimetic - phenylephrine
Parasympothalytic - Tropicamide, atropine
Drug classes & names for miosis
Parasympathomimetics - pilocarpine, carbachol, demecarium bromide
Sympatholytic - Timolol
Names of Glaucoma drugs
Dorzolamide - CAI
Latanoprost - PGF
Names of topical anesthetics
Proparacaine
Tetracaine
Cocaine
Local anesthetics
Lidocaine
Bupivacaine
Topical & systemic antiproteases
Topical - N-acetylcyteine
Systemic - tetracyclines, doxycycline in tears