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
