Ocular Pharmacology

Question 1

Categories of drugs in the eye

Answer 1

Glucocorticoids
NSAIDs
Immunomodulators - cyclosporine A

Question 2

Topical glucocorticoids

Answer 2

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

Question 3

Indications for topical glucocorticoids

Answer 3

Anterior segment inflammation
◦Conjunctivitis, keratitis, anterior uveitis ◦WITHOUT ULCERATION!!!
◦Systemic
Eyelid, posterior segment, orbital, optic nerve, CNS

Question 4

Formulations for topical glucocorticoids

Answer 4

Topical prednisolone acetate (1%)
Prednisolone sodium succinate or phosphate
Dexamethasone sodium phosphate
Hydrocortisone formulation …

Question 5

Topical prednisolone acetate 1% a

Answer 5

Topical prednisolone acetate (1%)
◦ Acetate increases ocular penetration (lipophilicity)
◦ Increases potency
◦ Appropriate for intraocular diseases (ie anterior uveitis)

Question 6

Prednisolone sodium succinate or phosphate

Answer 6

Prednisolone sodium (water soluble) succinate or phosphate
◦ Ophthalmic formulations also available
◦ Do not cross an intact cornea
◦ Appropriate for corneal surface diseases (ie IMMK?)

Question 7

Dexamethasone sodium phosphate (0.1%)

Answer 7

Penetrates an intact cornea
◦ Also available in an inexpensive ointment formulation
◦ Also available in formulations combined with antimicrobials
◦ Neo/poly/dex

Question 8

Hydrocortisone formulations

Answer 8

◦ Less potent
◦Do not penetrate intact cornea
◦Often combined with Abs Potency/penetration
◦ Prednisolone acetate ≈ dexamethasone SP > pred SS or SP&raquo_space;>hydrocortisone

Question 9

Adverse effects of topical glucocorticoids

Answer 9

◦ 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

Question 10

Mechanism of action for topical NSAIDs

Answer 10

◦ Inhibition of COX enzymes
◦ Decreased PG production
Currently available topical formulations non-selective
◦Inhibit both COX-1 and COX-2

Question 11

Adverse effects of topical NSAIDs

Answer 11

◦ 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

Question 12

Formulations for topical NSAIDs

Answer 12

◦ 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

Question 13

Systemic GCs and NSAIDs

Answer 13

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

Question 14

Cyclosporine A

Answer 14

Immunomodulators
◦ Binds calcineurin
◦Blocks IL-2 production which prevents activation of T cells
Useful in lymphocyte mediated diseases
◦ Anterior uveitis

Question 15

Cyclosporine A formation

Answer 15

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

Question 16

Cyclosporine A implant

Answer 16

◦ 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)

Question 17

Autonomic NS and the eye

Answer 17

Controls pupil size
Sympathetic activation - mydriasis - dilation
Parasympathetic activation - miosis

Question 18

Drugs that cause mydriasis

Answer 18

Sympathomimetic
Parasympatholytic

Question 19

Drugs for miosis

Answer 19

Sympatholytic
Parasympathomimetic

Question 20

Sympathomimetic drugs

Answer 20

Alpha 1 receptor agonists - phenylephrine

Question 21

Parasympatholytics

Answer 21

Cholinergic antagonisms (anticholinergic drugs)
Tropicamide
Atropine

Question 22

Phenylephrine

Answer 22

Effective in dogs
Not as effective in cats & horses
Can be combo therapy w anticholinergic drugs - maximum dilation

Question 23

Tropicamide

Answer 23

Short acting
More appropriate for diagnosis than treatment

Question 24

Atropine

Answer 24

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

Question 25

Adverse effects of atropine

Answer 25

Decreased tear production ◦Treated and untreated eye ◦May cause ileus Frequent admin Inflammation makes drugs less effective Concern for colic - taper asap

Question 26

Eye color that’s most effected by atropine

Answer 26

Blue eyes Dilated pupils for longer effects**

Question 27

Drugs that cause miosis

Answer 27

Parasympathomimetics Cholinergic agonists Pilocarpine - direct agonist Demecarium bromide - Indirect agonists, acetylcholinesterase inhibitor

Question 28

Use of parasympathomimetics

Answer 28

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

Question 29

use for pilocarpine

Answer 29

Local irritation and dilator muscle atrophy Carbachol ◦ Headaches, muscle spasm Demecarium bromide ◦ Carbamate ◦ Irritation, V/D

Question 30

Timolol

Answer 30

Sympatholytic Non selective beta blocker Reduces IOP by decreasing aqueous humor production Use w caution in patients w cardiovascular disease**

Question 31

Timolol n dogs and cats

Answer 31

Poor efficiency Bradycardia, mild bilateral miosis

Question 32

Timolol in horses

Answer 32

Better efficiency Fewer adverse effects

Question 33

Drugs for glaucoma

Answer 33

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%

Question 34

Prostaglandin analogues

Answer 34

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

Question 35

Topical /local anesthetics mechanism

Answer 35

Sodium channel blockers Prevent depolarization of nerves Block propagation of nerve signals

Question 36

Topical admin of anesthetics

Answer 36

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)

Question 37

Adverse effects of topical anesthetics

Answer 37

◦ CONTRAINDICATED AS THERAPY FOR ULCERATIVE KERATITIS!!! ◦ Toxic to epithelium ◦May destabilize tear film ◦Inhibit normal corneal blink reflex

Question 38

Topical Admin anesthetic drugs

Answer 38

Proparacaine - fast acting, lasts 25 cats 45 dogs min Tetracaine - shorter duration w more pain on instillation Cocaine - don’t use anymore

Question 39

Local admin for anesthetics

Answer 39

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

Question 40

Drugs for local admin anesthetics

Answer 40

Lidocaine - rapid onset, 45-60 minutes Bupivacaine - longer duration 5-10 hours. Some animals could be allergic

Question 41

Topical antiproteases

Answer 41

Elevated levels of proteases on corneal surface involved in pathogenesis of disease - matrix metalloproteinase - 9 - can cause corneal melting

Question 42

Use of antiproteases

Answer 42

Topical Autologous serum ◦ N-acetylcysteine Systemic ◦ Tetracyclines ◦ Doxycycline in tears

Question 43

Autologous serum - topical antiproteases

Answer 43

Contains α2 -macroglobulins and α1-antitrypsin ◦Inhibits serine proteases as well as MMPs ◦Cheap! ◦Need to collect aseptically ◦Maintain sterility

Question 44

Names for topical glucocorticoids

Answer 44

Prednisolone acetate (1%) Prednisolone sodium succinate or phosphate Dexamethasone sodium phosphate Hydrocortisone formulations

Question 45

Names for topical NSAIDs

Answer 45

Flurbiprofen (0.3%) Diclofenac sodium (0.1%) Ketorolac (0.5%) Nepafenac (0.1%) Bromfenac sodium (0.09%)

Question 46

Drug classes & names for mydriasis

Answer 46

Sympathomimetic - phenylephrine Parasympothalytic - Tropicamide, atropine

Question 47

Drug classes & names for miosis

Answer 47

Parasympathomimetics - pilocarpine, carbachol, demecarium bromide Sympatholytic - Timolol

Question 48

Names of Glaucoma drugs

Answer 48

Dorzolamide - CAI Latanoprost - PGF

Question 49

Names of topical anesthetics

Answer 49

Proparacaine Tetracaine Cocaine

Question 50

Local anesthetics

Answer 50

Lidocaine Bupivacaine

Question 51

Topical & systemic antiproteases

Answer 51

Topical - N-acetylcyteine Systemic - tetracyclines, doxycycline in tears