Ocular pharmacology

Penicillins and cephalosporins

Bactericidal block cell wall synthesis

Intraocular penetration poor unless BOB inflammed

May penetrate ant. chamber if corneal epithelium damaged

Mostly G +'ve activity

Aminopenicillins have increased G-'ve activity

Broad spec bacteriostatic

Block Folic acid synthesis

Good Ocular penetration

Potential KCS

Dobermann pinchers immune mediated polyarthritis

Broad spec bacteriostatic

Bind 30S subunit of bacterial ribosomes and block AA attachment

Systemically penetrate BOB poorly (except doxycycline)

Topically applied may reach therapeutic concentration in ant. chamber

Active against chlamydophila, mycoplasma, rickettsia, G-'ve and G+'ve

Resistance common

Bactericidal binds 30S subunit

Systemically does not penetrate BOB

Topically poor penetration

Activity against G-'ve and some G+'ve

Gentamicin used against pseudomonas

Tobramycin broad spec and used if genta resistance

Neomycin broad spec but poor penetration

Binds 50S subunit

Erythromycin, tylosin, lincomycin, clindamycin ar bacteriostatic with predominantly G+'ve activity

Newer Azithromycin is acteriocidal and broad spectrum

Good tissue penetration

Clindamycin effective against anaerobes

Broad spec bactericidal inhibiting DNA gyrase

Liver metabolism (except baytril) with renal excretion

• Good tissue distribution
• Topical application achieves high ant. chamber concentration

Effective against most G-'ve including pseudomonas

Some activity against G+'ve

Poor anaerobe activity

• Enrofloxacin
• - narrow therapeutic range with blindness from generalised retinal degeneration if given at a high dose
• - some Staph and Strep resistance, ineffective against anaerobes

Blocks binding of transfer RNA to bacterial ribosome inhibiting protein synthesis

Good G +'ve and some G-'ve activity

Good corneal penetration

Carbomer gel vehicle in Fucithalmic

Broad spectrum bacteriostatic

Binds 50S subunit blocking protein synthesis

• G -'ve, G+'ve, anaerobic activity
• Chlamydophila (not as good as tetracycline), mycoplasma and rickettsia sensitive
• Nocardia and Mycobacterium resistance

High lipid solubility gives good intraocular penetration and can access the CNS

Bactericidal inhibiting cell wall synthesis.

Toxic if given systemically

Bacitracin G +'ve range

Polymixin B G -'ve range

Often combined

Metronidazole bactericidal effective against anaerobes

Good tissue penetration given systemically

(Could be used in combination with cephalosporin to give aerobic cover)

(in orfer of decreasing efficacy):

• Trifluorothymidine (most effective in vitro efficacy against FHV-1) requires application4-6 times daily
• Idoxuridine
• vidarabine

bromovinyldeoxuridine

acyclovir only product available in th UK

Human interferon alpha 2 anecdotal reports of efficacy when applied topically

L-lysine - in vitro observation that it inhibits viral replication in the presence of low arginine levels

Topical application for mycotic keratitis

Systemic use for mycotic chorioretinitis

No licenced products for animals in UK

Itraconazole, ketoconazole, fluconazole, clotrimazole, amphotericin B

Glucocorticoids have minimal mineralocorticoid activity and powerful anti-inflamatory effect

Anti-inflammatory action is to induce lipocortin (intracellular protein)

Lipocortin inhibits phospholipase A₂ (PLA₂)

PLA₂ is an endogenous enzyme catalyses breakdown of cell membrane phospholipids to arachidonic acid

Arachidonic acid is the precursor to proinflammatory leucotrienes and prostoglandins




At higher concentrations glucocorticoids are immunosuppressive

Contraindicated in corneal ulceration as it may exacerbate stromal collegenolysis 'melting'

Long-term use in humans has been seen to lead to cataract development and glaucoma

Medium term topical glucocorticoid administration caused a reversible increase in intraocular pressure.... and....

Longer tx (7weeks) caused subcapsular cataract formation (experimental cats Zhan 1992)

Topical tx causes reversible increase in IOP in experimental beagles (Gelatt and brooks 1999)

Choice of topical product should depend on ability to penetrate into the eye

Inhibits cyclo-oxygenase pathway

At least 2 isoforms of cyclo-oxygenase exist

COX-1 inhibition may lead to side-effects (eg GI bleeding)

COX-2 is induced at sites of inflammation.



Used in postop pain relief and uveitis

Contraindicated in anterior segment bleeding

Ketorolac (Acular), Flubiprofen (Ocufen), Diclofenac (Voltarol Ophtha)

Optimmune 0.2% ointment

Multiple mechanisms of action

Acts as a Tcell suppressor by inhibiting interleukin 2

Induces production of transforming growth factor beta (TGF beta) which is a potent endogenous immunosupressant



Does not penetrate the intact cornea well

It can increase tear production in normal dogs, possibly via effects on a prolactin receptor (Kaswan 1989)

Used to tx autoimmune KCS

Can be effective for other immune mediated diseases (e.g. chronic superficial keratoconjunctivitis, plasmacytic conjunctivitis, episcleritis)

Has been used for eosinophilic keratoconjunctivitis in cats and ERU in horses

No evidence of systemic or ocular toxicity

Recommmended that bacterial or viral infections are tx'd before use

Can cause nephrotoxicity in humans

Immediate discomfort of topical application is common

Not advised to use within a 2 week period of live vaccines

Topical irritation reported in dogs

Zovirax 5% ointment

Inhibits viral replication (viral DNA polymerase) - depends on viral thymidine kinase for phosphorylation

Virostatic - unable to eradicate latent viral replication

Ocular irritation may occur

q4-6h for 3 weeks max

Has been used in the management of FHV-1 infections

In vitro studies suggest Aciclovir and human interferon combination to be more effective against FHV-1 than aciclovir on its own

In vivo efficacy unknown

Antagonises arginine, which is required for viral replication

Has been used in the management of FHV-1 infection

Limited clinical evidence regarding its efficacy in treating FHV-1

25-500mg PO q12-24h

Trifluridine, F3T, Viroptic (USA) 1% solution

Inhibits viral replication (viral DNA polymerase) - does not depend on viral thymidine kinase for phosphorylation

Virostatic and is unable to eradicate latent viral infection

Clinically the most useful antiviral for FHV-1

Safe to combine with human interferon

Short shelf life and expensive

q4-6h for 3 weeks max

Ciloxan, Ciproxin 0.3% solution

Bactericidal through inhibition of bacterial DNA gyrase

Broad spec activity against most G-'ve and some G+'ve aerobes

Some activity against Mycoplasma and Chlamydophila

Active against Staphylococcus and Pseudomonas

Increasing resistance against staphs and streps

Should be reserved for 2nd line tx

May cause local irritation

q6h

FML

Corticosteroid

0.1% drops

Phospholipase A2 inhibition (COX and lipoxygenase inhibition)

Used to tx superficial inflammation or anterior uveitis, rarely used in veterinary ophthalmology

Contraindicated in corneal ulceration and infectious keratitis

Theoretically could induce higher intraocular pressure and cataract development with long-term use

q6-12h

Diamox 500mg vial powder for reconstitution

Systemic carbonic anhydrase inhibitor

Reduces intraocular pressure by reducing aqueous humour production

Inhibits bicarbonate ion formation within the ciliary body epithelium

Can be used in acute cases, but topical carbonic anhydrase inhibitors are better

Avoid in anorexic dogs, those with hepatic or renal dysfunction and those with sulphonamide hypersensitivity

Cats are particularly sensitive

May cause GI disturbances, anorexia, V+, D+, panting, metabolic acidosis, diuresis, electrolyte disturbances

Dogs 5-10mg/kg iv, 4-8mg/kg PO q8-12

Iopidine 0.5% solution

Topical alpha 2 selective agonist.

Decreases aqueous humour production via inhibition of adenylate cyclase activity in the cilary body

Used to reduce IOP in glaucoma

Effect in dogs is inconsistant

Prudent to measure heart rate before and after application

Causes blanching of the conjunctival vessels, bradycardia and mydriasis in dogs

Considered toxic in cats

Do not use in dogs with uncontrolled cardiac disease

Betoptic 0.25% or 0.5% solution

Beta-1 selective beta blocker that decreases aqueous humour production

Beta-adrenoreceptor blockade in the ciliary body

Used in glaucoma management

Can be used in combination with carbonic anhydrase inhibitor

Avoid in uncontrolled heart failure and asthma

Can cause miosis, conjunctival hyperaemia and local irritation

q12h

No information on the use in cats

Azopt 10mg/ml (1%)

Carbonic anhydrase inhibitor

Reduces IOP by reducing the rate of aqueous humour production

Inhibits formation of bicarbonate ions in the ciliary body epithelium

Used to control glaucoma

May be better tolerated than Dorzolomide as it has a pH of 7.5

Effective in dogs and cats

Ineffective in normal cats

Contraindicated in severe hepatic or renal impairment

q8-12h

Trusopt 2%, Cosopt (2%+ 0.5% timolol)

Carbonic anhydrase inhibitor

Reduces IOP by decreasing aqueous humour production

Inhibits the formation of bicarbonate ions within the ciliary body epithelium

Used to control glaucoma in dogs and cats

pH 5.6 - not tolerated as well as brinzolomide

Effective in dogs and cats

Causes miosis and therefore not to be used in concurrent uveitis / lens luxation

Contraindicated in hepatic or renal impairment

Can cause local irritation and blepharitis

• Dogs q8h
• Cats q 12h
• Birds q12h

Glycerin(e) Glycerol 50% solution

Lowers intraocular pressure by reducing aqueous humour production and improving aqueous humour outflow (secondary to reducing vitreous humour volume)

Used in management of acute glaucoma

Superceded by topical agents

Maximal reduction in IOP 1 hour after administration.

Will last for 10hours

Induces less diuresis than mannitol

Contraindicated in diabetes, dehydration and renal dysfunction

Dogs and Cats: 1-2g/kg PO single dose

Xalatan 0.005%

Agonist for prostaglandin-F receptors

Reduces IOP by increasing uveoscleral outflow

Management of canine primary glaucoma

Can have a profound effect on IOP in the dog

Less predictable effect in cats

Often used in conjunction with carbonic anhydrase inhibitors

Miosis in dogs and cats, mild irritation of conjunctivae

(Increased iridal pigmentation in humans - not seen in dogs)

Contraindicated with uveitis and anterior lens luxation

1 drop per eye given in the evening

Most common concentration is 1%

Direct acting parasympathomimetic that stimulates cholinergic receptors

Lowers IOP by causing ciliary body muscle contraction, miosis and improved humour outflow

Used in the management of glaucoma

Use has been superceded by CAIs and prostaglandin analogues

Oral dosing increases lacrimation and can be used in neurogenic KCS

Produces miosis in 10-15min for 6-8hrs

Potentially toxic in the cat

Avoid in uveitis and anterior lens luxation

Can cause conjunctival hyperaemia (vasodilation) and local irritation from low pH

(Signs of systemic toxicity: hypersalivation, V+, D+, cardiac arrhythmias

1 drop 1% per 10kg PO q12h with food

Timolol, Timoptol, [CoSopt (combined with dorzolamide)]

Topical non-selective beta blocker

Decreases aqueous humour production via beta-adrenoreceptor blockade in the ciliary body

Used in the management of glaucoma

Can be used in combination with CAIs (may be more effective than either drug alone)

Miosis, therefore do not use with uveitis and anterior lens luxation

Systemic absorption ma occur from topical use resulting in bradycardia and lower BP

Avoid in uncontrolled heart failure and asthma

Can cause local irritation

• Dogs q8-12h
• Cats q12h

Travatan 0.004% solution

Agonist for prostaglandin F receptors

Reduces IOP by increasing uveoscleral outflow

May have a profound effect on IOP

Used in the management of primary glaucoma

Can be used in acute conditions

No published data for use in cats

Often used in combination with CAIs

• Comparable activity to latanoprost
• Contraindicated in uveitis and anterior lens luxation due to marked miosis

Conjunctival hyperaemia and mild irritation may develop

(Increased iridal pigmentation seen in humans- not in dogs)

1 drop per eye in evenings

Cyclopentolate hydrochloride, Mydrilate

Inhibits acetylcholine in the iris sphincter and ciliary body muscles

Causes mydriasis and cycloplegia

Mainly used pre-operatively for intraocular surgery

Prolonged action 60 hours

Rarely used in veterinary medicine

Contraindicated in glaucoma and lens luxation

May cause salivation in cats and chemosis in dogs

Ophthalmic 2.5% solution, Injectable 1% solution

Alpha-1 selective adrenergic agonist

Directly stimulates alpha-adrenergic receptors in the iris dilator musculature

Causes vasoconstriction and mydriasis (not cycloplegic)

Can be used to differentiate superficial conjunctival vessels from deeper episcleral vessels

Used to diagnose Horners syndrome

Slow onset for mydriasis - 2hours

Tropicamide, Mydriacyl 0.5% or 1%

Inhibits acetylcholine at the iris sphincter and ciliary body muscles

Causes mydriasis and cycloplegia

More potent mydriatic than cycloplegic and therefore less effective than atropine in relieving ciliary body muscle spasm

Synthetic

Rapid onset 20-30min

Short duration 4-12h

Avoid in glaucoma and use carefully in lens luxation

May cause salivation in cats (less than atropine)

Voltarol Ophtha 0.1% solution

NSAID COX inhibitor that produces local anti-inflammatory effects



Used to control pain and inflammation

Used in cataract surgery to prevent intraoperative miosis

Used to tx axonal miosis caused by ulcerative keratitis

Can often be used when corticosteroids are contrindicated

Can delay epithelial healing in ulcerative keratitis

Has been associated with an increased risk of keratomalacia in humans (not reported in vet med)

Potentially can increase IOP

As with other NSAIDs it may cause local irritation

q30min for 2hours pre-cataract op.

Ocufen 0.3% solution

Inhibits prostaglandin synthesis

NSAID COX inhibitor that produces local anti-inflammatory effects



Used to control pain and inflammation

Used in cataract surgery to prevent intraoperative miosis

Used to tx axonal miosis caused by ulcerative keratitis

Can often be used when corticosteroids are contrindicated

Can delay epithelial healing in ulcerative keratitis

Has been associated with an increased risk of keratomalacia in humans (not reported in vet med)

Potentially can increase IOP

As with other NSAIDs it may cause local irritation

q 6-12h

Acular 0.5%

NSAID COX inhibitor that produces local anti-inflammatory effects



Used to control pain and inflammation

Used in cataract surgery to prevent intraoperative miosis

Used to tx axonal miosis caused by ulcerative keratitis

Can often be used when corticosteroids are contrindicated

Can delay epithelial healing in ulcerative keratitis

Has been associated with an increased risk of keratomalacia in humans (not reported in vet med)

Potentially can increase IOP

As with other NSAIDs it may cause local irritation

q 6-24h

Viscotears, Lubrithal 0.2% gel

Mucomimetic

Replaces both aqueous and mucn components of the tear film

Longer corneal contact time than aqueous tear substitutes

Used in the management of KCS

q4-6h

Vislube 0.18% solution

Viscoelastic fluid (Sodium hyaluronate available in different formulations for intraocular surgery)

Mucomimetic properties

Longer corneal contact time than aqueous tear substitutes

Used in the management of KCS

q4-6h

Hypromellose, Isopto, Tears Naturale. 0.3%,0.5%, 1% solutions

Lacromimetic

Cellulose based tear substitute

Improves ocular surface lubrication

Used in KCS

Can be used as a vehicle v=base for compounding other drugs

q1h

Liquifilm Tears, Sno Tears 1.4%

Lacromimetic

Synthetic resin tear substitute

Used to lubricate eyes in KCS

More adherent and less viscous than hypromellose

q1h

0.5% solution

Local anaesthetic action

Reversible blockade of Na+ channel, preventing propagation of the action potential along the nerve fibre

Sensory nerve fibres are blocked before motor nerve fibres

Rapid action 10 seconds

Lasts for 20-55min depending on species

Serial application increases duration and depth of anaesthesia

Block reflex tear production and therefore STT1 should be performed before application

Store in the refrigerator

Conjunctival hyperaemia common

Toxic to corneal epithelium and will delay ulcer healing

0.5%, 1% solution

Local anaesthetic action

Proxymetacaine is used in preference to tetracaine

Reversible blockade of Na+ channel, preventing propagation of the action potential along the nerve fibre

Sensory nerve fibres are blocked before motor nerve fibres

Serial application increases duration and depth of anaesthesia

Block reflex tear production and therefore STT1 should be performed before application

Store in the refrigerator

Often causes marked conjunctival irritation, chemosis and pain on application.

Toxic to corneal epithelium and will delay ulcer healing

Protopic 0.03%, 0.1% creams

T lymphocyte inhibition

Used in cases of KCS than are non responsive to ciclosporin

Long-term effects and adverse effects are unknown

Wear gloves when handling

q12h