Ocular Pharmacology Stocking your clinic shelf
Marnie Ford, PhD, DVM, DACVO Animal Eye Care, Melbourne, Australia
The Chapter gratefully acknowledges Vet Strategy as the sponsor of this session
Factors to consider Drugs Common Conditions Summary Therapeutic Goals
to Administer a drug that will Reach Target Tissue at an Efficacious Concentration Without Reaching Ocular or Systemic Toxic Levels
Factors to consider Drugs Common Conditions Summary Stock a suitable range Stocking the pharmacy - for conditions seen regularly
- for emergencies -just a few bottles
Know the indications for use Demand Economics
Most ophthalmic drugs can be prescribed through human pharmacy
Know your compounding pharmacies
Factors to consider Drugs Common Conditions Summary Outline
A. Factors to consider when treating an eye
B. Therapeutic agents
C. Common conditions
D. Summary - the minimum drugs you need in your clinic
Factors to consider Therapeutic Agents Common Conditions Summary A. Factors to consider when treating an eye
The eye may be small but its defences are large lids, PCTF, bony orbit
1. Lesion Localization and Routes of Administration
2. Achieving Adequate Tissue Concentrations (potency and frequency)
3. Factors that affect how a drug reaches its target
Factors to consider Therapeutic Agents Common Conditions Summary 1. Lesion Localization and Routes of Administration
TOPICAL Eyelids Advantages: Conjunctiva -High local concentrations -Easy to apply Cornea Tear Disadvantages: Film -often requires high frequency of application (washed out by Topical Anterior tears) -drops Uvea -ointments Sclera -inserts -contact lenses
Factors to consider Therapeutic Agents Common Conditions Summary Drops vs Suspensions vs Emulsions vs Ointments
Drops -commercial drop = 50 µl -max tear film retention = 20 µl -excess – spills over lids, drains via nasolacrimal ducts -dosing by frequency not volume -ideal pH = 7.2 ± 0.2 – minimize irritation, excess lacrimation
Suspensions -finely dispersed drug particles in saturated aqueous solution -used for poorly water soluble drugs (CCS’s) -drug content can vary – shake well
Emulsions -small oil droplets, uniformly suspended
Ointments -high concentration of lipophilic drug, contact time -harder to apply, blurry, eyelid debris, systemic uptake, not for deep ulcers
Factors to consider Therapeutic Agents Common Conditions Summary Preservatives
Function -to increase the shelf life and minimize contamination
Irritating and Epitheliotoxic -Thimerosal – mercurial -Benzalkonium chloride – detergent -Chlorobutanol – detergent -Methyl Paraben – chelating -Sodium perborate – oxidative -EDTA – buffering agent New Generation Preservatives -stabilized oxychloro complex – oxidative -SofZia – ionic buffer J Ocul Pharmacol Ther 2009 Apr; 25(2): 113-119 Adv Ther 2001 Sep-Oct: 18(5): 205-215
Factors to consider Therapeutic Agents Common Conditions Summary 1. Lesion Localization and Routes of Administration SUBCONJUNCTIVAL Subconjunctival injections = epibulbar/subpalpebral
Cornea Advantages: -bypasses epithelium -high concentrations -difficult animals/wildlife
Anterior Uvea Disadvantages: Sclera -rapid absorption – sig systemic drug exposure
Vitreous
Factors to consider Therapeutic Agents Common Conditions Summary 1. Lesion Localization and Routes of Administration
SYSTEMIC
Eyelids Retrobulbar space Conjunctiva Retina Advantages: Systemic -nearly all parts of the eye -augments topical treatment -tablets -injections Optic nerve Disadvantages: Anterior -gastric upset Uvea -use may be restricted by systemic disease Sclera Choroid Vitreous
Factors to consider Therapeutic Agents Common Conditions Summary 1. Lesion Localization and Routes of Administration SUBCONJUNCTIVAL SYSTEMIC TOPICAL Combining Routes of Therapy
Eg -severe uveitis -corneal infection
Factors to consider Therapeutic Agents Common Conditions Summary 2. Achieving Adequate Tissue Concentrations
The eye and its barriers are unique: – intraocular structures are among the best protected in the body – guards the eye and its delicate structures from potentially dangerous substances in the environment and the blood.
If a drug cannot enter the eye for any of these reasons, it’s therapeutic efficacy will be greatly reduced
i. Physical
ii. Physiologic
iii. Other factors
Factors to consider Therapeutic Agents Common Conditions Summary 2. Achieving Adequate Tissue Concentrations i. Physical Barriers: Cornea =main barrier to topical therapy
- -lipophilic Epithelium -permeable to fat-soluble compounds -impermeable to ionized compounds
-hydrophilic Stroma -permeable to ionized solutions -impermeable to fat-soluble compounds
-lipophilic Endothelium -permeable to fat-soluble compounds -impermeable to ionized compounds
Drugs that pass easily through cornea need to be able to convert between ionized and non-ionized form
Factors to consider Therapeutic Agents Common Conditions Summary 2. Achieving Adequate Tissue Concentrations
Chloramphenicol/FQ’s * Epithelium Atropine Prednisolone acetate
Stroma *Why would you need this ability with an antibiotic?
When the epithelium is damaged (ulcerated) any drug will reach therapeutic concentrations! Endothelium Exceptions: corneal abscess, endophthalmitis
Factors to consider Therapeutic Agents Common Conditions Summary 2. Achieving Adequate Tissue Concentrations i. Physical Barriers: Blood-eye-barrier
-limits absorption of systemic drugs into the eye
-impedes the transfer of blood borne drugs into the eye
-fortunately, ocular inflammation reduces the blood eye barrier
-as inflammation subsides, the permeability of the blood eye barrier is restored
-this means that in the non-inflammed eye, drug permeability is not really a issue
Factors to consider Therapeutic Agents Common Conditions Summary 2. Achieving Adequate Tissue Concentrations
ii. Physiologic Barriers: Pre Corneal Tear Film Rapid turnover of intraocular fluids Active transport mechanisms within the eye that can eliminate substances Anatomical and physiological compartmentalization within the eye
iii. Other factors: Drug size – smaller molecular size → better penetration Drug concentration - higher concentration → better penetration (fortification) Drug irritation – more irritation → more tearing (wash out)
Factors to consider Therapeutic Agents Common Conditions Summary 3. Factors that Affect How a Drug Reaches its Target
a. Drug characteristics
b. Contact time
c. The Patient
Factors to consider Therapeutic Agents Common Conditions Summary 3. Factors that Affect How a Drug Reaches its Target
a. Drug characteristics i. Drug pH -dog tear pH = 6.5 -buffer -penetrability and shelf life
ii. Tonicity -isotonic with the precorneal tear film -generally small animals high tolerance -high concentrations can be irritating -ointments vs drops
iii. Viscosity -increased viscosity → longer contact times → greater intraocular penetration
iv. Wetting Agents -reduce surface tension -increase corneal penetration of ionised drugs
Factors to consider Therapeutic Agents Common Conditions Summary 3. Factors that Affect How a Drug Reaches its Target
b. Contact time
Prolong contact time by -increasing the drug concentration applied -increasing the viscosity of eye drops -using drug suspensions, emulsions and liposomes
Ointments - longer contact times than drops - may be a better choice than drops if unable to treat frequently -not indicated for -infected ulcers (need concentrated/fortified drops) -severe dry eye (need compounded drops) -severe uveitis (need potent preparations – drops only) -no effect on ulcer healing times
Factors to consider Therapeutic Agents Common Conditions Summary 3. Factors that Affect How a Drug Reaches its Target
c. The Patient – Tips and Tricks for the difficult patient
Keep in mind that the patients only experience with eye drops may be secondary to an injury – therefore, most of the time, a drop means pain.
Topical medications -positioning - come from behind - cradle on their back -apply drop to the conjunctiva vs cornea -positive association - drop THEN treat -form of medication – ointment vs drop, refrigerated vs non-refrigerated -muzzle if necessary (aggressive vs fearful)
Factors to consider Therapeutic Agents Common Conditions Summary Necessity
the mother of all invention
Factors to consider Therapeutic Agents Common Conditions Summary Oral Medications -crush, liquify, hide in food, compound it into better flavours
Last resort -subconjunctival injection
Factors to consider Therapeutic Agents Common Conditions Summary B. Therapeutic Agents
1. Anti-inflammatory 2. Anti-bacterial 3. Mydriatics 4. Glaucoma mediations 5. Topical anaesthetics 6. Dehydrating agents 7. Tear Simulants 8. Adjunct therapies
Factors to consider Therapeutic Agents Common Conditions Summary 1. Anti-inflammatory Glucocorticoid Pros: inhibit AA production ↓ chemotactic mediators ↓ fibroblast formation and neovascularization superior to NSAIDs for periocular structures ↓ reperfusion injury ↓ iridocyclitis associated with glaucoma
Cons: delays corneal healing Immunosuppression systemic absorption corneal degeneration steroid keratopathy
Phosphates = hydrophilic Acetates = lipophilic (better corneal penetration)
Topical: Prednisolone acetate (0.12-1%) Systemic: Prednisone tablet, Dexamethasone inj
Factors to consider Therapeutic Agents Common Conditions Summary 1. Anti-inflammatory
NSAID’s
Prostaglandin &Thromboxane A2 Inhibition
Reduce inflammation and prevent miosis
Topical: Flurbiprofen (Ocufen): +/- irritating Diclofenac (Voltaren): +/- corneal malacia Ketorolac (Acular) : +/- corneal malacia
?Contraindicated in glaucoma & hyphema?
Oral: Meloxicam 1.5 mg/m Carprofen (Rimadyl)
Factors to consider Therapeutic Agents Common Conditions Summary 2. Antibiotics Considerations Penetration -Where does the drug need to get? Topical Systemic Both Resistance?
Choices What am I treating? Cytology - Diff Quick/Gram Stain Gram positive cocci - Fluoroquinolones – streptococcus resistance - Cephalosporines Gram negative rods - Aminoglycosides - Tobramycin has less resistance than Gentamicin Culture and Sensitivity
Factors to consider Therapeutic Agents Common Conditions Summary Remember
Epithelium Topical antibiotics -ulcer - any antibiotic will reach the target Stroma -non ulcerated – need drug that can convert between ionized – non- ionized forms – fluoroquinolone
Endothelium Caution re resistance!
Factors to consider Therapeutic Agents Common Conditions Summary 3. Mydriatics -dilate the pupil for full ocular examination/intraocular surgery -treatment of miosis from uveitis, cycloplegia (pain control)
Tropicamide & Atropine = Cholinergic Antagonists -block smooth muscle cholinergic receptors
Phenylephrine & epinephrine – Sympathomimetics - intracameral injections
Factors to consider Therapeutic Agents Common Conditions Summary 1. Cholinergic antagonists
Tropicamide (0.5-1%) Atropine (0.5-2%) Onset and duration 30 min – 3 hours 1 hr, 4-5 days (not inflammed) Longer esp in dark irises Action Mydriasis – less potent then Mydriasis and cycloplegia Atropine Side effects Less likely to precipitate Salivation, vomiting, contact glaucoma/KCS dermatitis, old dog – circling/delirium +/- glaucoma/KCS
2. Sympathomimetics Phenylephrine - pharmacologic testing (Horner’s Syndrome) - hemorrhage control (topical intraop) Epinephrine - mydriasis intraop
Factors to consider Therapeutic Agents Common Conditions Summary 4. Glaucoma Medications
1. Dehydrate the eye = hyperosmotics
2. Reduce fluid production = carbonic anhydrase inhibitors (CAI’s) = beta blockers
3. Increase fluid outflow = prostaglandin analogues
4. old/out of date therapies
Factors to consider Therapeutic Agents Common Conditions Summary 4. Glaucoma Medications
1. Hyperosmotics – Mannitol, glycerine
MOA: -↓ aqueous production by ↓ the rate of plasma ultrafiltration in the choroidal blood vessels. -↑ plasma osmolality which promotes diffusion of water from the intraocular fluids back into the plasma → dehydrates the vitreous
This affects IOP in 2 ways: -↓ AH production
- ↑ AH drainage – by opening up the ICA
Note: Furosemide will not work – = a loop diuretic – it will make the dog urinate but won’t dehydrate the vitreous.
Factors to consider Therapeutic Agents Common Conditions Summary Name Mannitol 20% (200 mg/ml) Glycerin 50-70% (500 -700 mg/ml)
Dose 1-2 g/kg IV over 30 min 1.65 ml/kg PO
Eg: (9 kg dog)(1 g/kg) = 9000 mg/200 mg/ml = 45 ml No concurrent fluids/water for 4 hrs No water for 4 hours Filtered administration recommended Composition Vegetable sugar, not metabolized. Complex CHO, metabolized to glucose OK for diabetics Caution with diabetics Caution Renal, heart failure Nausea, vomiting, hyperglycaemia, glucosuria, weight gain Concern with uveitis Less (high mol wt) Yes
Onset 30 min 45 min
Duration 5-10 hrs 10 hrs
IOP reduction 9 mmHg after 1.5 hrs (variable) 10 mmHg after 45 min
Factors to consider Therapeutic Agents Common Conditions Summary Beta blocker CAI’s (Alpha-2 agonists)
normal ↓ production
PG analogues Cholinergics ↑ outflow Sympathomimetics
IN = OUT IN < OUT IN << OUT
Factors to consider Therapeutic Agents Common Conditions Summary Reduce Fluid Production Carbonic Anhydrase Inhibitors (CAI’s)
Dorzolamide (Trusopt) 2% Dorzolamide (2%) – Timolol (0.5%) (Cosopt) BID to TID Timolol augments CAI activity Increased Optic Nerve Head Blood Flow Side Effects: pH 5.6 – potential for severe blepharitis Timolol →mild miosis Sensitivity can prohibit use in some dogs Timolol → bradycardia and hypotension Dorzolamide →potential irritation Brinzolamide (Azopt) 1% Brinzolamide (1%) – Timolol (0.5%) (Azarga) BID to TID Timolol augments CAI activity pH 7.5 – less irritating Side Effects: As effective as dorzolamide Timolol →mild miosis Timolol → bradycardia and hypotension
Factors to consider Therapeutic Agents Common Conditions Summary Beta Blockers Timolol, Betaxolol (B1), Metipranolol, Carteolol, Levobunolol
Timolol 0.25 and 0.5% Nonselective β-blocker I Decreases aqueous production Small decreases in IOP Will not be effective in acute glaucoma Will cause Miosis - caution in Lens Luxation’s SIDE EFFECTS Bradycardia Systemic Hypotension Epitheliotoxic II
Factors to consider Therapeutic Agents Common Conditions Summary Increase Fluid Outflow
Prostaglandin Analogues Side effects: Extreme Miosis Hyperemia Uveitis Latanoprost (Xalatan) SID-TID, refrigerate Iris Pigmentation/Eyelash growth Binds to Prostaglandin FP receptors: Increases aqueous outflow Alters the protein make up of the drainage angle Possible changes in optic nerve blood flow
Travoprost (Travatan) SID-TID q24 hour application: ↓ IOP 59.2% BID application: ↓ IOP 75.2% SID at night - IOP spikes occur with am dosing, but not BID or pm only
Bimatoprost (Lumigan) SID-BID Dogs – q24h dosing ↓ IOP 78%
Factors to consider Therapeutic Agents Common Conditions Summary Glaucoma Medications No Longer Used
Oral diuretics - acetazolamide - methazolamide
Sympathomimetics -epinephrine, dipivefrin
Adrenergic agents - epinephrine, dipivefrin, apraclonidine, brimonidine
Parasympathomimetics – pilocarpine (direct acting) - demecarium (indirect acting)
Factors to consider Therapeutic Agents Common Conditions Summary 5. Topical Anaesthetics
MOA: Block sodium ion entrance and prevent nerve depolarization Ease examination Comfort for pet (and Owner) Most Common Proparacaine (Alcaine) -refrigerate after opening, lasts longer than tetracaine -in dogs onset: 30 sec – 15 min to maximum effect 45 min duration with one application 55 min duration with 2 drops applied 5 min apart -corneal epithelial toxicity w/ repeated applications -destabilizes the tear film -creates surface irregularities -uncommonly can cause ulcerations
Tetracaine -refrigeration not required -discomfort upon instillation significantly longer -anesthesia time shorter -greater epithelial toxicity -in dogs - ↑ Conjunctival hyperemia, chemosis, TEL elevation - duration of effect not reported
Factors to consider Therapeutic Agents Common Conditions Summary 6. Dehydrating Agents
5% Hypertonic saline (solution/ointment) eg Muro 128
- used to dehydrate the cornea - solution can sting some dogs, ointment does not sting - can be used with corneal ulcers, endothelial degeneration
Factors to consider Therapeutic Agents Common Conditions Summary 7. Tear Stimulants TOPICAL Cyclosporine & Tacrolimus MOA: -Calcineurin Inhibitors - Blocks T-cell activation CsA 1% CsA 2% Tac 0.02% -Local Immune suppression
Limited Anti-inflammatory Action -may decrease corneal vascularization -2% CSA may inhibit lymphocyte proliferation
Most Canine KCS - Immune mediated -mononuclear cell infiltration of lacrimal tissue -results in acinar atrophy -reversed w/immunosuppressive therapy
With initial STT > 5mm/min: ->80% will increase tears by 5mm/min -improved of tear film breakup time
If initial STT ≤ 2mm/min, tacrolimus seems to work better 0.2% cyclosporine
Factors to consider Therapeutic Agents Common Conditions Summary 7. Tear Stimulants
ORAL Pilocarpine -directly stimulates functional lacrimal tissue
-used for treatment of Neurogenic KCS
-oral therapy can create nausea. If using orally, please call an ophthalmologist for dosing regimen
-topical therapy at low concentration (0.1%) reported but not overly used Irritating if used at higher concentrations Irritating if KCS is not neurogenic
Factors to consider Therapeutic Agents Common Conditions Summary 8. Adjunct Therapies - antioxidants
Antioxidants - OcuGLO -retina - high O2 consumption and exposure to light → increased susceptibility to oxidative stress (increased free radical)-induced damage → photoreceptor death → blindness -3 main ingredients: Grapeseed extract - free radical scavengers with anti-inflammatory properties Lutein - antioxidants - protection of the retina and lens. Omega 3-FA - essential FA, anti-inflammatory effects, enriches photoreceptor function
-used as a presumed neuroprotective therapy prescribed by ophthalmologists for canine degenerative retinal and ON disease
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Factors to consider Therapeutic Agents Common Conditions Summary 8. Adjunct Therapies - lubricants 0.2 % HA 1.2 % HA
Lube
High viscosity -fewer applications Stabilized by amino acids, which are contained in the natural tears Linear, long-chained HA -high elasticity -long-lasting film -Preservation free
Factors to consider Therapeutic Agents Common Conditions Summary 8. Adjunct Therapies - serum
Some bacteria (beta hemolytic strep., pseudomonas) contain stomalysins (enzymes that rapidly breakdown “melt” the stroma of the cornea). Serum N-acetylcysteine Dimethylcysteine Alpha (α)-2 macroglobulin's (large proteins) in serum EDTA (Na/K) - inhibit the action of stromalysins Heparin Na Citrate Many medications will also stop stromalysin activity Penicillamine Na ascorbate Galardin (MMP Why use serum? FREE inhibitor) easily available Retinoid acid “Bankable”
Factors to consider Therapeutic Agents Common Conditions Summary C. Common Conditions SUBCONJUNCTIVAL SYSTEMIC TOPICAL 1. Acute Glaucoma 2. Ulcers a. Infected b. Not infected 3. Dry eye 4. Uveitis 5. Retrobulbar disease (abscess) 6. Conjunctivitis a. Bacterial b. Allergic 7. Immune-mediated keratitis (Pannus)
Factors to consider Therapeutic Agents Common Conditions Summary 1. Acute Glaucoma
REFER IMMEDIATELY if owners interested. The eye is potentially visual if history of glaucoma for less than 24-72 hours and fundus examination is normal. Emergency treatment (have a plan in place)
Carbonic Anhydrase Inhibitor (CAI) with Timolol: Brinzolamide (Azopt) + Timolol = Azarga TID or Dorzolamide (Trusopt) + Timolol = Cosopt TID Prostaglandin analogue: Xalatan® (latanoprost) or Travatan® (travoprost) (IF LENS IS NOT LUXATED) or Mannitol IV – if lens is luxated or you cannot see where it is or Glycerin PO – if the owner lives too far away to come to clinic for treatment
Factors to consider Therapeutic Agents Common Conditions Summary Iris behind the lens
Factors to consider Therapeutic Agents Common Conditions Summary 2. Corneal Ulcer – a. Not infected
Antibiotic Topical -Potent antibiotics are not required. -broad spectrum AB’s - BNP oint or Neosporin eye drops Oral -doxycycline (concentrates in the tears)
Atropine -small dogs 0.5% drops, larger dogs use the 1% drops. -BID until dilated, then prn to maintain the mydriasis. Anti-inflammatory -oral NSAID
Factors to consider Therapeutic Agents Common Conditions Summary 2. Corneal Ulcer – b. Infected
Antibiotic Topical -Fluoroquinolone – eg Ofloxacin, Ciprofloxacin q1-3 hrs -broad spectrum AB solution – tobramycin, cefazolin IV solution (50 mg/ml) Oral -doxycycline (concentrates in the tears)
Atropine -small dogs 0.5% drops, larger dogs use the 1% drops. -BID-TID until dilated, then prn to maintain the mydriasis. Anti-inflammatory -oral NSAID
Factors to consider Therapeutic Agents Common Conditions Summary 3. Dry eye – Keratoconjunctivitis sicca (KCS)
Tear Replacers -applied frequently (q2h) until the tears can be stimulated (drops, gels, ointments) -many options so try several -ideally contains hyaluronic acid
Tear Stimulants -recheck tears 4-6 weeks later. Ask owners not to apply any meds (even to clean) on morning of test
Cyclosporin (0.2% (Optimmune), 1%, 2%) BID Tacrolimus (0.02-0.03%) BID
-immunosuppressive properties - block the transcription of cytokine genes in activated T cells
Factors to consider Therapeutic Agents Common Conditions Summary 4. Uveitis Topical Treatment Steroids: Prednefrin Forte® (Prednisolone acetate 1%) -shake well before use. q2-4hrs Maxidex® (Dexamethasone 0.1%) - does not travel through the cornea as easily
Atropine 1%: -BID until dilated, then as needed to maintain dilation -warn owners to wash their hands after use.
Oral Antiinflammatory Prednisolone – if severe 1mg/kg twice daily for three days, then once daily for five days, then once every second day. Oral NSAID – if less severe or chronic. Treat for longer than you think.
Very severe cases of uveitis: Use all of the above and subconjunctival cortisone e.g. Celestone Chronodose ® one vial for a medium to large sized dog, or 0.25 to 1.0 mL of Dexafort® Subconjunctival atropine 0.1-0.3 mL of atropine for injection, e.g. Atropine Mitis ® (0.65mg/mL).
Factors to consider Therapeutic Agents Common Conditions Summary 5. Retrobulbar Abscess
Antibiotic Oral -Cephalexin, Amoxyclav, or Clindamycin
Anti-inflammatory -oral NSAID - very very important -oral steroid BUT only if you are sure it’s not fungal/neoplastic
Draining – rarely needed
-elevated TE -painful (very) to try to open mouth -painful to push on / around eye
Factors to consider Therapeutic Agents Common Conditions Summary 6. Conjunctivitis
Bacterial Conjunctivitis -check for predisposing cause (dry eye, foreign body) -ensure fluorescein negative -antibiotic with steroid combination – eg Tobradex TID x 5 days, if no response, reassess your diagnosis
Allergic Conjunctivitis -check for a predisposing cause (dry eye, poor eyelid conformation – eg long lower lids) -topical steroid - Maxidex (dexamethasone 0.1%) - Prednefrin Forte (prednisolone acetate 1%) - hydrocortisone if very mild
Factors to consider Therapeutic Agents Common Conditions Summary 7. Pannus Topical corticosteroids for rapid control -Prednisolone Forte (prednisolone acetate 1%) – BID-QID -Maxidex (dexamethasone 0.1%) – BID-QID
Immuno-modulator for long term control -Cyclosporine (0.2% (Optimmune), 1% or 2% - BID high UV months, - SID low UV months -Tacrolimus 0.02% BID as per cyclosporine -helps to thin corneal pigment and remove lipid deposits
Keep out of the sun, provide shade, visor, Doggles Maxidex - for breakout events in summer
Factors to consider Therapeutic Agents Common Conditions Summary D. Summary
When choosing therapy for an ocular condition you need to consider: 1. Location of the Problem 2. Ease of Medication 3. Potency of the Medication 4. Frequency of Therapy
Factors to consider Therapeutic Agents Common Conditions Summary SUBCONJUNCTIVAL On the Shelf SYSTEMIC TOPICAL Oral AB (retrobulbar abscess, Broad spectrum AB blepharitis, infected ulcer) (ulcer – infected/non-infected eg. cephalexin, amoxy-clav bacterial conjunctivitis*) eg. Tobramycin, BNP, BNPH* Oral NSAID Narrow spectrum AB (chronic uveitis (infected ulcer) eg. fluoroquinolone drop retrobulbar abscess, ulcer) eg meloxicam, carprofen NSAID (mild uveitis, LIU) eg Voltaren ̷ Acular Oral Steroid (acute uveitis) Steroid eg prednisone̷ predisolone (allergic conjunctivitis, Pannus, uveitis) eg Pred acetate 1% Glaucoma Tear Stimulant eg. mannitol IV, glycerin PO Steroid (severe uveitis) (dry eye, Pannus) eg cyclosporine̷ tacrolimus eg betamethasone, dexamethasone Glaucoma (CAI, PG analogue) Antibiotic (unmanageable patient) eg gentamicin, cefazolin Mydriatic eg Atropine 1% Mydriatic eg Atropine̷̷ Tropicamide * With mild steroid (H)
Factors to consider Therapeutic Agents Common Conditions Summary References
1. Blogg JR, Stanley RG. Common Eye Diseases. Proceedings 158, Post Graduate Committee in Veterinary Science 1991. 2. Slatter DH. Fundamentals of Veterinary Ophthalmology, 2nd Edition. WB Saunders, Philadelphia1990. 3. Severin GA. Severin Veterinary Ophthalmology Notes, 3rd Edition 1996. 4. Mathis G, Regnier A, Ward DA. Clinical Ophthalmic Pharmacology and Therapeutics in Veterinary Ophthalmology 3rd Edition, Editor Gelatt KN. Lippincott Williams & Wilkins, Philadelphia 1999.
Factors to consider Therapeutic Agents Common Conditions Summary Anti-inflammatory Medications Non-steroidals (NSAIDs) Topical Diclofenac sodium 0.1% Voltaren Flurbiprofen sodium 0.03% Ocufen Ketorolac tromethamine 0.5% Acular Suprofen 1% Profenal Systemic Meloxicam 1.5 mg/ml Metacam Carprofen 4.4 mg/kg Rimadyl Acetylsalicylic acid Aspirin Steroids Topical Prednisolone acetate 1% Prednisolone Forte Prednisolone acetate 0.12% Prednisolone Mild Dexamethasone 0.1% Maxidex, Maxitrol, Tobradex Systemic Prednisone tablets Dexamethasone inj. Subconjunctival Betamethasone Celestone Chronodose® Dexamethasone Dexafort® Medications used for Glaucoma
Carbonic Anhydrase Inhibitors (CAIs) Dorzolamide HCl 2% Trusopt BID-TID. May sting
(↓production) Brinzolamide 1% Azopt® BID-TID Dorzolamide and Timolol maleate Cosopt® BID-TID Brinzolamide 1% and Timolol maleate Azarga® BID-TID Methazolamide Neptazane® 4 mg/kg PO, BID. Nausea, anorexia, tachypnea Acetazolamide. Diuretic Diamox® 4-8 mg/kg PO, BID-TID. Nausea, anorexia, tachypnea. Caution met’c acidosis. Cholinergics (↑outflow) Pilocarpine 1% Isoptocarpine® BID Direct acting Not recommended
Demecarium bromide 0.125,0.25 % Compounded BID Indirect acting
Echothiophate iodide 0.03%,0.125,0.25% Phospholine Iodide®
Carbachol 0.01% intracameral
Beta blocker Timolol maleate (0.25% < 10 kg, 0.5% > 10 kg) BID. Not with ulcer.
(↓production) Betaxolol 0.5%, 0.25% Betoptic® / Betopic® BID
Adrenergics (? MOA) Dipivefrin HCl 0.1% Propine® BID Epinephrine 1%,2% BID (↓production) Apraclonidine 0.5% Iopidine® BID-TID (↑outflow) Brimonidine 0.15% Alphagan® BID Prostaglandin Analogues Travoprost 0.004% Travatan® BID-TID Latanoprost 0.005% Xalatan® BID-TID (↑ u-s outflow) Bimatoprost 0.03% Lumigan® BID-TID Medications used for Dry Eye *preservative free
Tear Stimulants Cyclosporine 0.2%, 1%, 2%, oil, aqueous, ointment Tacrolimus 0.02-0.03%, oil, aqueous, ointment Pimecrolimus in testing
Tear Substitutes PVA solutions AKWA Tears, Artificial tears, Dry eyes, Liquifilm Tears, Ocu-tears PF*, Teargen
Hyaluronic Acid Hylo-Forte*, An-Hypro*
Cellulose-Based solutions Celluvisc*, Comfort Tears, Gen Teal*, Isoptotears Plain, Murocel, Narture’s Tears, Refresh Plus*, Refresh Tears*, Teargen II. Polymer Combinations Aqua Site, Bion Tears*, Hypotears, Hypotears PF, Lacril, Lubi Tears, Lubrithal, Murine Eye Lubricant, Moisture Drops, Nature’s Tears, OcuCoat, Puralube Tears, Refresh*, Tears Naturale, Tears Naturale II, Tears Naturale Free*, Tears Plus, Tears Renewed Viscoelastic Products i-drop* Vasoclastic Products Hylashield*, Hylashield Nite* Glycerine Products Eye-Lube A Ointments AKWA Tears ointment*, Dry Eyes*, Duratears Naturale*, Hypo Tears*, Lacri-Lube NP*, Lacri- Lube SOP, Moisture Eyes PM*, Paralube*, Refresh PM* , Tears Renewed* Mucinolytics Acetylcysteine 5-10% solution, BID-QID Antimicrobial agents Broad spectrum topical antibiotic Tobrex, BNP, Fucithalmic acid Anti-inflammatory IF NO ULCERS Tobradex, Maxitrol Medication Dog Therapy while waiting for test Anti-inflammatory - topical Prednisolone acetate 1% or topical results in dogs (assuming no NSAID ulcers) Anti-inflammatory - oral Metacam if safe
Mydriatic (unless glaucoma) Atropine 1%
Antibiotic - oral Doxycycline (5 mg/kg BID)
Glaucoma – if indicated Carbonic anhydrase inhibitor +/- Beta blocker
Medication Dog Specific Therapy following test Add topical or oral anti-fungal If indicated Results (assuming no ulcers) Add topical anti-glaucoma If indicated
Add steroid If fungal negative or no signs of neoplasia Add antibiotic If indicated Treatment for Corneal Ulcers
Melting ulcers Narrow-Spectrum Ciprofloxacin 0.3% (Ciloxan) q1-6h, may sting Moxifloxacin (Vigamox) q1-6h
Norfloxacin 0.3% (Chibroxin) q1-6h
Ofloxacin 0.3% (Ocuflox) q1-6h
Broad-spectrum Cefazolin - Compounded in tear solution Keep refrigerated, 1 week shelf life in 100 mg/ml, q1-6h fridge
Tobramycin
Anti-proteases/Chelators Autologous serum = α 2-macroglobulins Keep refrigerated for 5-7 day, 6 months in freezer N-acetyl-cysteine = mucomyst 5-10% MMP inhibitor (Ca++ and Zn+ chelator), needs to be buffered to pH 7-7.5 EDTA (Na/K) 0.2% (add 5 ml sterile water MMP inhibitor (Ca++ and Zn+ chelator), to a commercial blood collection tube) q1h, topically Tetracycline (Doxycycline, 0.1%. Doxycycline can also be oral oxytetracycline) 10mg/kg SID. Ilomostast (Galardin) 0.1%, MMP inhibitor (Ca++ and Zn+ chelator) Na+ Citrate, Na+ ascorbate, Retinoid acid Non-melting ulcers Tobramycin Tobrex solution Least epitheliotoxic Gentamicin Gentocin solution Most epitheliotoxic Bacitracin/neomycin/polymyxin BNP/mycitracin/neobacimyx/trioptic/ Ointment/solution vetropolycin Chloramphenicol Pentamycetin Ointment/solution Oxytetracycline + polymyxin Terramycin Ointment Thank you!
The Chapter gratefully acknowledges Vet Strategy as the sponsor of this session
Factors to consider Therapeutic Agents Common Conditions Summary Factors to consider Therapeutic Agents Common Conditions Summary Factors to consider Therapeutic Agents Common Conditions Summary Factors to consider Therapeutic Agents Common Conditions Summary Factors to consider Therapeutic Agents Common Conditions Summary Factors to consider Therapeutic Agents Common Conditions Summary Factors to consider Therapeutic Agents Common Conditions Summary Factors to consider Therapeutic Agents Common Conditions Summary Factors to consider Therapeutic Agents Common Conditions Summary Factors to consider Therapeutic Agents Common Conditions Summary Factors to consider Therapeutic Agents Common Conditions Summary Factors to consider Therapeutic Agents Common Conditions Summary