Ocular Therapeutics Flashcards
1
Q
When is the prescribing cascade to be used and who set it out?
A
To be used when no licensed product for a particular condition in a particular species.
Set out by the VMD (Veterinary Medicines Regulations 2013) - all veterinary products must be prescribed in accordance with this.
2
Q
What does it mean when a product is prescribed under the cascade?
A
No data or insufficient data have been submitted to the VMD to support the authorisation of the drug, its use according to a different dosing regime to that authorised or for a different indication.
3
Q
What are the steps of the cascade?
A
If no licensed product:
1. Medicine with authorisation for use in NI (licensed in NI but not UK) for that condition in that species.
2. Licensed in UK or NI for different condition or same species - veterinary product
3. Human medicine authorised for use in UK or authorised veterinary product from outside UK (may need special import)
4. Extemporaneous preparation by veterinary surgeon, pharmacist or person with manufacturer’s authorisation.
5. In exceptional circumstances human medication imported from outside UK.
4
Q
What routes of administration are there for ocular drugs?
A
Topical
Systemic
Subconjunctival injection
Intracameral
Intravitreal
Retrobulbar
5
Q
Which tissues do topical medications typically reach?
A
Conjunctiva, cornea, anterior uvea, (eyelids)
6
Q
What tissues do subconjunctival medications typically reach?
A
Cornea, anterior uvea
7
Q
Which tissues do intracameral injections typically reach?
A
Anterior chamber, (Posterior segment)
8
Q
Which structures do retrobulbar injections typically reach?
A
Orbital cranial nerves, posterior segment
9
Q
What structures do intravitreal injections reach?
A
Posterior segment
10
Q
Which structures do systemic medications typically reach?
A
Eyelids, Posterior segment, optic nerve, anterior uvea
11
Q
What factors affect drug penetration with topical administration?
A
Anatomical drug barriers, molecular size of drug, lipid/water solubility, ionisation, penetration enhancers
12
Q
What anatomical barriers are there to topical ocular drug administration and how can movement occur across this structure? Which type of drugs move best across these routes?
A
Cornea TRILAMINAR STRUCTURE - anatomical barrier (epithelium, stroma, endothelium)
Movement may occur across cells - TRANSCELLULAR (relates to partition co-efficient of molecules, LIPOPHILIC/UNIONISED DRUGS can pass through phospholipid membrane)
or between cells - PARACELLULAR (zona occludens tight junctions, permeable to small HYDROPHILIC DRUGS/IONIZED)
13
Q
What is the rate limiting step for hydrophilic compounds through the corneal epithelium?
A
Epithelial transfer (small ,molecules only through paracellular route)
14
Q
Which type of molecules does the stroma of the cornea favour and why?
A
Hydrophilic molecules as 78% water - acts as a barrier to lipophilic molecules.
15
Q
How thick is the endothelium of the cornea and does it play any role in resistance to topically applied drugs?
A
Only one cell thick, limited resistance to either lipophilic or hydrophilic drugs
16
Q
What type of solubility is required to penetrate the cornea? What is the lipid/water partition co-efficient for this?
A
Intermediate lipid/water solubility.
10:1 to 1000:1 lipid/water partition co-efficient required.
17
Q
How can we increase corneal penetration?
A
Buffer solution - adjust pH, level of ionisation dissociation, pre-disposes to lipophilicity and epithelial transfer
Increase concentration/tonicity - increased gradient (short term effect)
Competitive inhibitors - (e.g cetylpyridium) - reduce protein binding to drug in tear film increasing bioavaliability
Epithelial removal for hydrophilic drugs (9x penetration when 25-50% epithelium removed)
18
Q
By which route is the conjunctiva more permeable than the cornea? Where do the drugs go after they have moved across the conjunctiva?
A
Paracellular route - no major difference between ionized/unionized drugs
Moves into sclera before entering eye - laterally into corneal stroma (epithelial bypass), anterior ciliary arteries then uvea.
19
Q
How much more permeable is the sclera compared to the cornea and why? What type of molecules are more permeable. What can enhance permeability of the sclera?
A
10x more permeable than the cornea due to lack of epithelium. Hydrophilic molecules more permeable than lipophilic. Prostaglandins (inflammation) enhance penetration.
20
Q
What happens to the vast majority of topically applied drugs? How does this occur and why?
A
Majority lost within 15-30 seconds of application
Excess of drug - drop of drug 25-75ul
Tear film 7-10uL
Nasolacrimal drainage
Spill over eyelids (especially if increased blinking/e.g blepharospasm)
21
Q
What is the rate of tear film turnover?
A
1ul/min - nearly all drugs lost via NL drainage within 10 minutes.
22
Q
What are the main barriers for systemic drug administration and what do they compose of?
A
Blood ocular barriers = blood-aqueous and blood-retinal barriers (enothelium and epithelium)
23
Q
Describe the composition of the blood-aqueous barrier.
A
Endothelial cells of iris and epithelial cells ciliary body
24
Q
Describe the composition of the blood-retinal barrier.
A
Endothelial cells of the retinal vessels, epithelial cells of the RPE
25
What blocks entry of systemic drugs at the blood-ocular barriers and what can increase penetration?
Tight junctions at these blood-ocular barriers limit the paracellular route
Become leaky in response to prostaglandins - increased permeability with inflammation.
26
What is the difference between a solution and a suspension?
Solution = drug entirely dissolved in solvent
Suspension = drug particles present in saturated aqueous vehicle that includes dispersing and suspending agents
27
What are the advantages and disadvantages of solutions/suspensions over ointments?
Ease of administration, minimal visual interference, reduced contact dermatitis, less toxic to anterior segment
Disadvantages - more frequent application due to reduce contact time, nasolacrimal drainage can lead to systemic absorption, non lubricating, readily diluted by tears.
28
What is the ideal osmolarity of a solution? What does this help reduce. What can help modify osmolarity.
300mosm/kg - as close to tear film osmolarity as possible, helps reduce irritation.
Sodium chloride, boric acid, dextrose can help modify.
29
What size must the particles be to be in a suspension? What can be some disadvantages of a suspension.
<10um, uniform size and micronised.
Disadvantages - irritation (more likely than solutions), need to mix suspension before use
30
What 3 things are often used as the base for ointments? What roles do they play?
Petrolatum - ointment base
Mineral oil- allows melting on contact with ocular surface
Lanolin - allow the base to absorb water and mix with tear film.
31
What benefits/disadvantages are there of using an ointment?
Benefits - larger molecules and longer retention times, less frequent administration (retained at least 4hrs), little effect on corneal healing, lubricating.
Disadvantages - can be associated with ocular/periocular dermatitis, avoid in perforated eyes as base toxic to corneal endothelium, visual interference
32
How can we improve ocular bioavailability via precorneal retention?
Ointment formulation
Viscosity enhancing polymers and mucoadhesives - cellulose derivatives and polyvinyl alcohol. Maximum bioavailability at 12-15cps - any more than this then increased risk of irritation. Enhance attachment to the mucin layer of the tear film. Sodium hyluoronate an example as similar to ocular mucus glycoprotein.
Colloidal drug delivery system - sustained drug delivery to eye and includes liposome, nanoparticles and microemulsions
Liposome = small vesicles composed of phospholipid bilayers separated by aqueous = lipophilic drugs trapped between phospholipids in aqueous compartment
Nanoparticles = polymeric colloidal particles in or on which drugs entrapped
Microemulsions = useful for delivery of water-insoluble drugs.
Solid polymeric devices - soft contact lenses of non biodegradable hydrophilic polymers which absorb drug when soaked in drug solution. Contact lens then applied over cornea and slowly releases drug. Corneal collagen shields. Lacrimal punctal plugs for more long standing drug delivery or subconjunctival implants e.g ciclosporin implants.
33
Why are preservatives used and what are possible toxic effects of these.
Preservatives e.g benzalkonium chloride used to inhibit microbial growth
Potential s/e - disrupt corneal epithelial healing, tear film disruption, inflammatory infiltrates at limbus/trabecular meshwork, discomfort, corneal endothelial toxicity.
34
How can drugs applied topically onto the ocular surface end up systemically?
How can we reduce this?
Nasolacrimal drainage (transmucosally or swallowed)
Conjunctival/episcleral vessels
Licking off face following spillover
Nasolacrimal occlusion can reduce and eyelid closure can reduce loss of drug and increase contact time.
35
How can we improve corneal penetration of drugs?
Ophthalmic prodrugs - for hydrophilic drugs which cannot transverse corneal epithelium a pro-drug may be considered, tend to be lipophilic esters or diesters (inactive versions of parent drug) Once across corneal epithelium enzymatic hydrolysis occurs to release active drug. Examples - prednisolone acetate (prodrug of prednisolone), nepafenac (prodrug to amfenac) and latanoprost/travoprost (prodrugs to PGF2a)
Penetration enhancers - EDTA or benzalkonium chloride - disrupt biological membranes - alter membrane permeability and expand transcellular route.
36
For intraocular drug distribution when does peak aqueous humour concentration occur - what structures have good/poor penetration?
0.5-3hr = peak AH concentration
Iris = good penetration with large surface area
Lens = poor due to anterior epithelium, dense lens fibres, limited to lipophilic drugs
37
How are drugs that penetrate the intraocular structures eliminated?
Melanin binding - iris and ciliary body - drug sink immediately reducing bioavailability slowing onset of action. e.g atropine faster onset in non pigmented eyes compared to pigmented but will have longer duration of action in pigmented eyes.
AH outflow - 5ul/min
Retinal blood flow
Metabolism within the ocular tissues
38
What are some of the indications for subconjunctival injections? How long do solutions last vs suspensions via this route.
Inflammation/infection of anterior segment or cornea
Potentially useful for posterior segment
Owner/patient compliance factor
Hydrophilic drugs for epithelial bypass
Solutions 8-12hrs duration
Suspensions 2-3 weeks but risk of granuloma formation.
39
What modes of penetration occur with subconjunctival injections and when are they typically used?
Absorption via conjunctival vessels = systemic
Diffuse across scleral/corneal stroma
Leak via injection site and absorb via cornea.
Typically used post cataract surgery -
40
When do we typically perform retrobulbar injections - what do we inject and what are the risks/complications?
Local anaesthesia for enucleations
Bupivicaine 0.5% (slower onset 5-10 min, longer duration 4-8hrs) or Lidocaine 0.2% (fast acting 2-5 mins, short duration 2-3hrs)
Curved retrobulbar needle - inferior transpalpebral approach
Risks - globe perforation, brainstem anaesthesia (intra-thecal administration), haemorrhage
41
When are intracameral injections typically performed and what are the risks involved with this?
Used during cataract surgery - tissue plasminogen activator, triamcinolone, carbachol, adrenaline, lidocaine
Injection across corneoscleral limbus (0.1-0.8mls, same amount removed to prevent raised IOP)
Risk - traumatic injury to iris/lens, intraocular haemorrhage, injury to cornea, toxicity
42
When may we use intra-vitreal injections and what are the risks.
Vitreous - avascular hydrogel, drug delivery to this region often low due to aqueous humour washout and poor penetration of blood vessels (blood-ocular barriers)
Indications = posterior segment inflammation/infection but very rarely used
Risks - haemorrhage, endophthlamitis, lens damage, retinal detachment
Potentially used for chemical ablation of ciliary body - gentamicin, cidofovir.
43
What indication are there for systemic administration of drugs in ocular diseases?
Eyelid disease, orbital disease, posterior segment disease.
44
What factors influence penetration of the blood-ocular barriers?
Lipophilicity, molecular weight, plasma drug levels, inflammation.
45
List the mechanisms of action antimicrobials can have - what do the exploit?
Exploit differences in structure and function between microbes and mammalian cells.
Bacterial cell wall (absent in mammals) - petidoglycan = essential component
Bacterial cell membrane - similarities to mammalian cell membrane (risk of toxicity)
Bacterial ribosome = different shape/structure to mammalian cell ribosome
Bacterial folic acid synthesis - bacteria make their own and mammals do not
Bacterial DNA gyrase and topoisomerase IV
46
What are the most common types of flora in dog eyes?
Gram +ve aerobes - staphylococcus and streptococcus but also rods such as bacillus and corynebacterium.
Grame -ve such as Neisseria cocci or pseudomonas are less common and anaerobes are rarely isolated.
47
In dogs with complicated corneal ulcers (infective or septic keratitis) how is the conjunctival flora altered?
Infective/septic keratitis (melting ulcers) - gram -ve more likely to be isolated - pseudomonas
Anaerobic bacteria - e.g clostridium also more likely to be seen in septic keratitis cases.
(Can still see streptococcus/staphylococcus so culture always indicated in these cases)
48
Which type of bacteria is commonly seen in the flora of healthy cats eyes?
What types are seen with complicated corneal ulceration?
Gram +ve aerobes - staphylococcus
Occasionally gram -ve moraxella
Complicated corneal ulcers - gram -ve more likely - pseudomonas
Occasionally anaerobic.
49
What type of bacteria is commonly seen in the flora of healthy rabbit eyes?
Gram +ve aerobes - corynebacterium, staphylococcus, micrococcus, bacillus
Gram -ve - pasteurella, moraxella
50
Which antibiotic groups inhibit bacterial cell wall synthesis?
Penicillins
Cephalosporins
Bacitracin
51
Are penicillins bactericidal or static? What is their key feature and what does this prevent?
When may penicillins be used in ophthalmology?
Bactericidal - Gram +ve activity (ampicillin/amoxicillin - some gram -ve range)
Thiazolidine ring.
B lactam ring - binds to bacterial tranpeptidases required for formation of peptide cross linkages between polysaccharide chains of peptidoglycan. - incomplete cell wall formation and bacterial death.
Indications:
Prophylactically after intraocular surgery/during cataract surgery
Treatment of orbital or eyelid infections
?Chlamydial conjunctivitis in cats
Rarely used topically in small animals as cloxacillin too narrow range for eye infections.
52
Are cephalosporins bactericidal or static? What is their mode of action.
List some uses for them in ophthalmology?
Bactericidal - excellent gram +ve activity
Similar to penicillins but different molecular structure
Dihydrothiazine ring
B lactam ring with side chain
Resistant to B lactamases produced by staph.aureus
Some gram -ve's are resistant
1st generation - cephalexin/cefazolin
2nd generation - cefuroxime, cefoxitin
3rd generation - cefixime, cefoxatime, ceftazidime
4th generation - cefepime
Increase in gram -ve activity with each generation.
Rarely any indication to use anything but 1st generation in veterinary ophthalmology.
Indications:
Cefazolin - off licence for corneal ulcers infected with gram +ve organisms. Reaches therapeutic concentrations in anterior chamber - good choice for intraocular surgery
Cephalexin - good choice for staphylococcal eyelid infections
53
Is bacitracin bacteriocidal or static?
What is its mode of action and when is it indicated in veterinary ophthalmology?
Bacteriocidal
Inhibits the movement of the precursor to bacterial petidoglycan across bacterial cell membrane thus inhibiting bacterial cell wall synthesis.
Gram +ve with little gram -ve activity
Usually combined with other drugs - neomycin/polymyxin B to provide wider spectrum of activity.
Poor corneal penetration - not useful for intraocular infections
Not used systemically
Indications:
"Triple" AB formulation with polymyxin B/neomycin - prophylactically for uncomplicated corneal ulcers/therapeutically for non specific ocular surface infections.
Hypersensitivity reaction is potential s/e - often ointment.
54
Which antimicrobials affect bacterial cell membranes?
Why are these not used systemically?
Polymyxin B
Gramicidin
Not used systemically due to similarity between mammalian cell membranes and bacterial cell membranes - high risk of toxicity.
55
Is Polymyxin B bactericidal or static?
What is it's mode of action and what indications are there for its use?
Bactericidal
Surfactant that interacts with phospholipids of cell membrane altering cell membrane permeability leading to cell death.
Reasonable gram -ve activity (including pseudomonas) and is used topically on combination with drugs with gram +ve activity (bacitracin)
Side effects - nephrotoxicity, hepatotoxicity, neurotoxicity (when used systemically) and local hypersensitivity when used topically.
56
Is gramicidin bactericidal or static? What is its mode of action? When may it be used?
Bactericidal
Gram +ve activity
Stable in solution and acts as ionophore.
Disrupts bacterial cell membrane
Often combined in place of bacitracin with drugs with gram -ve activity e.g polymyxin B/neomycin in topical preparations.
57
Which antimicrobials prevent bacterial protein synthesis?
What do they bind to in order to do this?
Aminoglycosides
Tetracyclines
Macrolides
Lincosamides
Chloramphenicol
Fusidic acid
Bind to 30S or 50S subunits of ribosomes.
58
Are aminoglycosides bactericidal or static?
What indications are there for their use in ophthalmology?
Bactericidal
Inhibit the 30S subunit of ribosomes
Excellent gram -ve activity (although neomycin generally inactive against pseudomonas)
Gram +ve activity limited to staphylococcus and inactive agains anaerobes.
Synergistic activity when given with B lactams but must be given separately otherwise may be inactivated.
Poorly absorbed when given orally so used topically or IV.
Neomycin - triple AB preparations (not in UK) - for prophylaxis/treatment of uncomplicated ulcers.
UK part of maxitrol with dexamethason and polymxycin B
Gentamicin - topical or subconjunctival injection to treat infectious keratitis particularly caused by pseudomonas (can be resistant to fluoroquinolones)
Tiacil = licensed
Subconjunctival injections may lead to therapeutic concentrations in anterior chamber but also s/e - can be epitheliotoxic
Tobramycin - similar activity/indications as gentamicin. Often combined with steroid as topical suspension (tobradex) - bacterial ulcers caused by pseudomonas strains resistant to gentamicin.
Amikacin - not avaliable as topical product but can be compounded. May also be injected subconjunctivally to reach intraocular concentration. Less retinotoxic than other aminoglycosides so may be used for endophthalmitis.
59
Are tetracyclines bacteriostatic or bactericidal?
What is their mode of action?
What indications are there for their use?
Bacteriostatic
Interact with 30s subunit of bacterial ribosome
Tetracycline/oxytetracycline = short acting
Doxycycline = long acting
Good activity against mycoplasma, chlamydophila, rickettsia and moraxella
Resistance common with staphs, streps and pseuodomonas.
Concentrate in cornea and lacrimal gland and may have beneficial ocular surface effects by number of actions - chelation of cations, inhibition of gene expression, inhibition of antitrypisin degredation and inhibition of leucotaxis.
Indications:
Cats - doxycycline systemically for chlamydophila/mycoplasma conjunctivitis
Chlortetracycline ointment avaliable (ophthocycline) - ocular surface infections
?melting corneal ulcers - anti-collagenase properties
?SCCED management
Side effects - tooth enamel discolouration, oesophagitis (always give with food/water to encourage to swallow and prevent oeosphageal stricture)
60
Are macrolides bactericidal or static? What is their mode of action?
When may they be used in ophthalmology?
Bacteriostatic
Inhibit 50s subunit of ribosome
Examples - erythromycin, azithromycin and clarithromycin
Mainly used sytemically
Gram +ve activity - accumulate intracellularly
Indications:
Azithromycin - bartonella/chlamydophila but lower efficacy than doxycycline
61
Are lincosamides bactericidal or static? What mode of action do they have?
Indications for use in opthalmology?
Bacteriostatic
Bind to 50s subunit of ribsome
Clindamycin most commonly used of this class
Prescribed orally - toxoplasma gondii
Good for anaerobes
62
Is chloramphenicol bactericidal or bacteriostatic?
Mode of action?
Indications for use in ophthalmology?
Bacteriostatic
Binds to 50s subunit of ribosomes inhibiting protein synthesis
Broad spectrum activity - gram +ve and -ve bacteria with efficacy also against rickettsia, chlamydophila and mycoplasma.
Pseudomonas are resistant.
Not used systemically as serious risk of bone marrow suppression.
Available as 0.5% solution or 1% ointment
Susceptible to thermal breakdown so must be kept in fridge
Indications:
Prophylactically - 1st line for uncomplicated corneal ulcers, after ocular surface/intraocular surgery
Therapeutically - non specific conjunctivitis, chlamydial/mycoplasma conjunctivitis
Excellent corneal penetration as high lipophilicity.
63
Is fusidic acid bacteriostatic or cidal?
Mode of action?
Indications for use in ophthalmology?
Bacteriostatic (cidal at high concentrations)
Prevents turnover of elongation factor G from bacterial ribosome. `
Primarily effective against gram +ve
Isathal - licensed for conjunctivitis but not ulceration
Indications:
Prophylaxis - uncomplicated corneal ulcers and ocular surface infections caused by gram +ve bacteria (no good for common feline pathogens chlamydophila/mycoplasma)
Therapeutic - non specific conjunctivitis
Lubricating due to carbomer 980 base.
64
Which drugs alter folic acid synthesis and are they bacteriostatic or cidal?
What is their mode of action?
Indications for use in ophthalmology?
Sulphonamides
Trimethoprim
Bacteriostatic
Often sulphonamides and trimethoprim combined as they are synergistic and inhibit different steps of folate synthesis.
Good gram +ve activity but variable gram -ve.
Poor intraocular penetration when given systemically.
S/E - blood dyscrasia, nephrotoxicity, hepatotoxicity
Can cause KCS due to toxic effect on lacrimal acinar cells when used systemically.
Indication for use - orbital infections
65
Which drugs inhibit DNA synthesis?
Are they bacteriostatic or cidal?
What is their mode of action?
Indications for use in ophthalmology?
Fluoroquinolones - inhibit bacterial DNA gyrase and topoisomerase IV - bactericidal
Spectrum of activity varies according to generation. Overall fairly broad spectrum. 2nd gens most common. Later gens better topoisomerase action and more gram +ve activity.
Enrofloxaxin (2nd gen) - good gram +ve and -ve activity. Indications - eyelid, orbital or intraocular infections. BUT RETINOTOXIC IN CATS - can cause acute retinal degeneration.
Marbofloxacin - not been reported to cause retinal degeneration. Also authorised in parenteral and oral formulations.
Ciprofloxacin/Ofloxacin - topical use
Indicated for complicated/infected corneal ulcers and intraocular infections.
Good corneal penetration
Ofloxacin preferred as better penetration and better tolerated.
AB of choice for melting corneal ulcers.
Can be cytotoxic.
66
What types of fungi exist - why are they more challenging to target therapy against?
When do we see fungal involvement in veterinary ophthalmology?
Yeasts, moulds, dimorphic forms
Have outer cell well like bacteria but it is much more similar to mammalian cell wall making increased risk of s/e when therapy targets them.
Not used prophylactically for this reason.
Rare in UK - keratomycoses (horses/dogs) and skin infections (malasezzia)
67
What are the 3 most common antifungal agent classes?
Polyenes, pyrimidines and azoles.
68
What is the mode of action of the polyenes? List some of the drugs that fall into this category and their uses.
Bind to ergosterol - essential fungal cell membrane component, binding = leakage of cytoplasmic contents from cell.
Amphotericin B - broad spectrum, Candida, blastomyces, coccidiodies, cryptococcus, histoplasma - useful for orbital infections caused by these. Poor ocular penetration both systemically/topically so only good for orbital infections.
Limited effect for filamentous fungi e.g aspergillosis therefore not useful for keratomycoses.
S/e - renal, haematological and hepatic toxicity.
Natamycin - avaliable in some countries as ophthalmic 5% solution, better against filamentous fungi so ok to use for keratomycoses but poor corneal penetration in presence of intact corneal epithelium.
69
What is the mode of action of pyrimidines? Indications in ophthalmology?
Block thymidine (building block of DNA) - fungistatic
Flucytosine-C - yeast activity (good against candida/cryptococcus), resistance fairly high so rarely used in ophthalmology.
70
What is the mode of action of the azoles? How are they further classified?
Indications for use in ophthalmology?
Inhibit ergosterol synthesis by inhibiting cytochrome P450 enzyme pathway, inhibiting fungal growth and cell membrane permeability. Fungistatic.
Further classified as imidazoles or triazoles based on parent ring structure.
Imidazoles - ketaconazole/miconazole
Ketaconazole - good efficacy against candida but poor against filamentous fungi, systemic s/e hepatotoxicity, can be compounded for topical use, good corneal penetration. Slow onset.
Miconazole - broad spectrum with better activity against filamentous fungi, well tolerated with good corneal penetration
Triazoles = fluconazole, itraconazole, voriconazole
Fluconazole = good activity against yeasts (candida/cryptococcus) but limited against filamentous fungi. Good intraocular penetration and tolerated well systemically. Useful for intraocular mycotic infections.
Itraconazole = broader spectrum than fluconazole and more effective against filamentous fungi. Intraocular penetration poor systemically but can be compounded as 1% ointment.
Voriconazole - very broad spectrum, good intraocular penetration when given systemically. IV solution can be used topically in treatment of keratomycosis in dogs and horses and is well tolerated. Good corneal penetration.
71
Which virus is the most common target in veterinary ophthalmology for antiviral use?
Feline herpes virus (FHV-1)
72
What is the life cycle of FHV-1 in a host cell?
Attachment
Penetration
Uncoating
Transcription
Replication
Assembly
Release (cell lysis)
73
What do antivirals target ?
Are they virostatic or virocidal?
Antivirals = nucleotide analogues
Inhibit nucleic acid synthesis of the virus
Are incorporated into the DNA blocking viral genome synthesis and replication.
Require host and/or viral phosphorylation to be effective.
Virostatic.
74
List the antivirals in descending order of efficacy (most effective to least)
Triflurothymidine
Ganciclovir
Idoxuridine
Cidofovir
Penciclovir
Aciclovir
75
How often do antivirals have to be applied in order to be effective?
5-6x daily application.
76
Which antiviral is a thymidine analogue and the most potent against FHV-1 - discuss its use in veterinary ophthalmology.
Triflurothymidine - most potent against FHV-1 when applied topically
Too toxic for systemic use
Not avaliable commercially but may be compounded as 1% solution
Expensive ++++
Can cause irritation on topical use
4-6x daily application
Reasonable ocular penetration
77
Which antiviral is an acyclic nucleoside analogue that requires three phosphorylation steps to be effective?
Discuss it's use in veterinary ophthalmology.
Ganciclovir
Requires initial viral (rather than host) phosphorylation by viral thymidine kinase
Avaliable commercially in UK (Virgan) as 0.15% gel
Formulation as gel = less frequent administration (4x daily)
MAIN CHOICE FOR MOST OPHTHALMOLOGISTS FOR FHV-1
78
Which antiviral is a thymidine analogue requiring intracellular phosphorylation to be effective?
Discuss its use in veterinary ophthalmology.
Idoxuridine - no commercial product avaliable
Too toxic for systemic use
Compounded to 0.1% solution or 0.5% ointment
Poor corneal penetration - 4-6x per day use
79
Which antiviral is a cytosine analogue and requires host mediated phosphorylation but no viral phosphorylation?
Cidofovir
Can be compounded and applied topically 0.5% or 1% solution
Long tissue half life - can be applied 2x daily.
Can reduce viral load in shelter cats
Expensive +++
80
Which antiviral is a nuceloside deoxyguanosine analogue? Discuss its use in veterinary ophthalmology.
Penciclovir - no commerically avaliable product.
Dermatological cream for humans
More potent than aciclovir but less than ganciclovir.
81
Which antiviral is a prodrug to penciclovir? How is it administered? When may it be used.
Famciclovir
Oral tablet (Famvir)
Can reduce clinical signs at dose of 90mg/kg q 8hrs
Not used topically
Very expensive +++
Useful if topical medications not possible
Dermatitis present
82
Which antiviral is an acyclic nuceloside that requires three phosphorylation steps to be effective and is the least effective antiviral for in vitro efficacy?
Discuss its use in veterinary ophthalmology.
Aciclovir
Requires initial viral (rather than host) phosphorylation via thymidine kinase.
10x less potent than ganciclovir
0.5% ointment is avaliable (Zovirax) - applied 5x daily
Low host toxicity
Affordable compared to other anti-virals
83
By which mechanism is L-lysine supposed to interrupt viral replication? How is it administered?
Antagonist of arginine which is essential for viral replication.
Arginine = essential amino acid in diet of cats so cannot be restricted
Administered orally 400-500mg once or twice daily by mouth (bolus not graze)
Limited evidence for efficacy - may reduce viral shedding and recrudescence of disease.
84
What are interferons? Which ones may have effect on FHV-1?
Interferons are cytokines released by cells in response to injury. Bind to receptors of neighbouring cells and alter gene conscription.
FHV -1 - feline IFN-w and human IFN-a have good in vitro efficacy
Pre-treatment with topical feline IFN-a had no beneficial effect on course of experimental infection with FHV-1.
No controlled clinical trial have been performed.
85
Which parasiticides have relevance to veterinary ophthalmology and what do they treat?
Periocular parasitic skin infections:
Selamectin - sarcoptic mange/heartworm
Amitraz - sarcoptic/demodectic mange
E.caniculi infection in rabbits/cats:
Fenbendazole
Lungworm:
Fenbendazole/milbemycin/moxidectin
Leishmania:
Allopurinol/sodium stibogluconate
86
How do anti-inflammatories (corticosteroids and NSAID's) exert their effects?
What do these mediators cause in the eye?
Cell damage = arachidonic acid release, induced via enzyme phospholipid A2
Inhibit the formation of pro-inflammatory products of the arachidonic acid pathway which includes prostaglandins, prostcyclins, thromboxane A2 and leucotrienes.
Products are generated via 2 pathways where aracidonic acid metabolised.
Lipoxygenase pathway = leucotrienes
Cycloxygenase pathway (COX) = prostaglandins + thromboxane A2.
Release of these mediators causes disruption to the blood aqueous barrier - miosis, cell and protein exudation (aqueous flare, fibrin deposition), conjunctival and iridal vasodilation, hypotony (decreased IOP) and leucocyte migration (hypopyon)
87
Where in the inflammatory pathway do corticosteroids act?
Increased expression of lipocortin = inhibition of phospholipase A2 which prevents release of arachidonic acid and hence prostaglandins, thromboxane A and leucotrienes all of which are mediators of inflammation.
88
Where in the inflammatory pathway do NSAIDs act?
What is the difference between COX-1 and COX-2?
COX pathway - inhibit cycloxygenase system (some may also inhibit LOX pathway) - prevents formation of thromboxane A and prostaglandins
If also inhibit LOX then will also reduce leucotriene release.
COX-1= constitutive, present in most tissues under normal circumstances
COX-2 = inducible, response to cell injury
Selection for COX-2 = fewer systemic side effects.
89
How may steroids be typically administered in an ophthalmic setting?
Topically
Systemically
Subconjunctival
Intracameral
90
How is the potency of glucocorticoids measured? List them in order of increasing anti-inflammatory potency.
Measured against hydrocortisone (cortisol)
Hydrocortisone
Prednisolone
Prednisolone triamcinolone
Methylprednisolone
Fludrocortisone
Dexamethasone = Bethamethasone
91
What factors affect ocular bioavailability of ophthalmic corticosteroids?
Anti-inflammatory potency of the base steroid
Concentration of the base steroid in the formulation
Type of formulation (ointment, suspension, solution)
Solubility of the base steroid
Patient factors - e.g presence/absence of intact corneal epithelium
92
List some of the main indications for corticosteroids in veterinary ophthalmology.
Blepharitis
Non ulcerative keratitis
Conjunctivitis
Episcleritis
Anterior uveitis
Posterior uveitis
Optic neuritis
Extraocular polymyositis
Orbital inflammation
93
What derivatives can increase corneal penetration of steroids and why?
How do alcohol/salt derivatives compare?
Acetate derivatives = increased penetration
Lipophilic
Alcohol = intermediate penetration
Salt (sodium phosphate/hydrochloride) = hydrophilic
94
What formulations of prednisolone are there and how do they compare?
Prednisolone phosphate (1% solution)
Poor corneal penetration (hydrophilic) - used for ocular surface inflammation
Prednisolone acetate (1% - Pred Forte)
Good corneal penetration (lipophilic)
Good for anterior segment inflammation (uveitis)
Severe inflammation 1-2hr then taper based on response.
95
How many more times potent than prednisolone is dexamethasone? When is it used in ophthalmology?
10x more potent
0.1% dexamethasone sodium phosphate suspension, combined with polymyxin B and neomycin (Maxitrol)
Poor corneal penetration - ocular surface only
Less effective at stabilsing blood-aqueous barrier than prednisolone.
96
What is the main indication for the use of triamcinolone in ophthalmology?
Intermediate acting corticosteroid
40mg/ml injectable suspension
Subconjunctival injection for treatment of anterior uveitis and intravitreal of treatment of posterior segment.
May also be injected intracamerally during intraocular surgery to aid in visualisation of anterior vitreous presentation prior to vitrectomy.
97
What are the potential side effects of topically applied corticosteroids?
Potentiate infection - reduce leucocyte migration, depress macrophage phagocytosis, FHV-1 recrudescence
Reduce corneal healing (contraindicated with ulceration) - increase collagenase activity (melting ulcers) - systemic steroids have minimal effect
Lipid keratopathy
Cataract formation (subcapsular)
Ocular hypertension (transient)
Destabilisation of diabetic patients
Systemic effects - iatrogenic cushings, insulin antagonism, abortion, hepatopathy
98
Which glucocorticoid is most commonly used for systemic immunosuppression? Which conditions may it be used systemically?
Prednisolone - uveodermatological syndrome, optic neuritis, streoid responsive retinal detachments, extraocular polymyositis, episcleritis, scleritis, chemotherapeutic protocol for lymphoma.
Usually 1mg/kg twice daily before tapering.
99
What are the 3 properties of NSAIDs?
Anti-inflammatory, anti-pyretic and analgesic.
100
What are the indications for the use of topical NSAIDs in veterinary ophthalmology? What are the potential side effects when used topically?
Indications:
Reduce intraocular inflammation (sometimes in conjunction with corticosteroids)
If corneal ulceration present may be safer to use than steroids?
Prevent miosis prior to cataract surgery
Reduce corneal vascularisation
Corneal analgesia
S/E - ?potentiate infection/delay corneal healing, ocular hypertension, systemic s/e rarely seen.
101
When is ketorolac (Acular) commonly used?
Ketorolac (Acular) - 0.5% solution, used for intraocular inflammation and post phacoemulsification surgery.
102
When is flurbiprofen (Ocufen) used?
0.03% solution - prevents miosis/maintains mydriasis for cataract surgery. Good corneal penetration but short intraocular residence time (4 hours)
103
When is bromfenac (Yellox) used?
0.09% solution
Good lipophilicity - good corneal penetration
Long duration of analgesia/anti-inflammatory and increased COX-2 inhibition
104
What is diclofenac (Voltaren) used for?
Mydriatic prior to cataract surgery, reduce ocular pain.
Does not penetrate an inflamed cornea well
Long intraocular residence time - 7hr
105
What is Nepafenac (Nevanac) used for?
Prodrug of amfenac - 0.1% suspension
Excellent corneal penetration and is hydrolysed within the eye to amfenac which demonstrates COX-2 inhibiition
More potent than ketorolac post phacoemulsification surgery.
106
What are the most common systemic NSAID's used in ophthalmology. What are their indications and side effects?
Meloxicam and Carprofen
Indications - analgesia, intraocular inflammation, cataract surgery (pre and post op)
Side effects - GI disturbances, inhibit platelet aggregation (contraindicated in bleeding disorders), renal disease
107
Which 2 drugs are calcineurin inhibitors?
How do they work?
Ciclosporin and tacrolimus - immunomodulatory agents
Inhibit T cell activation
Cyclosporin binds to cyclophilin
Tacroliums (aka FK506) binds to FK560 binding protein
Both inhibit calcineurin and thus nuclear factor of activated cells (NF-AT)
Prevents IL-2 expression - lack of T cell clonal expansion
108
How does ciclosporin improve clinical signs in canine KCS?
What feline conditions may ciclosporin be use for?
T cell suppression of immune mediated destruction of lacrimal tissue
Increased lymphocyte apoptosis
Decreased apoptosis of glandular and conjunctival epithelial cells
Direct lacrostimulant effect
Feline conditions = feline stromal keratitis, eosinophilic keratoconjunctivitis
109
What is the licensed form of ciclosporin and what are its authorised uses?
What other forms of ciclosporin are there and when may they be used?
Optimmune 0.2% ointment = licensed
Authorised for KCS and CSK
Higher concentrations may also be compounded in corn oil (off licence 1-2%)
Topical ciclosporin = poor corneal penetration, ocular surface only.
Oral tablet (Atopica) also avaliable - may be useful for management of uveodermatological syndrome or other non infectious uveitis, atopic disease.
Avoid if renal/hepatic insufficiency, not with live vaccines.
5mg/kg for 30 days then taper 2.5mg/kg
Episcleral implants of ciclosporin - off licence, indicated when patient unamenable for topical treatment.
110
If KCS refractory to ciclosporin what other medication can be used? Which preparations are avaliable?
Tacrolimus (also calcineurin inhibitor) - off licence use
0.02% solution - BOVA (ophthalmic preparation)
0.03% and 0.1% dermatological preparations (Protopic - human)
111
What do both ciclosporin and tacrolimus reduce in CSK?
Reduce corneal angiogenesis
Reduce corneal pigmentation
112
What are the potential side effects of ciclosporin/tacrolimus?
Local irritation/hypersensitivity
Increased development of tumours (wear gloves) - SCC in dog, avoid in animals with malignancy
Immunocompromise - avoid in cats with FIV/FELV, avoid live vaccines during use (systemic)
Do not use with aminoglycosides/trimethoprim
GI upset (systemic)
Gingival hyperplasia (systemic)
Diabetes mellitus (systemic)
113
Why may azathioprine be used and how does it work? Which conditions is it indicated for? Which species must it not be used in?
Used to be corticosteroid sparing - immunosuppressive.
Anti-metabolite and T cell suppressor - inhibits purine synthesis necessary for proliferation of cells particularly leucocytes.
Used for severe immune mediated disease - uveodermatological syndrome, episcleritis, scleritis, non infectious chorioretinitis, optic neuritis.
Used in conditions where fail to respond to steroid alone or used together to allow for reduced doses of steroids and corticosteroid related side effects.
Slow acting - up to 3 weeks to become evident
2mg/kg usually used then tapered down after 1 week
Monitor WBC, liver parameters and platelets.
NOT SAFE FOR USE IN CATS.
114
What is megoestrol acetate a derivative of and when may it be used? What are its side effects?
Derivative of progestin and progesterone. Potent agonist of progesterone receptors.
Used for feline eosinophilic keratoconjunctivitis sicca when refractory to first line topical treatments. (also anti-oestrus drug)
PUPD, weight gain, mammary hyperplasia, diabetes mellitus, renal insufficiency.
115
Which immunomodulatory agent is an alkylating agent and inhibits DNA replication. What is it used for in ophthalmology?
Cyclophosphamide - corticosteroid sparing medication in non infectious uveitis and in ocular lymphoma.
116
Name 3 mast cell stabilisers - when may they be used?
Cromoglycate, olaptadine, lodoxamide
Indicated to help prevent/treat seasonal allergic conjunctivitis - prevents release of histamine by blocking IgE mediated calcium channels.
Human eye drop preparations avaliable.
117
Name 3 anti-histamines - when may they be used? How are the administered.
Cetirizine (Piriteaze), Chlorphenamine (piriton), Loratidine (clarityn)
Given orally
Block histamine receptors - H1 receptors on mast cells
Given orally
Is one opthalmic preparation which is both anti-histamine and mast cell stabiliser (Ketotifen)
118
What consequences are there for fibrin in the eye? Name 3 fibrinolytic/antifibrotic drugs used in ophthalmology.
Consequences = synechiae - pupillary seclusion- iris bombe - glaucoma
Tissue plasminogen activator
Mitomycin C
5-fluorouracil
119
How does tissue plasminogen activator work?
Fibrinolytic
Fibrin clots form as part of clotting cascade, fibrinogen is converted to fibrin by action of thrombin.
TPA converts plasminogen to plasmin which leads to clot dissolution.
Recombinant human TPA may be injected intracamerally to effect fibrin clot dissolution.
Effective in 15-30 mins post injection and for 3 weeks later
Do not use within 48hrs of haemorrhage
(Potential to cause corneal endothelial toxicity at high doses)
120
When is mitomycin C used and what is its other possible indication?
Used to suppress fibrous tissue around glaucoma implant devices and applied to surgical site directly.
Other indication - may reduce corneal scarring when used in eye drop formulation.
121
When is 5-fluorouracil used? How is it administered?
Also used for glaucoma surgery
Administered by repeat subconjunctival injections
?monotherapy for dogs with corneal SCC
122
What are the applications for the use of mydriatics? What other considerations should be taken into account before their use?
Diagnostics - visualisation of fundus
Facilitation of lens placement/posterior segment surgery
Prevention of synechiae formation
Stabilise blood-aqueous barrier
Relieve pain of ciliary spasm (uveitis)
Considerations - duration of mydriasis required, requirement for cycloplegia, IOP
123
What are the 2 mechanisms of action for mydriatics? What factors effect their speed of onset, duration and extent of effect.
Work via paralysis of pupillary sphincter (cholinergic antagonists) - produce cycloplegia
OR
Stimulate iris dilator (sympathomimetics - adrenergic agonists), no cycloplegia
Affected by species, pigmentation of iris, degree of inflammation
124
What may cycloplegia be associated with - which patients should we use them with caution in?
Cycloplegia - associated with increase in IOP, relaxation of tension on trabecular meshwork and resultant resistance to AH outflow.
Even use of sympatomimetics which do not induce cycloplegia should still be used with caution in patients with raised IOP as may potentiate angle closure.
All mydriatics should be used with caution in patients with lens instability due to risk of anterior lens luxation.
125
Name 3 anticholinergic (parasympatholytic) mydriatics?
Tropicamide, Atropine, Cyclopentalate
126
Which mydriatic is the drug of choice for diagnostic purposes? What is its onset and duration of action.
Tropicamide - avaliable as 0.5% and 1% solution (mydriacyl)
Penetrates cornea well (unionised at physiological pH)
1% tropicamide = dilation within 30 mins
Duration - 12hrs dogs, 8hrs cats
Relatively low cycloplegic effect - usually associated with small increase in IOP
No effect on tear production in dogs, transient decrease in cats
127
Which mydriatic is generally used as a therapeutic agent? What is its onset and duration of action? What side effect is it associated with?
Atropine - 0.5% and 1% solution
Mydriatic-cycloplegic
Transcorneal penetration low - ionised form dominant at physiological pH but its potency maintains its utility.
Hypersalivation as bitter = most common side effect, occurs due to nasolacrimal drainage
Maximal dilation at 1hr and lasts 96-120hrs dogs, 60hrs in cats (effect reduced with inflammation)
Significantly reduces STT which may persist for days/weeks
Systemic side effects - tachycardia, reduced GI motility, urinary retention.
128
Which mydriatic drug has an intermediate potency?
Cyclopentolate - 0.5% and 1% solution
Intermediate properties
Mydriasis in 30 mins, lasts 60-72hrs in dogs
No effect on STT
Significant increase in IOP in cats.
129
Name 2 sympathomimetic/adrenergic agonist mydriatics? How do they work?
Adrenaline (Epinephrine)
Phenylephrine
Directly stimulate alpha adrenergic receptors in the iris dilator muscle
130
How is phenylephrine available. When is it used? Which species is it ineffective in and what side effects may it have?
2.5% and 10% solutions
Achieve adequate mydriasis prior to cataract surgery
Diagnosis of Horner's syndrome
Control of conjunctival/corneal bleeding during surgery
Ineffective as sole mydriatic in cats
S/E - systemic hypertension and reflex bradycardia - more pronounced under GA and therefore 10% solution best avoided perioperatively.
131
Why is epinephrine not used topically to induce mydriasis? When is it used?
Poor corneal penetration - not used topically
Used intracamerally either as direct injection or component of irrigating fluids in phacoemulsification surgery.
Used to maintain mydriasis and aid in haemostasis.
132
How do topical local anaesthetics work?
Block Na+ transport preventing generation of action potentials and conduction of nerve impulses.
133
What is the onset of action and duration of proxymetacaine?
Proxymetacaine 0.5%
Onset = 1 minute
Duration = max effect 15 minutes, up to 45 minutes (cats only 25 mins)
Keep refrigerated - loses efficacy after 2 weeks at room temperature
134
How does tetracaine compare to proxymetacaine?
0.5% and 1% (more irritating than proxymetacaine)
Signs of irritation - acute conjunctival chemosis, blepharospasm, conjunctival hyperaemia. TEL protrusion
Slower onset of action compared to proxymetacaine (few minutes), longer duration of effect.
135
When may injectable local anaesthetics be used in ophthalmology? Which drugs are used and what complications are associated with local anaesthetic techniques.
Retrobulbar injections - enucleations (analgesia and globe akinesia)
Splash block
1% lidocaine (rapid onset, short acting) often combined with 0.5% bupivicaine (slower onset, longer acting)
Inferiotemporal approach for retrobulbar block in dogs
Complications higher in cats due to reduced retrobulbar space and include globe perforation, inadvertent intravascular and intrathecal injection (brainstem anaesthesia)
Preservative free lidocaine may also be used intracamerally in phacoemulsification - improve extent of mydriasis and reduce intraoperative inhalation anaesthetic requirements + post operative analgesia.
136
What are the indications of lacrimomimetics? (Tear substitutes)
KCS - immune mediated, congential, neurogenic, iatrogenic
Qualitative tear film disorders - goblet cell/meibomian dysfunction
137
What layers are there to the pre-corneal tear film?
Trilaminar (lacrimomometics aim to mimic one or more of these layers)
Lipid (from meibomian glands)
Aqueous (lacrimal glands and nictitans)
Mucin (goblet cells)
138
How often do aqueous tear substitutes need application? What do they include?
Cellulose polymers and vinyl derivatives e.g hypromellose, celluvisc
1-2hr application needed to be useful for KCS (reality often cannot achieve this)
Inert so can be used for delivery of other drugs
139
Give an example of a mucinomimetic. How often are they applied?
Polyacrylic acid e.g carbomer 980 (viscotears, lubrithal, ocry-gel)
Replaces both aqueous and mucin layers of tear film
4-6x daily application - longer corneal retention time
Gel type - very viscous, may impede vision slightly
140
Give an example of a viscoelastic - what ability do they show?
Sodium hylauronate (Hyabak, Hylo-Forte) - involved in wound healing and increases corneal epithelial migration
Pseudoplasticity - allows blinking
Excellent corneal retention times due to high viscosity
Increase TFBUT
141
Give an example of a lipid based tear substitute. What are the pro/cons of these type of tear substitute?
Lanolin, petrolatum and mineral oil (Lacri-lube) - mimics lipid layer and prevents evaporation of tear film.
Excellent corneal retention 3-4x daily application
High viscosity ointment - blurred vision (useful for application at night)
142
How do calcineurin inhibitors (ciclosporin and tacrolimus) affect tear film?
T cell suppression = lacrimal adenitis (increased tear production)
Improve tear film mucin layers (prevent conjunctival cell and acinar apoptosis)
Stimulate neurotransmitter release
Direct lacrostimulant effect via prolactin receptors
143
What type of agonist is pilocarpine? What is its indication for use?
Muscarinic cholinergic agonist
Neurogenic KCS = indication
Stimulates tear production by mimicking acetylcholine at the effector lacrimal cell therefore useful where functional lacrimal tissue exists in face of parasympathetic denervation.
Given orally - 1 drop 1% pilocarpine per 10kg onto food once daily
Increase dose gradually to effect or until signs of toxicity seen
Signs of toxicity - urinary incontinence, diarrhoea, emesis
144
When are anti-collagenases indicated? In this condition what is released?
Melting ulcers (liquefactive corneal stromal necrosis)
Proteases produced as part normal healing to remove dead/devitalised cells (MMP's and serine proteases) - produced by corneal epithelium, fibroblasts, neutrophils and micro-orgamisms
Inappropriate/excessive upregulation and production = melting
Inhibition of these enzymes required = anti-collagenases.
145
In face of melting ulcer how often should therapeutics be applied?
Every 1-2hrs initially
146
What are the most frequent anti-collagenases used?
Serum (preferred)
EDTA
Tetracyclines
N-acetylcysteine
147
Why is autologous serum the anti-collagenase of choice? What does it contain and how is it prepared?
Readily avaliable, broad spectrum of activity
Contains both a2 macroglobulin and a1 antitrypsin
Also relatively high (compared to plasma) epithelial growth factor, platelet derived growth factor and vitamin A which are thought to be important in corneal wound healing.
Preparation:
Take fresh blood sample - collect in aseptic manner and add to plain or serum gel tube
Allow to coagulate at room temp for 30 mins
Centrifuge and the (serum) supernatant removed and transferred to sterile dropper bottle
Store in fridge at 4 degrees
Owing to lack of preservatives should be discarded after 48hrs
148
What is the mode of action of EDTA, tetracyclines and N-acetylcysteine?
Chelate calcium
MMP inhibitors
149
When are hyperosmotic agents indicated? What is their mechanism of action? What potential s/e are there and in which patients are they contraindicated?
Acute glaucoma
Administered orally (Glycerol) /IV (Mannitol)
Distributed to extracellular compartment and creates osmotic gradient between plasma and aqueous and vitreous humour.
Water moves via diffusion from aqueous/vitreous into plasma
IOP reduced by movement of water, reduction in AH production, movement of iris-lens diaphragm posteriorly.
Effect increased by withholding water from 4hr before
S/E - dehydration from osmotic diuresis (monitor electrolytes and hydration)
Contraindicated - CHF, renal disease, pulmonary oedema
150
List the 4 classes of anti-glaucoma medications.
Hyperosmotic agents - e.g mannitol
Prostaglandins analogues - e.g latanoprost, travoprost, tafluprost, bimatanoprost
Carbonic anhydrase inhibitors e.g dorzolamide, brinzolamide
Autonomic agents:
Cholinergic receptors - pilocarpine, carbachol
Alpha agonists - adrenaline, bromidine, apraclonidine
Beta antagonists - timolol, betaxolol, carteolol, levobunonol
151
How is mannitol used and how long does it last for?
IV - 1-2g/kg over 30 min
IOP reduces within 1hr - effect lasts 24hrs
152
How is glycerol used and how long does it last for? When is it contraindicated?
Given orally
1-2g per kg
Reduces IOP within 1hr - effect for up to 10hrs
Metabolised to glucose - causes hyperglycaemia
Contraindicated in diabetics
153
What is the mechanism of action for prostaglandin analogues? Why do they have minimal effect in cats?
Interact with prostanoid FP receptors in the uveal tract and trabecular meshwork = causes increase in uveoscleral outflow
Minimal effect in cats due to lack of FP receptors in their trabecular meshwork
154
When are prostaglandin analogues indicated and when are they contraindicated?
What are the 2 most common prostaglandin analogues used? How often are they used?
Acute/chronic glaucoma
Miosis required - e.g lens subluxation
Contraindicated - anterior lens luxation (due to miosis), uveitis (de-stabilisation of blood-aqueous barrier)
Latanoprost - 0.005% solution (Xalatan)
Travoprost 0.004% (Travatan)
q 8-24hrs typically
155
What is the mechanism of action of carbonic anhydrase inhibitors? What are potential s/e of these drugs?
Carbonic anyhydrase = enzyme that facilitates bicarbonate and hydrogen ions from water and CO2
Bicarbonate and Sodium ions enter AH and water follows
CAI 's inhibit formation of bicarbonate ions and therefore lead to a reduction in the production of AH
CA enzymes present throughout the body including renal tubules
S/e - metabolic acidosis & hypokalaemia , anorexia, V+, diarrhoea
156
What are the most common carbonic anhydrase inhibitors used?
Used topically q 6-12hrs
Dorzolamide - (Trusopt) - 2% solution
pH 5.6 - can be irritating due to this
Reduces IOP in both normal cats and dogs
Brinzolamide (Azopt) - 1% solution
pH 7.5 - less irritating
Reduces IOP in normal dogs but no effect on normal cats
157
Which receptors does pilocarpine act on? What are its side effects and contraindications?
Cholinergic receptors - parasympathomimetic
Stimulates the neuromuscular ACh receptors of the pupillary sphincter
1, 2 and 4% solutions
Very rarely used for glaucoma management - indicated for neurogenic KCS
Systemically or topically (0.1% solution)
S/e - destabilises BAB and miosis, systemic toxicity (V+/D+, hypersalivation)
Contraindicated for uveitis/anterior lens luxation
158
What receptors does carbachol work on and what does it inhibit? When may it be used?
Direct and indirect acting parasympathomimetic
Injected intracamerally - used in cataract surgery
Stimulates NM receptor and blocks cholinesterase
Reduces incidence of post op hypertension
0.3-0.5ml 0f 0.01%
159
What is the mechanism of action for beta blockers?
Blockage of B receptors in ciliary body epithelium - reduced activation of adenylate cyclase - reduction in cAMP formation and AH production
Inhibition of Na/K+ ATPase activity - reduced AH production
Vasodilative effect - increased AH outflow
160
What are potential s/e of beta blockers and which ones are commonly used?
Which animals should they be avoided in?
S/e - miosis, bradycardia, hypotension, bronchoconstriction
Used in combination with other drugs
Avoid in animals with cardiorespiratory disease
Timolol (0.25 and 0.5%)
Timolol/dorzolamide (Cosopt)
Timolol/brinzolamide (Azarga)
Timolol/travoprost (DuoTrav)
