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Ocular Pharmacology
Ocular Pharmacology
Acute Eye CourseDr. Sonya Bennett
May 2011
Acute Eye CourseDr. Sonya Bennett
May 2011
Eye drops
most ocular medications are delivered topically - maximizes anterior segment concentrations and minimizes systemic toxicity
drug gradient from tear reservoir to corneal and conjunctival epithelium forces passive absorption
Eye drops
Factors affecting absorption:
drug concentration (limited by tonicity) and solubility (aqueous solution v’s suspension)
viscosity (increased residence time)
Eye drops
lipid solubility: lipid rich epithelial cell membrane v’s water rich stroma
pH and ionic charge - most eye drops are weak bases existing in both charged and uncharged forms enhancing absorption
Eye drops
Surfactants - preservatives used are surface-active agents that alter cell membranes in the cornea as well as bacteria, increasing drug permeability and preventing bacterial contamination
Eye drops
Reflex tearing: ocular irritation and secondary tearing wash out of the drug reservoir in the tears and reduce contact time with cornea. This occurs when drops are not isotonic, have non-physiological pH or contain irritants
Eye drops
Tissue binding: proteins in the tears and on the ocular surface may bind drug making the drug unavailable or creating a slow release reservoir. This may affect peak effect and duration of action as well as delayed local toxicity eg. ongoing toxic retinal effects of hydroxychloroquine even after discontinuation
Eye ointments
increases contact time of drug with ocular surface
mixture of petrolatum and mineral oil
water-soluble drugs are insolvent in the ointment and are present as microcrystals. The surface microcrystals dissolve in the tears, the rest are trapped until the ointment melts
Eye ointments
only drugs with high lipid solubility and some water solubility will get into both tears and corneal epithelium eg. chloramphenicol and tetracycline both achieve higher aqueous levels as ointment rather than drops
Peri-ocular injections
subconjunctival, subTenon’s and retrobulbar
allow drugs to bypass the conjunctival/corneal epithelial barrier and reach therapeutic levels in the posterior segment
eg anaesthetic agents, steroids, botulinum toxin
Intraocular injections
allow instant drug delivery at therapeutic concentrations to target site
intracameral eg. antibiotics, viscoelastics, miochol
intravitreal eg. triamcinolone, avastin
Systemic
drug getting into eye from systemic circulation limited by tight junctions in vascular endothelium of retinal vessels, and non-pigmented epithelium of ciliary body
drugs with higher lipid solubility pass through blood-ocular barrier more readily
Systemicextent of drug bound to plasma proteins also effects access of drug into eye - only unbound form can pass blood-ocular barrier
bolus administration exceeds the capacity of a drug to bind to plasma proteins and so leads to higher intraocular drug levels than with slow IV drip
Sustained release devices
devices available for steroid, gancyclovir delivery within vitreous cavity
Adrenergic agents
direct acting eg.phenylephrine
indirect acting eg. brimonidine
agonists eg dipivefrin
Steroids
prevent or suppress local hyperthermia, vascular congestion, oedema, pain of inflammatory responses.... and late inflammatory responses such as capillary and fibroblast proliferation, collagen deposition and scarring
so many.....
pick one drug per week and learn its indications, contraindications, actions, side effects
Presentation
48 yr old man with five year history of low grade anterior uveitis OD
VA 6/5
IOP 38mmHg on cosopt BD, brimonidine BD, pred forte QID
clear cornea
quiet anterior chamber
larger area of iris transillumination
open drainage angle, though surface appeared irregular
clear lens
disc 0.7, full HVF, healthy macula
QuestionsWhat other IOP lowering drops are safe to use?
Is the steroid having an effect on the IOP?
Should I give him Diamox tablets?
Can he be controlled medically?
the roller coaster ride starts.....
Choice of IOP lowering agents
potential for exacerbation of uveitis (and CMO) with hypotensive lipids and brimonidine
Choice of IOP lowering agentsOrder of introduction of agents that I use: timolol, brinzolamide, brimonidine, latanoprost
speed of effect of drops important?
yes want fast response
hypotensive lipids can lower IOP sooner than initially thought (days not weeks)
Choice of IOP lowering agents
theoretically using topical NSAIDs may reduce the effectivity of hypotensive lipids, though clinical evidence lacking
Choice of IOP lowering agentsDiamox
long list of side effects, interaction with cyclopsorin and folic acid antagonists
in chronic uveitis, ciliary body aqueous production can be reduced, and so may be exquisitely sensitive to CAIs (oral or topical)
Is it a Steroid Response?not often evident as to if it is directly related to steroids or attributable to uveitis
more likely in younger patient
need to treat uveitis adequately or the IOP can elevate due to trabeculitis or increased aqueous viscosity
balancing act!
Treating steroid response
reduce the steroid as much uveitis allows
choice of steroid: prednisone, dexamethasone, fluoromethalone
Progressreduced the pred forte quickly and added diamox
IOP reduced so came off diamox
several weeks later IOP bounced up again so latanoprost added
excellent response initially but after a couple of months IOP back up at 42mmHg
Progress
Added diamox and increased pred forte
reduced pred forte but IOP didn’t lower enough to stop diamox.....
time for a trabeculectomy (after 5 months)
Progress
Trab with MMC - IOP 12 mmHg
Phaco/PCIOl with IOL and Morcher implants to block iris defects
VA 6/6 IOP 14
Recommended