acute-eye-conditions-ocular-pharmacology

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Ocular Pharmacology:

Ocular Pharmacology Acute Eye Course Dr. Sonya Bennett May 2011

Routes of Administration:

Routes of Administration

Overview:

Overview delivery methods - eye drops, ointments, injections drug classifications case

Eye drops:

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:

Eye drops Factors affecting absorption: drug concentration (limited by tonicity) and solubility (aqueous solution v’s suspension) viscosity (increased residence time)

Eye drops:

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:

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:

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:

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:

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:

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:

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:

Intraocular injections allow instant drug delivery at therapeutic concentrations to target site intracameral eg. antibiotics, viscoelastics, miochol intravitreal eg. triamcinolone, avastin

Systemic:

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

Systemic:

Systemic extent 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:

Sustained release devices devices available for steroid, gancyclovir delivery within vitreous cavity

Classes of Drugs:

Classes of Drugs

Cholinergics:

Cholinergics Muscarinic Nicotinic

Adrenergic agents:

Adrenergic agents direct acting eg.phenylephrine indirect acting eg. brimonidine agonists eg dipivefrin

Beta-blockers:

Beta-blockers important to be aware of side effect profile before administering

Carbonic anhydrase inhibitors:

Carbonic anhydrase inhibitors dorzolamide, brinzolamide, acetazolamide

Osmotic agents:

Osmotic agents glycerol, mannitol

NSAIDs:

NSAIDs topical, oral

Steroids:

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

Antivirals:

Antivirals acyclovir, gancyclovir, foscarnet

Local anaesthetics:

Local anaesthetics oxybuprocain, alacaine, tetracaine lignocaine, bupivacaine

so many.....:

so many..... pick one drug per week and learn its indications, contraindications, actions, side effects

Case AJ:

Case AJ

Presentation:

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

Case AJ:

Case AJ

Slide31:

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

Questions:

Questions What 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:

Choice of IOP lowering agents potential for exacerbation of uveitis (and CMO) with hypotensive lipids and brimonidine

Choice of IOP lowering agents:

Choice of IOP lowering agents Order 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:

Choice of IOP lowering agents theoretically using topical NSAIDs may reduce the effectivity of hypotensive lipids, though clinical evidence lacking

Choice of IOP lowering agents:

Choice of IOP lowering agents Diamox 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?:

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:

Treating steroid response reduce the steroid as much uveitis allows choice of steroid: prednisone, dexamethasone, fluoromethalone

Progress:

Progress reduced 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:

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:

Progress Trab with MMC - IOP 12 mmHg Phaco/PCIOl with IOL and Morcher implants to block iris defects VA 6/6 IOP 14

Thank you!:

Thank you!

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