Ocular Pharmacology

Ocular Pharmacology

Acute Eye CourseDr. Sonya Bennett

May 2011

Acute Eye CourseDr. Sonya Bennett

May 2011

Routes of Administration

Routes of Administration

Overview

delivery methods - eye drops, ointments, injections

drug classifications

case

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

Classes of DrugsClasses of Drugs

Cholinergics

Muscarinic

Nicotinic

Adrenergic agents

direct acting eg.phenylephrine

indirect acting eg. brimonidine

agonists eg dipivefrin

Beta-blockers

important to be aware of side effect profile before administering

Carbonic anhydrase inhibitors

dorzolamide, brinzolamide, acetazolamide

Osmotic agents

glycerol, mannitol

NSAIDs

topical, oral

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

acyclovir, gancyclovir, foscarnet

Local anaesthetics

oxybuprocain, alacaine, tetracaine

lignocaine, bupivacaine

so many.....

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

Case AJCase AJ

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 AJCase AJ

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

Thank you!Thank you!