Ocular Pharmacology
Acute Eye Course
Dr. Sonya Bennett
May 2011
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
Systemic
extent of drug bound to plasma proteins
also effects access of drug into eye only unbound form can pass bloodocular 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 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 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 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
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
potential for exacerbation of uveitis (and
CMO) with hypotensive lipids and
brimonidine
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
theoretically using topical NSAIDs may
reduce the effectivity of hypotensive
lipids, though clinical evidence lacking
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?
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
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
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!