Ocular pharmacology

Ocular pharmacology
 Glaucoma
The normal Intra Ocular Pressure (IOP) is
about 15 mmHg.
This is maintained by a balance of aqueous
humour :
formation by the ciliary body and
outflow through the trabecular meshwork in to
the canal of schlemm
 Aqueous humor dynamics
Receptor systems controlling aqueous inflow have
not been elucidated fully.

Aqueous humor in the anterior chamber leaves the

eye by two routes:
Filtration through the trabecular meshwork (conventional
outflow) to the Schlemm canal (80% to 85%) and

Through the ciliary body and the suprachoroidal space

(uveoscleral outflow or unconventional outflow).
 Open-angle glaucoma
In open-angle glaucoma, the IOP remains above 24
mmHg because pathological changes in the
trabecular meshwork decrease the outflow of
aqueous.
Because the elevated IOP will eventually damage the
optic nerve, the pressure is reduced, usually with
drugs.
This can be achieved either by:
Increasing aqueous outflow with muscarinic agonists,
such as pilocarpine or
By reducing aqueous formation with a variety of
drugs, especially timolol, a -blocker
 Drugs
Cholinergic agonists direct acting (Carbachol, Pilocarpine)
All increase aqueous humor outflow through trabecular
meshwork
Prostaglandin analogs (Latanoprost)
Increases aqueous uveoscleral outflow and to a lesser extent
trabecular outflow
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-Adrenergic blocking agents (timolol)
reduce aqueous production of ciliary body
Carbonic anhydrase inhibitors (CA type II inhibition)
Topical (Brinzolamide, Dorzolamide)
Systemic (Acetazolamide, Methazolamide)
All reduce aqueous humor production of ciliary body
Specific 2-agonist (brimonidine )
reduce aqueous humor production
known to also increase uveoscleral outflow
 Pilocarpine:
Tertiary amine---diffuses readily through the cornea
Reduces IOP by contracting the ciliary muscle. This
pulls the scleral spur and results in the trabecular
meshwork being stretched and separated.
The fluid pathways are opened up and aqueous
outflow is increased
All parasympathomimetics cause miosis, resulting in
poor night vision and complaints of dimming of
vision
Ciliary muscle spasm increase near-sightedness
causing blurred vision
Prostaglandin analogues
Latanoprost
Instilled in the eye, this PGF2 derivative has shown
efficacy similar to timolol
It acts by increasing uveoscleral outflow, possibly by
increasing permeability of tissues in ciliary muscle or
by an action on episcleral vessels
become the first choice drugs in developed
countries.
High cost limits their use in resource poor countries
Adrenergic blockers
Topical -blockers are one of the first line drugs,

but PG F2 analogues are increasingly used now.

In contrast to miotics, -blockers donot affect pupil size,

tone of ciliary muscle or outflow facility, but lower IOP
by reducing aqueous formation.
Probably b/se of reduced cAMP.
 Cont.
In the ciliary epithelium
2 stimulation causes increased production of aqueous
humor
Can we use b-adrenergic agonists for glaucoma?
Timolol
It is the prototype of ocular -blockers
Is nonselective (1 + 2)
After chronic use, effect on i.o.t. persists for 2-
3 weeks following discontinuation.
This feature, in contrast to pilocarpine drops,
gives a high level of clinical safety, i.e. 1 or 2
missed doses will not affect i.o.t. control
Carbonic anhydrase inhibitors
Acetazolamide, Dorzolamide
Inhibit CA and limit generation of bicarbonate
Sodium transport is linked with bicarbonate
 Angle closure (narrow angle, acute congestive) glaucoma
It occurs in individuals with
a narrow iridocorneal angle
and
shallow anterior chamber
The i.o.t. Rises rapidly to
very high values (40-60
mmHg).
It is an emergent
condition;
 Angle closure (narrow angle, acute congestive) glaucoma

failure to lower i.o.t. quickly may result in loss of

sight.
IOP must be reduced by
IV acetazolamide
IV hypertonic mannitol (an osmotic agent)
intensive instillation of pilocarpine eye drops
an attack is precipitated, usually by mydriasis
Fig: development of angle closure glaucoma and its reversal by miotic
A. Mydriasis occurs in an eye with narrow iridocorneal angle and iris makes
contact with lens blocking passage of aqueous from posterior to anterior
chamber
B. Pressure builds up behind iris which bulges forward and closes the
iridocorneal angle thus blocking aqueous outflow
C. Miotic makes the iris thin and pulls it away from the lens removing the
pupillary block and restoring aqueous drainage
 At the front of the eye, the sclera runs into the
cornea whose transparency is obtained by alignment
of the collagen fibers.
Many superficial manipulations, such as tonometry
(measurment of IOP) and the removal of corneal
foreign bodies, require the instillation of a local
anaesthetic.
Fluorescein is commonly instilled into the eye to
reveal damaged areas of corneal epithelium, which
are stained bright green by the dye
Antibiotics
Antiviral drugs
Anti-inflammatory drugs
 Inflammation of the cornea resulting from allergy or
chemical burns is treated with topical anti-
inflammatory drugs.
Infections are not treated with anti-inflammatory
agents except together with an effective
chemotherapeutic agent.
because anti-inflammatory drugs reduce
resistance to invading microorganisms
 Mydriatics
Mydriasis (dilation of the pupil) is required for
opthalmoscopy
The iris possesses a sphincter muscle, which receives
parasympathetic nerves, and a dilator muscle which
is innervated by sympathetic fibers
Thus, muscarinic antagonists and -adrenoceptor
agonists dilate the pupil (mydriasis), while
muscarinic agonists and -adrenoceptor antagonists
constrict the pupil (miosis)
 The drops most commonly used are the
relatively short acting muscarinic antagonists
tropicamide and cyclopentolate, wich produce
both mydriasis and cycloplegia
The -adrenoceptor stimulant phenylephrine
may be used to produce mydriasis without
affecting accomodation
 Contraction of the parasympathetically
innervated ciliary muscle allows the lens to
become thicker and accomodation for near
vision occurs
Thus, muscarinic antagonists paralyse the
ciliary muscle (cycloplegia) and prevent
accomodation for near vision, while agonists
cause accomodation and a loss of far vision.
 The lens provides the adjustable part of the
eyes refractive power.
Opacity of the lens is called a cataract.
Some drugs, notably corticosteroids, may
cause cataracts
 The retina is the part of the CNS but it seems
little affected by drugs, probably because of
the effective bloodretinal barrier.
Verteporfin is a new drug used to treat age-
related macular degeneration (AMD)
The retina may occasionally be damaged by
drugs (e.g chloroquine)
Cholinergic effects: Adrenergic effects:

Contraction of pupillary constrictor muscle Contraction of pupillary dilator muscle

-- miosis -- mydriasis
Contraction of ciliary muscle - bulge of lens Stimulation of ciliary epithelium
-- near vision, outflow of aqueous humor -- production of aqueous humor

Pupillary dilator muscle (a1)

Pupillary constrictor muscle (M3)

Trabecular meshwork
(opened by pilocarpine)

Lens

(M3)
Secretion of aqueous humor (b)