346 Therapy of Selected Diseases
prost. Both substances can be used for
‡ Local Treatment of Glaucoma
Currently, glaucoma therapy remains fo-
cused on mechanisms designed to decrease
intraocular pressure (IOP) and this approach
is considered effective also in normal tension
glaucoma.
Normal values of IOP lie between 15 and
20 mmHg, that is, above the venous pres-
sure. IOP reflects the ratio of production
and outflow of aqueous humor. Aqueous hu-
mor is secreted by the epithelial cells of the
ciliary body and, following passage through
the trabecular meshwork, is drained via the
canal of Schlemm (blue arrows in A). This
route is taken by 85–90% of aqueous humor;
a smaller portion enters the uveoscleral ves-
sels and, thus, the venous system. In the so-
called open-angle glaucoma, passage of
aqueous humor through the trabecular
meshwork is impeded so that drainage
through Schlemm’s canal becomes inef -
cient. The much rarer primary angle-closure
glaucoma features a narrowed iridocorneal
angle or a tight contact between iris and lens
(‘pupillary block’). Secondarily, blockade by
the iris of the trabecular meshwork may be
due to various causes (e. g., synechiae). Topo-
graphical relationships in the chamber angle
are shown enlarged in the red box.
For topical therapy of open-angle glauco-
ma, the following groups of drugs can be
used: for reducing production of aqueous
humor, β-blockers (e. g., timolol), α2-agonists
(clonidine, brimonidine), and inhibitors of
carbonic anhydrase (dorzolamide, brinzola-
mide).
For promoting drainage through the tra-
becular meshwork, parasympathomimetics
(e. g., pilocarpine) are effective, and through
the uveoscleral route, prostaglandin deriva-
tives. Pilocarpine excites the ciliary muscle
and the pupillary sphincter. The contraction
of both muscles widens the geometrical ar-
rangement of trabeculae, resulting in im-
proved drainage of aqueous humor. Uveo-
scleral drainage is augmented by the prosta-
glandin derivatives lanatoprost and bimato-
Luellmann, Color Atlas of Pharmacology © 2005 Thieme
All rights reserved. Usage subject to terms and conditions of license.
topical monotherapy or combined with oth-
er active principles. A peculiar side effect is
notable: dark pigmentation of iris and eye-
lashes.
The therapy of angle-closure glaucoma
involves chiefly reduction of aqueous humor
production (osmotic agents, β-blockers) and
surgical procedures.
The topical application of pharmaceuticals
in the form of eye-drops is hampered by a
pharmacokinetic problem. The drug must
penetrate from the ocular surface (cornea
and conjunctiva) to its target sites, namely,
the smooth muscle of the ciliary body or the
iris, the secretory epithelium of the ciliary
body, or the uveoscleral vessels (B). The ap-
plied drug concentration is diluted by lacri-
mal fluid and drains via the tear duct to the
nasal mucosa, where the drug may be ab-
sorbed. During permeation through the cor-
nea, transport through blood vessels takes
place. The drug concentration reaching the
anterior chamber is diluted by aqueous hu-
mor and, finally, drug molecules are also
transported away via Schlemm’s canal. In
order to reach the required concentrations
at the target site (10–8 to 10–6 M, depending
on the substance), the concentration needed
in the eye drops is ~ 10–2 M (equivalent to
~ 0.5 mg per droplet, depending on molecu-
lar weight). The amount of drug contained in
a single drop is large enough to elicit a gen-
eral reaction with systemic use. Even when
applied properly, eye drops can therefore
evoke side effects in the cardiovascular sys-
tem or the bronchial space. This possibility
leads to corresponding contraindications.
Thus, in patients with severe congestive
heart failure, bradycardia, or obstructive
lung disease, eye drops containing β-block-
ers must be avoided at all times.
 Local Treatment of Glaucoma 347

A. Local pharmacotherapy of glaucoma

Conjunctiva

Sclera

Increased drainage M. ciliaris

Pilocarpine
Prostaglandin derivatives
Proc. ciliaris

Schlemm’s canal Inhibitors of aqueous humor

production: β-Blocker,
CAH-inhibitors, α2-agonist

Cornea
Aqueous humor

Schlemm’s canal Sclera M. ciliaris

(drainage into
Iris venous system)

Lens Trabecular
labyrinth
B. Diffusion barriers for eye drops

Concentration:
-7
~10 M
Cornea Iris
Tear
film
Aqueous humor

Potential target
organs:

M. sphincter pup.

M. dilatator pup.

Ciliary epithelium
Eye drops
Concentration: M. ciliaris
-2
~10 M
Removal through
Schlemm’s canal

to nasal Removal through

mucosa blood vessels

Luellmann, Color Atlas of Pharmacology © 2005 Thieme

All rights reserved. Usage subject to terms and conditions of license.
Luellmann, Color Atlas of Pharmacology © 2005 Thieme
All rights reserved. Usage subject to terms and conditions of license.