DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

Table 64–1
Autonomic Pharmacology of the Eye and Related Structures
ADRENERGIC RECEPTORS
CHOLINERGIC RECEPTORS
TISSUE SUBTYPE RESPONSE SUBTYPE RESPONSE
Corneal epithelium 2
Unknown M a Unknown
Corneal endothelium 2
Unknown Undefined Unknown
Iris radial muscle 1
Mydriasis
Iris sphincter muscle M 3
Miosis
Trabecular meshwork 2
Unknown
Ciliary epithelium b 2
/ 2
Aqueous production
Ciliary muscle 2
Relaxation c M 3
Accommodation
Lacrimal gland 1
Secretion M 2
, M 3
Secretion
Retinal pigment epithelium 1
/ 2
H 2
O transport/unknown
a
Although acetylcholine and choline acetyltransferase are abundant in the corneal epithelium of most species, the function of this neurotransmitter
in this tissue is unknown. b The ciliary epithelium also is the target of carbonic anhydrase inhibitors. Carbonic anhydrase isoenzyme II is localized
to both the pigmented and nonpigmented ciliary epithelium. c Although 2
adrenergic receptors mediate ciliary body smooth muscle relaxation,
there is no clinically significant effect on accommodation.
epithelial layer comprises five to six cell layers. The basal epithelial
cells lie on a basement membrane that is adjacent to Bowman’s membrane,
a layer of collagen fibers. Constituting ~90% of the corneal
thickness, the stroma, a hydrophilic layer, is uniquely organized with
collagen lamellae synthesized by keratocytes. Beneath the stroma lies
Descemet’s membrane, the basement membrane of the corneal
endothelium. Lying most posteriorly, the endothelium is a monolayer
of cells adhering to each other by tight junctions. These cells maintain
corneal integrity by active transport processes and serve as a
hydrophobic barrier. Hence, drug absorption across the cornea requires
penetration of the trilaminar hydrophobic–hydrophilic–hydrophobic
domains of the various anatomical layers.
At the periphery of the cornea and adjacent to the sclera lies
a transitional zone (1-2 mm wide) called the limbus. Limbal structures
include the conjunctival epithelium, which contains the corneal
epithelial stem cells, Tenon’s capsule, episclera, corneoscleral
stroma, canal of Schlemm, and trabecular meshwork (Figure
64–3B). Limbal blood vessels, as well as the tears, provide important
nutrients and immunological defense mechanisms for the
cornea. The anterior chamber holds ~250 μL of aqueous humor. The
peripheral anterior chamber angle is formed by the cornea and the
iris root. The trabecular meshwork and canal of Schlemm are located
just above the apex of this angle. The posterior chamber, which holds
~50 μL of aqueous humor, is defined by the boundaries of the ciliary
body processes, posterior surface of the iris, and lens surface.
Aqueous Humor Dynamics and Regulation of Intraocular Pressure.
Aqueous humor is secreted by the ciliary processes and flows from
the posterior chamber, through the pupil, and into the anterior chamber
and leaves the eye primarily by the trabecular meshwork and canal
of Schlemm. From the canal of Schlemm, aqueous humor drains into
an episcleral venous plexus and into the systemic circulation. This
conventional pathway accounts for 80-95% of aqueous humor outflow
and is the main target for cholinergic drugs used in glaucoma
therapy. Another outflow pathway is the uveoscleral route (i.e., fluid
flows through the ciliary muscles and into the suprachoroidal space),
which is the target of selective prostanoids (see “Glaucoma” and
Chapter 33).
The peripheral anterior chamber angle is an important
anatomical structure for differentiating two forms of glaucoma:
open-angle glaucoma, which is by far the most common form of
glaucoma in the U.S., and angle-closure glaucoma. Current medical
therapy of open-angle glaucoma is aimed at decreasing aqueous
humor production and/or increasing aqueous outflow. The preferred
management for angle-closure glaucoma is surgical iridectomy, by
either laser or incision, but short-term medical management may be
necessary to reduce the acute intraocular pressure (IOP) elevation
and to clear the cornea prior to surgery. Long-term IOP reduction
may be necessary, especially if the peripheral iris has permanently
covered the trabecular meshwork. In anatomically susceptible eyes,
anticholinergic, sympathomimetic, and antihistaminic drugs can lead
to partial dilation of the pupil and a change in the vectors of force
between the iris and the lens. The aqueous humor then is prevented
from passing through the pupil from the posterior chamber to the
anterior chamber. The change in the lens-iris relationship leads to
an increase in pressure in the posterior chamber, causing the iris base
to be pushed against the angle wall, thereby covering the trabecular
meshwork and closing the filtration angle and markedly elevating
the IOP. The result is known as an acute attack of pupillary-block
angle-closure glaucoma. Unfortunately, individuals with susceptible
angles usually are not aware of a risk of angle-closure glaucoma.
Furthermore, drug warning labels do not always specify the type of
glaucoma for which this rare risk exists. Thus, unwarranted concern
is raised among patients who have open-angle glaucoma who need
not be concerned about taking these drugs.
Iris and Pupil. The iris is the most anterior portion of the uveal
tract, which also includes the ciliary body and choroid. The anterior
surface of the iris is the stroma, a loosely organized structure
containing melanocytes, blood vessels, smooth muscle, and