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

their chemistry and pharmacology are described in
Chapter 42.
Therapeutic Uses. Currently, the glucocorticoids formulated for topical
administration to the eye are dexamethasone (DEXASOL, others),
prednisolone (PRED FORTE, others), fluorometholone (FML, others),
loteprednol (ALREX, LOTEMAX), rimexolone (VEXOL), and difluprednate
(DUREZOL). Because of their anti-inflammatory effects, topical
corticosteroids are used in managing significant ocular allergy, anterior
uveitis, external eye inflammatory diseases associated with some
infections and ocular cicatricial pemphigoid, and postoperative inflammation
following refractive, corneal, and intraocular surgery. After
glaucoma filtering surgery, topical steroids can delay the woundhealing
process by decreasing fibroblast infiltration, thereby reducing
potential scarring of the surgical site (Araujo et al., 1995). Steroids
commonly are given systemically and by sub-Tenon’s capsule injection
to manage posterior uveitis. Intravitreal injection of steroids now
is being used to treat a variety of retinal conditions including agerelated
macular degeneration (ARMD), diabetic retinopathy, and cystoid
macular edema. Two intravitreal triamcinolone formulations,
TRIVARIS and TRIESENCE, are approved for ocular inflammatory conditions
unresponsive to topical corticosteroids and visualization during
vitrectomy, respectively. Parenteral steroids followed by tapering oral
doses is the preferred treatment for optic neuritis (Kaufman et al.,
2000; Trobe et al., 1999). An ophthalmic implant of fluocinolone
(RETISERT) is marketed for the treatment of chronic, non-infectious
uveitis.
Toxicity of Steroids. Steroid drops, pills, and creams are associated
with ocular problems, as are intravitreal and intravenous steroids.
Ocular complications include the development of posterior subcapsular
cataracts, secondary infections (see Chapter 42), and secondary
open-angle glaucoma (Becker and Mills, 1963). There is a
significant increase in the risk for developing secondary glaucoma
when there is a positive family history of glaucoma. In the absence
of a family history of open-angle glaucoma, only ~5% of normal
individuals respond to topical or long-term systemic steroids with a
marked increase in IOP. With a positive family history, however,
moderate to marked steroid-induced IOP elevations may occur in up
to 90% of patients. The pathophysiology of steroid-induced glaucoma
is not fully understood, but there is evidence that the GLCIA
gene may be involved (Stone et al., 1997). Typically, steroid-induced
elevation of IOP is reversible once administration of the steroid
ceases. However, intraocular or sub-Tenon’s steroid-related pressure
elevation may persist for months and may require treatment with
glaucoma medication or even filtering surgery. Newer topical
steroids, so-called “soft steroids” (e.g., loteprednol), have been
developed that reduce, but do not eliminate, the risk of elevated IOP.
Nonsteroidal Anti-Inflammatory Agents
General Considerations. Nonsteroidal drug therapy for
inflammation is discussed in Chapter 34. Nonsteroidal
anti-inflammatory drugs (NSAIDs) now are being
applied to the treatment of ocular disease.
Therapeutic Uses. Currently, there are five topical NSAIDs (see
Chapter 34) approved for ocular use: flurbiprofen (OCUFEN, others),
ketorolac (ACULAR, others), diclofenac (VOLTAREN, others), bromfenac
(XIBROM), and nepafenac (NEVANAC). Flurbiprofen is used to counter
unwanted intraoperative miosis during cataract surgery. Ketorolac is
given for seasonal allergic conjunctivitis. Diclofenac is used for postoperative
inflammation. Both ketorolac (Weisz et al., 1999; Almeida
et al., 2008) and diclofenac (Asano et al., 2008) have been found to be
effective in treating cystoid macular edema occurring after cataract
surgery. Bromfenac and nepafenac are indicated for treating postoperative
pain and inflammation after cataract surgery. In patients treated
with PG analogs such as latanoprost or bimatoprost, ketorolac and
diclofenac may help decrease postoperative inflammation. They also
are useful in decreasing pain after corneal refractive surgery. Topical
and systemic NSAIDs occasionally have been associated with sterile
corneal melts and perforations, especially in older patients with ocular
surface disease, such as dry eye syndrome.
Antihistamines and Mast-Cell Stabilizers. Pheniramine
(Chapter 32) and antazoline, both H 1
receptor antagonists,
are formulated in combination with naphazoline,
a vasoconstrictor, for relief of allergic conjunctivitis;
emedastine difumarate (EMADINE) also is used.
Cromolyn sodium (CROLOM, others), which reportedly
prevents the release of histamine and other autacoids
from mast cells, has found limited use in treating conjunctivitis
that is thought to be allergen mediated, such
as vernal conjunctivitis. Lodoxamide tromethamine
(ALOMIDE) and pemirolast (ALAMAST), mast-cell
stabilizers, also are available for ophthalmic use.
Nedocromil (ALOCRIL) also is primarily a mast-cell
stabilizer with some antihistamine properties.
Olopatadine hydrochloride (PATANOL, PATADAY), ketotifen
fumarate (ZADITOR, ALAWAY), bepotastine
(BEPREVE), and azelastine (OPTIVAR) are H 1
antagonists
with mast cell–stabilizing properties. Epinastine
(ELESTAT) antagonizes H 1
and H 2
receptors and
exhibits mast cell–stabilizing activity.
Immunosuppressive and Antimitotic Agents
General Considerations. The principal application of
immunosuppressive and antimitotic agents to ophthalmology
relates to the use of 5-fluorouracil and mitomycin
C in corneal and glaucoma surgeries. Interferon
-2b also has occasionally been used. Certain systemic
diseases with serious vision-threatening ocular
manifestations—such as Behçet’s disease, Wegener’s
granulomatosis, rheumatoid arthritis, and reactive arthritis
(Reiter’s syndrome)—require systemic immunosuppression
(see Chapter 35).
Therapeutic Uses. In glaucoma surgery, both fluorouracil and mitomycin
(MUTAMYCIN), which also are anti-neoplastic agents (see
Chapter 61), improve the success of filtration surgery by limiting the
postoperative wound-healing process. Mitomycin is used intraoperatively
as a single subconjunctival application at the trabeculectomy
site. Meticulous care is used to avoid intraocular penetration, because
mitomycin is extremely toxic to intraocular structures. Fluorouracil
may be used intraoperatively at the trabeculectomy site and/or
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CHAPTER 64
OCULAR PHARMACOLOGY