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

1794 myopia and presumed ocular histoplasmosis syndrome.
Verteporfin is a mixture of two regioisomers (I and II):
SECTION IX
SPECIAL SYSTEMS PHARMACOLOGY
Verteporfin is administered intravenously, and
once it reaches the choroidal circulation, the drug is
light activated by a nonthermal laser source. Depending
on the size of the neovascular membrane and concerns
of occult membranes and recurrence, multiple photodynamic
treatments may be necessary. Activation of the
drug in the presence of oxygen generates free radicals,
which cause vessel damage and subsequent platelet
activation, thrombosis, and occlusion of choroidal neovascularization.
The t 1/2
of the drug is 5-6 hours. It is
eliminated predominantly in the feces. The potential
side effects include headache, injection-site reactions,
and visual disturbances. The drug causes temporary
photosensitization, and patients must avoid exposure of
the skin or eyes to direct sunlight or bright indoor lights
for 5 days after receiving it.
Pegaptanib (MACUGEN) is approved for neovascular
(wet) ARMD. Pegaptanib is a selective vascular endothelial
growth factor (VEGF) antagonist. It is a pegylated
anti-VEGF aptamer, a single strand of nucleic acid that
binds to the major pathological VEGF isoform, extracellular
VEGF 165
, thereby inhibiting VEGF 165
binding to
VEGF receptors. VEGF 165
induces angiogenesis and
increases vascular permeability and inflammation, all of
which are thought to contribute to the progression of the
neovascular (wet) form of ARMD, a leading cause of
blindness. Pegaptanib reduced vision loss in patients with
wet ARMD (Gragoudas et al., 2004). Dose levels >0.3 mg
did not demonstrate any additional benefit.
Pegaptanib (0.3 mg) is administered once every 6 weeks by
intravitreous injection into the eye to be treated. Side effects are
largely related to the injection. Following the injection, patients
should be monitored for elevation in IOP and for endophthalmitis.
Rare cases of anaphylaxis/anaphylactoid reactions have been
reported. No special dosage modification is required for any of the
populations that have been studied (i.e., gender, elderly).
Bevacizumab (AVASTIN) is a monoclonal murine
antibody that targets VEGF-A and thereby inhibits vascular
proliferation and tumor growth (see Chapter 62).
Ranibizumab (LUCENTIS) is a variant of bevacizumab
that has had the Fab domain affinity matured (Lien and
Lowman, 2008).
In the eye, several diseases that involve neovascularization such
as proliferative diabetic retinopathy, macular edema, retinopathy of
prematurity (Hubbard, 2008), ARMD (Patel et al., 2008), and neovascular
glaucoma have been treated off label with bevacizumab, while
ranibizumab generally has been reserved for both classic (Brown et al.,
2009) and occult (Chang et al., 2007) choroidal neovascular membranes
associated with ARMD. Both drugs are delivered by intravitreal
injection and often are used on a weekly or monthly basis for
maintenance therapy. Aside from the risks of hemorrhage and infection
from intravitreal injections, both drugs have been associated with
the risk of cerebral vascular accidents (Dafer et al., 2007; Shima et al.,
2008). A multicenter clinical trial evaluating the effectiveness of the
two medications for treating ARMD is currently under way.
Use of Anesthetics in Ophthalmic
Procedures
Topical anesthetic agents used clinically in ophthalmology
include proparacaine and tetracaine drops, lidocaine
gel (see Chapter 20), and intranasal cocaine. Pro -
paracaine and tetracaine are used topically to perform
tonometry, to remove foreign bodies on the conjunctiva
and cornea, to perform superficial corneal surgery, and to
manipulate the nasolacrimal canalicular system. They
also are used topically to anesthetize the ocular surface
for refractive surgery using either the excimer laser or
placement of intrastromal corneal rings. Cocaine may be
used intranasally in combination with topical anesthesia
for cannulating the nasolacrimal system.
Lidocaine and bupivacaine are used for infiltration and retrobulbar
block anesthesia for surgery. Potential complications and risks
relate to allergic reactions, globe perforation, hemorrhage, and vascular
and subdural injections. Both preservative-free lidocaine (1%),
which is introduced into the anterior chamber, and lidocaine jelly
(2%), which is placed on the ocular surface during preoperative
patient preparation, are used for cataract surgery performed under
topical anesthesia. This form of anesthesia eliminates the risks of the
anesthetic injection and allows for more rapid visual recovery after
surgery. General anesthetics and sedation are important adjuncts for
patient care for surgery and examination of the eye, especially in children
and uncooperative adults. Most inhalational agents and CNS
depressants are associated with a reduction in IOP. An exception is
ketamine, which has been associated with an elevation in IOP. In the
setting of a patient with a ruptured globe, the anesthesia should be
selected carefully to avoid agents that depolarize the extraocular muscles,
which may result in expulsion of intraocular contents.
Other Agents for Ophthalmic Therapy
Vitamins and Trace Elements
General Considerations. Table 64–9 summarizes the current understanding
of vitamins related to eye function and disease, especially
the biochemistry of vitamin A.