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

1788 Such combinations reduce the number of drops needed and
may improve compliance. Other combination products involving PG
analogs and blockers are in development.
Topical miotic agents are historically important glaucoma
medications but are less commonly used today. Miotics lower IOP
by causing muscarinic-induced contraction of the ciliary muscle,
which facilitates aqueous outflow. They do not affect aqueous production.
Multiple miotic agents have been developed. Pilocarpine
and carbachol are cholinomimetics that stimulate muscarinic receptors.
Echothiophate (PHOSPHOLINE IODIDE) is an organophosphate
inhibitor of acetylcholinesterase; it is relatively stable in aqueous
solution and, by virtue of its quaternary ammonium structure, is
positively charged and poorly absorbed. The usefulness of these
medicines is lessened by their numerous side effects and the need
to use them three to four times a day (Kaufman and Gabelt, 1997).
If combined topical therapy fails to achieve the target IOP or
fails to halt glaucomatous optic nerve damage, then systemic therapy
with CAI is a final medication option before resorting to laser or incisional
surgical treatment. The best-tolerated oral preparation is acetazolamide
in sustained-release capsules (see Chapter 25), followed by
methazolamide. The least well tolerated are acetazolamide tablets.
Toxicity of Agents in the Treatment of Glaucoma. Ciliary body spasm
is a muscarinic cholinergic effect that can lead to induced myopia and
a changing refraction due to iris and ciliary body contraction as the
drug effect waxes and wanes between doses. Headaches can occur from
the iris and ciliary body contraction. Epinephrine-related compounds,
effective in IOP reduction, can cause a vasoconstriction–vasodilation
rebound phenomenon leading to a red eye. Ocular and skin allergies
from topical epinephrine, related prodrug formulations, apraclonidine,
and brimonidine are common. Brimonidine is less likely to
cause ocular allergy and therefore is more commonly used. These
agents can cause CNS depression and apnea in neonates and are contraindicated
in children <2 years of age.
Systemic absorption of epinephrine-related drugs and
adrenergic antagonists can induce all the side effects found with
direct systemic administration. The use of CAIs systemically may
give some patients significant problems with malaise, fatigue,
depression, paresthesias, and nephrolithiasis; the topical CAIs may
minimize these relatively common side effects. These medical strategies
for managing glaucoma do help to slow the progression of this
disease, yet there are potential risks from treatment-related side
effects, and treatment effects on quality of life must be recognized.
Uveitis. Inflammation of the uvea, or uveitis, has both
infectious and non-infectious causes, and medical treatment
of the underlying cause (if known), in addition to
the use of topical therapy, is essential. Cyclopentolate
(CYCYLOGYL, others), tropicamide (MYDRIACYL) or
sometimes even longer-acting antimuscarinic agents
such as atropine, scopolamine (ISOPTO HYOSCINE), and
homatropine frequently are used to prevent posterior
synechia formation between the lens and iris margin and
to relieve ciliary muscle spasm that is responsible for
much of the pain associated with anterior uveitis.
If posterior synechiae already have formed, an adrenergic
agonist may be used to break the synechiae by enhancing pupillary
dilation. A solution containing scopolamine 0.3% in combination
SECTION IX
SPECIAL SYSTEMS PHARMACOLOGY
with 10% phenylephrine (MUROCOLL-2) is available for this purpose.
Two others, 1% hydroxyamphetamine hydrobromide combined with
0.25% tropicamide (PAREMYD) and 1% phenylephrine in combination
with 0.2% cyclopentolate (CYCLOMYDRIL) are only indicated for
induction of mydriasis. Topical steroids usually are adequate to
decrease inflammation, but sometimes they must be supplemented
with systemic steroids.
Strabismus. Strabismus, or ocular misalignment, has
numerous causes and may occur at any age. Besides
causing diplopia (double vision), strabismus in children
may lead to amblyopia (reduced vision). Nonsurgical
efforts to treat amblyopia include occlusion therapy,
orthoptics, optical devices, and phar macological agents.
An eye with hyperopia, or farsightedness, must constantly
accommodate to focus on distant images. In some hyperopic children,
the synkinetic accommodative-convergence response leads to
excessive convergence and a manifest esotropia (turned-in eye). The
brain rejects diplopia and suppresses the image from the deviated eye.
If proper vision is not restored by ~7 years of age, the brain never
learns to process visual information from that eye. The result is that
the eye appears structurally normal but does not develop normal
visual acuity and is therefore amblyopic. Unfortunately, this is a fairly
common cause of visual disability. In this setting, atropine (1%)
instilled in the preferred seeing eye produces cycloplegia and the
inability of this eye to accommodate, thus forcing the child to use the
amblyopic eye (Pediatric Eye Disease Investigator Group, 2002;
Pediatric Eye Disease Investigator Group, 2003). Echothiophate
iodide also has been used in the setting of accommodative strabismus.
Accommodation drives the near reflex, the triad of miosis,
accommodation, and convergence. An irreversible cholinesterase
inhibitor such as echothiophate causes miosis and an accommodative
change in the shape of the lens; hence, the accommodative drive
to initiate the near reflex is reduced, and less convergence will occur.
Surgery and Diagnostic Purposes. For certain surgical
procedures and for clinical funduscopic examination, it
is desirable to maximize the view of the retina and lens.
Muscarinic cholinergic antagonists and sympathomimetic
agents frequently are used singly or in combination
for this purpose (Table 64–7).
Intraoperatively, there are circumstances in which miosis is preferred,
and two cholinergic agonists are available for intraocular use,
acetylcholine (MIOCHOL-E) and carbachol. Patients with myasthenia
gravis may first present to an ophthalmologist with complaints of double
vision (diplopia) or lid droop (ptosis); the edrophonium test is helpful
in diagnosing these patients (see Chapter 10). For surgical
visualization of the lens, trypan blue (VISIONBLUE) is marketed to facilitate
visualization of the lens and for staining during surgical vitrectomy
procedures to guide the excision of tissue (MEMBRANEBLUE).
Use of Immunomodulatory and
Antimitotic Drugs for Ophthalmic Therapy
Glucocorticoids. Glucocorticoids have an important
role in managing ocular inflammatory diseases;