Carbonic Anhydrase Inhibitors (CAIs)
Dorzolamide
 This 2% solution of Trusopt
(Merck) reduces IOP about 15 to 20%. Like the prostaglandins,
dorzolamide may be very useful for asthmatics and patients with
normotensive glaucoma where vasoconstrictive effects may be a
concern. Dorzolamide is FDA-approved for tid use, but clinical
studies have shown that bid administration is nearly as effective
as tid dosing, particularly when used in additive therapy. For
the rare occasions when a CAI would be used as monotherapy, tid
administration may be needed to achieve maximum IOP reduction.
In most cases, topical therapy with this CAI can replace systemic
CAI therapy with good preservation of IOP control. If a systemic-to-topical
switch is done (which is a wise therapeutic trial), be sure to
monitor IOP to ensure no unacceptable loss of IOP control has
occurred. An excellent study in the January 1997 Archives of
Ophthalmology demonstrated that systemic acetazolamide reduced
aqueous flow by 30% whereas topical dorzolamide reduced flow
only 17%. They conclude: “Clinicians who prescribe dorzolamide
should expect less of an ocular hypotensive effect than that
experienced from systemically administered acetazolamide.” The
judicious use of systemic therapy may well enable the achievement
of target IOP with minimal side effects, and remains a viable
therapeutic approach in select patients. One-quarter of patients
notice a bitter taste in their throat when taking dorzolamide.
Gentle eyelid closure for three minutes tends to eliminate or
minimize systemic absorption.
 Brinzolamide
This newest addition
to the CAI family is a 1% ophthalmic suspension marketed as Azopt
(Alcon). Trusopt and Azopt perform equally well in clinical use.
Clinical data does show that it tends to produce less stinging
and burning than dorzolamide. Although it is a suspension, minimal
shaking is required because of its unique Carbopol suspension
system, which is also the suspension vehicle in Betoptic-S and
Vexol. While both brinzolamide and dorzolamide are very much
interchangeable, we generally use brinzolamide for the above
stated reasons.
Dorzolamide / Timolol Maleate
 This is the first combination drug for glaucoma (dorzolamide
2% with timolol maleate 0.5% ophthalmic solution) since
pilocarpine/epinephrine, and is far more advanced. Cosopt
(Merck) is intended for use when beta-blocker therapy alone
does not achieve the target IOP. It may reduce IOP about
30% in most patients responsive to each of its component
drugs. Cosopt is to be used bid.
We are disappointed that Cosopt is only available with 0.5%
timolol maleate. This will force the prescriber to needlessly
overexpose the patient to the potential adverse effects of
beta-blockade. Combining dorzolamide with 0.25% timolol maleate
would have honored the knowledge extensively published in the
ophthalmic literature. For this reason our use of Cosopt should
be reserved for unique cases where the risk/benefit to our
patient is met.
For example, a patient taking a beta-blocker
who is non-responsive to an alpha-agonist and the prostaglandin
class of drugs, yet requires additional topical therapy to
achieve target IOP, may benefit from Cosopt. Another exception
may be found in some patients of African descent where a higher
concentration of beta-blocker is sometimes required to achieve
maximum response to a beta-blocker, and where the beta-blocker
nearly achieved target IOP.
The addition of newer drugs in
the anti-glaucoma cauldron does indeed make therapeutic decision-making
more complex. Where will Cosopt fit into the algorithm of glaucoma
therapy? Our opinion is that it could be used after a therapeutic
trial of a beta-blocker where:
1. The target IOP was nearly
achieved yet an additional 2 or 3mm Hg of reduction is desired,
andx
2. Switching to Cosopt demonstrated an improved—and sustained—reduction.
It seems to us much simpler to try this alternative approach:
If the beta-blocker comes close, yet is still 2 or 3mm Hg shy
of target, stop the beta-blocker and try a prostaglandin. It
may well be that this approach will achieve target IOP simpler,
safer and more economically.
Alternatively, what if the beta
blocker qd combined with a prostaglandin (total daily instillation
frequency of bid) does not achieve target IOP? Rather than
add brimonidine to the beta-blocker (which would now result
in tid therapy), a trial of Cosopt bid could be considered,
based on the principle that the simpler the therapy, the better
the patient compliance. There are now several ways to mix and
match the glaucoma drugs, so try to use the least amount of
drug to meet the IOP target goal while minimizing the impact
on the patient’s overall quality of life.
Acetazolamide
 Known under
the brand name Diamox by Bausch & Lomb, this systemic CAI
is available in both tablets and time-release capsules. Oral
acetazolamide is rarely used alone in glaucoma care, but added
to a sub-optimal topical treatment regimen. It is commonly
administered in 250mg dose tablets every six hours, or one
500mg sequel bid, the latter causing fewer side effects. Diamox,
generally administered at 1000mg/d is a mainstay of therapy
in treating pseudotumor cerebri. It is also used in the prevention
and treatment of high altitude-associated cerebral edema. It’s
a very clinically effective drug, but its common systemic side
effects, including paresthesias and digestive problems, limit
its use. It is contraindicated in patients with renal or advanced
pulmonary problems.
Methazolamide
 Methazolamide, marketed as Neptazane (Wyeth), is very similar
to acetazolamide. Like acetazolamide, it is used almost exclusively
as an additive drug. Common dosage is 25 or 50mg bid or tid.
Because this drug does not alter the acid-base balance as
much as acetazolamide, it is a better choice for patients
with pulmonary problems. It is also less disturbing to the
renal system, and can usually be used in many patients with
renal problems. The side effects are essentially the same
as acetazolamide, but they are less common. Patients who
cannot tolerate acetazolamide may be able to tolerate methazolamide.
All CAIs can be added to all other glaucoma therapy; however,
if the patient is already taking one or more aqueous secretion
suppressing agents, the additive effect may well be dampened
or eliminated.
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