Beta-adrenergic blockers

These are, presently, the most frequently used
antiglaucoma drugs. The commonly used
preparations are timolol and betaxolol. Other available
preparations include levobunolol, carteolol and
metipranolol.
Mechanism of action. Timolol and levobunolol are
non-selective beta-1 (Cardiac) and beta-2 (smooth
muscle, pulmonary) receptor blocking agents.
Betaxolol has 10 times more affinity for beta-1 than
beta-2 receptors.
The drugs timolol and levobunolol lower IOP by
blockade of beta-2 receptors in the ciliary processes,
resulting in decreased aqueous production. The exact
mechanism of action of betaxolol (cardioselective
beta-blocker) is unknown.
Indications. Beta adrenergic blockers are useful in
all types of glaucomas, viz., developmental, primary
and secondary; narrow as well as open angle. Unless
contraindicated due to systemic diseases, betablockers
are frequently used as the first choice drug
in POAG and all secondary glaucomas.
Contraindications. These drugs should be used with
caution or not at all, depending on the severity of the
systemic disease in patients with bronchial asthma,
emphysema, COPD, heart blocks, congestive heart
failure or cardiomyopathy. Betaxolol is the beta
blocker, of choice in patients at risk for pulmonary
diseases. The other contraindication includes known
drug allergies.
Additive effects. Beta-blockers have very good
synergistic effect when combined with miotics; and
are thus often used in combination in patients with
POAG, unresponsive to the single drug.
Side-effects
1. Ocular side-effects are not frequent. These include
burning and conjunctival hyperaemia, superficial
punctate keratopathy and corneal anaesthesia.
2. Systemic side-effects are also unusually low.
However, these are reported more often than ocular
side-effects. These include (i) Cardiovascular effects
which result from blockade of beta-1 receptors. These
are bradycardia, arrhythmias, heart failure and
syncope. (ii) Respiratory reactions: These include
bronchospasm and airway obstruction, especially in
asthmatics. These occur due to blockade of beta-2
receptors; and thus are not known with betaxolol.
(iii) Central nervous system effects. These include
depression, anxiety, confusion, drowsiness,
disorientation, hallucinations, emotional lability,
dysarthria and so on. (iv) Miscellaneous effects are
nausea, diarrhoea, decreased libido, skin rashes,
alopecia and exacerbation of myasthenia gravis.
Preparations
1. Timolol. It is a non-selective beta-1 and beta-2
blocker. It is available as 0.25 per cent and 0.5 percent
eye drops. The salt used is timolol maleate. Its action
starts within 30 minutes, peak reaches in 2 hours and
effects last up to 24 hours. Therefore, it is used once
or twice daily. The drug is very effective, however,
the phenomenon of ‘short-term escape’ and ‘longterm
drift’ are well known. ‘Short-term escape’ implies
marked initial fall in IOP, followed by a transient rise
with continued moderate fall in IOP. The ‘long-term
drift’ implies a slow rise in IOP in patients who were
well controlled with many months of therapy.
2. Betaxolol. It is a cardioselective beta-blocker and
thus can be used safely in patients prone to attack of
bronchial asthma; an advantage over timolol. It is
available as 0.5 percent suspension, and 0.25 percent
suspension, and is used twice daily. Its action starts
within 30 minutes, reaches peak in 2 hours and lasts
for 12 hours. It is slightly less effective than timolol
in lowering the IOP.
3. Levobunolol. It is available as 0.5 percent solution
and its salient features are almost similar to timolol.
4. Carteolol. It is available as 1 percent and 2 per
cent solution and is almost similar to timolol except
that it induces comparatively less bradycardia.
5. Metipranolol. It is available as 0.1 percent, 0.3
percent and 0.6 percent solution and is almost similar
to timolol in all aspects.
Carbonic anhydrase inhibitors (CAIs)
These are potent and most commonly used systemic
antiglaucoma drugs. These include acetazolamide
(most frequently used), methazolamide,
dichlorphenamide and ethoxzolamide.
Mechanism of action. As the name indicates CAIs
inhibit the enzyme carbonic anhydrase which is
related to the process of aqueous humour production.
Thus, CAIs lower the IOP by reducing the aqueous
humour formation.
Indications. These are used as additive therapy for
short term in the management of all types of acute
and chronic glaucomas. Their long-term use is
reserved for patients with high risk of visual loss,
where all other treatments fail.
Side-effects. Unfortunately, 40-50 percent of patients
are unable to tolerate CAIs for long term because of
various disabling side-effects. These include:
1. Paresthesias of the fingers, toes, hands, feet and
around the mouth are experienced by most of the
patients. However, these are transient and of no
consequence.
2. Urinary frequency may also be complained of by
most patients due to the diuretic effect.
3. Serum electrolyte imbalances may occur with
higher doses of CAIs. These may be in the form of (i)
Bicarbonate depletion leading to metabolic acidosis.
This is associated with ‘malaise symptom complex’,
which includes: malaise, fatigue, depression, loss of
libido, anorexia and weight loss. Treatment with
sodium bicarbonate or sodium acetate may help to
minimize this situation in many patients. (ii) Potassium
depletion. It may occur in some patients, especially
those simultaneously getting corticosteroids, aspirin
or thiazide diuretics. Potassium supplement is
indicated only when significant hypokalemia is
documented. (iii) Serum sodium and chloride may be
transiently reduced; more commonly with
dichlorphenamide.
4. Gastrointestinal symptom complex. It is also very
common. It is not related to the malaise symptom
complex caused by biochemical changes in the serum.
Its features include—vague abdominal discomfort,
gastric irritation, nausea, peculiar metallic taste and
diarrhoea.
5. Sulfonamide related side-effects of CAIs, seen
rarely, include renal calculi, blood dyscrasias,
Stevens-Johnson syndrome, transient myopia,
hypertensive nephropathy and teratogenic effects.
Preparations and doses
1. Acetazolamide (diamox). It is available as tablets,
capsules and injection for intravenous use. The
acetazolamide 250 mg tablet is used 6 hourly. Its action
starts within 1 hour, peak is reached in 4 hours and
the effect lasts for 6-8 hours.
2. Dichlorphenamide. It is available as 50 mg tablets.
Its recommended dose is 25 to 100 mg three times a
day. It causes less metabolic acidosis but has a
sustained diuretic effect.
3. Methazolamide. It is also available as 50 mg tablets.
It has a longer duration of action than acetazolamide.
Its dose is 50-100 mg, 2 or 3 times a day.
4. Ethoxzolamide. It is given in a dosage of 125 mg
every 6 hours and is similar to acetazolamide in all
aspects.
5. Dorzolamide (2%). It is a topical carbonic
anhydrase inhibitor. It is water soluble, stable in
solution and has excellent corneal penetration. It
decreases IOP by 22% and has got additive effect
with timolol. It is administered thrice daily. Its side
effects include burning sensation and local allergic
reaction.
6. Brinzolamide (1%). It is also a topical CAI which
decreases IOP by decreasing aqueous production. It
is administered twice daily (BD).