Newer Anti-glaucoma Drugs
Dr. R. K. Mishra (Prof. Emeritus)
Rajendra Eye Hospital, Jabalpur (M.P.)
The glaucomas are a family of diseases characterized by progressive
optic neuropathy and associated visual field loss.
40% of the ganglion cells may be lost before the earliest functional
damage can be determined.
Since surgery is associated with complications and needs surgical
man power, effective medical treatment remains a valid option.
Target I.O.P
Definition:
The mean lOP obtained with treatment that prevents further glaucomatous
damage.
Target I.O.P. - The mean l.O.P. obtained with treatment that prevents
further glaucomatous damage.
T.I.O.P is difficult to assess in advance... However, aiming to achieve
at least a 30% reduction from the initial pressure at which damage
occurred is a useful arbitrary way.
Goal of medication - The amount of medication which achieves desired
result with minimal side effects, should be the goal of therapy.
Topical treatment should be started in one eye at a time. The differential
IOP will give a better idea of the effect.
Categories of medicaiton:
(1)Adrenergic agonists
(2)Adrenergic antagonists: Beta-blockers
(3).Carbonic anhydrase inhibitors (CAIs)(a) Systemic(b) Topical
(4).Parasympathomimetics
(5).Prostaglandins and hypotensive lipids
(6).Combined drugs preparations
Adrenergic antagonists (Beta-blockers)
Action: Reduce aqueous humor formation, thus reduce IOP. Selective
beta-1 blockers are said to be neuroprotective as well.
Selective Beta-1 blocker - Betaxolol 0.5% (Betopic, Glaucoptic, Iobet)
Non-selective - Levobunolol 0.25%, 0.5% (Betagan), Timolol 0.25%,
0.5% (Optipres, Timolol-G, Glaucomol, Iotim), Carteolol 1% (Ocupres).
Caution in drug selection: In the elderly, it is important
that we do not inadvertently facilitate cardiac / pulmonary disturbances.
Contraindications: Non-selective: Asthma, pulmonary disease,
sinus bradycardia(<60 beats/mm) , heart block, or cardiac failure
Beta- 1 selective: As above but has no cardiac involvement
Side-effects: Cardio pulmonary, occasionally Epithelial keratopathyeta-1
selective: Better tolerated in most patients sensitive to non-selective
agents.
Pregnancy and nursing mothers, infants and children safety is not
proved.
Adrenergic Agonists
Non-selective: Dipivefrin 0.1% (Propine) - reduces aqueous formation
and increases outflow.
Alpha-2 selective: Apraclonidine 0.5%, 1% (Lopidine) and Brimonidine
0.2% (Alphagan). Apraclonidine reduces aqueous formation, Brimonidine
in addition increases outflow.
Propine - Alphagan - Useful as adjunctive or as mono therapy..
Caution - In occludable angle a patent iridotomy needed. Use
in children and infants& lactating mothers safety not known.
Brimonidine 0.2% b.d. is highly effective as mono and adjunctive
therapy for ocular hypertension and glaucoma. Provides sustained IOP
lowering effect comparable to that of timolol. Alphagan combines well
with pilocarpin and Beta blockers. It is claimed by Allergan that
alphagan a2 adrenergic agonist has neuroprotective property. Conclusive
clinical reports are yet to come. Brimonidine inhibits ischemia-induced
apoptosis in retina (animal expariment)
Carbonic anhydrase inhibitors (CAI's)
Topical - Dorzolamide 2% (Trusopt) BD or TDS
Systemic - Acetazolamide 250, 500 mg (Diamox, Avva, Actamide) 2-4
tablets in divided doses.
The topical ones have made things easier and safer. Two of them have
come in the market Dorzolamide and Brinzolamide.
Dorzolamide+Timolol is sold under market name Trusopt where as Brinzolamide+Betaxolol
is marketed as cosopt.Yet an other product is marketed as Actamide
drop.
Drug combinations
Antiglaucoma drops can be combined .but not of the same group e.g.
do not combine two different beta-blockers or topical and oral CAIs.
Use of more than two drugs not recommended. (compliance). unless no
alternative left
Precautions
In renal impairment C.A.I. should not be used. Concomitant use of
topical and oral C.A.I. is not additive and not recommended.
C.A.I. should not be used in sulpha sensitives. Increase in dose may
produce drowsiness and paresthesia.
Parasympathomimetics (Cholinergic drugs)
Direct Acting - Pilocarpine 1%, 2%, 4% (Pilocar, Pilopingel, Pilagan),
Carbachol (Isoptocarbachol).
Indirect Acting - Physostigmine (Eserin)
Action - Increase in facility of outflow of aqueous humor.through
trabecular mesh work by direct action on longitudinal ciliary muscle.
Prostaglandins
MOTO - Why reduce aqueous formation which is vital for lens &
cornea. Why not increase exit of aqueous.
Dosage and administration
One drop in the evening
Latanoprost (Xalatan)
Good systemic safety profile. No cardiopulmonary contraindications
No significant effect on systolic or diastolic pressure, on heart
rate, on pulmonary function, depression, nausea, impotence, or CNS
effects
While prostaglandins may not augment flow through the trabecular
meshwork, they do preserve the normal rate of aquious humour flow,
to the benefit of cornea and lens.
Mode of action - All prostaglandin like drugs act by increasing
uveo-scleral outflow
(Prof. Kaufman)
Indications - Open angle primary glaucoma.
Angle closer primary glaucoma in presence of patent iridotomy.
Caution - Known hypersensitivity.
With contact lens on, should not be instil but contact lenses can
be reinserted 15 minutes latter.
Complications - C.M.E. in aphakes/pseudophakes. uveitis; hypertrichosis
of the eyelashes, permananet darkning of the iris.
Systemic: Non reported So far.
Not safe in pregnant women and lactating mothers.
Side effects - Blepharitis, darkening of skin.
Eyeless lengthening, pigmentation.
Epithelialkeratopathy
Permanent Iris Pigmentation
Conjunctival Histopathology - Ocular surface changes induced
by long term topical treatment for glaucoma are well recognized. Xalatan
mono therapy did not alter conjunctival epithelium goblet cell population
or mucus quality
(Dr. Andreas Petounis)
Other drugs
Name of Mitomycin C and 5 flurourocil are not congruous when talking
about anti glaucoma medicine but they can not be ignored either. MMC
in particular has appreciably improved the surgical out come in otherwise
difficult cases.
Need for multiple drugs
Approximately 40% of patients on medical therapy will require multiple
drugs to control I.O.P.
(N. Pfeiffer)
Pilocarpine - We are very familiar with this drug and yet
certain things have to be remembered.
1. Can not be used with latanoprost due to its contractile action
on ciliary muscle.
2. In narrow angle glaucoma, pupillary constriction - produce pupillary
block glaucoma. Lead to Ant. Peripheral synechia .particularly if
the iris is inflamed. Patent peripheral iridotomy is a must for safty.
3. In high axial myopes and Aphakiks - Ret. Detechment.
4. Spastic myopia of up to 8 D. can occur
5. Lens opacity - grossly effect the vision.
6. Contraindicated in neovascular glaucoma & uveitis.
7. Caution in pregnancy and lactation.
Washout time
Betablockers - 2-4 weeks
Sympathicomimetics - 2 weeks
Direct acting miotics - 1-3 days
Indirect miotics - 4 weeks-permanent
Topical CAI's - 1 week
Oral CAI's - 2 days
Prostaglandins - 3-4 weeks
General Principles of Glaucoma Treatment
The goal is to maintain visual function. Lowering the lOP.is the
only way at present.For Optic nerve head blood flow improvement ,
no drug has yet been shown to be effective clinically.
Neuro protection refers to the concept of protecting ganglion cells
from early death As yet there is no known way.
Beta-blockers may be used as the first line of therapy since they
are effective and usually well tolerated. Caution must be exercised
in bronchopulmonary or cardiac arhythmia, problems
Not only the action of the drug but the side effects too must be
considered. If more than two topical drugs are required then Laser
trabeculoplasty or surgery, should be considered.
If in addition to other Anti glaucoma drugs oral CIA is needed to
control IOP surgery is generally indicated.
If particular drug combination is not effective, change the combination,
not the dose. When available prefer a combination drug.
Drug Compliance in Glaucoma
Glaucoma is a long-standing, progressive disease, requires frequent
topical medication and regular follow-up. Patient’s continuous
co-operation is essential for successful management.
Compliance is considerably less than presumed by doctors. Many patients
fail to attend follow-ups. Non-compliance is estimated to cause 10
% of the glaucomatous visual loss.
Compliance issues must be taken into account when the type of treatment
is selected.
Bad compliance - Failure to instil eye drops.
Ineffective technique of self-administration
Excessive use of eye drops (systemic side effects)
Use of non-prescribed drops.
Future Diagnosis
"Tests through buccal swabs or blood test would allow physician
to assess whether an individual is at risk for glaucoma or has glaucoma."
(Prof. Robert Weinreb)