Medical management of glaucoma
Dr. Rita Singh
Introduction:
The primary goal in the treatment of glaucoma is to prevent or retard the loss of visual function caused by damage to the optic nerve.
Our therapeutic approaches, however, are currently limited to reducing IOP. This approach of lowering a potentially harmful pressure will apply to patients with documented optic nerve damage and visual field loss as well as those with elevated IOP or other well described risk factors so that treatment is indicated to prevent the onset of damage.
We now have five major randomized glaucoma clinical trials stating that intraocular pressure is important for protecting the susceptible optic nerve in patients with glaucoma.
Basic Pharmacology:
Before going in to the details of the drugs used in glaucoma, let us have a look at the basic pharmacologic principles in topical ocular treatment.
Bioavailability of topical ocular medications: The penetration of topically applied medication into the eye is proportional to the concentration of the drug that comes in contact with the cornea over time, which gets diluted by tears and gets washed out into the lacrimal drainage system.
The half life of various drugs in the tears is said to be 2-20 mins.
Alteration of the molecule or vehicle in a way that increases the half life, such as increasing the viscosity will increase the efficacy and duration.
Normal volume of the conjunctival sac is 7 micro liters. After installation of an eye drop it increases to 30 micro liters.
Most drugs are available between 30 to 70 micro liters. Thus a single drop will exceeds the capacity.
Tear Film: Under normal circumstances the turnover of tear films is 15% per minute, when an eye drop is installed this increases to 30% per minute, which helps in the drug getting drained off faster.
Also every drop added cause an increasing in blinking, squeezing which propels tears towards the sac.
It is possible to stop this by placing pressure on the canaliculi and closing the eye lids gently after eye drops.
The drugs that pass on to the lacrimal sac come directly in contact with the nasolacrimal system, were it gets absorbed rapidly and gets directly into the system, which means, they bypass the liver, thereby, causing systemic effects. For this reason, the installation of multiple eye drops over a short period is not recommended.
For example:- when saline is instilled in rabbits eye 30 seconds after pilocarpine administration the effect of the drug is reduced by 45%, if administered within 2 minutes - 17% after 5 minutes there is little loss to pilocarpine.
Cornea: The one thing to remember about the cornea as a barrier is that it is like a lipid - water - lipid sandwich. The lipid content of the epithelium and the endothelium is 100 times more than that of stroma. And therefore allow lipophilic than to hydrophilic substance. Because of the dual nature of the corneal barriers, drugs possessing both lipid and water solubility penetrate the cornea more readily.
Drug Elimination:
Most of the drug is lost in the cui de sac, because of the over flow.
Once in the anterior chamber the drug is eliminated with the bulk flow of the aqueous humor via the trabecular mesh work or the uvea scleral out flow.
Some of them through the limbal, conjunctival and scleral vessels.
There are many enzymes which metabolize the drugs in the cornea. This metabolic capability is used by the prodrug dipivefrin.
Anti Glaucoma drugs: It can be grouped into the following categories:-
- Miotics
- Alpha - Adrenergic receptor agonists
- Beta - Adrenergic receptors antagonist or beta blockers
- Sympathomimetics
- Carbonic anhydrase inhibitors
- Prostaglandin related agents or hypotensive lipids. Hyperosmotics.
- Calcium channel Blockers.
- Antimetabolites.
- Neuroprotection and other investigational Anti glaucoma drugs.
Miotics:
- Cholinergic agents.
- Acetylcholine chloride.
- Pilocarpine hydrochloride and nitrate Pilocarpine combination.
- Carbachol.
Cholinergic agents: The cholinergic drugs are the oldest effective medical treatment for glaucoma. More than 100 years ago, Laqueur used physostigmine (eserine) an extract from the calabar or ordeal bean for the treatment of glaucoma and Weber described the effects of pilocarpine.
Basic Considerations: Acetylcholine (ACh) is the neuro transmitter at autonomic preganglionic, parasympathetic, postganglionic and some motor nerve endings. Endogenously released ACh is hydrolised rapidly by acetylcholinesterase located in cholinergic nerves.
Cholinergic drugs either act directly by stimulating cholinergic receptors or indirectly by inhibiting the enzyme cholinesterase thereby protecting endogenous acetylcholine.
Topical administration of cholinergic drugs in the eye produces pupillary constriction, dilatation of conjunctival and iris blood vessels and increase aqueous out flow.
Acetylcholine: It is used only for intraocular (intracameral route) administration to induce miosis during ocular surgery. It produces complete miosis during ocular surgery.
Used in Cataract surgery, Penetrating keratoplasty, Peripheral Iridectomy and other anterior segment surgery.
Dosage: it is available as powder and fresh ophthalmic solution (1:100 acetyl choline chloride). Usually 0.5 - 2 ml of this solution is required to produce good miosis. Solution need not be washed as it has a short duration 10-20 mins.
Pilocarpine:Pilocarpine, the oldest and most widely used cholinergic agent, derived from the plant pilocarpus microphylus.
Pilocarpine is well absorbed by the cornea and released slowly in to the aqueous.
Topically administered, produces a reduction in IOP that starts after one hour and lasts for 4 - 8 hours. The drug is administered every 6 hours to ensure good reduction in IOP.
Mechanism of action in various types of Glaucoma: In OAG - By increasing the outflow, by stimulating the ciliary muscles, pulling traction on the scleral spur and the trabecular mesh work. This action separates the trabecular sheets and the schlem’s canal is kept open.
Fig 1.: Mechanism of action of pilocarpine in OAG
In ACG - for short term management of angle closure glaucoma till laser or surgery is done. It helps in constricting the pupil, tighten the iris, and decrease the volume of iris in the periphery away from the trabecular tissue.
Fig.2-Mechanism of action of pilocarpine in ACG
Dosage: It is available in topical ophthalmic solutions, ocuserts and gel form.
- Topical solution is available in two salts:
- Pilocarpine hydrochloride in the strengths of 0.25, 0.50, 1, 2, 3, 4, 6, 8, 10%.
- Pilocarpine nitrate in the strengths of 1, 2 & 4%.
- Gel Doses: Available in 4% and also 1-2% onset of action is 10-30mins and duration is 4-6 hours.
- Ocusert:
- Pilocarpine can be given in ocusert form. Ocusert P - 20, P - 40 or by soft contact lens.
- Pilocarpine when given with a polmer vehicle (1.6% polyvinyl pyrolidine) has a prolonged duration of action.
- Ocuserts are changed weekly and have to be kept in refrigeration at 2°- 8° centigrade.
It has been clinically shown that ocusert 20 mcg is roughly equal to 0.5% to 1% and 40 mcg is about 2 - 4%.
Ocuserts initially release the drugs at 3 times the rated value in 151 hours and declines to the rated value approximately 6 hours. During the reminder of the 7 days period the release rate is within 20% the rated value. It is advised that it is placed in the night to avoid myopic shift in the first few hours.
The disadvantages include increased cost, foreign body sensation. Occasional burst can cause myopic shift and intense miosis.
