The Medicines Control Agency

Betablockers, sympathometics, miotics, and the new ocular hypotensives carbonic anhydrase inhibitors, prostaglandin analogues and alpha2 agonists. All reduce aqueous production except prostaglandins and miotics which increase uveoscleral and trabecular meshwork outflow respectively.

BETABLOCKERS

Used to be first choice therapy and still remains the typical treatment for glaucoma. Introduced in the 1970's they became popular for their potent hypotensive properties without the side effects of miotics. Now notorious for serious side effects. Not for chronic bronchitis or asthma.

Decreases secretions (dry eye), aqueous production, heart rate, blood pressure.

Adverse synergistic reaction to verapramil (calcium channel blocker for angina hypertension).

Timolol is the reference standard. Despite reducing IOP by up to 40% in 90% of cases its efficacy diminishes over subsequent months in 20% cases. The 0.25% is for lightly pigmented irides and 0.5% is for dark eyes.

Betablockers can have life-threatening cardiopulmonary side effects as they are non-selective and block both types of beta-adrenergic receptors

Beta1 receptors in cardiac muscle
stimulation - tachycardia (heart rate up)
block = bradycardia

Beta2 receptors in bronchial muscle
stimulation - bronchial dilation
block = bronchial constriction.

In a seven year period there were 32 deaths attributable to topical timolol. Before prescribing the patient's pulse should be checked to see if its low( norm is 70-75 bpm). Punctal compression after instillation -important for large ducts.

Carteolol - some sympathomimetic action
Betaxolol - blocks b1 only - cardioselective

Betablockers, even those with cardioselectivity, should not be used in patients with asthma or obstructive airway disease unless no alternative is available.

Brimonidine has supplanted both adrenaline and its pro-drug dipivefrin as the adrenergic drug of choice because its very efficacious, has an excellent safety profile and has been shown to have neuroprotective properties.

Alpha1 in smooth muscle of arterioles
agonist = vasoconstriction

Alpha2 in pre-synaptic nerve terminals
agonist = decreases nerve transmission

Adrenaline is mainly an alpha1 agonist causing vasoconstriction and decreased blood supply to the ciliary body and reduces IOP through decreased aqueous production.

Brimonidine, an alpha2 agonist, causes stimulation of presynaptic a₂-receptors preventing the release of noradrenaline; lowering the sympathetic tone at the ciliary process level so reducing aqueous production.

[The neurotransmitter at the end-organ is noradrenaline which acts on a or b receptors. These are further divided into a1 a2 b1 b2 subtypes. There are alpha1 receptors and beta2 receptors in arterioles.

Stimulation of alpha1 receptors results in vasoconstriction, while stimulation of beta2 receptors causes vasodilatation.

This explains why beta blockers cause dry eyes since it is thought basal lacrimal gland production is under sympathetic control. Arterioles supplying the lacrimal gland are vasoconstricted.

Despite peripheral vasoconstriction, betablockers reduce blood pressure by profoundly lowering cardiac output.]

Unfortunately Alphagan-P with Purite as preservative (as in Refresh tears) is not yet available in the UK. All are multi-dose preserved with benzalkonium chloride.

Owing to their superior safety and potent hypotensive effects prostaglandin analogues are currently the choice treatment in the majority of glaucoma cases. They work differently to other drugs lowering IOP by increasing uveoscleral outflow.

Reported side effects of latanoprost are cystoid macular oedema!! and uveitis, so contra-indicated in patients with a history of cataract surgery or uveitis.

Adverse ocular reactions are hyperaemia and increased iris and eyelash pigmentation and growth. Not for blue eyed light haired female patients with unilateral glaucoma.

Although preserved with BC only one evening application is needed from the fridge.

The adverse reactions of Travoprost are similar to Latanaprost. It is superior for patients of African descent.

Bimatoprost reduces IOP by 30% and is instilled once daily in the evening. When compared to Timolol 0.5% bds, the IOP reduction achieved following administration of Brimatoprost od is unrivalled.

Both Latanaprost and Travoprost bind to PF receptors increasing uveoscleral outflow.

Bimatoprost does not bind to PF receptors. Furthermore the drug promotes outflow via the trabecular route aswell as increasing uveoscleral outflow.

These inhibit the carbonic anhydrase enzyme which is needed to generate bicarbonate ions for the secretion of aqueous humour.

Because Carbonic Anhydrase is found in the corneal endothelium, CAI's can cause irreversible corneal oedema in patients with endothelial compromise eg Fuch's dystrophy. Contra-indicated for cornea guttata.

Oral CAIs are no longer used because of their serious and potentially fatal side effects (eg. aplastic anaemia). Topical CAIs don't have the same systemic risks their but ocular side effects are so numerous, they may mitigate against their use in many patients. The most common complaint is a burning/stinging upon insertion. Conjunctival hyperaemia and allergic reactions are common.

The cholinergic drugs are the oldest and for POAG have been superseded due to their troublesome adverse ocular effects -

Miosis
Accommodative spasm
Anterior lens opacites
Retinal detachment
Lacrimation and salivation.

Pilocarpine is the most frequently prescribed drug of its class for the initial management of angle-closure glaucoma.

Parasympathomimetics increase aqueous outflow by contracting the cilairy body muscle and opening the trabecular meshwork by traction on the scleral spur.

Lantanaprost (Xalatan) is the drug of first choice as it has no negative vascular effects. Brimonidine is a good additive if visual fields continue to deteriorate.

There is a fault in the blood-brain barrier for microvessels at the level of the prelaminar optic nerve head. There are a several recent reports of alpha2 adrenoreceptor agonists eg. Brimonidine having a neuroprotective effect on retinal ganglion cells when these are subjected to ischaemia.

Calcium channel blockers such as Nifedipine have shown some efficacy in improving the visual field of low tension glaucoma cases.
Nifedipine (Adalat) actually lowers blood pressure by vasodilation (Ca ions are prevented from entering into vascular smooth muscle that normally causes it to constrict).
Calcium channel blockers are widely known to produce eye pain as a side effect..

Studies are controversial as to whether dorsolomide improves nerve head perfusion, but it's lipisomal properties promote crossing of the blood brain barrier.

VISUAL FIELDS

The GDX Access measures the thickness of the nerve fibre layer around the optic nerve using a low powered laser. Apparently retinal nerve fibre layer damage is visible up to 6 years before visual field damage.