* Alpha-adrenergic agents (Alphagan, Iopidine) reduce the production of eye fluid while increasing its outflow rate.

Downside: The most common side-effects are burning or itching of the eye, browache, headache, a slight raising of the upper lids, dry eye/mouth/nose, light sensitivity, dizziness, mild sedation, fatigue and depression.

* Beta-blockers have been the mainstay of glaucoma treatment for most of the 20 years following their launching in the late 1970s. They lower eye pressure by reducing aqueous production. Despite their eroding popularity due to the arrival of the newer prostaglandin analogues (see below), these agents are still commonly prescribed for OHT and glaucoma.

Downside: Beta-blockers as eyedrops can cause the same systemic adverse effects as if taken orally. The most common side-effects involving the eye include superficial punctate keratitis (scattered pinpoints of corneal inflammation), corneal numbness and visual disturbances (J Am Optom Assoc, 1985; 56: 108-12; Am J Ophthalmol, 1979; 88: 739-43).

Beta-blockers are either non-specific (targetting both beta-1 and -2 receptors) or specific (targetting either beta-1 or -2 receptors). Non-specific drops such as timolol (Timoptic, Betimol), levobunolol (Betagen) and carteolol (Ocupress) are generally thought to be more effective in lowering IOP than specific beta-blockers such as betaxolol (Betoptic). However, the latter cause fewer systemic side-effects.

Beta-blocker eyedrops, as with all other ophthalmic drops, enter the body via tear ducts that connect with the nasal cavity. This enables the drug to bypass the liver and directly enter the body’s circulation. Consequently, a significant amount of drug is absorbed - a typical dose (one drop of 0.5 per cent timolol solution in each eye) is as potent as a 10-mg oral dose for treating hypertension and angina (Ophthalmology, 1984; 91: 1361-3).

It’s well known that beta-blockers come with an extensive list of side-effects - some of which may be lethal. A review of nearly 550 reports of adverse reactions with timolol, sent to the National Registry for Drug-Induced Ocular Side Effects, found that half of these were linked to systemic reactions affecting the heart, lungs, central nervous system, digestion and skin (Ophthalmology, 1980; 87: 447-50).

Cardiovascular effects range from arrhythmias (heart-rate disturbances) to full-blown congestive heart failure (Clin Physiol Funct Imaging, 2002; 22: 271-8; Acta Anaesthesiol Scand, 1996; 40: 379-81; Am J Hosp Pharm, 1981; 38: 699-701).

Ironically, these drugs, which are supposed to help high blood pressure, cause disturbances in blood-fat levels, which could be a risk factor for heart disease. Several studies have shown how beta-blockers altered the ratio of low-density lipoprotein (LDL, the ‘bad’ cholesterol) to high-density lipoprotein (HDL, the ‘good’ cholesterol).

A study of postmenopausal women with either eye hypertension or glaucoma found that those treated with timolol had significant decreases in HDL cholesterol, while total (and LDL) cholesterols were increased (J Glaucoma, 1999; 8: 388-95).

Respiratory problems are also a common complication of beta-blockers, particularly in those with a history of lung disease. One case report described a 67-year-old man with stable chronic obstructive lung disease going into respiratory arrest just 30 minutes after receiving his first dose of timolol (Chest, 1983; 84: 640-1). Another report told of a 74-year-old long-term asthmatic who developed a severe - and fatal - attack of asthma several hours after taking timolol (Nihon Kyobu Shikkan Gakkai Zasshi, 1990; 28: 156-9).