Beta Blockers


/n 1948, Raymond P. Ahlquist proposed that two distinct classes of adrenergic receptors exist in the autonomic nervous system, which he classified as alpha and beta.1 In 1958, adrenergic receptor antagonists were developed, initiating the pursuit of pharmaceutical agents designed to take advantage of manipulation of these receptors. Propranolol, introduced in 1964, was the first beta-adrenergic antagonist with widespread clinical application. This medication was used for the treatment of systemic hypertension, angina, and cardiac arrhythmias. Phillips et al.2 observed that intraocular pressure (IOP) was lowered in patients with glaucoma following systemic administration of propranolol. Others observed similar IOP-lowering effect when the medication was administered intravenously, orally, and topically. However, local adverse effects, such as ocular stinging, irritation, and corneal anesthesia, limited the development of this drug as an IOP-lowering medication. Practolol, a beta-1-selective antagonist, exerted IOP-lowering effects similar to those of propranolol but without the corneal anesthetic activity. Other adverse effects were related to an immunologically mediated oculomucocutaneous syndrome limiting the utility of this drug.

Investigations of timolol as an IOP-lowering drug were initiated in the 1970s. The current era of topical glaucoma therapy began when timolol maleate was granted approval by the FDA in the United States in 1978. The ocular beta blockers (OBBs) are topical beta-adrenergic antagonists. These drugs have been approved for use in the US since 1978. With more than three decades of accumulated experience, the OBBs remained the favored choice for initial monotherapy for lowering IOP, even well after the introduction of topical prostaglandin analogues. The OBBs are well accepted due to their efficacy at lowering IOP, generally well-tolerated local and systemic adverse effects, and familiarity. Prior to the introduction of the OBB, available IOP-lowering medications included the nonselective adrenergic agonists, the parasympathomimetic agonists, and the oral carbonic anhydrase inhibitors (CAIs). Each of these classes of drugs had significant limitations. In recent years, the prostaglandin analogues have largely replaced OBBs as initial monotherapy, but the OBBs remain an alternative and a popular choice for adjunctive therapy.

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