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of IOP to topical timolol treatment was influenced by the dose of the systemic beta blocker, with the expected effect at low doses, moderate response at intermediate doses, and little or no response at high doses of oral propranolol.19 In patients using concurrent systemic beta blocker therapy, the ocular hypotensive efficacy of topical timolol was reduced, whereas the effect of brimonidine was not altered.20 For this reason, topical beta blockers may not be the optimal therapy in patients treated with high-dose systemic beta blockers.

Initiation of topical treatment with beta blocker is unlikely to cause additional systemic side effects in patients already treated with oral beta blockers. Systemic absorption of timolol instilled into one eye of propranolol-treated patients had no effect on the pulse or the blood pressure.19 In patients on long-term therapy with timolol eye drops, addition of systemic propranolol therapy may cause a significant reduction of IOP, presumably due to blockade of additional beta receptors by the systemic drug.21

9.1.2 Central Sympatholytics. The blood-pressure-lowering effect of central sympatholytics results from the passage of the drug through the blood-brain barrier and the stimulation of alpha-adrenergic receptors, resulting in decreased efferent sympathetic activity and increased vagal activity. After systemic administration, an initial direct stimulation of peripheral alpha-adrenergic receptors may cause a transient vasoconstriction, which is eventually inhibited by the central effect of the drug. Central sympatholytic drugs (table 9.2) are potent medications used for the treatment of systemic hypertension.

Clonidine was developed in 1962 as a potential decongestive drug and was unexpectedly found to cause decreased systemic blood pressure, which later proved therapeutically useful. This drug is a lipophilic alpha-2 agonist with some alpha-1-agonist activity. In 1966, Makabe22 reported a reduction of normal and elevated IOP following intravenous administration of clonidine. In addition to oral and intravenous routes of administration, instillation of clonidine eye drops effectively lowered IOP.23,24 However, topical use of the drug was limited because systemic

Systemic Drugs and Intraocular Pressure 169 Table 9.2 Systemic Central Sympatholytics (Alpha-2 Agonists)

Usual Dosage

(total mg/day)

Frequency

Clonidineb

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Blood Pressure Health

Your heart pumps blood throughout your body using a network of tubing called arteries and capillaries which return the blood back to your heart via your veins. Blood pressure is the force of the blood pushing against the walls of your arteries as your heart beats.Learn more...

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