THE JOURNAL OF PEDIATRICS BERLIN ET AL

VOLUME 138, NUMBER 3

443

Adverse effects caused by oph-thalmic agents often go unrecognizedfor 2 reasons. First, physicians may notspecifically ask about ophthalmicdrops in a medication inquiry. Second,the standard dosing principles weapply to oral medications are often notconsidered for ophthalmic drops.

Consideration of the followingguidelines may help reduce the inci-dence of adverse systemic effects ofophthalmic agents in children4,12: (1)administer the lowest effective dose,(2) have the pharmacist dilute solu-tions, (3) immobilize the child proper-ly before instillation, (4) blot excessdrops from the lids, and (5) apply digi-tal pressure to the punctum for 3 min-utes after instillation.

This case clearly illustrates central α2-agonist adverse effects caused by bri-monidine ophthalmic solution. Reversalof symptoms with naloxone, elevatedserum levels of brimonidine, low levelsof norepinephrine metabolites in theCSF, and cessation of symptoms afterdiscontinuation of this medication sup-

port this hypothesis. More importantly,it emphasizes the potential for systemicadverse effects of ophthalmic prepara-tions and the need to reconsider dosingin children. Pharmaceutical companiesshould be encouraged to investigate theefficacy, dosing, and safety of theseagents in children.

We thank Keith Hyland, PhD, for performingthe neurotransmitter measurements.

REFERENCES

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2. Fiser DH, Moss MM, Walker W. Crit-ical care for clonidine poisoning in tod-dlers. Crit Care Med 1990;18:1124-8.

3. Palmer E. How safe are pediatric ocu-lar drugs? Ophthalmology 1986;93:1038-40.

4. Hugues FC, Le Jeune C. Systemic andlocal tolerability of ophthalmic drugformulations. Drug Saf 1993;8:365-80.

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erties and clinical potential in the man-agement of open-angle glaucoma andocular hypertension. Drugs Aging1998;12:225-41.

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7. Stewart PA, Hayakawa EM. Interen-dothelial junctional changes underliethe developmental tightening of theblood-brain barrier. Dev Brain Res1987;32:271-81.

8. Farsang C, Kunos G. Naloxone re-verses the antihypertensive effects ofclonidine. Br J Pharmacol 1979;67:161-4.

9. Farsang C, Kapocsi J, Vajda L, VargaK, Malisak Z, Fekete M, et al. Rever-sal by naloxone of the antihypertensiveaction of clonidine: involvement of thesympathetic nervous system. Circula-tion 1984;69:461-7.

10. Banner W, Lund ME, Clawson L.Failure of naloxone to reverse cloni-dine toxic effect. Am J Dis Child 1983;137:1170-1.

11. Tenenbein M. Naloxone in clonidinetoxicity. Am J Dis Child 1984;138:1084-5.

12. Isenberg SJ. The eye in infancy. StLouis: Mosby; 1994. p. 87-98.

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