Fellowships
1
THE JOURNAL OF PEDIATRICS BERLIN ET AL VOLUME 138, NUMBER 3 443 Adverse effects caused by oph- thalmic agents often go unrecognized for 2 reasons. First, physicians may not specifically ask about ophthalmic drops in a medication inquiry. Second, the standard dosing principles we apply to oral medications are often not considered for ophthalmic drops. Consideration of the following guidelines may help reduce the inci- dence of adverse systemic effects of ophthalmic agents in children 4,12 : (1) administer the lowest effective dose, (2) have the pharmacist dilute solu- tions, (3) immobilize the child proper- ly before instillation, (4) blot excess drops from the lids, and (5) apply digi- tal pressure to the punctum for 3 min- utes after instillation. This case clearly illustrates central α 2 - agonist adverse effects caused by bri- monidine ophthalmic solution. Reversal of symptoms with naloxone, elevated serum levels of brimonidine, low levels of norepinephrine metabolites in the CSF, and cessation of symptoms after discontinuation of this medication sup- port this hypothesis. More importantly, it emphasizes the potential for systemic adverse effects of ophthalmic prepara- tions and the need to reconsider dosing in children. Pharmaceutical companies should be encouraged to investigate the efficacy, dosing, and safety of these agents in children. We thank Keith Hyland, PhD, for performing the neurotransmitter measurements. REFERENCES 1. Wiley JF, Wiley CC, Torrey SB, Hen- retig FM. Clonidine poisoning in young children. J Pediatr 1990;116: 654-8. 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 and local tolerability of ophthalmic drug formulations. Drug Saf 1993;8:365-80. 5. Adkins JC, Balfour JA. Brimonidine: a review of its pharmacological prop- erties and clinical potential in the man- agement of open-angle glaucoma and ocular hypertension. Drugs Aging 1998;12:225-41. 6. Loebstein R, Koren G. Clinical phar- macology and therapeutic drug moni- toring in neonates and children. Pedi- atr Rev 1998;19:423-8. 7. Stewart PA, Hayakawa EM. Interen- dothelial junctional changes underlie the developmental tightening of the blood-brain barrier. Dev Brain Res 1987;32:271-81. 8. Farsang C, Kunos G. Naloxone re- verses the antihypertensive effects of clonidine. Br J Pharmacol 1979;67: 161-4. 9. Farsang C, Kapocsi J, Vajda L, Varga K, Malisak Z, Fekete M, et al. Rever- sal by naloxone of the antihypertensive action of clonidine: involvement of the sympathetic 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 clonidine toxicity. Am J Dis Child 1984;138: 1084-5. 12. Isenberg SJ. The eye in infancy. St Louis: Mosby; 1994. p. 87-98. FELLOWSHIPS Fellowships available in pediatric subspecialties and those for general academic pediatric training are listed once a year, in January, in The Journal of Pediatrics. Each June, forms for listing fellowships available for the academic year beginning 18 months after publication are sent to the Chairman of the Department of Pediatrics at major hospitals in the United States and Canada. In addition, a copy of the application form appears in the July, August, and September issues of The Journal (please use the current form). Should you desire to list fel- lowships, a separate application must be made each year for each position. All applications must be returned to Mosby, Inc, by October 15 preceding the listing year to ensure publication. Additional forms will be supplied on request from the Periodical Editing Department, Mosby, Inc, 11830 Westline Industrial Dr, St Louis, MO 63146-3318 (phone: 800-325-4177, ext 2838, or 314-579-2838).
Transcript of Fellowships
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
1. Wiley JF, Wiley CC, Torrey SB, Hen-retig FM. Clonidine poisoning inyoung children. J Pediatr 1990;116:654-8.
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.
5. Adkins JC, Balfour JA. Brimonidine:a review of its pharmacological prop-
erties and clinical potential in the man-agement of open-angle glaucoma andocular hypertension. Drugs Aging1998;12:225-41.
6. Loebstein R, Koren G. Clinical phar-macology and therapeutic drug moni-toring in neonates and children. Pedi-atr Rev 1998;19:423-8.
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.
FELLOWSHIPS
Fellowships available in pediatric subspecialties and those for general academic pediatrictraining are listed once a year, in January, in The Journal of Pediatrics. Each June, forms forlisting fellowships available for the academic year beginning 18 months after publication aresent to the Chairman of the Department of Pediatrics at major hospitals in the United Statesand Canada. In addition, a copy of the application form appears in the July, August, andSeptember issues of The Journal (please use the current form). Should you desire to list fel-lowships, a separate application must be made each year for each position. All applications mustbe returned to Mosby, Inc, by October 15 preceding the listing year to ensure publication.Additional forms will be supplied on request from the Periodical Editing Department, Mosby,Inc, 11830 Westline Industrial Dr, St Louis, MO 63146-3318 (phone: 800-325-4177, ext 2838,or 314-579-2838).
