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門診處方討論 Acetazolamide用於 Epilepsy 的治療 報 告 者: 蔡靜薇 94 .05.20 Topiramate100mg/tab 1#TID Carbamazepine CR 200mg/tab 2#bid Sennoside A+B 12mg/tab 1#hs Acetazolamide 250mg/tab 1#bid OVERVIEW » A. Acetazolamide is a carbonic anhydrase inhibitor. » B. DOSING INFORMATION: As adjunctive therapy in seizures, doses of 8 to 30 mg/kg/day are used for both adults and pediatric patients. » C. CLINICAL APPLICATIONS: ACETAZOLAMIDE is useful as an adjunct to other drugs in the treatment of glaucoma, seizures, edema, and congestive heart failure. It has also been used to prevent acute mountain sickness (AMS). » » » » » » » » Dosage, Adult (usual) Epilepsy: 8-30 mg/kg ORALLY daily, q8h-q12h Dosage, Pediatric, (usual) not FDA approved for pediatric patients Dosage, Pediatric, (usual) not FDA approved for pediatric patients Epilepsy: initial, 4 mg/kg ORALLY daily Epilepsy: maintenance, 8-30 mg/kg ORALLY daily, q8q12h Mechanism of action • 1.本品可抑制carbonic anhydrase,減少H+ 和 HCO3- 離子 的形成. 它可延緩中樞神經原過量或異常的放電 • 2.主要作用在近端的腎小管和遠端的腎小管,因此可減少供 給遠端腎小管和集 尿管做為N+, H+交換的H+離子量. • 3.因增加尿液排出Na+ 和HCO3- K+ 水份,因而限制利尿 作用,若較長時間治療會導制代謝性酸中毒(細胞外的Na+ 和HCO3-會漏失掉) Indications • FDA labeled indications • Edema, drug-induced • Edema, due to congestive heart failure • Epilepsy • Glaucoma (is useful in the treatment of glaucoma ) Dosage • a. The initial dose is recommended :4mg /kg daily • b. The suggested total daily dose for epilepsy : 8 -30 mg/kg daily optimum range :375 -1000 mg daily. • c. When given in addition to other anticonvulsant therapy the recommended starting dose : 250 mg once daily (Prod Info Diamox(R), 1996). • d. Slow withdrawal of acetazolamide over at least 6 weeks is recommended when discontinuing treatment to minimize the risk of precipitating seizure activity Clinical applications SEIZURES • FDA Labeled Indication – – – FDA APPROVAL: Adult, yes; pediatric, yes EFFICACY: Adult, effective; pediatric,effective DOCUMENTATION: Adult, excellent; pediatric, excellent Effective for the adjunctive treatment of centrencephalic seizure disorders such as unlocalized ABSENCE SEIZURES (Prod Info Diamox(R), 1996) Therapeutic uses • ADULT: a. Acetazolamide has been shown to be effective in the treatment of PETIT MAL SEIZURES (Millichap, 1956) in a dosage range of 500 to 1500 milligrams (mg) (Millichap & Aymat, 1967; Woodbury, 1972; Millichap, 1956; Ziegler, 1980) and is indicated as adjunctive treatment of centrocephalic seizure disorders (Prod Info Diamox(R), 1996). • The drug works best in patients with EEG patterns of 3/second bilateral spike and dome, other paroxysmal slow waves, 14 to 16/second positive spikes, or extreme response to hyperventilation (Ziegler, 1980) • One study showed that in 650 patients with petit mal seizures, complete control could be achieved in 50%, while another 26% had at least 75% control gained (Millichap & Aymat, 1967). Therapeutic uses • Acetazolamide was added to existing carbamazepine regimens of 48 patients with complex partial seizures (n=22), complex partial seizures with secondary generalization (n=17), simple partial (n=1), simple and complex partial seizures (n=6), or simple and complex partial seizures with secondary generalization (n=2) • Response was defined as seizure frequency reduction of 50% or more from baseline when averaged over 3 months of therapy • Acetazolamide monotherapy is considered effective when used cyclically to control seizures exacerbated by menstruation (CATAMENIAL EPILEPSY) • The dose is 250 milligrams (mg) 1 to 2 times daily for 5 to 7 days prior to menses onset. For irregular cycles, acetazolamide should begin on day 22 following the first day of bleeding. • If the patient is on oral contraceptives, acetazolamide is taken during the last 7 days, when active contraceptive tablets are stopped (Poser, 1974). Adverse Effect – SERIOUS • metabolic acidosis • sulfonamide reaction (including anaphylaxis, blood dyscrasias, erythema multiforme, fulminant hepatic necrosis, StevensJohnson syndrome, toxic epidermal necrolysis) • tinnitus (frequent, early in therapy) Precautions – adverse reactions common to sulfonamide derivatives may occur, including StevensJohnson syndrome and toxic epidermal necrosis – concomitant high-dose aspirin – high dose may decrease diuresis – high dose may increase drowsiness and/or paresthesia – pulmonary obstruction or emphysema References • • • • • • • • 1974 - 2005 Thomson MICROMEDEX. All rights reserved. MICROMEDEX(R) Healthcare Series Vol 22. Bear R, Goldstein M, Phillipson E et al: Effect of metabolic alkalosis on respiratory function in patients with chronic obstructive lung disease. Can Med Assoc J 1977; 117:900-903. 65. Dickinson GE, Myers ML, Goldbach M et al: Acetazolamide in the treatment of ventilatory failure complicating acute metabolic alkalosis. Anesth Analg 1981; 60:608610. 77. Epstein DL & Grant WM: Carbonic anhydrase inhibitor side effects. Arch Ophthalmol 1977; 95:1378-1382. 86. Folkersen L, Knudsen NA & Teglbjaerg PS: Licorice. A basis for precautions one more time! Ugeskr Laeger 1996; 158(51):7420-7421. 87. Folkerson L, Knudsen NA & Teglbjaerg PS: Licorice. A basis for precautions one more time! Ugeskr Laeger 1996; 158(51):7420-7421. 107. Greene MK, Kerr AM, McIntosh IB et al: Acetazolamide in prevention of acute mountain sickness: a double-blind controlled crossover study. Br Med J 1981; 283:811-813. 183. Maus TL, Larsson LI, McLaren JW et al: Comparison of dorzolamide and acetazolamide as suppressors of aqueous humor flow in humans. Arch Ophthalmol 1997; 115(1):45-49.