112/06/20「兒童用藥安全講座」 主題一：「兒童用藥安全-苯巴比妥用藥注意事項」 講　師：高雄醫學大學附設中和紀念醫院小兒神經科 林龍昌 主任

1. 兒童用藥安全-苯巴比妥
類用藥注意事項
高雄醫學大學附設醫院
小兒神經科
林龍昌
6-20-2023

2. Outlines
⚫ 苯巴比妥事件衝擊與省思
⚫ Phenobarbital: indication, side effects
⚫ Benzodiazepam: indication, side effects

5. ⚫ 誰可以開立、使用管制藥品?
⚫ 管制藥品的使用時機?
⚫ 兒童不當對待的徵候?通報時機?
⚫ 藥品的適當管理

6. ⚫ 孩子受到之不當對待，分為身心虐待及疏忽兩種型態：
⚫ 1.身心虐待的樣態包括身體虐待、精神虐待及性虐待，身體虐待是指對孩
子施加任何非意外性之身體傷害，導致孩子受傷、死亡、外型損毀或任何
身體功能毀壞；精神虐待包括言語的羞 辱、孤立、控制、漠視孩子的情
緒需求等；性虐待是指直接或間接對孩子做出與性有關的侵害或剝削行為，
如性騷擾、猥褻及性侵害等。
⚫ 2.疏忽則為孩子的基本需求，如飲食、穿著、居住環境、教育、醫療照顧
等，受到嚴重或長期 忽視，以致危害或損害兒童健康或發展，以及將6歲
以下或需要特別照顧的孩子單獨留在家中，或交給不適當的人照顧。

7. ⚫ 兒少保護法第 53 條:醫事人員、社會工作人員、教育人員、保育人
員、教保服務人員、警察、司法人員、移民業務人員、戶政人員、
村（里）幹事及其他執行兒童及少年福利業務人員，於執行業務時
知悉兒童及少年有下列情形之一者，應立即向直轄市、縣（市）主
管機關通報，至遲不得超過二十四小時
⚫ 一、施用毒品、非法施用管制藥品或其他有害身心健康之物質。
⚫ 無故未通報罰則：六千元以上三萬元以下罰鍰

8. ⚫ 醫師法第19條:醫師除正當治療目的外，不得使用管制藥品及毒劇藥
品。

9. 管制藥品
⚫ 所謂管制藥品，是指成癮性麻醉藥品、影響精神藥品以及有加強管
理必要之藥品，且這些管制藥品僅限醫藥及科學上使用。
⚫ 目前我國的管制藥品依習慣性、依賴性、濫用性及社會危害性的程
度，共分為四級管理，第一級、大部分的第二級及少部分的第三級
為麻醉性止痛藥品，如嗎啡（Morphine）、吩坦尼（Fentanyl）；
大部分的第三級及第四級管制藥品為鎮靜安眠藥，如氟硝西泮
(Flunitrazepam，俗稱FM2)、佐沛眠(Zolpidem)。

10. 第四級管制藥品
⚫ Phenobarbital
⚫ Diazepam
⚫ Estazolam
⚫ Lorazepam
⚫ Midazolam

13. 君者，舟也；庶人者，水也；水則載舟，
水則覆舟。
《荀子·王制》

17. Mechanism of Action of phenobarbital
⚫ Phenobarbital increases the amount of time chloride channels are open,
consequently depressing the central nervous system.
⚫ This action occurs by acting on GABA-A receptor subunits.
⚫ When phenobarbital binds to these receptors, the chloride ion gates open
and stay open, allowing a steady flow of these ions into neuronal cells.
⚫ The half-life of phenobarbital is between 60-100 hours.

18. ⚫ Phenobarbital is recommended by the WHO for the treatment of certain
types of epilepsy in developing countries.
⚫ In the developed world, it is commonly used to treat seizures in young
children.

19. Indication of phenobarbital
⚫ Status Epilepticus
⚫ Seizures
⚫ Sedation
⚫ Hypnotic
⚫ Insomnia
⚫ Physician-Assisted Dying
⚫ Hyperbilirubinemia

20. Indication of levetiracetam
⚫ 十六歲以上病患之局部癲癇發作(併有或不併有次發性全身發作)之
單獨治療。
⚫ 四歲以上孩童或成人病患之局部癲癇發作(併有或不併有次發性全身
發作)，十二歲以上青少年與成人病患之肌抽躍性癲癇發作，以及十
六歲以上青少年與成人患有體質性泛發性癲癇的原發性泛發性強直
陣攣發作之輔助治療。

22. Etiology of neonatal seizure
⚫ HIE
⚫ Stroke
⚫ Hemorrhage
⚫ Infection
⚫ Brain malformation
⚫ Pyridoxine responsive epilepsy
⚫ Drug withdrawal
⚫ Glucose transporter defect
⚫ KCNQ2 mutation
⚫ Unknown cause

23. ⚫ Patients confirmed to have electrographic seizures received infusion of
either levetiracetam at 40 mg/kg, or the control treatment with
phenobarbital at 20 mg/kg.
⚫ Patients given levetiracetam loading doses received maintenance
levetiracetam at 10 mg/kg per dose, given IV every 8 hours for 5 days.
⚫ Patients given phenobarbital loading doses received maintenance
phenobarbital at 1.5 mg/kg per dose, given IV every 8 hours for 5 days.

26. ⚫ A rare catastrophic epileptic encephalopathy characterized by acute
manifestation of recurrent seizures or refractory status epilepticus.
⚫ Inflammation seems to play an important but not exclusive role in the
development of FIRES.
⚫ The treatment of FIRES represents a significant challenge.

27. ⚫ In relation to the role of inflammation in the pathogenesis of FIRES,
high-dose intravenous steroids have been tried despite the risk of
severe adverse events.
⚫ High doses of phenobarbital have also been proven effective and with
fewer side effects than anesthetics.

29. ⚫ The major effect of phenobarbital is to increase hepatic glucuronosyl
transferase (UGT) activity and the conjugation of bilirubin.
⚫ (1)Barbital plus phototherapy group (n = 103), and (2) the
phototherapy-only group (n = 97).
⚫ Of the total 186 who completed the study, only 22 underwent blood
exchange transfusion [7 from group 1, and 15 from group 2 (P =
0.0478).

31. Adverse Effects
⚫ Coma
⚫ Decreased effort to breathe
⚫ Low blood pressure
⚫ Incoordination
⚫ Impaired balance
⚫ Drowsiness
⚫ Stevens-Johnson syndrome

36. ⚫ The proportion of patients remaining free of subsequent seizures did
not differ significantly between treatment groups (Placebo 46% vs.
Phenobarbital 38%).

38. Mechanism of Action
of Benzodiazepam
⚫ Benzodiazepines are a class of drugs that act upon benzodiazepine
receptors (BZ-R) in the central nervous system (CNS).
⚫ The receptor is a protein comprised of five transmembrane subunits
that form a chloride channel in the center, i.e., the GABA-A receptor.
⚫ The mean half-life of unconjugated lorazepam in human plasma is
about 12 hours.

39. Indication of Benzodiazepam
⚫ Alprazolam: Anxiety disorders and panic disorders
⚫ Clobazam: Lennox-Gastaut syndrome
⚫ Clonazepam: Myoclonic seizures and absence seizures
⚫ Midazolam: Convulsive status epilepticus, sedation
⚫ Diazepam: Rectal diazepam is also indicated for treating febrile seizures
⚫ Chlordiazepoxide: Alcohol withdrawal syndrome
⚫ Flurazepam: Insomnia

41. ⚫ Sleep terrors (often called night terrors) typically occur between 4 and
12 years of age.
⚫ The events occur during the first one-third of nocturnal sleep.
⚫ The child awakens abruptly from sleep with a loud scream, is agitated,
and has a flushed face, sweating, and tachycardia.

42. ⚫ For sporadic sleep terrors, reassurance that the child will outgrow the
disorder.
⚫ Attempts to interrupt a sleep terror episode should be avoided.
⚫ Clonazepam can markedly suppress stages three and four NREM
sleep, may be tried on a short-term basis at bedtime if sleep terrors
are frequent and severe.

43. Adverse Effects
⚫ Respiratory depression
⚫ Respiratory arrest
⚫ Drowsiness
⚫ Confusion
⚫ Headache
⚫ Syncope
⚫ Nausea/vomiting
⚫ Diarrhea
⚫ Tremor

44. 檢驗
⚫ Benzodiazepine metabolites may be detected up to 72 hours after
ingestion.
⚫ The urine benzodiazepine screening test detects the presence of the
benzodiazepine/diazepam at a concentration of 200 ng/mL or greater.
⚫ Antidepressants, decongestants, and dextromethorphan (an ingredient
in Robitussin, Delsym) are examples of medications that can cause
false positive results.

45. ⚫ 1. 血液測 phenobarbital 是定量檢驗法，血中 phenobarbital 檢測主
要為治療藥物的血中濃度監測，做為臨床調整用藥劑量使用，檢驗方法為
免疫比濁法，最低可定量濃度為 2 μg/mL。依據 phenobarbital 半衰期
約 100 小時，如果距離最後一次用藥時間超過 3-4 週，應已在體內完全
代謝檢測不到。
⚫ 2. 尿液篩檢 Barbiturates 和 Benzodiazepines(BZD)藥物，主要作為濫
用藥物篩檢，檢測方法為酵素免疫法，檢測數值依照試劑廠商建議閾值判
定陰陽性發出報告。
⚫ 3. 尿液篩檢 Barbiturates 及 Benzodiazepines 如檢驗結果為陽性，應
進一步進行確認檢驗，確認試驗通常以質譜法進行，可定量，以避免篩檢
結果偽陽性。

46. Thank you for your attention !