Generic Name: phenobarbital

通用名：苯巴比妥

Brand Name: Luminal®

商标名：鲁米那®

Drug Category: barbiturate, nonselective central nervous system depressant

类别：巴比妥类药，非选择性中枢神经系统抑制药

Dosage Form: Tablet, Elixir

剂型：片剂、酏剂

Indication

适用症

a. Sedatives.

b. Hypnotics, for the short-term treatment of insomnia

c. Preanesthetics.

d. Long-term anticonvulsants for the treatment of generalized tonic-clonic and cortical local seizures.

a. 镇静

b. 催眠，短期治疗失眠症

c. 前驱麻醉

d. 抗惊厥药，治疗全身强直阵挛性癫痫发作和皮质局部抽搐

Inactive Ingredients

辅助成份

Oral Tablets - corn starch, lactose, magnesium stearate and sodium starch glycolate

Oral Elixir - ethyl alcohol, glycerin, oil of orange, sucrose, water

口服片剂－玉米淀粉、乳糖、硬脂酸镁和羟甲基淀粉钠

口服酏剂－乙醇、甘油、橙油、蔗糖、水

Mechanism of Action

作用原理

Phenobarbital acts on GABA receptors, increasing synaptic inhibition. This has the effect of elevating seizure threshold and reducing the spread of seizure activity from a seizure focus. Phenobarbital may also inhibit calcium channels, resulting in a decrease in excitatory transmitter release. The sedative-hypnotic effects of phenobarbital are likely the result of its effect on the polysynaptic midbrain reticular formation, which controls CNS arousal.

苯巴比妥作用于γ-氨基丁酸受体，增加突触后神经抑制，提高发作阈值，减少发作病灶效能的扩散。苯巴比妥还对钙通道起抑制作用，减少兴奋性递质的释放。苯巴比妥的镇静催眠效果很可能是其对多突触中脑网状结构作用的结果，它控制CNS觉醒。

Toxicity

毒性作用

CNS and respiratory depression which may progress to Cheyne-Stokes respiration, areflexia, constriction of the pupils to a slight degree (though in severe poisoning they may show paralytic dilation), oliguria, tachycardia, hypotension, lowered body temperature, and coma. Typical shock syndrome (apnea, circulatory collapse, respiratory arrest, and death) may occur.

CNS和呼吸抑制可导致潮式呼吸、反射消失、瞳孔微缩（中毒严重时可表现为无力性扩张）、少尿、心动过速、低血压、低温和昏迷。也可能出现典型的休克综合症（呼吸暂停、循环衰竭、呼吸停止、死亡）。

Half Life: 53 to 118 hours (mean 79 hours)

半衰期：53至118小时（平均79小时）。

Pharmacology

药理学

Phenobarbital is capable of producing all levels of CNS mood alteration, from excitation to mild sedation to hypnosis, and deep coma. Over-dosage can produce death. In high enough therapeutic doses, Phenobarbital induces anesthesia. Phenobarbital depresses the sensory cortex, decreases motor activity, alters cerebellar function, and produces drowsiness, sedation, and hypnosis. Phenobarbital-induced sleep differs from physiological sleep. Sleep laboratory studies have demonstrated that Phenobarbital reduces the amount of time spent in the rapid eye movement (REM) phase of sleep or the dreaming stage. Also Stages III and IV sleep are decreased. Following abrupt cessation of Phenobarbital used regularly, patients may experience markedly increased dreaming, nightmares and/or insomnia. Therefore, withdrawal of a single therapeutic dose over 5 or 6 days has been recommended to lessen the REM rebound and disturbed sleep which contribute to drug withdrawal syndrome (for example, decrease the dose from 3 to 2 doses a day for 1 week).

苯巴比妥可导致CNS状态改变，由兴奋至轻度镇静至催眠，直至深度昏迷。用药过量可致死。足够的治疗剂量可诱发麻醉。苯巴比妥抑制感觉皮层，减弱运动活力，改变小脑功能，引起困倦、镇静和催眠。苯巴比妥诱导的睡眠与生理睡眠不同。睡眠实验证明，苯巴比妥缩短睡眠眼速动期或睡梦期时间，睡眠第三期和第四期也被缩短。若在定期使用苯巴比妥一段时间后突然停药，病人睡梦、梦魇和/或失眠明显增加，因此，有人建议用5－6天时间逐渐停止单次治疗剂量以减少快速眼动睡眠反跳和睡眠混乱，避免戒断综合症（如将一周剂量由一天三次减为一天两次）。

Phenobarbital has little analgesic action at subanesthetic doses. Rather, in sub anesthetic doses, this drug may increase the reaction to painful stimuli. All barbiturates exhibit anticonvulsant activity in anesthetic doses. However, of the drugs in this class, only phenobarbital, mephobarbital, and metharbital are effective as oral anticonvulsants in sub hypnotic doses.

苯巴比妥亚麻醉剂量时几无镇痛作用，反倒会增加对疼痛刺激的反应。所有麻醉剂量的巴比妥类药都有抗惊厥作用，不过，在此类药物中，只有苯巴比妥、甲苯比妥和美沙比妥的亚催眠剂量效果和口服抗惊厥剂相同。

Phenobarbital is a respiratory depressant. The degree of respiratory depression is dependent upon the dose. With hypnotic doses, respiratory depression produced by Phenobarbital is similar to that which occurs during physiologic sleep with slight decrease in blood pressure and heart rate. Studies in laboratory animals have shown that Phenobarbital causes reduction in the tone and contractility of the uterus, ureters, and urinary bladder. However, concentrations of the drug required to produce this effect in humans are not reached with sedative-hypnotic doses.

Phenobarbital does not impair normal hepatic function but has been shown to induce liver microsomal enzymes, thus increasing and/or altering the metabolism of barbiturates and other drugs.

苯巴比妥为呼吸抑制剂，呼吸抑制程度取决于剂量。催眠剂量苯巴比妥产生的呼吸抑制效果类似于生理睡眠状态，血压、心率略有降低。动物实验表明，苯巴比妥导致子宫、输尿管、膀胱张力和收缩力降低。然而，镇静-催眠剂量无法达到人体产生这种效果所需的药物浓度。

苯巴比妥不损害肝脏的功能，但可诱导肝微粒体酶，从而增加或改变巴比妥类和其他药物的代谢。

Drug Abuse and Dependence

药物依赖

Tolerance, psychological dependence, and physical dependence may occur especially following prolonged use of high doses of phenobarbital. As tolerance to phenobarbital develops, the amount needed to maintain the same level of intoxication increases; tolerance to a fatal dosage, however, does not increase more than two-fold. As this occurs, the margin between an intoxicating dosage and fatal dosage becomes smaller.

苯巴比妥可导致耐受性、精神性和身体性依赖，尤其是长期大剂量服用。随着苯巴比妥耐药性的增强，保持相同宿醉状态所需的药量也随之增加，但是，对致死剂量耐受性的增加却不会超过两倍。此时，中毒剂量和致死剂量之间的差距缩短。

Symptoms of acute intoxication with phenobarbital include unsteady gait, slurred speech, and sustained nystagmus. Mental signs of chronic intoxication include confusion, poor judgment, irritability, insomnia, and somatic complaints.

苯巴比妥急性中毒症状包括步态不稳、言语不清和持续眼震。慢性中毒心理症状包括意识混乱、判断力差、易怒、失眠及躯体不适。

Symptoms of phenobarbital dependence are similar to those of chronic alcoholism. If an individual appears to be intoxicated with alcohol to a degree that is radically disproportionate to the amount of alcohol in his or her blood, the use of barbiturates should be suspected. The lethal dose of a barbiturate is far less if alcohol is also ingested. The symptoms of phenobarbital withdrawal can be severe and may cause death. Minor withdrawal symptoms may appear 8 to 12 hours after the last dose of phenobarbital. These symptoms usually appear in the following order: anxiety, muscle twitching, tremor of hands and fingers, progressive weakness, dizziness, distortion in visual perception, nausea, vomiting, insomnia, and orthostatic hypotension. Major withdrawal symptoms (convulsions and delirium) may occur within 16 hours and last up to 5 days after abrupt cessation of this drug. Intensity of withdrawal symptoms gradually declines over a period of approximately 15 days. Individuals susceptible to phenobarbital abuse and dependence include alcoholics and opiate abusers, as well as other sedative- hypnotic and amphetamine abusers.

苯巴比妥依赖症状与慢性酒精中毒症状相似。如果病人出现酒精中毒症状，血液酒精浓度异常，就应怀疑使用苯巴比妥。饮酒者的苯巴比妥致死量更小。苯巴比妥戒断症状会很严重，可能引起死亡，轻微的戒断症状可能在末次剂量8－12小时后出现，症状出现顺序通常为：焦虑、肌肉颤搐、手及手指发颤、进行性无力、头昏、视觉失真、恶心、呕吐、失眠和体位性低血压。16小时内出现重大戒断症状（抽搐和谵妄），从突然停药起可持续5天。在大约15天左右的时间里，戒断症状强度逐渐减弱。苯巴比妥滥用和依赖易感个体包括滥用酒精和鸦片及其他镇静-催眠、苯丙胺药物者。

Drug dependence on phenobarbital arises from repeated administration of the barbiturate or an agent with barbiturate-like effect on a continuous basis, generally in amounts exceeding therapeutic dose levels. The characteristics of drug dependence on phenobarbital include: (a) a strong desire or need to continue taking the drug, (b) a tendency to increase the dose, (c) a psychic dependence on the effects of the drug related to subjective and individual appreciation of those effects, and (d) a physical dependence on the effects of the drug requiring its presence for maintenance of homeostasis and resulting in a definite, characteristic, and self-limited abstinence syndrome when the drug is withdrawn.

苯巴比妥药物依赖缘于巴比妥类或具有巴比妥样效用的制剂的连续重复使用，其剂量通常都超出治疗量。苯巴比妥药物依赖特征：1、有继续服用的强烈愿望或需要；2、增加剂量趋势明显；3、对药物效果的精神性依赖与个体对这些效果的主观认识有关；和4、对药物效果的躯体依赖要求通过药物来保持体内稳定，一旦停药，就会导致明显、特异和自限性戒断综合症。