(2)少数患者可出现皮疹、药热、剥脱性皮炎等过敏反应。
Phenobarbital
Phenobarbital, also known as phenobarbitone or phenobarb, is a medication recommended by the World Health Organization for the treatment of certain types of epilepsy in developing countries.[4] In the developed world, it is commonly used to treat seizures in young children,[5]while other medications are generally used in older children and adults.[6] It may be used intravenously, injected into a muscle, or taken by mouth.[2] The injectable form may be used to treat status epilepticus.[2] Phenobarbital is occasionally used to treat trouble sleeping, anxiety, and drug withdrawal and to help with surgery.[2] It usually begins working within five minutes when used intravenously and half an hour when administered orally.[2] Its effects last for between four hours and two days.[2][3]
Side effects include a decreased level of consciousness along with a decreased effort to breathe.[2] There is concern about both abuse and withdrawal following long-term use.[2] It may also increase the risk of suicide.[2] It is pregnancy category B or D (depending on how it is taken) in the United States and category D in Australia, meaning that it may cause harm when taken by pregnant women.[2][7] If used during breastfeeding it may result in drowsiness in the baby.[8] A lower dose is recommended in those with poor liver or kidney function, as well as elderly people.[2] Phenobarbital is a barbiturate that works by increasing the activity of the inhibitory neurotransmitter GABA.[2]
Phenobarbital was discovered in 1912 and is the oldest still commonly used anti-seizure medication.[9][10] It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system.[11] It is the least expensive anti-seizure medication at around US$5 a year in the developing world.[12] Access, however, may be difficult as some countries label it as a controlled drug.[12]
Medical uses
Phenobarbital is used in the treatment of all types of seizures, except absence seizures.[13][14] It is no less effective at seizure control than phenytoin, however phenobarbital is not as well tolerated.[15] Phenobarbital may provide a clinical advantage over carbamazepine for treating partial onset seizures. Carbamazepine may provide a clinical advantage over phenobarbital for generalized onset tonic-clonic seizures.[16] Its very long active half-life (53–118 hours) means for some people doses do not have to be taken every day, particularly once the dose has been stabilized over a period of several weeks or months, and seizures are effectively controlled.[citation needed]
The first-line drugs for treatment of status epilepticus are benzodiazepines, such as lorazepam or diazepam. If these fail, then phenytoin may be used, with phenobarbital being an alternative in the US, but used only third-line in the UK.[17] Failing that, the only treatment is anaesthesia in intensive care.[14][18] The World Health Organization (WHO) gives phenobarbital a first-line recommendation in the developing world and it is commonly used there.[4][19]
Phenobarbital is the first-line choice for the treatment of neonatal seizures.[20][21][22]Concerns that neonatal seizures in themselves could be harmful make most physicians treat them aggressively. No reliable evidence, though, supports this approach.[23]
Phenobarbital is sometimes used for alcohol detoxification and benzodiazepine detoxification for its sedative and anti-convulsant properties. The benzodiazepines chlordiazepoxide (Librium) and oxazepam (Serax) have largely replaced phenobarbital for detoxification.[24]
While phenobarbital has been used for insomnia, such use is not recommended due to the risk of addiction and other side affects.[25]
Other uses
Phenobarbital properties can effectively reduce tremors and seizures associated with abrupt withdrawal from benzodiazepines.
Phenobarbital is a cytochrome P450 inducer, and is used to reduce the toxicity of some drugs.
Phenobarbital is occasionally prescribed in low doses to aid in the conjugation of bilirubin in people with Crigler-Najjar syndrome (Type II),[26] or in patients with Gilbert syndrome.[citation needed]
Phenobarbital can also be used to relieve cyclic vomiting syndrome symptoms.
Phenobarbital is a commonly used agent in high purity and dosage for lethal injection of "death row" criminals.
In infants suspected of neonatal biliary atresia, phenobarbital is used in preparation for a 99mTc-IDA hepatobiliary (HIDA; hepatobiliary 99mTc-iminodiacetic acid) study that differentiates atresia from hepatitis or cholestasis.
Phenobarbital is used as a secondary agent to treat newborns with neonatal abstinence syndrome, a condition of withdrawal symptoms from exposure to opioid drugs in utero.
In massive doses, phenobarbital is prescribed to terminally ill patients to allow them to end their life through physician-assisted suicide.[27]
Like other barbiturates, phenobarbital can be used recreationally,[28] but this is reported to be relatively infrequent.[29]
Contraindications
Acute intermittent porphyria, hypersensitivity to any barbiturate, prior dependence on barbiturates, severe respiratory insufficiency (as with chronic obstructive pulmonary disease), severe liver failure, pregnancy, and breastfeeding are contraindications for phenobarbital use.[30]
Overdose
Phenobarbital causes a depression of the body's systems, mainly the central and peripheral nervous systems. Thus, the main characteristic of phenobarbital overdose is a "slowing" of bodily functions, including decreased consciousness (even coma), bradycardia, bradypnea, hypothermia, and hypotension (in massive overdoses). Overdose may also lead to pulmonary edema and acute renal failure as a result of shock, and can result in death.
The electroencephalogram (EEG) of a person with phenobarbital overdose may show a marked decrease in electrical activity, to the point of mimicking brain death. This is due to profound depression of the central nervous system, and is usually reversible.[33]
Treatment of phenobarbital overdose is supportive, and mainly consists of the maintenance of airway patency (through endotracheal intubationand mechanical ventilation), correction of bradycardia and hypotension (with intravenous fluids and vasopressors, if necessary), and removal of as much drug as possible from the body. Depending on how much time has elapsed since ingestion of the drug, this may be accomplished through gastric lavage (stomach pumping) or use of activated charcoal. Hemodialysis is effective in removing phenobarbital from the body, and may reduce its half-life by up to 90%.[33] No specific antidote for barbiturate poisoning is available.[34]
British veterinarian Donald Sinclair, better known as the character Siegfried Farnon in the "All Creatures Great and Small" book series by James Herriot, committed suicide at the age of 84 by injecting himself with an overdose of phenobarbital. Activist Abbie Hoffman also committed suicide by consuming phenobarbital, combined with alcohol, on April 12, 1989; the residue of around 150 pills was found in his body at autopsy.[35] Also dying from an overdose in 1996 was actress/model Margaux Hemingway. The Japanese officers aboard the German submarine U-234 killed themselves with phenobarbital while the German crew members were on their way to the US to surrender (but before Japan had surrendered).
Thirty-nine members of the Heaven's Gate UFO religious group committed mass suicide in March 1997 by drinking a lethal dose of phenobarbital and vodka "and then lay down to die" hoping to enter an alien spacecraft.[36]
Mechanism of action
Through its action on GABAA receptors, phenobarbital increases the flow of chloride ions into the neuron which decreases the excitability of the post-synaptic neuron. Hyperpolarizing this post-synaptic membrane leads to a decrease in the general excitatory aspects of the post-synaptic neuron. By making it harder to depolarize the neuron, the threshold for the action potential of the post-synaptic neuron will be increased. Phenobarbital stimulates GABA to accomplish this hyperpolarization.[37] Direct blockade of excitatory glutamate signaling is also believed to contribute to the hypnotic/anticonvulsant effect that is observed with the barbiturates.[38]
