Phenobarbital , also known as phenobarbitone or phenobarb , is a drug recommended by the World Health Organization for the treatment of certain types of epilepsy in developing countries.. In developed countries it is commonly used to treat seizures in young children, while other drugs are commonly used in older children and adults. It can be used intravenously, injected into muscle, or drunk. Injection forms can be used to treat epileptic status. Phenobarbital is sometimes used to treat sleeping difficulties, anxiety, and drug withdrawal and to aid surgery. It usually starts working within five minutes when used intravenously and half an hour when given orally. The effect lasted for four hours and two days.
Side effects include decreased level of consciousness as the effort to breathe decreases. There are concerns about abuse and withdrawal after long-term use. It can also increase the risk of suicide. This is the category of pregnancy B or D (depending on how it is taken) in the United States and Category D in Australia, which means that it can cause harm when taken by a pregnant woman. If used during breastfeeding can cause sleepiness in infants. Lower doses are recommended in those with poor liver or kidney function, as well as parents. Phenobarbital is a barbiturate that works by increasing the activity of GABA inhibitory neurotransmitters.
Phenobarbital was discovered in 1912 and is the most commonly used anti-seizure drug. It's in the List of Essential Medicines of the World Health Organization, the most effective and safe drugs needed in the health system. This is the cheapest anti-seizure drug about $ 5 USD a year in developing countries. But access may be difficult because some countries mark it as a controlled drug.
Video Phenobarbital
Medical use
Phenobarbital is used in the treatment of all types of seizures unless there are no seizures. It is no less effective in seizure control than phenytoin, but phenobarbital is not well tolerated. Phenobarbital may provide a clinical advantage over carbamazepine to treat partial onset seizures. Carbamazepine may provide a clinical advantage over phenobarbital for generalized tonic-clonic seizures. A very long active half-life means that for some people the dosage should not be taken daily, especially once the dose has stabilized for several weeks or months, and the seizures are effectively controlled.
First-line drugs for the treatment of epileptic status are benzodiazepines, such as lorazepam or diazepam. If this fails, then phenytoin may be used, with phenobarbital being an alternative in the US, but using only the third line in the UK. Failing that, the only treatment is anesthesia in intensive care. The World Health Organization provides phenobarbital as a first-line recommendation in the developing world and is usually used there.
Phenobarbital is the first-line choice for the treatment of neonatal seizures. Worries that a neonatal seizure in themselves can be dangerous makes most doctors treat them aggressively. However, there is no reliable evidence to support this approach.
Phenobarbital is sometimes used for alcohol detoxification and benzodiazepine detoxification for sedative and anticonvulsant properties. The benzodiazepines chlordiazepoxide (Librium) and oxazepam (Serax) have replaced phenobarbital for detoxification.
While phenobarbital has been used for insomnia, such use is not recommended because of the risk of addiction and affecting the other side.
Other uses
The phenobarbital properties can effectively reduce the tremors and seizures associated with the sudden withdrawal of benzodiazepines.
Phenobarbital is a cytochrome P450 inducer, and is used to reduce the toxicity of some drugs.
Phenobarbital is sometimes prescribed in low doses to help bilirubin conjugate in people with Crigler-Najjar syndrome (Type II), or in patients with Gilbert's syndrome.
Phenobarbital can also be used to relieve symptoms of cyclic vomiting syndrome.
Phenobarbital is a common agent used in purity and high doses for deadly injection of "death row" criminals.
In infants with suspected neonatal biliary atresia, phenobarbital is used in preparation for hepatobiliary studies that differentiate atresia from hepatitis or cholestasis.
Phenobarbital is used as a secondary agent to treat newborns with neonatal abstinent syndrome, a condition of withdrawal symptoms from exposure to opioid drugs in the uterus.
In large doses, phenobarbital is prescribed for severely ill patients to enable them to end their lives through physician-assisted suicide.
Like other barbiturates, phenobarbital can be used in recreation, but these are reported relatively rarely.
Maps Phenobarbital
Side effects
Sedation and hypnosis are the main side effects (sometimes, they are also the desired effect) of phenobarbital. The effects of the central nervous system, such as dizziness, nystagmus and ataxia, are also common. In elderly patients, it can cause excitement and confusion, while in children, may result in paradox hyperactivity. Another very rare side effect is amelogenesis imperfecta.
Phenobarbital is a cytochrome P450 liver enzyme inducer. This binds to the receptor transcription factors that activate the transcription of cytochrome P450, thus increasing the amount and thus its activity. Due to this higher amount of CYP450, drugs metabolized by the CYP450 enzyme system will have decreased effectiveness. This is because the increased activity of CYP450 improves drug cleansing, reducing the amount of time they have to work.
Caution should be used with children. Among anticonvulsant drugs, behavioral disorders most commonly occur with clonazepam and phenobarbital.
Contraindications
Acute intermittent porphyria, hypersensitivity to any barbiturates, previous dependence on barbiturates, severe respiratory insufficiency and hyperkinesia in children are contraindicated for phenobarbital use.
Overdose
Phenobarbital causes depression in the system of the body, especially the central and peripheral nervous system. Thus, the main characteristic of phenobarbital overdose is "to slow down" body functions, including decreased awareness (even coma), bradycardia, bradyphnea, hypothermia, and hypotension (in large overdoses). Overdose can also cause pulmonary edema and acute kidney failure as a result of shock, and can lead to death.
A person's electroencephalogram with phenobarbital overdose can show a significant reduction in electrical activity, to the point of imitating brain death. It is caused by deep depression in the central nervous system, and is usually reversible.
Phenobarbital overdose treatment is supportive, and consists primarily of maintenance of airway patency (via endotracheal intubation and mechanical ventilation), correction of bradycardia and hypotension (with intravenous fluids and vasopressors, if necessary) and removal of as much of the drug from the body as possible. Depending on how much time has elapsed since drug consumption, this can be achieved through gastric lavage (gastric pump) or active charcoal use. Hemodialysis is effective in removing phenobarbital from the body, and can reduce half-lives by up to 90%. There is no specific antidote for barbituric poisoning available.
British vet Donald Sinclair, better known as "Siegfried Farnon" in James Herriot's All Creatures Great and Small, committed suicide at the age of 84 by injecting himself with a phenobarbital overdose. Activist Abbie Hoffman also committed suicide by consuming phenobarbital, combined with alcohol, on April 12, 1989; a residue of about 150 pills was found in his body during autopsy. Also died of an overdose in 1996 was actress/model Margaux Hemingway. Japanese officers on the German U-234 submarine committed suicide with phenobarbital while German crew members were on their way to the US to surrender (but before Japan surrendered).
39 members of the Heaven Gate UFO religious group committed mass suicide in March 1997 by drinking fatal doses of phenobarbital and vodka "and then lying to death" hoping to enter a foreign spacecraft.
Action mechanism
Through its action on GABA receptors, phenobarbital increases the flux of chloride ions into the neurons that decrease stimulation. The direct blockade of stimulated glutamate signaling is also believed to contribute to the hypnotic/anticonvulsant effects observed with barbiturates.
Pharmacokinetics
Phenobarbital has an oral bioavailability of about 90%. Peak plasma concentrations reach eight to 12 hours after oral administration. This is one of the longest barbiturates in action - it stays in the body for a very long time (two to seven days) and has very low protein bonds (20 to 45%). Phenobarbital is metabolized by the liver, mainly through hydroxylation and glucuronidation, and induces many isozymes from the P450 cytochrome. Cytochrome P450 2B6 (CYP2B6) is specifically induced by phenobarbital through the CAR/RXR nuclear receptor heterodimer. It is excreted mainly by the kidneys.
Veterinary use
Phenobarbital is one of the earliest alternative medicines for treating epilepsy in dogs, and is the earliest alternative medicine for treating epilepsy in cats.
It is also used to treat cat hyperesthesia syndrome in cats when anti-personnel therapy proves ineffective.
It may also be used to treat seizures in horses when benzodiazepine treatment fails or is contraindicated.
History
The first barbiturate drug, barbital, was synthesized in 1902 by the German chemists Emil Fischer and Joseph von Mering and was first marketed as Veronal by Friedr. Bayer and comp. In 1904, several related drugs, including phenobarbital, were synthesized by Fischer. Phenobarbital was brought into the market in 1912 by the Bayer drug company as the Luminal brand. It remained the commonly prescribed sedative and hypnotic until the introduction of benzodiazepines in the 1960s.
Phenobarbital's sleeping pills, a known sedative and hypnosis in 1912, but not yet known to be an effective anticonvulsant. The young doctor Alfred Hauptmann gave it to his epilepsy patients as a sedative and found that their seizures were susceptible to the drug. Hauptmann conducted a careful study of his patients over a long period. Most of these patients use the only effective drug available then, bromide, which has poor side effects and limited efficacy. In phenobarbital, their epilepsy is much better: The worst patients suffer fewer and lighter seizures and some patients become seizure-free. In addition, they are increasing physically and mentally as bromides have been removed from their regimen. Patients who have been instituted because of the severity of their epilepsy can leave and, in some cases, resume work. Hauptmann dismissed concerns that his effectiveness in stopping the seizures can cause patients to suffer from accumulation that must be "discarded". As expected, withdrawal of the drug causes an increase in seizure frequency - it is not a drug. The drug was quickly adopted as the first effective anticonvulsant, although World War I delayed its introduction in the US.
In 1939, a German family asked Adolf Hitler to have their handicapped son killed, a five-month-old boy was given a lethal dose of Luminal after Hitler sent his own doctor to examine him. A few days later 15 psychiatrists were summoned to Hitler's Chancellor and directed to start a secret euthanasia program. In 1940, at a clinic in Ansbach, Germany, about 50 intellectually disabled children were injected with Luminal and killed in that way. A plaque was erected in their memory in 1988 at a local hospital in Feuchtwanger, Strasse 38, although newer plaques do not mention that patients were killed using barbiturates on site. Luminal was used in the euthanasia program of Nazi children until at least 1943.
Phenobarbital is used to treat neonatal jaundice by increasing liver metabolism and thereby decreasing bilirubin levels. In the 1950s, phototherapy was discovered, and became standard treatment.
Phenobarbital is used for more than 25 years as prophylaxis in the treatment of febrile seizures. Although treatment is effective in preventing recurrent febrile seizures, it has no positive effect on patient outcomes or the risk of developing epilepsy. Treatment of simple febrile seizures with anticonvulsant prophylaxis is no longer recommended.
Name
Phenobarbital is INN and phenobarbitone is a BAN.
Synthesis
The barbiturate drug is obtained by a condensation reaction between the derivatives of diethyl malonate and urea in the presence of a strong base. Phenobarbital synthesis uses this general approach as well but differs in the way in which this malonate derivative is obtained. The reason for this difference is due to the fact that aryl halides typically do not undergo nucleophilic substitution in the synthesis of the Malison ester in the same way as aliphatic or halocarbonic organosulfates. To address this lack of chemical reactivity, two dominant synthetic approaches using benzyl cyanide as starting material have been developed:
The first of these methods consists of the Pinner reaction of benzyl cyanide, giving the phenylacetic acid ethyl ester. Furthermore, this ester undergoes a cross-Claisen condensation using diethyl oxalate, administering diethyl ester of phenylocyutaric acid. After heating these intermediates easily lose carbon monoxide, yielding diethyl phenylmallonate. Synthesis of malonik ester using ethyl bromide leads to ester formation? -filil -? - ethylmalonik. Eventually the condensation reaction with urea gives phenobarbital.
The second approach uses diethyl carbonate in the presence of a strong base to give esters? -phenylcyanoacetic. The alkylation of this ester using ethyl bromide results through a nitrile anion intermediate to give the ester? -phenyl-? - Ethyl esterenaacetate. The product is then converted again into 4-iminoderivatives after condensation with urea. Eventually the acid hydrolysis of the resulting product produces phenobarbital.
Rules
Levels of regulation include Schedule IV Non-Narcotic (depressant) (ACSCN 2285) in the United States under the Textured Texture Act 1970 - but along with some other barbiturates and at least one benzodiazepine, and codeine, dionin or dihydrochlorine at low concentrations, as well has a free prescription and has at least one known OTC combination drug now more strictly regulated for ephedrine content. Phenobarbitone/phenobarbital is present in subterapeutic doses added to effective doses to counter overstimulation and possible seizures of a deliberate overdose of ephedrine tablets for asthma, now set at federal and state levels as: OTC drugs are limited and/or supervised precursors, prescription drugs which is not supervised but supervised/restricted & amp; overseeing precursors, restricted controls & amps prescribed II, III, IV. overseeing precursors, or Schedule V (which also has possible regulations in districts/parishes, cities, towns or districts as well as the fact that pharmacists may choose not to sell it, and photo ID and signing lists are required) narcotics limited/watched OTC.
References
External links
- US. National Drug Library: Drug Information Portal - Phenobarbital
Source of the article : Wikipedia
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