ブタバルビタール

log Kow = 1.65

1.5

WHITE POWDER; PRACTICALLY INSOL IN BENZENE & ABS ETHER /SODIUM SALT/

1.39e+00 g/L

Breast Feeding; Lactation; Milk, Human; Barbiturates; Hypnotics and Sedatives; GABA Modulators

Pharmaceuticals

165-168 °C

166.5 °C

Danger

H301 (100%): Toxic if swallowed [Danger Acute toxicity, oral]

P264, P270, P301+P316, P321, P330, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 43 reports by companies from 1 notifications to the ECHA C&L Inventory.

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, including butabarbital sodium, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Butabarbital sodium/

Butabarbital sodium is a chemical derivative of barbituric acid, named in section 502(d) of the Federal Food, Drug, and Cosmetic Act, and is hereby designated as habit forming. /Butabarbital sodium/

Schedule III shall consist of the drugs and other substances, by whatever official name, common or usual name, chemical name, or brand name designated, listed in this section. Each drug or substance has been assigned the DEA Controlled Substances Code Number set forth opposite it. ... Depressants: Unless specifically excepted or unless listed in another schedule, any material, compound, mixture, or preparation which contains any quantity of the following substances having a depressant effect on the central nervous system: Any substance which contains any quantity of a derivative of barbituric acid or any salt thereof. DEA Code Number: 2100. /Derivatives of barbituric acid or any salt thereof/

Water spray, dry chemical, carbon dioxide, or foam as appropriate for surrounding fire and materials.

As with all fires, evacuate personnel to a safe area. Firefighters should use self-contained breathing equipment and protective clothing.

Store in tight container as defined in the USP-NF. This material should be handled and stored per label instructions to ensure product integrity.

Store at controlled room temperature 20-25 °C (68-77 °F). Dispense in a tight container.

SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.

SRP: At the time of review, regulatory criteria for small quantity disposal are subject to significant revision, however, household quantities of waste pharmaceuticals may be managed as follows: Mix with wet cat litter or coffee grounds, double bag in plastic, discard in trash.

This material is assumed to be combustible. As with all dry powders, it is advisable to ground mechanical equipment in contact with dry material to dissipate the potential buildup of static electricity.

As a general rule, when handling USP Reference Standards avoid all contact and inhalation of dust, mists, and/or vapors associated with the material. Wash thoroughly after handling.

/Use/ safety goggles and protect exposed skin.

Engineering controls such as exhaust ventilation are recommended.

Use a NIOSH-approved respirator, if it is determined to be necessary by an industrial hygiene survey involving air monitoring. In the event that a respirator is not required, an approved dust mask should be used.

Concurrent administration of disulfiram with barbiturates may result in inhibition of metabolism of the barbiturates and an increased incidence of barbiturate toxic effects. /Barbiturates/

Concurrent use with barbiturates may result in increased metabolism, leading to decreased serum concentrations and reduced elimination half-lives of carbamazepine or succinimide anticonvulsants because of induction of hepatic microsomal enzyme activity. Monitoring of serum concentrations as a guide to dosage is recommended, especially when carbamazepine or a succinimide anticonvulsant is added to or withdrawn from an existing regimen. /Barbiturates/

Concurrent use with barbiturates, especially phenobarbital, may induce microsomal metabolism to increase formation of alkylating metabolites of cyclophosphamide, thereby reducing the half-life and increasing the leukopenic activity of cyclophosphamide. /Barbiturates/

Concurrent use with barbiturates, especially phenobarbital, may reduce serum disopyramide to ineffective concentrations; therefore, monitoring of its serum concentrations is necessary during concurrent therapy. /Barbiturates/

For more Interactions (Complete) data for Butabarbital (38 total), please visit the HSDB record page.

Butabarbital binds at a distinct binding site associated with a Cl^- ionopore at the GABA_A receptor, increasing the duration of time for which the Cl^- ionopore is open. The post-synaptic inhibitory effect of GABA in the thalamus is, therefore, prolonged. All of these effects are associated with marked decreases in GABA-sensitive neuronal calcium conductance (gCa). The net result of barbiturate action is acute potentiation of inhibitory GABAergic tone. Barbiturates also act through potent (if less well characterized) and direct inhibition of excitatory AMPA-type glutamate receptors, resulting in a profound suppression of glutamatergic neurotransmission.

Signs of overdose include confusion (severe), decrease in or loss of reflexes, drowsiness (severe), fever, irritability (continuing), low body temperature, poor judgment, shortness of breath or slow or troubled breathing, slow heartbeat, slurred speech, staggering, trouble in sleeping, unusual movements of the eyes, weakness (severe).

/SIGNS AND SYMPTOMS/ Symptoms of acute intoxication with barbiturates include unsteady gait, slurred speech, and sustained nystagmus. Mental signs of chronic intoxication include confusion, poor judgment, irritability, insomnia, and somatic complaints. Barbiturate intoxication may be confused with alcoholism, bromide intoxication, and with various neurological disorders.

/SIGNS AND SYMPTOMS/ Acute overdosage with barbiturates is manifested by 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.

/SIGNS AND SYMPTOMS/ In extreme overdose, all electrical activity in the brain may cease, in which case a "flat" EEG normally equated with clinical death cannot be accepted. This effect is fully reversible unless hypoxic damage occurs. Consideration should be given to the possibility of barbiturate intoxication even in situations that appear to involve trauma.

/SIGNS AND SYMPTOMS/ Symptomatology ... Drowsiness is usually first symptom. Transient period of confusion, excitement, delirium, and perhaps hallucinations is not uncommon. Ataxia, vertigo, slurred speech, headache, paresthesias, and subjective visual disturbances. Stupor progressing through deepening states of coma, with inhibition or absence of superficial and deep reflexes. Responses to painful stimuli gradually cease. Babinski toe sign may become positive. Respirations may be rapid and shallow or slow and labored, but min vol (pulmonary ventilation) is always reduced. Mild but progressive cardiovascular collapse, evidence by cyanosis, hypotension, weak rapid pulse, and cold and clammy skin. Circulatory insufficiency may or may not be result of hypoxia from respiratory depression. Transient electrocardiographic changes may be seen ... Pupils ... usually slightly constricted ... They may dilate during terminal asphyxia. Urine formation is slowed or suppressed completely. Body temp ... usually reduced. If fever develops, it usually signals bronchopneumonia but paradoxical hyperpyrexia is recognized as rare complication. Respirations become irregular, sometimes Cheyne-Stokes in character, and eventually cease. Although death is usually due to respiratory arrest, circulatory shock may be proximal cause. Occasionally severe grades of pulmonary edema ... are encountered ... Hypostatic or aspiration pneumonia late in course of illness may prove lethal. Renal shutdown due to circulatory collapse can complicate illness but is rarely irreversible. Among survivors, residual damage is rare, but occasional patient who has suffered prolonged and severe hypoxia during acute phase may exhibit permanent neurological damage. Irregular erythematous cutaneous lesions and bullae containing clear fluid are seen in many patients. Allergic reactions from acquired hypersensitivity are ... asthma, urticaria, angioneurotic edema, dermatitis, fever, delirium, liver necrosis. /Barbiturates/

For more Human Toxicity Excerpts (Complete) data for Butabarbital (6 total), please visit the HSDB record page.

Hypersensitivity reactions to barbiturates include urticaria, angioedema, morbilliform or scarlatiniform rash, fever, serum sickness, erythema multiforme, or Stevens-Johnson syndrome. Hypersensitivity reactions are most likely to occur in patients with asthma, urticaria, or angioedema. Rarely, photosensitivity reactions have been reported. Phenobarbital, metharbital, and mephobarbital appear to cause rashes more frequently than do other barbiturates. Exfoliative dermatitis, which may be accompanied by hepatitis and jaundice, has occurred rarely and has resulted in a few fatalities. Rarely, cutaneous reactions have preceded the development of barbiturate-induced systemic lupus erythematosus. Adverse cutaneous reactions may proceed to an irreversible stage even though the medication has been discontinued, because barbiturates are slowly metabolized and excreted. /Barbiturates General Statement/

Barbiturates may elevate blood ammonia. Animal studies indicate that thiopental impairs the ability of the liver to metabolize ammonia. For this reason, it has been suggested that barbiturate administration be avoided in patients with ammonia intoxication. /Barbiturates/

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/

/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/

/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

Emergency and supportive measures. Protect the airway and assist ventilation if necessary. Treat coma, hypothermia, and hypotension if they occur. /Barbiturates/

For more Antidote and Emergency Treatment (Complete) data for Butabarbital (6 total), please visit the HSDB record page.

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, including butabarbital sodium, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Butabarbital sodium/

Butabarbital sodium is a chemical derivative of barbituric acid, named in section 502(d) of the Federal Food, Drug, and Cosmetic Act, and is hereby designated as habit forming. /Butabarbital sodium/

Schedule III shall consist of the drugs and other substances, by whatever official name, common or usual name, chemical name, or brand name designated, listed in this section. Each drug or substance has been assigned the DEA Controlled Substances Code Number set forth opposite it. ... Depressants: Unless specifically excepted or unless listed in another schedule, any material, compound, mixture, or preparation which contains any quantity of the following substances having a depressant effect on the central nervous system: Any substance which contains any quantity of a derivative of barbituric acid or any salt thereof. DEA Code Number: 2100. /Derivatives of barbituric acid or any salt thereof/

Butabarbital potentiates GABAergic neurons while inhibiting neuronal acetylcholine and glutamate receptors to produce sedation. Butabarbital is an intermediate acting barbiturate with a duration of action of approximately 6-8 hours. The therapeutic index is quite wide as doses vary considerably from patient to patient. Patients should be counselled regarding the risk of worsening insomnia, drowsiness, falls, and complex behaviour while not fully awake.

Barbiturates like butabarbital potentiate GABA-A receptors and inhibit receptors for neuronal acetylcholine, and kainate. GABA-A receptors are predominantly on the post-synaptic membrane, and upon activation, open chloride channels to hyperpolarize the neuron and decreased firing rate. Potentiation of GABAergic neurons produces sedation. Inhibition of neuronal acetylcholine receptors and glutamate receptors of the kainate subtype desensitize their respective neurons, producing sedation.

The exact mechanism(s) by which barbiturates exert their effect on the CNS, has not been fully elucidated. However, it is believed that such effects are related, at least partially, to the drugs' ability to enhance the activity of gamma-aminobutyric acid (GABA), the principal inhibitory neurotransmitter in the CNS, by altering inhibitory synaptic transmissions that are mediated by GABAA receptors. /Barbiturates General Statement/

Although the drugs act throughout the CNS, a site of particular sensitivity is the polysynaptic midbrain reticular formation which is concerned with the arousal mechanism. Barbiturates induce an imbalance in central inhibitory and facilitatory mechanisms influencing the cerebral cortex and the reticular formation. The significance of the effect of barbiturates on neurotransmitters is unclear. It appears that the drugs decrease the excitability of both presynaptic and postsynaptic membranes. It has not been determined which of the various actions of barbiturates at cellular and synaptic levels are responsible for their sedative and hypnotic effects. /Barbiturates General Statement/

Relatively low doses of the barbiturates depress the sensory cortex, decrease motor activity, and produce sedation and drowsiness. In some patients, however, drowsiness may be preceded by a period of transient elation, confusion, euphoria, or excitement, especially after subhypnotic doses of aprobarbital, pentobarbital, or secobarbital. /Barbiturates General Statement/

Larger doses distort judgment, cloud perception, suppress motor activity, and produce drowsiness and sleep. Still larger doses induce anesthesia. Barbiturate-induced sleep differs from physiologic sleep. Barbiturates reduce the rapid eye movement (REM) or dreaming stage of sleep. Stages III and IV sleep are also decreased. Although tolerance develops to the REM-suppressant effects during chronic administration, REM rebound occurs when the drugs are withdrawn, and the patient may experience markedly increased dreaming, nightmares, and/or insomnia. /Barbiturates General Statement/

For more Mechanism of Action (Complete) data for Butabarbital (13 total), please visit the HSDB record page.

Butabarbital has a half life of 100 hours but its duration of action is only 6-8 hours.

The average plasma half-life for butabarbital is 100 hours in the adult.

The elimination half-life of butabarbital was reportedly 34-42 hours in one study; one manufacturer states that the plasma half-life averages 100 hours in adults.

Data regarding the metabolism of butabarbital in humans are not readily available. In dogs, butabarbital undergoes metabolism to a final glucuronide metabolite.

Butabarbital is metabolized in the liver by oxidation of the sec-butyl substituent at C5 to form 5-ethyl-5-(1-methyl-2-carboxyethyl) barbituric acid, an inactive metabolite, which is then excreted in the urine.

Most barbiturates are transformed in body to inactive metabolites. Principal site of biotransformation is liver. /Barbiturates/

Barbiturates are transformed by 4 routes: 1. Oxidation of radical at C5. This is by far most important pathway ... Products are ... polar alcohols, ketones, phenols, or carboxylic acids ... /Barbiturates/

With the exception of the less lipid-soluble aprobarbital and phenobarbital, nearly complete metabolism and/or conjugation of barbiturates in the liver precedes their renal excretion. The oxidation of radicals at C5 is the most important biotransformation responsible for termination of biological activity. Oxidation results in the formation of alcohols, kentones, phenols, or carboxylic acids, which may appear in the urine as such or as glucuronic acid conjugates. In some instances (eg, phenobarbital), N-glucosylation is an important metabolic pathway. Other biotransformations include N-hydroxylation, desulfuration of thiobarbiturates to oxybarbiturates, opening of the barbituric acid ring, and N-dealkylation of N-alkylbarbiturates to active metabolites (eg, mephobarbital to phenobarbital).

Route of Elimination: Barbiturates are metabolized primarily by the hepatic microsomal enzyme system, and most metabolic products are excreted in the urine.

Barbiturates such as butabarbital are predominantly eliminated in the urine. In dogs, 3-5% of the dose is eliminated in the urine as the unchanged parent compound.

Butabarbital sodium tablets and butabarbital sodium oral solution, is the sodium salt of a weak acid. Barbiturates are weak acids that are absorbed and rapidly distributed to all tissues and fluids with high concentrations in the brain, liver, and kidneys. Barbiturates are bound to plasma and tissue proteins. The rate of absorption is increased if it is ingested as a dilute solution or taken on an empty stomach.

Butabarbital sodium is absorbed from the GI tract. Peak plasma concentrations are achieved within 3-4 hours following oral administration of the drug. Plasma butabarbital concentrations of 2-3 ug/mL produce sedation, and plasma concentrations of 25 ug/mL produce sleep in most patients. Plasma butabarbital concentrations of greater than 30 ug/mL may produce coma, and those in excess of 50 ug/mL are potentially lethal.

Approximately 1-2% of an oral dose /of butabarbital/ is excreted unchanged in the urine.

Fluid & tissue specimens collected from 30 subjects at autopsy were assayed for amylobarbitone (amobarbital), butobarbitone (butethal), pentobarbitone (pentobarbital), quinalbarbitone (secobarbital) and the corresponding hydroxylated metabolites by gas liquid chromatography. Where one barbiturate was ingested, an inverse relationship between lipid solubility of the drug and the distribution in fluids and tissues was observed. In most cases the liver, and in the remainder the spleen, contained the highest concn of barbiturate. Bile concn were often in excess of those in the corresponding liver. The metabolites of the 4 sedative barbiturates were usually present in lower amounts than the parent drugs in the fluids and tissues of most subjects but urine often contained much higher concn of metabolites, sometimes exceeding that of the parent drug in the liver. Admin of 2 or more barbiturates together did not appear to affect the distribution and metabolism of the individual drugs.

For more Absorption, Distribution and Excretion (Complete) data for Butabarbital (13 total), please visit the HSDB record page.

... DEA /substance II /controlled substance

THERPEUTIC CATEGORY: Sedative; hypnotic /Butabarbitol sodium/

MEDICATION

Useful for certain applications such as treating severe insomnia and relieving anxiety before surgical procedures;

(1977) No data

(1979) No data

(1975) 2.80 x 10+6 g (Princpl Custms Dists)

(1979) No data

(1977) Probably > 9.08 x 10+5 g

(1979) Probably > 9.08 x 10+5 g

The 5,5-disubstituted barbituric acids are still synthesized by the classical condensation of substituted malonic esters, malonic amides, or cyanoacetic esters with urea, thiourea, guanidine, or dicyanodiamide, followed by the hydrolysis of the resulting imino- or cyanobarbiturate. /5,5-Disubstituted barbituric acids/

Treatment of diethyl malonate with metallic sodium, ethyl bromide, and 1-methylpropyl bromide, followed by heating in an alcoholic solution with sodium and urea.

By treating an alcoholic solution of butabarbital with an equimolar quantity of NaOH and removing the solvent by evaporation. /Na salt/