アモバルビタール

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop.

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 in airtight containers. /Amobarbital sodium/

SMALL SPILLS AND LEAKAGE: Should a spill occur while you are handling this chemical, FIRST REMOVE ALL SOURCES OF IGNITION, then you should dampen the solid spill material with 60-70% ethanol and transfer the dampened material to a suitable container. Use absorbent paper dampened with 60-70% ethanol to pick up any remaining material. Seal the absorbent paper, and any of your clothes, which may be contaminated, in a vapor-tight plastic bag for eventual disposal. Solvent wash all contaminated surfaces with 60-70% ethanol followed by washing with a soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned.

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.

RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with an organic vapor/acid gas cartridge (specific for organic vapors, HCl, acid gas and SO2) with a dust/mist filter. (NTP, 1992)

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.

Use safety glasses or goggles /and/ protect exposed skin.

To determine the effect of human growth hormone (somatropin) on human metabolism, 6 somatropin deficient children were given single oral doses of amobarbital sodium 3-5 mg 3 times/wk. The half-life of amobarbital sodium rose from 13.89 to 22.75 hr, vol of distribution was unchanged, and clearance fell. Results indicate that somatropin slows the metabolism of amobarbital sodium, probably through an effect on hepatic microsomal drug oxidizing system. /Amobarbital sodium/

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/

For more Interactions (Complete) data for Amobarbital (39 total), please visit the HSDB record page.

LC50; Species: Pimephales promelas (Fathead minnow, age 29 days, mean length 15.4 mm, mean weight 0.052 g); Conditions: flow through, 24.8 °C, pH 7.8, hardness 44.4 mg/L CaCO3, alkalinity 51.5 mg/L CaCO3, dissolved oxygen 7.1 mg/L; Concentration: 85.4 mg/L for 96 hr (95% confidence limit: 78.6-92.7 mg/L) /99+% purity/

Because barbiturates are distributed into the milk of nursing women, nursing should be discontinued if nursing infants of barbiturate-treated women exhibit signs of toxicity. /Barbiturates General Statement/

Antibiotic-associated pseudomembranous colitis, caused by toxin-producing clostridia (e.g., C. difficile), has been reported with the use of nearly all anti-infectives, including IV vancomycin, and should be considered in the differential diagnosis of patients who present with diarrhea subsequent to administration of anti-infectives. Pseudomembranous colitis may occur during or following discontinuance of anti-infective therapy and ranges in severity from mild to life-threatening. Mild cases of colitis may respond to discontinuance of the drug alone, but diagnosis and management of moderate to severe cases should include appropriate bacteriologic studies and treatment with fluid, electrolyte, and protein supplementation as indicated. If colitis is moderate to severe and is not relieved by discontinuance of the drug, appropriate anti-infective therapy (e.g., metronidazole) should be administered. Nausea also has been reported in patients receiving vancomycin therapy.

The /barbiturates/ are distributed into milk in concentrations much lower than those in plasma. /Barbiturates General Statement/

Amobarbital (like all barbiturates) works by binding to the GABAA receptor at either the alpha or the beta sub unit. These are binding sites that are distinct from GABA itself and also distinct from the benzodiazepine binding site. Like benzodiazepines, barbiturates potentiate the effect of GABA at this receptor. This GABAA receptor binding decreases input resistance, depresses burst and tonic firing, especially in ventrobasal and intralaminar neurons, while at the same time increasing burst duration and mean conductance at individual chloride channels; this increases both the amplitude and decay time of inhibitory postsynaptic currents. In addition to this GABA-ergic effect, barbiturates also block the AMPA receptor, a subtype of glutamate receptor. Glutamate is the principal excitatory neurotransmitter in the mammalian CNS. Amobarbital also appears to bind neuronal nicotinic acetylcholine receptors.

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/

Daily admin of 600-800 mg of amobarbital ... for approx 8 wk will produce some degree of physical dependence. ... Symptoms of barbiturate dependence are similar to those of chronic alcoholism, but can be more severe than those associated with alcohol or opiate abstinence syndrome & may result in fatalities.

/HUMAN EXPOSURE STUDIES/ Effects on reaction time, rotary pursuit, and weight discrimination have ... been /studied/ with amobarbital sodium in normal volunteers ... Amobarbital /was/ given iv /and/ the tests were administered immediately. ... An increase in reaction time, ... /little or no effect on the/ ability to trace a rotating disc ... /and no effect on/ weight discrimination task /were observed/. /Amobarbital sodium/

/HUMAN EXPOSURE STUDIES/ Eleven right-handed subjects were administered a dichotic listening test to assess cerebral hemispheric dominance, both under a drug-free condition and following systemic injection of the barbiturate, amobarbital. The finding of increased right ear advantage during the drug period reflects increased left cerebral dominance, and suggests that amobarbital may have an asymmetric, pharmacological effect on the two cerebral hemispheres.

For more Human Toxicity Excerpts (Complete) data for Amobarbital (14 total), please visit the HSDB record page.

Drug-Induced Liver Injury Severity and Toxicity (DILIst)

Amobarbital

DILI Negative

Intramuscular; Intravenous, oral

DOI:10.1016/j.drudis.2019.09.022

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Thirty male F344/NRCFCRC rats were injected with 75 mg DENA (dissolved in saline) intraperitoneally at 4 weeks of age. Amobarbital (AB), 500 ppm, was given in the drinking water from week 6 to 78. This group was compared to a N-nitrosodiethylamine only treated group (30 animals). There were no significant differences between the groups in survival, weight gain, or induced tumors. At 52 weeks, when 1/2 of the animals were autopsied, 1/15 amobarbital and N-nitrosodiethylamine treated animals with hepatocellular tumors compared with 2/15 for the N-nitrosodiethylamine alone treated group. At 78 weeks, 8/15 of the amobarbital and N-nitrosodiethylamine treated animals had hepatocellular tumors compared with 10/15 for the N-nitrosodiethylamine alone treated group. There were no increases in any other tumors over the N-nitrosodiethylamine group. Additionally, Amobarbital was tested alone. Twenty-five animals were injected with saline (5 ml/kg body weight) at 4 weeks of age and given 500 ppm amobarbital in the drinking water from 6 to 78 weeks. They were compared to the saline injected only group. There were no effects of amobarbital on survival or body weight for the 78 weeks of the experiment. There were no hepatocellular tumors in the amobarbital or the saline groups at 52 or at 78 weeks. There were no significant differences in the number of tumors at other sites.

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Tumor-promoting abilities of four barbiturates, phenobarbital [(PB) CAS: 50-06-6], amobarbital [(AB) CAS: 57-43-2], barbital sodium [(BB) CAS: 144-02-5], and barbituric acid [(BA) CAS: 67-52-7], on the development of neoplasms in livers and other organs of rats following initiation with N-nitrosodiethylamine [(DENA) CAS: 55-18-5] were compared. Four-week-old F344/NCr male rats were given a single ip injection of 75 mg DENA/kg body weight. Beginning 2 weeks later, they were given either tap water (group 1) or drinking water containing 500 ppm of PB (group 2), the sodium salt of BB (group 3), AB (group 4), or BA (group 5) for the remaining experimental period. Control groups (groups 6-10) received an ip injection of saline alone and 2 weeks later were given either tap water or drinking water containing barbiturates as listed above. Animals were sacrificed at either 52 weeks or 78 weeks. None of the barbiturates altered the growth and survival of animals. PB and BB increased liver weights and significantly enhanced the development of hepatocellular foci and hepatocellular adenomas at 52 weeks and hepatocellular foci, hepatocellular adenomas, and trabecular carcinomas at 78 weeks in DENA-treated rats. No such enhancing effects were observed with AB or BA. PB or BB did not significantly enhance the incidence of nonhepatic tumors at 52 weeks. However, at 78 weeks BB significantly enhanced the development of renal tubular adenomas and carcinomas, while PB enhanced the development of thyroid follicular cell neoplasms in DENA-treated rats. These results clearly showed that barbiturates exhibited structure-promoting activity relationships and that their promoting abilities were not restricted to liver alone. Substitution of both hydrogen atoms at the C-5 position of the pyrimidine ring by alkyl or aryl groups appears to be essential but not sufficient for tumor-promoting activity of barbiturates.

Geriatric patients may react to usual doses of barbiturates with excitement, confusion, or depression. Many patients experience increased dreaming, nightmares, or increased insomnia when hypnotic doses of barbiturates are discontinued. /Barbiturates General Statement/

Because barbiturates are distributed into the milk of nursing women, nursing should be discontinued if nursing infants of barbiturate-treated women exhibit signs of toxicity. /Barbiturates General Statement/

Phenobarbital frequently produces paradoxical excitement and hyperactivity in children or exacerbates existing hyperactivity. /Barbiturates General Statement/

/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 Amobarbital (6 total), please visit the HSDB record page.

Schedule II 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 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, including its salts, isomers, and salts of isomers whenever the existence of such salts, isomers, and salts of isomers is possible within the specific chemical designation: Amobarbital. DEA Code Number: 2125.

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 compound, mixture or preparation containing amobarbital or any salt thereof and one or more other active medicinal ingredients which are not listed in any schedule.. DEA Code Number: 2126.

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 suppository dosage form containing amobarbital or any salt of any of these drugs and approved by the Food and Drug Administration for marketing only as a suppository. DEA Code Number: 2126.

... DEA /schedule III /controlled substance

... DEA /schedule II /controlled substance

THERAPEUTIC CATEGORY: Sedative; hypnotic

THERAPEUTIC CATEGORY (VETERINARY): Sedative; hypnotic

For more Uses (Complete) data for Amobarbital (6 total), please visit the HSDB record page.

A typical method starts with monochloroacetic acid, which is treated with sodium cyanide to form cyanoacetic acid; the latter is reacted with hydrochloric acid in the presence of alcohol, yielding the diethyl ester of malonic acid. This ester, in absolute alcohol solution, is treated with the theoretical quantity of metallic sodium to replace one hydrogen of the CH2 group, then a slight excess of the theoretical amount of an ethylating agent, such as ethyl bromide, is added. The second hydrogen is replaced similarly, using isopentyl bromide as the alkylating agent. The diethyl ester of ethyl isopentyl malonic acid thus obtained is heated in an alcoholic solution, in the presence of sodium, with urea. Sodium amobarbital is formed, from which amobarbital is liberated with HCl. The alkylation of the CH2 group of the malonic ester ... may be done in two stages, introducing one alkyl group at a time.

By reacting amobarbital with a solution containing a chemically equivalent quantity of sodium hydroxide or sodium carbonate, evaporating to dryness, and crystallizing the residue from a solution in a suitable solvent such as alcohol. /Amobarbital sodium/

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/

Amobarbital Sodium preparations: (AHFS, 2009):

Amsebarb, amytal sodium, barbamyl, dorminal, inmetal /Amobarbital sodium/

Grade: USP