Secobarbital

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 20 - 25 deg C (68 - 77 deg F). Dispense in a tight container.

Store in airtight containers

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 glasses or 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.

Although barbiturates compete with other weak acids for binding to plasma albumin, the only clinically important displacement is that of thyroxine. /Hypnotics & sedatives/

Therapeutic effects of acetaminophen may be decreased when the medication is used concurrently in patients receiving chronic barbiturate therapy because of increased metabolism resulting from induction of hepatic microsomal enzymes; risk of hepatotoxicity with single toxic doses or prolonged use of high doses of acetaminophen may be increased in alcoholics or in patients regularly using hepatic enzyme inducers such as barbiturates. /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 Secobarbital (40 total), please visit the HSDB record page.

Secobarbital 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.

/HUMAN EXPOSURE STUDIES/ ...Thirty healthy volunteers who gave valid written consent were studied. Secobarbital 2.0 mg/kg intravenously caused a significant (P < .05) decrease in arterial oxygen pressure (PaO2), peaking at 10 minutes (n = 10; mean age, 23.4 years). Morphine, 0.2 mg/kg intravenously also caused a significant decrease in PaO2 at 5 minutes (n = 10; mean age, 26.3 years). The combination of the same doses of morphine and secobarbital caused a significantly (P < .01) greater decrease in PaO2 at 5 and 10 minutes than the sole administration of either drug (n = 10; mean age, 23.5 years). Arterial oxygen pressure remained significantly (P < .05) reduced for 30 minutes. Although the PaCO2 increases after secobarbital and morphine did not reach statistical significance, their combination caused a significant (P < .05) increase in PaCO2. Both secobarbital and morphine alone caused significant (P < .05) decrease in pHa at 30 minutes. Their combination caused a significant (P < .01) reduction in pHa from 5 minutes until 60 minutes. In conclusion, both secobarbital and morphine alone caused ventilatory depression. The duration of ventilatory depression was greater with the intravenous combination than with either drug alone.

/HUMAN EXPOSURE STUDIES/ This study examined the effects of secobarbital on human aggressive responding in a controlled laboratory setting. Sixty minutes prior to experimental sessions, male subjects were administered either placebo or 50, 100 or 200 mg per 70 kg of body weight doses of secobarbital double-blind. During these sessions, subjects could press a button to accumulate points exchangeable for money (non-aggressive response) or press another button ostensibly to subtract points from a fictitious person (aggressive response). Aggressive responding was occasioned by subtracting points from the subject. Subjects were instructed that points were subtracted by another person. Aggressive responding was maintained by contingent presentation of periods free of point subtractions, ie, provocations. Acute secobarbital administration produced dose-dependent decreases in non-aggressive responding, and increases in aggressive responding.

/SIGNS AND SYMPTOMS/ Symptoms of oral overdose may occur within 15 minutes and begin with central nervous system depression, underventilation, hypotension, and hypothermia, which may progress to pulmonary edema and death. Hemorrhagic blisters may develop, especially at pressure points.

/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 as indicative of brain death. 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.

For more Human Toxicity Excerpts (Complete) data for Secobarbital (13 total), please visit the HSDB record page.

Drug-Induced Liver Injury Severity and Toxicity (DILIst)

secobarbital

DILI Negative

Oral

DOI:10.1016/j.drudis.2019.09.022

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ To test predictions that barbiturates which are long-acting sedatives and/or strong inducers of CYP2B-mediated monooxygenase activities would be effective promoters of hepatocarcinogenesis, a series of clinically-useful barbiturates and structural analogs were tested for ability to promote hepatocellular carcinogenesis in male F344/NCr rats initiated with N-nitrosodiethylamine and for efficacy as inducers of CYP2B activity in non-initiated rats of the same sex and strain. The barbiturates were administered in the diet at concentrations equimolar to 500 p.p.m. of the known liver tumor promoter phenobarbital, which served as the positive control for this study. Phenobarbital, which has the longest duration of sedative action of this series of compounds, caused the greatest induction of CYP2B activity, and displayed strong liver tumor promoting effects. Allobarbital and aprobarbital, two intermediate-duration sedatives, were found to promote hepatocarcinogenesis, with allobarbital proving to be as effective as phenobarbital in this respect and aprobarbital being somewhat weaker as a promoter. These intermediate-duration sedatives were each relatively weak CYP2B-type inducers, causing approximately 25% of the induction displayed by phenobarbital. The nonsedatives, 5-phenyl- and 5-ethyl-barbituric acids, were essentially inactive as CYP2B-type inducers and were also found to be relatively inactive as promoters of hepatocarcinogenesis. Of the shorter-duration sedatives, pentobarbital was found to promote, and was relatively effective as a CYP2B-type inducer, while secobarbital showed little or no promoting activity and was less effective as an inducer of CYP2B activities. Pentobarbital thus proved an important exception to /the/ hypothesis that only long-acting sedative barbiturates would promote hepatocarcinogenesis. ...

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Phenobarbital sodium is carcinogenic in mice and rats after lifetime administration. In mice, it produced benign and malignant liver cell tumors. In rats, benign liver cell tumors were observed very late in life.

/LABORATORY ANIMALS: Acute Exposure/ Male Sprague-Dawley rats were injected with either a single subcutaneous dose of 75 mg of secobarbital, or once daily injections of 20 mg of secobarbital for 7 days. Plasma was collected prior to treatment and 18 hours later (75 mg) or 8 and 15 days later (20 mg). Plasma was analyzed for the platelet count (PLT), prothrombin time (PT), fibrinogen (FIB), and coagulation factor activities for factors II, V, VII, IX, and X. Treatment with a single subcutaneous injection of 75 mg of secobarbital caused statistically significant alterations in every clotting activity measured whereas 7 days of treatment with 20 mg once daily resulted in only 2 clotting factors being abnormal. These two factors returned to pretreatment levels following 7 days of withdrawal of secobarbital. The data indicates that a single larger dose of secobarbital is more influential on hepatic synthesized clotting factor activity than is longer treatment with a lesser dose.

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/

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/

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

Parenteral secobarbital sodium should be used with caution in pregnant women with toxemia or history of bleeding. Parenteral admin of the drug is contraindicated if delivery is expected at a time when the effect of the drug would be maximal; fetal immaturity is relative contraindication. /Secobarbital sodium/

Barbiturates are weak acids that are absorbed and rapidly distributed to all tissues and fluids, with high concentrations in the brain, liver, and kidneys. Lipid solubility of the barbiturates is the dominant factor in their distribution within the body. The more lipid soluble the barbiturate, the more rapidly it penetrates all tissues of the body. Barbiturates are bound to plasma and tissue proteins to a varying degree, with the degree of binding increasing directly as a function of lipid solubility. Phenobarbital has the lowest lipid solubility, lowest plasma binding, lowest brain protein binding, the longest delay in onset of activity, and the longest duration of action. At the opposite extreme is secobarbital, which has the highest lipid solubility, highest plasma protein binding, highest brain protein binding, the shortest delay in onset of activity, and the shortest duration of action.

Protect the patient's airway and support ventilation and perfusion. Meticulously monitor and maintain, within acceptable limits, the patient's vital signs, blood gases, serum electrolytes, etc. Absorption of drugs from the gastrointestinal tract may be decreased by giving activated charcoal, which, in many cases, is more effective than emesis or lavage; consider charcoal instead of or in addition to gastric emptying. Repeated doses of charcoal over time may hasten elimination of some drugs that have been absorbed. Safeguard the patient's airway when employing gastric emptying or charcoal.

Diuresis and peritoneal dialysis are of little value; hemodialysis and hemoperfusion enhance drug clearance and should be considered in serious poisoning. If the patient has chronically abused sedatives, withdrawal reactions may be manifest following acute overdose.

Treatment of barbiturate overdose is primarily supportive and consists of the following: 30 to 60 g of activated charcoal in a glass of water or sorbitol may be administered to prevent absorption and increase excretion of the barbiturate. Activated charcoal should be left in the stomach and a saline cathartic may be administered. To enhance elimination - If renal function is normal, forced diuresis may help to eliminate the barbiturate. Alkalinization of the urine increases renal excretion of some barbiturates, especially phenobarbital, also aprobarbital, and mephobarbital (which is metabolized to phenobarbital). Although hemodialysis or hemoperfusion is not recommended as a routine procedure, it may be used in severe barbiturate poisoning or if the patient is anuric or in shock. Monitoring - Vital signs and fluid balance should be monitored. Supportive care - An adequate airway should be maintained, with assisted respiration and administration of oxygen as needed. Blood pressure and body temperature should be maintained. Fluid therapy and other standard treatment for shock should be administered, if necessary. A vasopressor may be required if hypotension occurs. Fluid or sodium overload should be avoided, especially if cardiovascular status is decreased. Chest physiotherapy should be administered. If pneumonia is suspected, appropriate cultures should be taken and antibiotics should be administered. Also, appropriate care should be taken to prevent hypostatic pneumonia, decubiti, aspiration, and other complications that may occur with altered states of consciousness. Patients in whom intentional overdose is known or suspected should be referred for psychiatric consultation. /Barbiturates/

For extravasation into subcutaneous tissues, recommended treatment includes application of moist heat to affected area and injection of a 0.5% procaine solution into the affected area. For accidental intra-arterial injection, recommended treatment includes release of tourniquet or restrictive garments to permit dilution of injected medication; injection of 10 mL of a 1% procaine solution into the artery and, if necessary, brachial plexus block to relieve spasm; anticoagulant therapy may prevent thrombosis; and supportive treatment. /Barbiturates/

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

The Generic Animal Drug and Patent Restoration act requires that each sponsor of an approved animal drug must submit to the FDA certain information regarding patents held for the animal drug or its method of use. The Act requires that this information, as well as a list of all animal drug products approved for safety and effectiveness, be made available to the public. Secobarbital sodium is included on this list. /Secobarbital sodium/

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: Secobarbital. DEA Code Number: 2315.

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 secobarbital or any salt thereof and one or more other active medicinal ingredients which are not listed in any schedule.. DEA Code Number: 2316.

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 secobarbital 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: 2316.

... DEA /schedule II/ controlled substance

... DEA /schedule III/ controlled substance

MEDICATION

THERAPEUTIC CATEGORY: Sedative; hypnotic /Secobarbital sodium/

THERAPEUTIC CATEGORY (Vet): Short-acting hypnotic; sedative. Pre-anesthetic /Secobarbital sodium/

For the Short-term treatment of intractable insomnia for patients habituated to barbiturates

Prepn: U.S. pat. 1,954,429 (1934) /Secobarbital 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/

Secobarbital Sodium preparations: (AHFS, 2009)

Seconal