Butalbitalum
Butalbitalum Uses, Dosage, Side Effects, Food Interaction and all others data.
Butalbitalum, or 5-allyl-5-isobutylbarbituric acid, is a derivative of barbituric acid which the hydrogens at position 5 are substituted by an allyl group and an isobutyl group. It is a short-to-intermediate acting member of barbiturates that exhibit muscle-relaxing and anti-anxiety properties that produce central nervous system (CNS) depression that ranges from mild sedation to general anesthesia. Butalbitalum has a low degree of selectivity and a narrow therapeutic index. Typically indicated to manage tension (or muscle contraction) headaches, butalbital is often combined with one or more therapeutic agents, such as acetylsalicylic acid, acetaminophen, aspirin, and caffeine. There have not been clinical trials that evaluate the clinical efficacy of butalbital in migraines thus it is not indicated for such condition. As with other barbiturates, butalbital carries a risk of abuse or misuse potential, intoxication, hangover, tolerance, dependence, and overdosage possibly leading to death. Butalbitalum‐containing analgesics can also produce a drug‐induced headache in addition to tolerance and dependence. Due to these risks, the use of butalbital-containing combination products is typically limited for use only in cases where other medications are deemed ineffective and such usage is advised to be carefully monitored.
Butalbitalum is a short to intermediate-acting barbiturate that reversibly depresses the activity of excitable tissues, including the central nervous system in a nonselective manner. Barbiturates exhibit muscle-relaxing and anti-anxiety properties and they are capable of producing all levels of CNS mood alteration from excitation to mild sedation, hypnosis, and deep coma. The sedative dose of butalbital in nontolerant individuals is 5-100 mg and the hypnotic dose is 100-200 mg. Pain perception and reaction are relatively unimpaired until the moment of unconsciousness. In some cases, an unwanted paradoxical response of excitement may be observed instead of sedation with barbiturate treatment, which may be due to their depressant effects on inhibitory centers of the CNS. At sufficiently high therapeutic doses, barbiturates induce anesthesia; however, barbiturates are reported to lose their effectiveness for sleep induction and sleep maintenance after 2 weeks. Barbiturates are habit-forming; they can produce tolerance and both dependence and addiction, which is partly explained by decreased drug concentration at the site of action due to enhanced drug metabolism by induced enzymes, or to cellular adaptive changes. In addition, butalbital may lead to analgesic overuse headache.
While butalbital is expected to mediate similar actions as other members of the barbiturate drug class, the effects of butalbital in isolation are not well understood. It is suggested that butalbital is added in combination products to antagonize the unwanted central stimulating effect of stimulatory ingredients such as caffeine. Butalbitalum may decrease blood pressure and heart rate when administered at sedative and hypnotic doses.
| Trade Name | Butalbitalum |
| Availability | Prescription only |
| Generic | Butalbital |
| Butalbital Other Names | Allylbarbital, Allylbarbitone, Allylbarbituric acid, Butalbarbital, Butalbital, Butalbitalum, iso-butylallylbarbituric acid, Itobarbital, Tetrallobarbital |
| Related Drugs | diazepam, promethazine, Valium, Phenergan, midazolam, chlorpromazine |
| Type | |
| Formula | C11H16N2O3 |
| Weight | Average: 224.2563 Monoisotopic: 224.116092388 |
| Protein binding | The in vitro plasma protein binding of butalbital is 45% over the concentration range of 0.5-20 mcg/mL. This falls within the range of plasma protein binding (20%-45%) reported with other barbiturates such as phenobarbital, pentobarbital, and secobarbital sodium. |
| Groups | Approved, Illicit |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Butalbitalum is a barbiturate drug used for symptomatic treatment of tension-type headache in various combinations with acetaminophen, aspirin, caffeine, and codeine.
Indicated for the management of the symptom complex of tension (or muscle contraction) headache, when other non-opioid analgesics and alternative treatments are inadequate, in various combinations with acetaminophen, aspirin, caffeine, and codeine .
Butalbitalum is also used to associated treatment for these conditions: Tension Headache
How Butalbitalum works
Butalbitalum is a CNS depressant that suppresses neuronal excitability, impulse conduction, and the release of neurotransmitters, similar to actions of other barbiturates. Barbiturates primarily mediate suppressive actions on polysynaptic neuronal responses by diminishing facilitation while enhancing inhibition. Inhibition occurs at GABAergic synapses that express GABA-A receptors, which are transmembrane chloride ion channels that bind an inhibitory neurotransmitter GABA, barbiturates, benzodiazepines, neurosteroids, and ethanol. Upon activation, GABA-A receptors allow Cl- influx and K+ efflux into the postjunctional terminal, resulting in inhibition of the postsynaptic neuron. It is suggested that barbiturates, including butalbital, enhances GABA binding to the GABA-A receptors by binding to the α+/β− interface in the intracellular domain (ICD) as an allosteric modulator. Additionally, barbiturates promote benzodiazepine binding to the receptor. Barbiturates potentiate GABA-induced increases in chloride conductance and depress voltage-activated calcium currents while prolonging the duration of GABA-induced chloride channel opening. Butalbitalum may also inhibit the excitatory effects mediated by AMPA receptors by reducing glutamate-induced depolarizations of the receptor. It is also proposed that barbiturates and opioids may potentiate the analgesic effects of each other when co-administered, although there are inconsistencies across preclinical data.
Toxicity
Reported oral TDLO (woman) is 400 mg/kg and subcutaneous LD50 in rat is 160 mg/kg. The lowest acute dose of butalbital alone associated with death in adults is 2.0 g. Symptoms of acute barbiturate poisoning include drowsiness, confusion, coma, respiratory depression, hypotension, and shock. Due to the CNS depressant effects, an overdose of barbiturates may lead to death. Barbiturates are also associated with withdrawal reactions, which may lead to death if severe.
Food Interaction
- Avoid alcohol. Profound CNS depression can occur.
Butalbitalum Alcohol interaction
[Major] GENERALLY AVOID:
Concurrent acute use of barbiturates and ethanol may result in additive CNS effects,
including impaired coordination, sedation, and death.
Tolerance of these agents may occur with chronic use.
The mechanism is related to inhibition of microsomal enzymes acutely and induction of hepatic microsomal enzymes chronically.
The combination of ethanol and barbiturates should be avoided.
Butalbitalum Drug Interaction
Moderate: diphenhydramine, duloxetine, cyclobenzaprine, clonazepam, escitalopram, pregabalin, quetiapine, montelukast, topiramate, cholecalciferol, alprazolam, sertraline, cetirizineMinor: fluoxetineUnknown: aspirin / butalbital / caffeine, sumatriptan, esomeprazole, clopidogrel, albuterol, cyanocobalamin
Butalbitalum Disease Interaction
Major: acute alcohol intoxication, drug dependence, liver disease, porphyria, rash, respiratory depressionModerate: adrenal insufficiency, depression, hematologic toxicity, osteomalacia, paradoxical reactions
Volume of Distribution
The volume of distribution of butalbital is reported to be approximately 0.8 L/kg. Butalbitalum is expected to distribute to most of the tissues in the body , including the mamillary glands and placenta. The plasma-to-blood concentration ratio was almost unity indicating that there is no preferential distribution of butalbital into either plasma or blood cells.
Elimination Route
Butalbitalum gets readily and rapidly absorbed from the gastrointestinal tract. The time to reach the peak plasma concentrations is reported to be approximately 2 hours. Typical blood concentrations of butalbital peaked at 2.1 mg/L and declined to 1.5 mg/L at 24 hr. Plasma concentrations of 10 to 20 μg/mL have been associated with toxicity; coma and fatalities have occurred with concentrations of 25 to 30 μg/mL.
Half Life
The plasma half-life is about 35 hours. In a study of 5 healthy volunteers receiving 100 mg butalbital in combination with aspirin and caffeine, the mean plasma elimination half-life of butalbital was 61 hours, with the range of 35 to 88 hours.
Clearance
There is limited data on the clearance of butalbital.
Elimination Route
Butalbitalum predominantly undergoes renal elimination with 59 to 88% of the total dose administered being excreted from the kidneys as unchanged parent drug or metabolites. Urinary excretion products included parent drug (about 3.6% of the dose), 5-isobutyl-5-(2,3-dihydroxypropyl) barbituric acid (about 24% of the dose), 5-allyl-5(3-hydroxy-2-methyl-1-propyl) barbituric acid (about 4.8%), products with the barbituric acid ring hydrolyzed with excretion of urea (about 14% of the dose), as well as unidentified materials. Of the material excreted in the urine, 32% is conjugated. Elimination is not complete within 24 hours, and the drug accumulates with frequent administration.
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