Butalbital

Butalbital

Systematic (IUPAC) name
5-(2-methylpropyl)-5-(2-propenyl)- 2,4,6(1H,3H,5H)-pyrimidinetrione
Clinical data
AHFS/Drugs.com	Micromedex Detailed Consumer Information
MedlinePlus	a601009
Pregnancy category	US: C (Risk not ruled out)
Legal status	CA: Schedule IV DE: Anlage II (Prohibited) US: Schedule III
Routes of administration	oral
Pharmacokinetic data
Bioavailability	20-45%
Metabolism	hepatic mainly CYP3A4
Biological half-life	35 hours
Excretion	renal
Identifiers
CAS Number	77-26-9 Y
ATC code	none
PubChem	CID: 2481
IUPHAR/BPS	7138
DrugBank	DB00241 Y
ChemSpider	2387 Y
UNII	KHS0AZ4JVK Y
KEGG	D03182 Y
ChEBI	CHEBI:102524 Y
ChEMBL	CHEMBL454 Y
Chemical data
Formula	C11H16N2O3
Molecular mass	224.256
SMILES O=C1NC(=O)NC(=O)C1(CC(C)C)C\C=C
InChI InChI=1S/C11H16N2O3/c1-4-5-11(6-7(2)3)8(14)12-10(16)13-9(11)15/h4,7H,1,5-6H2,2-3H3,(H2,12,13,14,15,16) Y Key:UZVHFVZFNXBMQJ-UHFFFAOYSA-N Y
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Butalbital is a barbiturate with an intermediate duration of action. Butalbital is often combined with other medications, such as acetaminophen (paracetamol) or aspirin, and is commonly prescribed for the treatment of pain and headache. The various formulations combined with codeine are FDA-approved for the treatment of tension headaches. Butalbital has the same chemical formula as talbutal but a different structure—one that presents as 5-allyl-5-isobutylbarbituric acid.

Preparations

Combinations include:

• Butalbital and acetaminophen (paracetamol) (trade names: Axocet, Bucet, Bupap, Cephadyn, Dolgic, Phrenilin, Phrenilin Forte, Sedapap)
• Butalbital, paracetamol (acetaminophen), and caffeine (trade names: Fioricet, Esgic, Esgic-Plus)
• Butalbital and aspirin (trade name: Axotal)
• Butalbital, aspirin, and caffeine (trade names Fiorinal, Fiormor, Fiortal, Fortabs, Laniroif)
• Butalbital, paracetamol (acetaminophen), caffeine, and codeine phosphate (Fioricet#3 with Codeine)
• Butalbital, aspirin, caffeine, and codeine phosphate (trade name: Fiorinal#3 with Codeine)
• Ergotamine tartrate, caffeine, butalbital, belladonna alkaloids (trade name: Cafergot-PB)

Contraindications

Butalbital is not suggested as a first-line treatment for headache because it impairs alertness, brings risk of dependence and addiction, and increases the risk that episodic headaches will become chronic. When other treatments fail or are unavailable, butalbital may be appropriate for treating headache if the patient can be monitored to prevent the development of chronic headache.

There are specific treatments which are appropriate for targeting migraines and headaches which are preferable to butalbital when available as an option. It is a least preferable option to be used if other available treatments fail.

Side effects

Side effects for any psychoactive drug are difficult to predict, though butalbital is usually well tolerated. Commonly reported side effects for butalbital, which tend to subside with continued use, include:

Dizziness Drowsiness Intoxicated feeling Light-headedness Nausea Sedation Euphoria Severe impairment of judgment Diarrhea Memory Loss Constipation

Fioricet (50/40/325)

Rare side-effects include Stevens–Johnson syndrome, an adverse reaction to barbiturates, and anaphylaxis.

The risk and severity of all side effects is greatly increased when butalbital (or butalbital-based medications, such as Fioricet) are combined with other sedatives (ex. ethanol, opiates, benzodiazepines, antihistamines), and other side effects, which are not typically associated with butalbital, may occur. Inhibitors of the hepatic enzyme CYP3A4 may also increase the risk, severity, and duration of side effects, many drugs inhibit this enzyme as do some foods such as grapefruit and the blood orange. Taking butalbital-based medications with some other drugs may also increase the side effects of the other medication.

Dangers and risks

Butalbital is a physically and psychologically addictive barbiturate. Mixing with alcohol increases the risk of intoxication, increases respiratory depression, and increases liver toxicity when it is a butalbital combination including paracetamol (acetaminophen). Many opioid-dependent persons frequently use barbiturates as a potentiator to their normal dose of opiates in order to increase the effects, or with a less than normal dose as means of conserving their supply. Especially when used with the stronger narcotics, suicide or accidental death occurs much more frequently than first reported with one drug alone. Use of alcohol, benzodiazepines, and other CNS-depressants often also contribute to respiratory depression, coma, and in extreme cases fatality.

When benzodiazepines are co-administered with barbiturates, the sum effect of the drugs is far greater than would be expected considering the effect of both drugs separately. This is due to complementary mechanisms at the GABA_A receptor, where benzodiazepines increase the rate of chloride channel opening while barbiturates increase the duration. A dose of a benzodiazepine causes a channel which normally opens once every 30 seconds to open 3 times faster, while a barbiturate causes the channel to pass three chloride ions per opening instead of the normal one. When combined, the channel is now passing nine ions every 30 seconds instead of one, a 9-fold increase in activity.

As with most barbiturates, butalbital is a general inducer of P450 enzymes in both rodents and humans, particularly CYP3A4 (hence inducing its own metabolism), CYP2D6, and CYP2C9, although its P450 enzyme induction capability is far less than that of equivalent doses of phenobarbital or secobarbital (the most potent known enzyme inducers in the barbiturate molecular family). At very high doses it has also been demonstrated to induce glutathione S-transferase A1/glutathione S-transferase A2 in rats, although the doses required to achieve this effect to a clinically significant degree fall within the range of butalbitals LD50, making its use for this purpose impractical and highly dangerous (this effect has not yet been tested in human models, it is therefore unknown whether or not GS-T induction plays a significant role in butalbital's effects in humans, or even occurs at all).