Butalbital Compound

Brand Name: Aspirin, ASA; Butalbital; Caffeine
Butalbital Compound®, Farbital®, Fiorinal®, Fiormor®, Fortabs®, Laniroif®

Classification:
» Analgesics
» Salicylates

Musculoskeletal Agents
» Antiinflammatory Agents
» Salicylates

Psychotropic Agents
» Anxiolytics, Sedatives, and Hypnotics
» Barbiturates

Psychotropic Agents
» Psychostimulants

NOTE: This monograph discusses the use of aspirin, butalbital, and caffeine as a combination product for management of mild to moderate pain and headaches. Clinicians may wish to consult the individual monographs for more information about the specific mechanism of action and pharmacokinetics of each agent.

Description: Aspirin, butalbital, and caffeine are used together in an oral preparation to treat tension headaches, migraines, and mild to moderate pain, especially when antianxiety or relaxant effects are needed. Treatment of multiple recurrent headaches with this combination has not been well studied. According to published guidelines for the acute management of migraine, the use of butalbital-containing analgesics should be limited and carefully monitored due to concerns of overuse, medication-overuse headache, and withdrawal. Aspirin is a salicylate analgesic with similar analgesic potency to NSAIDs. Butalbital is a short-to-intermediate acting barbiturate that is used in this combination for its sedative and relaxant effects. Caffeine is found in many analgesic formulations and may be beneficial in some vascular headaches such as tension and cluster headaches and migraines. Fiorinal® was originally approved by the FDA in May 1976.

Mechanism of Action: The roles and interactions of aspirin, butalbital, and caffeine in the treatment of tension headaches are not well understood.

Aspirin, ASA; Butalbital; Caffeine Capsules (Cap 325;50;40 mg;mg;mg)

Aspirin, ASA: The analgesic activity of aspirin is due to its ability to inhibit cyclooxygenase (COX). Cyclooxygenase is responsible for the conversion of arachidonic acid to prostaglandin G2 (PGG2), the first step in prostaglandin synthesis. In vivo, aspirin is hydrolyzed to salicylic acid and acetate, and many of its properties are due to salicylic acid. However, hydrolysis is not required for aspirin activity. Aspirin irreversibly inhibits COX by acetylation of a specific serine moiety. Aspirin appears to inhibit COX through two pathways and seems to have a different mechanism of action than other salicylates. The antiinflammatory action of aspirin is believed to be a result of peripheral inhibition of COX-1 and COX-2, but aspirin may also inhibit the action and synthesis of other mediators of inflammation. Salicylates are effective in cases where inflammation has caused sensitivity of pain receptors (hyperalgesia). It appears prostaglandins, specifically prostaglandins E and F, are responsible for sensitizing the pain receptors; therefore, salicylates have an indirect analgesic effect by inhibiting the production of further prostaglandins and does not directly affect hyperalgesia or the pain threshold.
Butalbital: Sedative-hypnotic effects of butalbital are similar to phenobarbital and result from producing or enhancing the inhibitory affects of gamma-aminobutyric acid (GABA) in the thalamus. Barbiturates inhibit ascending conduction in the reticular formation, which interferes with conduction of impulses to the cortex causing sensory cortex depression, decreased motor activity, drowsiness, sedation, and changes in cerebral function. Barbiturates also cause a nonselective depressant effect throughout the CNS and are capable of producing all types of CNS mood alterations.
Caffeine: Caffeine causes cerebral vasoconstriction, which decreases blood flow and oxygen tension. In combination with aspirin, caffeine may provide a quicker onset of action and enhance pain relief allowing for lower doses of analgesics. In some patients, caffeine relieves headaches by treating the effects of caffeine withdrawal.

Pharmacokinetics: Aspirin-butalbital-caffeine is administered orally. All three components are well absorbed from the GI tract. During migraines, gastric stasis may occur which could alter the pharmacokinetic parameters of these agents. Time to onset of analgesia is about 1 - 2 hours. All three agents undergo hepatic metabolism.

Aspirin, ASA: Aspirin is partially hydrolyzed to salicylic acid on the first pass through the liver and is widely distributed into most body tissues. Aspirin is poorly bound to plasma proteins, but it should be used cautiously in patients already receiving other highly protein-bound drugs due to the high protein binding of salicylic acid. Aspirin is 99% metabolized to salicylic acid and other metabolites. The elimination half-life of aspirin in plasma is about 15 - 20 minutes. Salicylic acid, but not aspirin itself, undergoes saturable kinetics. At low doses, the elimination is first-order and the half-life remains constant at 2 - 3 hours; however, at higher doses, the enzymes responsible for metabolism become saturated and the apparent half-life can increase to 15 - 30 hours. Because of this, 5 - 7 days may be required before a steady-state concentration is reached. Salicylic acid and its metabolites are excreted primarily by the kidneys. The excretion of salicylic acid is enhanced by alkalinization of the urine.
Butalbital: Butalbital is metabolized by the CYP450 hepatic microsomal enzyme system and has an average half-life of 61 hours. Butalbital induces hepatic enzymes but to a lesser degree than phenobarbital. Butalbital is almost completely renally eliminated as metabolites, although a small amount (3 - 4%) is excreted as unchanged drug.
Caffeine: Caffeine undergoes hepatic metabolism via CYP 1A2 to paraxanthine, theobromine, and theophylline. Elimination of caffeine is renal as inactive metabolites. The elimination half-life of caffeine in adults ranges between 3 - 7 hours.

[1 of 20 - Click here to see more photos]

References
_{. Silberstein SD and McCrory DC. Butalbital in the treatment of headache: History, pharmacology, and efficacy. Headache 2001;41:953 - 67.}

. Matchar DB, Young WB, Rosenberg JH, et al. Evidence-based guidelines for migraine headache in the primary care setting: pharmacological management of acute attacks. Retrieved March 30, 2004. Available on the World Wide Web at: http://www.aan.com/professionals/practice/pdfs/gl0087.pdf.

[ Revised 4/28/2006 10:04:00 AM ]

Related entries

Monthly Archives

Syndicate

• RSS 1.0 • RSS 2.0 • Atom