Fioricet is a combination pain-reliever (analgesic) containing acetaminophen, butalbital, and caffeine.
How Does Acetaminophen Work?
Researchers have been guessing at acetaminophen’s mechanism of action for decades. Some explanations involve chemical messengers of inflammation and pain. Others invoke aspects of neurotransmission in the brain and spinal cord. None of the proposals have accumulated enough supporting evidence to satisfy everyone.
This mystery might seem like minutiae in the grand scheme of things. Acetaminophen has been used clinically for many decades, with more than 27 billion doses sold in 2009 alone. But the drug’s well-known danger to the liver makes understanding its mechanism more than a minor detail.
The drug’s safety margin—the difference between a safe dose and a toxic dose—is narrow. So it is deceptively easy to take too much and cause a trip to the emergency room, permanent liver damage, or even death. Deaths from accidental acetaminophen poisoning are rare—approximately 150 in the U.S. each year, according to a 2013 investigation by the nonprofit newsroom ProPublica. Even that number is too many to the researchers puzzling over acetaminophen’s mechanism of action and seeking safer alternatives.
ACETAMINOPHEN AT A GLANCE
AKA: N-(4-hydroxyphenyl)acetamide, paracetamol, APAP
U.S. brand name: Tylenol
First synthesized: 1878
Over-the-counter debut: 1960
Sales: 27 billion doses in 2009
SOURCES: Tylenol.com, ProPublica, Merck Index
One mechanism researchers have kicked around is that acetaminophen blocks cyclooxygenase (COX) enzymes. These help to form prostaglandins, which are pain- and inflammation-mediating signaling molecules. This would make acetaminophen similar to aspirin, or to ibuprofen and other nonsteroidal anti-inflammatory drugs (NSAIDs).
How Does Butalbital Work ?
Butalbital belongs to the class of medicines called barbiturates. When used for pain due to tension headaches experts believe it works by relaxing muscle contractions and causing sedation via an enhancement of the inhibitory effects of GABA (a neurotransmitter that regulates communication between brain cells).
Barbiturates increase the activity of a chemical in the brain that helps transmit signals. This chemical is known as gamma amino butyric acid (GABA). As a medication, they reduce muscle spasms, relieve anxiety, prevent seizures, and induce sleep.
How Does Caffeine Work ?
Caffeine is thought to enhance the pain-relieving effects of acetaminophen by up to 40%. In addition, it has vasoconstrictive properties, narrowing blood vessels in the brain thereby decreasing blood flow and oxygen tension (before a headache or a migraine, blood vessels tend to enlarge). This also helps to relieve pain.
Fioricet belongs to the class of medicines known as barbiturates because it contains butalbital. It may also be called a combination analgesic.