ANTICONVULSANT
PHENOBARBITAL EGEND HAS IT THAT IN 1 8 6 4 , product of hemoglobin, creates the typJohann Friedrich Wilhelm Adolf ical yellow hue of jaundiced babies. Sevon Baeyer, of Bayer Pharma- vere jaundice can create neurological ceuticals fame, popped into a problems. Phénobarbital lowers bilirulocal pub after conbin levels by increasing liver cocting a new compound, metabolism. H malonylurea. Apparently, he Q Nv^-0 Phototherapy (exposure to walked in on a lively celebraI light) replaced phénobarbital tion of St. Barbara, patron saint •Ν" after it was accidentally dis of artillerymen. Inspired by the covered in the 1950s to effec revelry Bayer renamed his new ^ // tively and safely lower bilirubin compound barbituric acid, a levels; it remains the most com combination of the words Barmon treatment option today bara and urea. Part of the long-lasting appeal of phénobarbital, especially in developing counThough several compounds would be derived from barbituric acid over time, tries, is its lowprice—a 30-day supply gencreating a whole class of compounds erally costs $10 or less. known as the barbiturates, Baeyer did not St. Barbara's compound is not a comsee much therapeutic use for his acid and plete "wonder drug," however, and has set it aside. some serious side effects. Some of the Emil Fischer andJoseph von Mering undrawbacks of phénobarbital include covered the medical value of the barbiturates in 1903. Their compound, diethylbarbituric acid, or Veronal, helped dogs fall asleep. Barbiturates became the patron saint of insomniacs. Barbiturates also provided a safer and more effective relief option for people suffering from epileptic seizures. Before the barbiturates, potassium bromide was the first chemical treatment for controlling seizures. Sir Charles Locock first used the compound to control seizures in patients in 1857 Though potassium bromide caused serious side effects, such as psychosis and dermatitis, it remained the only form of treatment for seizures until the beginning of the 20th century In 1912, Bayer Pharmaceuticals introduced phénobarbital to the market under the name Luminal. Not only was the compound an effective sleeping aid, but it also exhibited properties as an anticonvulsant without the toxicity of potassium bromide. Phénobarbital blocks certain receptors in the brain, preventing the abnormal electrical discharges that trigger epileptic seizures. Though no longer relied upon as a firstPATRON S A I N T Barbituric acid was line treatment, phénobarbital still remains an active component in the treat- supposedly named after St. Barbara, ment of seizures, making it the oldest depicted here in an icon. epilepsy medicine still in use. Even pets suffering from seizures now benefit from drowsiness and behavioral changes. And barbiturates in general are notorious for phénobarbital. their tolerance issues. Over time, inThe barbiturate also found a calling creasing doses are necessary to maintain treating jaundice in newborns. A high levthe same level of effectiveness. The therel of bilirubin, an insoluble breakdown
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apeutic dose limit for barbiturates, however, is dangerously close to its toxic level. Accidental overdose or mixture with alcohol can prove fatal, as was probably the case with Marilyn Monroe's death in 1962. Phénobarbital played a role in an earlier scandal and indirectly influenced the development of current Good Manufacturing
PHENOBARBITAL Name: 5-Ethyl-5-phenyl-2A6 (1H,3H5H)-pyhmidinethone CAS Registry: 50-06-6 Other names: Luminal, Eskabarb, Solfoton, Talpheno, phenobarbitone First marketed: 1912, Bayer Did you know that phénobarbital may reduce the effectiveness of birth control pills?
Practices. In December 1940, Winthrop Chemical accidentally produced sulfathiazole tablets contaminated with phénobarbital. Each tablet contained about 350 mg of phénobarbital, while the average adult sleep-inducing dose was only 100-150 mg. Used to treat bacterial infections, sulfathiazole had relatively low toxicity and was often prescribed in large doses. Hundreds of deaths and injuries resulted from the accidental intake of such large amounts of phénobarbital. A Food & Drug Administration investigation revealed that the contamination most likely occurred during the tabletmaking process. Winthrop produced sulfathiazole and phénobarbital tablets in the same room on adjacent machines, which were often used interchangeably. Even though Winthrop knew of the contamination in December, cases of the contaminated pills were still surfacing three months later. Winthrop's poor quality-control system, failure to report the contamination to FDA, and failure to quickly and effectively recall the tainted pills prompted FDA to require detailed controls of sulfathiazole production at Winthrop. The incident strongly influenced the 1962 drug amendments to the 1938 Food, Drug & Cosmetic Act, which tightened controls over pharmaceuticals and mandated Good Manufacturing Practices. Few pharmaceuticals share phenobarbitaTs claim to fame: A saint's namesake that is capable of taming seizures and is responsible for both the death of movie stars and the birth of Good ManufacturingPractices.—RACHEL PEPLING WWW.CEN-0NLINE.ORG
