SULFANILAMIDE TRAGEDY – THE LESSON LEARNT
Introduction
Sulfanilamide, is a medication used to treat streptococcal infections in tablet and powder form. Based on demand in the liquid dosage form of Sulfanilamide, the company prepared the Sulfanilamide elixir using diethylene glycol as solvent media. The Elixir Sulfanilamide was prescribed for patients with throat infections after a small laboratory test inclusive of color, odor, and taste, and not tested for its safety in any preclinical or clinical trials.
Patients treated with Elixir Sulfanilamide for sore throat, many of them were children and produced severe poisoning effects. They were not well for about three weeks with symptoms such as severe abdominal pain, nausea, vomiting, dysuria, stupor, and convulsions. They suffered intense and unrelenting pain. At the time there was no known antidote or treatment, hence more than 100 people died.
A woman wrote to U.S. President Roosevelt and described the death of her daughter: “The first time I ever had to call in a doctor for [Joan] and she was given Elixir of Sulfanilamide. All that is left to us is caring for her little grave. Even the memory of her is mixed with sorrow for we can see her little body tossing to and fro and hear that little voice screaming with pain and it seems as though it would drive me insane. It is my plea that you will take steps to prevent such sales of drugs that will take little lives and leave such suffering behind and such a bleak outlook on the future as I have tonight”.
Congress responded to public outrage by passing the 1938 Food, Drug, and Cosmetic Act, which required companies to perform animal safety tests on their proposed new drugs and submit the data to the FDA before being allowed to market their products.
What is sulfanilamide?
Sulfanilamide is an organic sulphur compound structurally similar to p-aminobenzoic acid (PABA) with antibacterial properties.
Mechanism of Action
Sulfanilamide blocks the synthesis of dihydrofolic acid by inhibiting the enzyme dihydropteroate synthase and thus exhibits its bacteriostatic effect.
4. Therapeutic uses of sulfanilamide
It was effective against wide range of Gram-positive and Gram-negative bacteria, and chlamydia.
5. The Elixir sulfanilamide
Elixirs are clear sweetened, hydroalcoholic preparations intended for oral use and usually flavored for palatability. Sulfanilamide was prepared as an elixir using Di-ethylene glycol.
6. Which is the assailant? Sulfanilamide or Di-ethylene glycol
Obviously it is Di-ethylene glycol. Di-ethylene glycol is a commonly used solvent and ingredient in numerous commercial products. Diethylene glycol is rapidly absorbed and distributed to the kidneys, brain, liver, spleen, and adipose tissue. Di-ethylene glycol is metabolized into 2-hydroxyethoxyacetic acid and diglycolic acid by alcohol dehydrogenase. The metabolite diglycolic acid was identified to be the primary nephrotoxic metabolite in Di-ethylene glycol poisoning. Di-ethylene glycol may cause seizures, depressed mental status, renal failure, and profound metabolic acidosis. Now it may be treated as methanol poising with fomipezole.
Conclusion: The Lesson learnt from the tragedy
Before treating the drug for its intended use in humans, it is necessary to test the active ingredients as well as the diluents for its efficacy and safety to prevent the unwanted effect. Sulfanilamide tragedy is a term that is still wrongly applied because the actual is Di-ethylene glycol tragedy. However, this tragedy and public outrage led Congress to pass the Food, Drug, and Cosmetic Act of 1938. Before new pharmaceuticals were permitted for sale, the act obliged businesses to do animal safety tests and clinical trials on their proposed formulations.
References:
https://www.fda.gov/files/about%20fda/published/The-Sulfanilamide-Disaster.pdf
R.S.Satoskar, Nirmala N.Rege, Raakhi K. Tripathi and S.D. Bhandarkar. Textbook of Pharmacology and Pharmacotherapeutics, 25th Edition. Elsevier co-published with popular prakashan.
https://www.sciencedirect.com/topics/medicine-and-dentistry/diethylene-glycol
Student Name: Mahalakshmi G
Student ID: 013/012023
Qualification: M.Pharm., Ph.D
e-Mail ID: mahamaya2603@gmail.com
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