Sulfanilamide Tragedy

The sulfonylamide tragedy refers to a historical event that occurred in the 1930s, which resulted in the deaths of many patients who were treated with certain medications containing sulfa drugs.

Sulfa drugs were discovered in the early 20th century and were considered a revolutionary breakthrough in the treatment of bacterial infections. They were widely used during World War II and saved countless lives.

However, in the 1930s, the pharmaceutical industry was still in its infancy and drug safety regulations were not as stringent as they are today. This led to the production and distribution of poorly tested and inadequately regulated drugs.

One such drug was Elixir Sulfanilamide, which contained the sulfa drug sulfanilamide and diethylene glycol as a solvent. The drug was marketed as a safe and effective treatment for streptococcal infections.

Unfortunately, the solvent used in Elixir Sulfanilamide was highly toxic, causing severe liver and kidney damage. This led to the deaths of over 100 people, including many children.

The tragedy resulted in the passing of the Federal Food, Drug, and Cosmetic Act in 1938, which established new safety requirements for drugs and food additives. It also highlighted the need for thorough testing and regulation of pharmaceutical products before they are released to the market.

Today, sulfa drugs are still used in the treatment of bacterial infections, but they are much safer and undergo rigorous testing and regulation before being approved for use.

1. Welcome SULFANILAMIDE TRAGEDY – THE LESSONS LEARNT Khateeb Arshad Syed Anwar SB M Pharmacy Student ID :- 001/012023 2/7/2023 www.clinosol.com | follow us on social media @clinosolresearch 1

2. Index 2/7/2023 www.clinosol.com | follow us on social media @clinosolresearch 2 Introduction Mechanism of action History Chemical and physical properties Contraindications Adverse effects Pharmacokinetics References…

3. Introduction Sulfanilamide  (also spelled  sulphanilamide ) is a  sulfonamide   antibacterial  drug. Chemically, it is an  organic compound  consisting of an  aniline   derivatized  with a  sulfonamide  group. Powdered sulfanilamide was used by the  Allies  in  World War II  to reduce infection rates and contributed to a dramatic reduction in mortality rates compared to previous wars. Sulfanilamide is rarely if ever used  systemically  due to  toxicity  and because more effective sulfonamides are available for this purpose. The term " sulfanilamides " is also sometimes used to describe a family of molecules containing these  functional groups . Examples include: Furosemide , a  loop diuretic Sulfadiazine , an  antibiotic Sulfamethoxazole , an  antibiotic 2/7/2023 www.clinosol.com | follow us on social media @clinosolresearch 3 SULFANILAMIDE TRAGEDY – THE LESSONS LEARNT

4. Mechanism of action 2/7/2023 www.clinosol.com | follow us on social media @clinosolresearch 4 As a sulfonamide antibiotic, sulfanilamide functions by  competitively inhibiting  (that is, by acting as a substrate analogue) enzymatic reactions involving  para -aminobenzoic acid  (PABA). Specifically, it  competitively inhibits  the enzyme  dihydropteroate synthase .  PABA is needed in enzymatic reactions that produce  folic acid , which acts as a  coenzyme  in the synthesis of  purines  and  pyrimidines .  Mammals  do not synthesize their own folic acid so are unaffected by PABA inhibitors, which selectively kill bacteria. However, this effect can be reversed by adding the end products of one-carbon transfer reactions, such as  thymidine ,  purines ,  methionine , and  serine . PABA can also reverse the effects of sulfonamides.

5. History Sulfanilamide was first prepared in 1908 by the Austrian chemist Paul Josef Jakob Gelmo (1879–1961) as part of his dissertation for a doctoral degree from the  Technische Hochschule  of  Vienna . It was patented in 1909. Gerhard Domagk , who directed the testing of the  prodrug   Prontosil  in 1935, and  Jacques Tréfouël  and  Thérèse Tréfouël , who along with Federico Nitti and  Daniel Bovet  in the laboratory of  Ernest Fourneau  at the  Pasteur Institute , determined sulfanilamide as the active form, are generally credited with the discovery of sulfanilamide as a chemotherapeutic agent. Domagk was awarded the Nobel Prize for his work. In 1937,  Elixir sulfanilamide , a medicine consisting of sulfanilamide dissolved in  diethylene glycol  poisoned and killed more than 100 people as a result of acute  kidney failure , prompting new US regulations for drug testing. In 1938, the  Food, Drug and Cosmetic Act  was passed. It was only the solvent and not the sulfanilamide that was the problem, as sulfanilamide was widely and safely used at the time in both tablet and powder form. 2/7/2023 www.clinosol.com | follow us on social media @clinosolresearch 5

6. Chemical and physical properties Sulfanilamide is a yellowish-white or white crystal or fine powder. It has a  density  of 1.08 g/cm 3  and a  melting point  of 164.5-166.5 °C. The  pH  of a 0.5%  aqueous solution  of Sulfanilamide is 5.8 to 6.1. It has a λ max  of 255 and 312 nm. 2/7/2023 www.clinosol.com | follow us on social media @clinosolresearch 6 Solubility : One gram of sulphanilamide dissolves in approximately 37 ml  alcohol  or in 5 ml  acetone . It is practically insoluble in  chloroform ,  ether , or  benzene

7. Contraindications Sulphanilamide is contraindicated in those known to be hypersensitive to sulfonamides, in nursing mothers, during pregnancy near term and in infants less than 2 months of age. 2/7/2023 www.clinosol.com | follow us on social media @clinosolresearch 7 Adverse effects Since sulfanilamide is used almost exclusively in topical vaginal preparations these days, adverse effects are typically limited to  hypersensitivity  or local skin reactions. If  absorbed , systemic side effects commonly seen with sulfanilamides may occur. Pharmacokinetics A small amount of sulfanilamide is absorbed following topical application or when administered as a  vaginal  cream or  suppository  (through the vaginal mucosa). It is  metabolized  by  acetylation  like other  sulfonamides  and excreted through the urine.

8. References… Actor P, Chow AW, Dutko FJ, McKinlay MA. "Chemotherapeutics".  Ullmann's Encyclopedia of Industrial Chemistry . Weinheim : Wiley-VCH.  doi : 10.1002/14356007.a06_173 Steinert D (2000).  "The Use of Sulfanilamide in World War II" .  The History of WWII Medicine . Archived from  the original  on 2016-06-07. "Class 9 Items: Drugs, Chemicals and Biological Stains Sulfa Drugs" .  Library of Congress Web Archives . Archived from  the original  on 2013-12-04. Retrieved 2014-06-13.   "Sulfanilamide" .  PubChem . National Center for Biotechnology Information (NCBI), U.S. National Library of Medicine. " Drugs@FDA : FDA-Approved Drugs" .  www.accessdata.fda.gov . Retrieved 2021-10-02. 2/7/2023 www.clinosol.com | follow us on social media @clinosolresearch 8

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