Uses, common brands, and safety information

Sulfonamides, also commonly known as sulfa drugs, were first discovered to have antibacterial properties in the 1930s. A German scientist isolated a sulfonamide called Prontosil and, ironically, treated his own daughter with it, saving her arm from being amputated. The discovery of Prontosil led to a new era in medicine, as sulfonamides were the first broadly effective drugs to treat bacterial infections. Prontosil led the way to the discoveries of other antibacterial sulfonamides: sulfapyridine, which was effective against pneumonia, sulfacetamide, which was effective against urinary tract infections, and sulfathiazole, which was effective against gastrointestinal (GI) tract infections. Sulfathiazole was also commonly used in pill and powder form during World War II to treat soldiers’ wounds to prevent infection. 

The chemical activity of sulfonamides provides for more than just anti-infective properties. There are many other disease states that drugs in the sulfonamide class are used for including diabetes, inflammatory diseases, HIV-1, epilepsy, high blood pressure, and topically for certain skin conditions. The table below lists common sulfonamide medicines followed by information on how they work, what conditions they treat, safety, and cost.

Other sulfonamides

Topicals

• Silvadene (silver sulfadiazine)
• Aczone (dapsone)
• Klaron (sodium sulfacetamide)
• Sulfamylon (mafenide acetate)

Ophthalmics

• Azopt (brinzolamide)
• Bleph-10 (sulfacetamide sodium) 
• Trusopt (dorzolamide HCl)

What are sulfonamides?

Sulfonamides are synthetic, or man-made, medicines that all share a common chemical structure. Sulfonamides treat a variety of disorders and illnesses and, based on their therapeutic activity, are divided into one of two general groups: the antibacterial sulfonamides that are used to treat infections and the non-antibacterial sulfonamides that are used to treat a variety of other illnesses including diabetes, inflammatory diseases, HIV-1, epilepsy, high blood pressure, glaucoma, and certain skin conditions.

How do sulfonamides work?

Antibacterial sulfonamide drugs work by binding to and stopping a specific enzyme, or protein, from carrying out its normal function of helping provide nutrients to the infectious bacteria cell. Sulfonamides don’t kill bacteria, but instead, they stop the reproduction of infectious bacteria. This action is called “bacteriostatic,” meaning it prevents the growth of bacteria. 

Less is known about how the non-antibacterial sulfonamide drugs work, although they are thought to have anti-inflammatory activity and effects on the body’s immune system. Examples: 

• In treating Type 2 diabetes, sulfonamide drugs increase the release of insulin by stimulating the pancreatic beta cells. 
• For treating high blood pressure, sulfonamide drugs act as diuretics and increase the amount of water and salt, or sodium, eliminated from the body by increasing urination frequency and amount. 
• Sulfonamide derivatives act as anti-inflammatory medicines by blocking the hormones in the body responsible for causing pain and inflammation.  
• In HIV patients, sulfonamide drugs act to block protease enzymes and stop the virus from multiplying. 

What are sulfonamides used for?

• Bacterial infections
  • Bactrim (sulfamethoxazole-trimethoprim)
  • Bactrim DS (sulfamethoxazole-trimethoprim double strength)
  • Sulfatrim Pediatric (sulfamethoxazole-trimethoprim)
• Type 2 diabetes
  • Amaryl (glimepiride)
  • Glucotrol (glipizide)
  • Glynase PresTab (glyburide micronized)
  • Tolbutamide
• High blood pressure
  • Acetazolamide 
  • Bumetanide
  • Chlorthalidone
  • Lasix (furosemide)
  • Hydrochlorothiazide
  • Indapamide
  • Metolazone
• Glaucoma
  • Methazolamide
  • Azopt (brinzolamide)
  • Trusopt (dorzolamide HCl)
• Gout
  • Probenecid 
• Inflammatory diseases (e. g., rheumatoid arthritis, Crohn’s disease)
  • Celebrex (celecoxib)
• Human immunodeficiency virus type 1 (HIV-1)
  • Lexiva (fosamprenavir calcium)
• Epilepsy
  • Zonegran (zonisamide)
• Irregular heartbeat
  • Tikosyn (dofetilide)
  • Betapace (sotalol HCl)
• Benign prostatic hyperplasia (BPH)
  • Flomax (tamsulosin HCl)
• Migraine headaches
  • Imitrex (sumatriptan succinate)

Types of sulfonamides

Sulfonamides are divided into one of two general groups: the antibacterial sulfonamides, used to treat infections, and the non-antibacterial sulfonamides that treat a variety of different diseases.

Antibacterial sulfonamides

• Bactrim (sulfamethoxazole/trimethoprim)
• Sulfatrim Pediatric (sulfamethoxazole/trimethoprim)

Non-antibacterial sulfonamides

• Azulfidine (sulfasalazine)
• Amaryl (glimepiride)
• Glucotrol (glipizide)
• Glynase PresTab (glyburide micronized)
• Chlorthalidone
• Lasix (furosemide)
• Hydrochlorothiazide
• Zonegran (zonisamide)
• Lexiva (fosamprenavir calcium)
• Celebrex (celecoxib)
• Tikosyn (dofetilide)
• Betapace (sotalol HCl)
• Flomax (tamsulosin HCl)
• Probenecid 
• Imitrex (sumatriptan succinate)

Who can take sulfonamides?

Adult men and women can take sulfonamides. However, they should also be used with extreme care in patients with liver problems, kidney problems, and certain types of anemia.

Pregnancy and breastfeeding

In general, animal studies have shown that some sulfonamides cause birth defects. Sulfonamides are not recommended for use if you’re pregnant or might become pregnant. Sulfonamides enter into breast milk and therefore they are not recommended for use while breastfeeding. A woman’s healthcare provider is the best source of information when managing sulfonamide treatment before becoming pregnant, during pregnancy, or while breastfeeding.

Children

The most common use for sulfonamides in children is the treatment of infections. Sulfisoxazole, in combination with the antibiotic erythromycin, is commonly used for the treatment and prevention of ear infections and prevention of meningococcal infections. Sulfasalazine is used in children 4 years and older to treat ulcerative colitis and inflammatory bowel disease. Sulfonamides should never be used in infants younger than 2 months old.

Seniors

In general, older adults can take sulfonamides. Older patients may be more sensitive to the adverse effects of sulfonamides, e.g., severe skin and blood problems may be more likely to occur in seniors, especially when complicating conditions exist such as impaired kidney or liver function, or use of other drugs concurrently.

Are sulfonamides safe?

Because all sulfonamides share a common chemical structure, if you have an allergy to one sulfonamide or sulfa drug, you may be allergic to other sulfonamide drugs—even across the two general groups. According to a recent SingleCare survey, 10% of survey respondents with a drug allergy were reportedly allergic to sulfa drugs. Talk to your healthcare professional if you have any type of drug allergy or if you have had a hypersensitivity reaction to any sulfonamide.

Anaphylaxis, or anaphylactic shock, is a severe allergic reaction that may occur if you are hypersensitive to a sulfonamide, or sulfa drug, that requires immediate medical care. Symptoms of an anaphylactic reaction may include:

• Skin rash
• Nausea
• Vomiting
• Difficulty breathing
• Shock

Stevens-Johnson syndrome is a rare but severe form of a sulfonamide allergy that requires immediate medical care. Symptoms may include:

• Flu-like symptoms
• Painful red blisters around the mouth, throat, eyes, or genitals
• Red or purple skin rash
• Peeling skin
• Fatigue
• Diarrhea
• Nausea and vomiting
• Fever

Recalls

• Accord Healthcare Inc. issues voluntary nationwide recall of hydrochlorothiazide tablets USP 12.5 mg due to labeling mix-up, March 2020

Restrictions

You should not take sulfonamide medicines if you are allergic to sulfa drugs. The presence of other medical problems and conditions may affect the use of sulfonamides. You should not use sulfonamides or they should be used cautiously if you have any of the following conditions:

• Porphyria (a group of disorders that result from a buildup of natural chemicals that produce porphyrin in your body)
• Certain types of anemia (e.g., from low blood levels of folic acid or from pyruvate kinase and glucose-6-phosphate dehydrogenase [G6PD] deficiencies) 
• Impaired or decreased liver or kidney function

Drug-drug interactions

Using sulfonamide medicines with any of the following is not recommended: 

• Coumadin (warfarin)
• Toradol (ketorolac)
• Orlaam (levomethadyl)
• Hiprex (methenamine)

This is not a complete list of drugs that may interact with sulfonamides. Talk to your healthcare professional before starting a sulfonamide about any other prescription or over-the-counter medicines you may take.

Are sulfonamides controlled substances?

Sulfonamides are not controlled substances.

Common sulfonamides side effects

The following are potential common side effects when taking sulfonamides. This is not an exhaustive list and you should always talk to your healthcare professional and seek medical advice about what adverse reactions to expect and how to address them.

• Skin rash
• Itching
• Headache
• Dizziness
• Diarrhea
• Tiredness
• Nausea or vomiting
• Pale skin
• Joint pain
• Sensitivity to light

How much do sulfonamides cost?

Sulfonamides have a wide price range depending on the specific drug, quantity, and dosage. Almost all Medicare and insurance plans will cover sulfonamides. Since most sulfonamides are available in generic formulations, they are much less expensive than their brand-name counterpart. A SingleCare discount card could reduce prescription costs up to 80% at participating pharmacies.

Sulfonamide (medicine) – wikidoc

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

There are several sulphonamide-based groups of drugs. The original antibacterial sulfonamides (sometimes called simply sulfa drugs) are synthetic antimicrobial agents that contain the sulfonamide group. Some sulfonamides are also devoid of antibacterial activity, e.g., the anticonvulsant sultiame. The sulfonylureas (main article: sulfonylureas) and thiazide diuretics (main article thiazide) are newer drug groups based on the antibacterial sulfonamides.

Sulfa allergies are common, hence medications containing sulfonamides are prescribed carefully.

Contents

• 1 Function
• 2 History
• 3 Preparation
• 4 List of Sulfonamides
• 5 Side effects
• 6 See also
• 7 External links

Function

In bacteria, antibacterial sulfonamides act as competitive inhibitors of the enzyme dihydropteroate synthetase, DHPS. DHPS catalyses the conversion of PABA (para-aminobenzoate) to dihydropteroate, a key step in folate synthesis. Folate is necessary for the cell to synthesize nucleic acids (nucleic acids are essential building blocks of DNA and RNA), and in its absence cells will be unable to divide. Hence the sulfonamide antibacterials exhibit a bacteriostatic rather than bactericidal effect.

Folate is not synthesized in mammalian cells, but is instead a dietary requirement. This explains the selective toxicity to bacterial cells of these drugs.

History

Sulfonamide drugs (known widely as “sulfa drugs”) were the first antimicrobial drugs, and paved the way for the antibiotic revolution in medicine. The first sulfonamide was trade named Prontosil, which is a prodrug. Experiments with Prontosil began in 1932 in the laboratories of Bayer AG, at that time a component of the huge German chemical trust IG Farben. The dye-based drug was synthesized by Bayer chemist Josef Klarer and tested in animals under the direction of physician/researcher Gerhard Domagk. Domagk quickly won the 1939 Nobel Prize in Medicine and Physiology, an honor that Adolf Hitler forbade him to accept (Hitler was incensed at the awarding of a Nobel Peace Prize a few years earlier to an anti-Nazi activist). Domagk’s prize also caused some bad feeling between him and Klarer. The discovery was in fact a team effort in which Domagk played a central role, operating under the general direction of Heinrich Hoerlein, a Farben executive later tried (and acquitted) at Nuremberg. The first official communication about the breakthrough discovery was not published until 1935, more than two years after the drug was patented by Klarer and his research partner Fritz Mietzsch. Prontosil was the first medicine ever discovered that could effectively treat a range of bacterial infections inside the body. It had a strong protective action against infections caused by streptococci, including blood infections, childbed fever, and erysipelas, and a lesser effect on infections caused by other cocci. Perplexingly, it had no effect at all in the test tube, exerting its antibacterial action only in live animals. Later it was discovered by a French research team at the Pasteur Institute that the drug was metabolized into two pieces inside the body, releasing from the inactive dye portion a smaller, colorless, active compound called sulfanilamide. The discovery helped establish the concept of “bioactivation” and dashed the German corporation’s dreams of enormous profit; the active molecule sulfanilamide (or sulfa) had first been synthesized in 1906 and was widely used in the dye-making industry; its patent had since expired and the drug was available to anyone.

The result was a sulfa craze. For several years in the late 1930s hundreds of manufacturers produced tens of thousands of tons of myriad forms of sulfa. This and nonexistent testing requirements lead to the Elixir Sulfanilamide disaster in the fall of 1937, wherein at least 100 people were poisoned with diethylene glycol. This led to the passage of the Federal Food, Drug, and Cosmetic Act in 1938. As the first and only effective antibiotic available in the years before Penicillin, sulfa drugs continued to thrive through the early years of World War II. They are credited with saving the lives of tens of thousands of patients including Franklin Delano Roosevelt, Jr. (in 1936) and Winston Churchill. Sulfa had a central role in preventing wound infections during the war. American soldiers were issued a first aid kit containing sulfa powder and were told to sprinkle it on any open wound. During the years 1942 to 1943, Nazi doctors conducted sulfanilamide experiments on prisoners in concentration camps.

The sulfanilamide compound is more active in the protonated form, which in case of the acid works better in a basic environment. The solubility of the drug is very low and sometimes can crystalize in the kidneys, due to its first pK_a of around 10. This is a very painful experience so patients are told to take the medication with copious amounts of water. Newer compounds have a pK_a of around 5-6 so the problem is avoided.

Many thousands of molecules containing the sulfanilamide structure have been created since its discovery (by one account, over 5400 permutations by 1945), yielding improved formulations with greater effectiveness and less toxicity. Sulfa drugs are still widely used for conditions such as acne and urinary tract infections, and are receiving renewed interest for the treatment of infections caused by bacteria resistant to other antibiotics.

Sulpha is an alternate (British English) spelling of the common name for sulfonamide antibiotics.

Preparation

Sulfonamides are prepared by the reaction of a sulfonyl chloride with ammonia or an amine.
Certain sulfonamides (sulfadiazine or sulfamethoxazole) are sometimes mixed with the drug trimethoprim, which acts against dihydrofolate reductase.
Also known as Sulfa Powder. Used largely in WWII to treat any wound.

List of Sulfonamides

• Benzolamide
• Bumetanide
• Celecoxib
• Chlorthalidone
• Clopamide
• Dichlophenamide
• Ethoxzolamide
• Indapamide
• Mafenide
• Mefruside
• Metolazone
• Probenecid
• Sulfacetamide
• Sulfanilamides
• Sulfamethoxazole
• Sulfasalazine
• Sultiame
• Sumatriptan
• Xipamide

Side effects

Sulfonamides have the potential to cause a variety of untoward reactions, including urinary tract disorders, haemopoietic disorders, porphyria and hypersensitivity reactions. When used in large dose, it may develop a strong allergic reaction. One of the most serious is Stevens Johnson syndrome (or toxic epidermal necrolysis). Some of the original sulfonamide drugs were derived from azo dyes and had the interesting effect of temporarily turning the patient red.

See also

• Antibiotic
• Timeline of antibiotics
• Sulfa drug
• Elixir Sulfanilamide

External links

• http://www.nlm.nih.gov/cgi/mesh/2004/MB_cgi?field=entry&term=Sulfonamides – List of sulfonamides
• http://www.thomashager.net – author of “The Demon under the Microscope,” a history of the discovery of the sulfa drugs
• http://www.lung.ca/tb/tbhistory/treatment/chemo.html – A History of the Fight Against Tuberculosis in Canada (Chemotherapy)
• http://www.nobel.se/medicine/laureates/1939/press.html – Presentation speech, Nobel Prize in Physiology and Medicine, 1939
• http://home.att.net/~steinert/wwii.htm – The History of WW II Medicine
• http://www. life.umd.edu/classroom/bsci424/Chemotherapy/AntibioticsHistory.htm – A history of antibiotics

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Sulfanilamide – description of the substance, pharmacology, use, contraindications, formula

Contents

• Structural formula

• Russian name

• English name

• Latin name

• chemical name

• Gross formula

• Pharmacological group of the substance Sulfanilamide

• Nosological classification

• CAS code

• pharmachologic effect

• Characteristic

• Pharmacology

• Application of the substance Sulfanilamide

• Contraindications

• Application restrictions

• Use during pregnancy and lactation

• Side effects of the substance Sulfanilamide

• Interaction

• Dosage and administration

• Precautionary measures

• Trade names with the active substance Sulfanilamide

Structural formula

Russian name

Sulfanilamide

English name

Sulfanilamide

Latin name

genus Sulfanilamidi)

Chemical name

4-Aminobenzenesulfonamide

General formula

C ₆ H ₈ N ₂ O ₂ S

Pharmacological group of the substance Sulfanilamide

Sulfonamides

Nosological classification

ICD-10 code list

CAS code

63-74-1

Pharmacological action

Pharmacological action 90 097-

antimicrobial .

Description

Refers to short-acting sulfa drugs. Sulfanilamide is a white, odorless, crystalline powder with a slightly bitter taste and a sweet aftertaste. Easily soluble in boiling water (1:2), difficult – in ethanol (1:37), soluble in solutions of hydrochloric acid, caustic alkalis, acetone (1:5), glycerin, propylene glycol; practically insoluble in ether, chloroform, benzene, petroleum ether. Molecular weight – 172.21.

Also used as sodium methane sulfate (Streptocide soluble) – white crystalline powder; soluble in water, practically insoluble in organic solvents.

Pharmacology

The mechanism of antimicrobial action of sulfanilamide is associated with the antagonism of PABA, with which it has a chemical similarity. Sulfanilamide is captured by the microbial cell, prevents the incorporation of PABA into dihydrofolic acid and, in addition, competitively inhibits the bacterial enzyme dihydropteroate synthetase (the enzyme responsible for the incorporation of PABA into dihydrofolic acid), as a result, the synthesis of dihydrofolic acid is disrupted, and the formation of metabolically active tetrahydrofolic acid from it, which is necessary for the formation of purines and pyrimidines, stops the growth and development of microorganisms (bacteriostatic effect).

Active against gram-positive and gram-negative cocci (including streptococci, pneumococci, meningococci, gonococci), Escherichia coli, Shigella spp. Chlamydia spp. , Actinomyces israelii, Toxoplasma gondii.

When applied topically, promotes rapid wound healing.

When taken orally, it is rapidly absorbed from the gastrointestinal tract. max”>C _max in the blood is created after 1–2 hours and decreases by 50%, usually in less than 8 hours. It passes through the histohematic, including the BBB, placental barriers. It is distributed in tissues, after 4 hours it is found in the cerebrospinal fluid. It is acetylated in the liver with loss of antibacterial properties. It is excreted mainly (90-95%) by the kidneys.

There is no information on carcinogenicity, mutagenicity and effects on fertility with long-term use in animals and humans.

Sulfanilamide used to be used orally to treat angina, erysipelas, cystitis, pyelitis, enterocolitis, prevention and treatment of wound infection. Sulfanilamide (Streptocid soluble) has been used in the past as 5% aqueous solutions for intravenous administration, which were prepared ex tempore ; currently used only in the form of liniment for external use.

Application of Sulfanilamide Sulfanilamide Sulfanilamide

local : tonsillitis, purulent-inflammatory lesions of the skin, infected wounds of various etiologies (including ulcers, cracks), furunculus, carbuncle, pyoderma, erysipelas, vulgar acne, impetigo, burns (I and II degrees).

Contraindications

Hypersensitivity (including to other sulfonamides and sulfonamides), diseases of the hematopoietic system, anemia, renal / hepatic insufficiency, congenital deficiency of glucose-6-phosphate dehydrogenase, azotemia, porphyria.

Restrictions for use

Pregnancy, lactation.

Use in pregnancy and lactation

Systemically absorbed sulfanilamide can rapidly cross the placenta and be detected in the blood of the fetus (the concentration in the blood of the fetus is 50-90% of that in the mother’s blood), as well as cause toxic effects. The safety of sulfanilamide during pregnancy has not been established. It is not known whether sulfonamide can cause fetal harm when taken by pregnant women. In experimental studies in rats and mice treated during pregnancy with certain short, intermediate and long-acting sulfonamides (including sulfanilamide) orally at high doses (7-25 times the therapeutic oral dose for humans), a significant increase in the incidence of cleft palate and other fetal bone malformations.

Passes into breast milk, may cause kernicterus in neonates.

Adverse effects of the substance Sulfanilamide

Allergic reactions; with prolonged local use in large quantities – a systemic effect: headache, dizziness, paresthesia, tachycardia, nausea, vomiting, dyspepsia, leukopenia, agranulocytosis, crystalluria, cyanosis.

Interaction

Myelotoxic drugs increase hematotoxicity.

Dosage and administration

Local . With superficial infectious diseases of the skin and mucous membranes of the nasal cavity and ear, with burns, ulcers, etc. used in the form of 10% ointment, 5% liniment or powder. Liniment or ointment is applied directly to the affected surface or smeared on a gauze; dressings are made in 1-2 days. For deep wounds, sulfanilamide is introduced into the wound cavity in the form of a carefully ground sterilized powder (5–10–15 g), while sulfanilamide or other antibacterial drugs are administered orally. In a mixture with sulfathiazole, benzylpenicillin and ephedrine, it is sometimes used topically (for acute rhinitis) in powder form (by blowing or drawing it into the nose when inhaling).

Precautions

Periodic peripheral blood testing is necessary for long-term use.

Trade names with active ingredient Sulfanilamide

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Lek. form
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Dosage
All dosages 10 g 10% 15 g 2 g 25 g 5 g 5% No dosage

Manufacturer
All manufacturers Avexima Siberia LLC Aromasintez LLC BioPharmCombinat LLC Biosintez OJSC Biosintez PJSC Zelenaya Dubrava CJSC Ivanovskaya Pharmaceutical Factory Irbit Chemical and Pharmaceutical Plant OJSC Lekar Lumi LLC [St. Petersburg] Meligen FP CJSC Moscow Pharmaceutical Factory NIZHFARM OAO Ozone LLC Samaramedprom Tver Pharmaceutical Factory OJSC Technopark -Center LLC Tula Pharmaceutical Factory LLC Tyumen Chemical-Pharmaceutical Plant Usolye-Sibirsky CPP JSC Usolye-Sibirsky CPP JSC Flora of the Caucasus JSC Flora of the Caucasus JSC Hubei Maxpharm Industries Co. Zhejiang Kemsen Pharm Co., Ltd. Empils-Foch JSC YuzhFarm LLC Yaroslavl Pharmaceutical Factory (ZAO YAFF)

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