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There are several sulfonamide-based groups of drugs. The original antibacterial sulfonamides (sometimes called simply sulfa drugs) are synthetic antimicrobial agents that contain the sulfonamide group. In Chemistry, the sulfonamide Functional group (also spelt sulphonamide) is -S(=O2-NH2 a Sulfonyl group connected to Some sulfonamides are also devoid of antibacterial activity, e. g. , the anticonvulsant sultiame. The anticonvulsants, also called antiepileptic drugs (abbreviated "AEDs" are a diverse group of pharmaceuticals used in the treatment of epileptic Sultiame ( rINN, also known as sulthiame) is a Sulfonamide and Inhibitor of the Enzyme carbonic anhydrase. The sulfonylureas (main article: sulfonylureas) and thiazide diuretics (main article thiazide) are newer drug groups based on the antibacterial sulfonamides. Sulfonylurea (UK Sulphonylurea derivatives are a class of Antidiabetic drugs that are used in the management of Diabetes mellitus type 2 ("adult-onset" Thiazide is a term used to describe a type of molecule and a class of Diuretic.

Sulfa allergies are common, hence medications containing sulfonamides are prescribed carefully. It is important to make a distinction between sulfa drugs and other sulfur-containing drugs and additives, such as sulfates and sulfites, which are chemically unrelated to the sulfonamide group, and do not cause the same hypersensitivity reactions seen in the sulfonamides.

Contents

Function

In bacteria, antibacterial sulfonamides act as competitive inhibitors of the enzyme dihydropteroate synthetase, DHPS. The Bacteria ( singular: bacterium) are a large group of unicellular Microorganisms Typically a few Micrometres in length bacteria have Competitive inhibition is a form of enzyme inhibition where binding of the inhibitor to the Enzyme prevents binding of the substrate and vice versa Dihydropteroate synthetase is an enzyme classified under. It produces Dihydropteroate in Bacteria, but does not function in Humans. DHPS catalyses the conversion of PABA (para-aminobenzoate) to dihydropteroate, a key step in folate synthesis. 4-Aminobenzoic acid (also known as para -aminobenzoic acid or PABA) is an Organic compound with the molecular formula C7H7NO2 Dihydropteroate is a Pterin created from Para-aminobenzoic acid (PABA by the enzyme Dihydropteroate synthetase. Folic acid (also known as Vitamin M and Folacin) and Folate (the Anionic form are forms of the water-soluble Vitamin B9 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. A nucleic acid is a Macromolecule composed of chains of monomeric Nucleotides In Biochemistry these Molecules carry Genetic information Deoxyribonucleic acid ( DNA) is a Nucleic acid that contains the genetic instructions used in the development and functioning of all known Ribonucleic acid ( RNA) is a Nucleic acid that consists of a long chain of Nucleotide units Hence the sulfonamide antibacterials exhibit a bacteriostatic rather than bactericidal effect. Bacteriostatic Antibiotics limit the growth of bacteria by interfering with bacterial Protein production DNA replication or other aspects of A bactericide or bacteriocide is a substance that kills bacteria and preferably nothing else

Folate is not synthesized in mammalian cells, but is instead a dietary requirement. This explains the selective toxicity to bacterial cells of these drugs. These antibiotics are used to treat pneumocystis jiroveci pneumonia, urinary tract infections, shigellosis, and certain protozoan infections. Shigellosis, also known as bacillary dysentery in its most severe manifestation is a Foodborne illness caused by infection by bacteria of the genus The sulfonamide chemical moiety is also present in other medications that are not antimicrobials, including thiazide diuretics (including hydrochorothiazide, metolazone, and indapamide, among others), sulfonylureas (including glipizide, glyburide, among others), and acetazolamide.

Sulfasalazine, in addition to its use as an antibiotic, is also utilized in the treatment of inflammatory bowel disease.

History

Sulfonamide 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. Prontosil, the first commercially available antibacterial Antibiotic (with a relatively broad effect (against Gram-positive cocci but not against A prodrug is a pharmacological substance ( drug) that is administered in an inactive (or significantly less active form 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. Year 1932 ( MCMXXXII) was a Leap year starting on Friday of the Gregorian calendar. For other uses see Bayer (disambiguation or Beyer or Buyer. Bayer AG (German ˈbaɪə () is a German IG Farben (short for Interessen-Gemeinschaft Farbenindustrie AG, "syndicate of dyestuff corporations" and also called I The dye-based drug was discovered by a team under the general direction of Farben executive Heinrich Hoerlein, synthesized by Bayer chemist Josef Klarer and tested under the direction of physician/researcher Gerhard Domagk. Gerhard Johannes Paul Domagk ( October 30, 1895 &ndash April 24, 1964) was a German Pathologist and Bacteriologist 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. Year 1935 ( MCMXXXV) was a Common year starting on Tuesday (link will display full calendar of the Gregorian calendar. 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. Streptococcus is a Genus of spherical Gram-positive bacteria belonging to the phylum Firmicutes and the Perplexedly, 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 Pasteur Institute (Institut Pasteur is a French Non-profit private foundation dedicated to the study of Biology, Micro-organisms Diseases 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. The Elixir Sulfanilamide disaster was a mass Poisoning in the United States in 1937 Diethylene glycol (DEG is an Organic compound described by the structural formula HO-CH2-CH2-O-CH2-CH2-OH This led to the passage of the Federal Food, Drug, and Cosmetic Act in 1938. The United States Federal Food Drug and Cosmetic Act (abbreviated as FFDCA FDCA or FD&C is a set of laws passed by Congress in 1938 giving authority to the 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. Penicillin (sometimes abbreviated PCN or pen) is a group of Beta-lactam antibiotics used in the treatment of Bacterial Infections World War II, or the Second World War, (often abbreviated WWII) was a global military conflict which involved a majority of the world's nations, including They are credited with saving the lives of tens of thousands of patients including Franklin Delano Roosevelt, Jr. (son of President Franklin Delano Roosevelt) (in 1936) and Winston Churchill. Franklin Delano Roosevelt Jr ( August 17, 1914 – August 17, 1988) was the fifth child of Anna Eleanor Roosevelt and Franklin Year 1936 ( MCMXXXVI) was a Leap year starting on Wednesday (link will display the full calendar of the Gregorian calendar. Sir Winston Leonard Spencer-Churchill, KG, OM, CH, TD, FRS, PC, PC (Can ( 30 November 1874 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 pKa 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 pKa 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. Year 1945 ( MCMXLV) was a Common year starting on Monday (link will display the full calendar 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. British English or UK English ( BrE, BE, en-GB) is the broad term used to distinguish the forms of the English language used in the

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. Sulfamethoxazole is a sulfonamide Bacteriostatic Antibiotic. It is most often used as part of a synergistic combination with Trimethoprim Trimethoprim ( INN) (traɪˈmɛθəprɪm is a bacteriostatic Antibiotic mainly used in the Prophylaxis and treatment of Urinary tract infections Dihydrofolate reductase, or DHFR, reduces Dihydrofolic acid to Tetrahydrofolic acid, using NADPH as Electron donor, which can be converted It is also known as Sulfa Powder. It received widespread use in the treatment of wounds during the Second World War.

List of Sulfonamides

Side effects

Sulfonamides have the potential to cause a variety of untoward reactions, including urinary tract disorders, haemopoietic disorders, porphyria and hypersensitivity reactions. Acetazolamide, sold under the trade name Diamox, is a Carbonic anhydrase inhibitor that is used to treat Glaucoma, Epileptic seizures Benign Bumetanide is a Loop diuretic Celecoxib ( INN) (sɛlɨˈkɒksɪb is a Non-steroidal anti-inflammatory drug (NSAID used in the treatment of Osteoarthritis, Rheumatoid arthritis Chlortalidone (formerly spelled chlorthalidone in the UK and still so called in the United States is a drug used to treat hypertension Clopamide is a Piperidine Diuretic. Mechanism of Action of Clopamide Clopamide is categorised as a thiazide like drug and works in similar way as the Diclofenamide (or dichlorphenamide) is a Sulfonamide and a Carbonic anhydrase inhibitor Ethoxzolamide (alternatively known as Ethoxyzolamide) is a Sulfonamide Medication that functions as a Carbonic anhydrase inhibitor Furosemide ( INN) or frusemide (former BAN) is a Loop diuretic used in the treatment of congestive Heart failure and Edema Hydrochlorothiazide, sometimes abbreviated HCT, HCTZ, or HZT is a popular Diuretic drug of the Thiazide class that acts by inhibiting Indapamide is a non-thiazide sulphonamide Diuretic drug marketed by Servier, generally used in the treatment of Hypertension, as well as Mafenide ( INN; usually as mafenide Acetate, trade name Sulfamylon) is a Sulfonamide often used to treat severe burns. Not to be confused with Metaxalone, a muscle relaxant Metolazone is a Thiazide diuretic marketed under the brand names Zaroxolyn Probenecid is a Uricosuric drug primarily used in treating Gout or Hyperuricemia, that increases uric acid removal in the urine Sulfacetamide is a Sulfonamide Antibiotic. It may also have Anti-inflammatory properties when used to treat Blepharitis or even Conjunctivitis Sulfadimethoxine (DI-METHOX is a Sulfonamide Antibacterial. Sulfadoxine (also spelled sulphadoxine) is an ultra-long-lasting Sulfonamide often used in combination with Pyrimethamine to treat or prevent Sulfanilamide is a molecule containing the sulfonamide functional group attached to an Aniline. Sulfamethoxazole is a sulfonamide Bacteriostatic Antibiotic. It is most often used as part of a synergistic combination with Trimethoprim Sulfasalazine (brand name Azulfidine in the US, Salazopyrin in Europe) is a Sulfa drug, a derivative of Mesalazine Sultiame ( rINN, also known as sulthiame) is a Sulfonamide and Inhibitor of the Enzyme carbonic anhydrase. Sumatriptan ( Imitrex, Imigran, Imigran Recovery) is a Triptan drug including a Sulfonamide group which was marketed Xipamide is a sulfonamide Diuretic drug marketed by Eli Lilly under the trade names Aquaphor (in Germany and Aquaphoril (in Austria Porphyrias are a group of inherited or acquired disorders of certain Enzymes in the Heme biosynthetic pathway (also called Porphyrin pathway 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). Stevens-Johnson syndrome (SJS is a life-threatening Condition affecting the Skin in which Cell death causes the epidermis to separate from the Some of the original sulfonamide drugs were derived from azo dyes and had the interesting effect of temporarily turning the patient red. Azo compounds are compounds bearing the Functional group R-N=N-R' in which R and R' can be either Aryl or Alkyl.

Adverse reactions

Approximately 3% of the general population have adverse reactions when treated with sulfonamide antimicrobials. Of note is the observation that patients with HIV have a much higher prevalence, at about 60%[1]. Human immunodeficiency virus ( HIV) is a Lentivirus (a member of the Retrovirus family that can lead to acquired immunodeficiency syndrome People who have a hypersensitivity reaction to one member of the sulfonamide class are likely to have a similar reaction to others.

Hypersensitivity reactions are less common in non-antibiotic sulfonamides, and, though controversial, the available evidence suggests those with hypersensitivity to sulfonamide antibiotics do not have an increased risk of hypersensitivity reaction to the non-antibiotic agents[2].

Two regions of the sulfonamide antibiotic chemical structure are implicated in the hypersensitivity reactions associated with the class.

The non-antibiotic sulfonamides lack both of these structures[3].

The most common manifestation of a hypersensitivity reaction to sulfa drugs are rash and hives. Hypersensitivity (also called hypersensitivity reaction refers to undesirable (damaging discomfort-producing and sometimes fatal reactions produced by the normal immune system However, there are several life-threatening manifestations of hypersensitivity to sulfa drugs, including Stevens-Johnson syndrome, toxic epidermal necrolysis, agranulocytosis, hemolytic anemia, thrombocytopenia, and fulminant hepatic necrosis, among others[4]. Stevens-Johnson syndrome (SJS is a life-threatening Condition affecting the Skin in which Cell death causes the epidermis to separate from the Toxic epidermal necrolysis (TEN also known as Lyell's syndrome, is a life-threatening dermatological condition that is frequently induced by a reaction to medications Agranulocytosis is an acute condition involving a severe and dangerous Leukopenia particularly of neutrophils causing a Neutropenia in the circulating blood Hemolytic anemia is Anemia due to Hemolysis, the abnormal breakdown of Red blood cells (RBCs either in the Blood vessels (intravascular hemolysis Thrombocytopenia (or -paenia, or thrombopenia in short is the presence of relatively few Platelets in Blood.

See also

References

  1. ^ SA Tilles (Aug 2001). In modern usage an antibiotic is a Chemotherapeutic agent with activity against Microorganisms such as Bacteria, fungi or Protozoa This is the timeline of antimicrobial (anti-infective therapy The Elixir Sulfanilamide disaster was a mass Poisoning in the United States in 1937 "Practical issues in the management of hypersensitivity reactions: sulfonamides". Southern Medical Journal 94 (8): 817-24.  
  2. ^ CG Slatore (Aug 2004). "Sulfonamide hypersensitivity". Immunology and Allergy Clinics of North America 24 (3): 477-90,vii.  
  3. ^ CC Brackett (Jul 2004). "Likelihood and mechanisms of cross-allergenicity between sulfonamide antibiotics and other drugs containing a sulfonamide functional group". Pharmacotherapy 24 (7): 856-70.  
  4. ^ (1994) Harrison's Principles of Internal Medicine, 13th Ed. . McGraw-Hill Inc. , 604.  

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