Sulfamethoxazole ( SMZ or SMX ) is an antibiotic. It is used for bacterial infections such as urinary tract infections, bronchitis, and prostatitis and is effective against gram negative and positive bacteria such as Listeria monocytogenes and E. coli .
Common side effects include nausea, vomiting, loss of appetite, and skin rashes. These are sulfonamides and bacteriostatic. It resembles a component of folic acid. This prevents the synthesis of folic acid in bacteria that must synthesize their own folic acid. Mammalian cells, and some bacteria, do not synthesize but require preformed folic acid (vitamin B9), therefore they are not sensitive to sulfamethoxazole.
It was introduced to the United States in 1961. It is now mostly used in combination with trimethoprim (abbreviated SMX-TMP). Other names include: sulfamethalazole, sulfisomezole, and sulfamethazole.
Video Sulfamethoxazole
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The most common side effects of sulfamethoxazole are gastrointestinal disorders (nausea, vomiting, anorexia) and skin allergic reactions (such as rashes and urticaria). There is a rare occurrence in which severe adverse reactions have resulted in death. These include Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias.
Allergic reactions to sulfonamide have been shown to cover the entire spectrum of Gel-Coombs hyperactive reactions. Type 1 reactions include immunoglobulin E (IgE) reactions such as urticaria, angioedema, and anaphylaxis. In contrast, non-type 1 hypersensitivity is believed to be caused by sulfonamid metabolites. Therefore, the liver and kidneys are the determinants of other hypersensitivity reactions; changes in kidney or liver function can increase or decrease the frequency of this reaction. One study has shown an allergic reaction rate of about 3.0% over 359 types of therapy. Of allergic reactions, skin rashes, eosinophilia and drug fever are the most common, while serious reactions are less common.
Sulfamethoxazole is contraindicated in people with known hypersensitivity in trimethoprim or sulfonamides.
Maps Sulfamethoxazole
Action mechanism
Sulfamethoxazole, sulfanilamide, is a structural analogue of para -aminobenzoic acid (PABA). They compete with PABA to bind dihydropteroate synthetase and inhibit the conversion of PABA and dihydropteroate diphosphate to dihydrofolic acid, or dihydrofolate. Inhibiting the production of dihydrofolate intermediates interferes with the normal bacterial synthesis of folic acid (folate). Folate is an important metabolite for bacterial growth and replication because it is used in DNA synthesis, especially in the biosynthesis of thymidylate and purine, and amino acid synthesis, including serine, glycine and methionine. Therefore, blockage of folate production inhibits the process of folate-dependent metabolism for bacterial growth. Because it inhibits bacterial growth, sulfamethoxazole is considered a bacteriostatic antibiotic.
Sulfonamides are selective against bacteria because they interfere with folate synthesis, a process that does not occur in humans. Humans do not synthesize folate, and must obtain it through diet.
Pharmacokinetics
Absorption
Sulfamethoxazole is well absorbed when administered topically. It is rapidly absorbed when administered orally.
Distribution
Sulfamethoxazole spreads to most tissues of the body as well as to sputum, vaginal fluid, and middle ear fluid. It also crosses the placenta. About 70% of the drug is bound to plasma proteins. Tmax (or the time to reach the maximum drug concentration in plasma) occurs 1 to 4 hours after oral administration. Mean serum half sulfamethoxazole was 10 hours. However, medication half-life is seen to increase in people with creatinine clearance levels equal to or less than 30 mL/min. A half-life of 22-50 hours has been reported for people with creatinine clearance less than 10 mL/min.
Metabolisme
Sulfamethoxazole is metabolized in the human liver for at least 5 metabolites. These metabolites are N4-acetyl-, N4-hydroxy-, 5-methylhydroxy-, N4-acetyl-5-methylhydroxy-sulfamethoxazole metabolites, and N-glucuronide conjugates. The CYP2C9 enzyme is responsible for the formation of the N4-hydroxy metabolite. In vitro studies showed sulfamethoxazole not the substrate of P-glycoprotein transporter.
Excression
Sulfamethoxazole is primarily excreted through glomerular filtration and tubular secretion. About 20% of sulfamethoxazole in urine is unchanged, about 15-20% is an N-glucuronide conjugate, and about 50-70% is an acetylation metabolite. Sulfamethoxazole is also excreted in breast milk.
See also
- Sulfisoxazole
- List of cytochrome P450 modules
Note
External links
- Sulfamethoxazole in ChemIDplus database
Source of the article : Wikipedia
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