Co-trimoxazole Bactrim

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Description

Antibacterial; fixed combination of sulfamethoxazole (intermediate-acting sulfonamide) and trimethoprim; both sulfamethoxazole and trimethoprim are folate-antagonist anti-infectives.

Sulfamethoxazole is a bacteriostatic antibacterial agent that interferes with folic acid synthesis in susceptible bacteria. Its broad spectrum of activity has been limited by the development of resistance.

Trimethoprimis a pyrimidine inhibitor of dihydrofolate reductase, it is an antibacterial related to pyrimethamine. The interference with folic acid metabolism may cause a depression of hematopoiesis. It is potentiated by sulfonamides and the trimethoprim-sulfamethoxazole combination is the form most often used. It is sometimes used alone as an antimalarial. Trimethoprim resistance has been reported.

Co-trimoxazole is used in treatment of: Acute Otitis Media, GI Infections, Respiratory Tract Infections, Urinary Tract Infections (UTIs), Brucellosis, Burkholderia Infections, Cholera, Cyclospora Infections, Granuloma Inguinale (Donovanosis), Isosporiasis, Listeria Infections, Mycobacterial Infections, Nocardia Infections, Pertussis, Plague, Pneumocystis jiroveci (Pneumocystis carinii) Pneumonia, Toxoplasmosis, Typhoid Fever and Other Salmonella Infections, Wegener’s Granulomatosis, Whipple’s Disease.

Brand

Sulfonamide

Additional information

Doses

800/160mg

Package

30 pills, 60 pills, 90 pills, 120 pills, 180 pills

Pharmacodynamics

Sulfamethoxazole is a sulfonamide drug that inhibits bacterial synthesis of dihydrofolic acid by competing with para-aminobenzoic acid (PABA) for binding to dihydropteroate synthetase (dihydrofolate synthetase). Sulfamethoxazole is bacteriostatic in nature. Inhibition of dihydrofolic acid synthesis decreases the synthesis of bacterial nucleotides and DNA. Sulfamethoxazole is normally given in combination with Trimethoprim, a dihydrofolate reductase inhibitor, which inhibits the reduction of dihydrofolic acid to tetrahydrofolic acid. Studies have shown that bacterial resistance develops more slowly with the combination of the two drugs than with either Trimethoprim or Sulfamethoxazole alone.

Trimethoprim is a pyrimidine analogue that disrupts folate synthesis, an essential part of the thymidine synthesis pathway. Inhibition of the enzyme starves the bacteria of nucleotides necessary for DNA replication.The drug, therefore, exhibits bactericidal activity.

Mechanism of action

Sulfonamides inhibit the enzymatic conversion of pteridine and p-aminobenzoic acid (PABA) to dihydropteroic acid by competing with PABA for binding to dihydrofolate synthetase, an intermediate of tetrahydrofolic acid (THF) synthesis. THF is required for the synthesis of purines and dTMP and inhibition of its synthesis inhibits bacterial growth. Pyrimethamine and trimethoprim inhibit dihydrofolate reductase, another step in THF synthesis, and therefore act synergistically with the sulfonamides.

Trimethoprim binds to dihydrofolate reductase and inhibits the reduction of dihydrofolic acid (DHF) to tetrahydrofolic acid (THF). THF is an essential precursor in the thymidine synthesis pathway and interference with this pathway inhibits bacterial DNA synthesis. Trimethoprim’s affinity for bacterial dihydrofolate reductase is several thousand times greater than its affinity for human dihydrofolate reductase. Sulfamethoxazole inhibits dihydrofolate synthetase (aka dihydropteroate synthetase), an enzyme involved further upstream in the same pathway. Trimethoprim and sulfamethoxazole are commonly used in combination due to their synergistic effects. This drug combination also reduces the development of resistance that is seen when either drug is used alone.

Metabolism

Metabolism: Sulfamethoxazole – Hepatic. The metabolism of sulfamethoxazole occurs predominately by N4-acetylation, although the glucuronide conjugate has been identified. / Trimethoprim – Hepatic metabolism to oxide and hydroxylated metabolites.

Absorption: Sulfamethoxazole – Rapidly absorbed following oral administration. Also well-absorbed topically. / Trimethoprim – Readily and almost completely absorbed in the GI tract with peak serum concentrations attained 1-4 hours after oral administration.

Route of elimination: Ten to twenty percent of trimethoprim is metabolized, primarily in the liver; the remainder is excreted unchanged in the urine.

Half life: Sulfamethoxazole – 10 hours / Trimethoprim – 8-11 hours in adults with normal renal function

Affected organisms: Gram negative and gram positive bacteria, Listeria monocytogenes, Escherichia coli.

Side effects

All medicines may cause side effects, but many people have no, or minor, side effects.Some medical conditions may interact with Co-trimoxazole.

Tell your doctor or pharmacist if you have any medical conditions.

Sulfamethoxazole may cause nausea, vomiting, diarrhea and hypersensitivity reactions. Hematologic effects such as anemia, agranulocytosis, thrombocytopenia and hemolytic anemia in patients with glucose-6-phosphate dehydrogenase deficiency may also occur. Sulfamethoxazole may displace bilirubin from albumin binding sites causing jaundice or kernicterus in newborns.

Trimethoprim common side effects may include: stomach pain, vomiting, diarrhea,sore or swollen tongue or mild itching or skin rash.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider.

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