TRIPLE SULPHA WATER SOLUBLE POWDER ( Sulphadimidine Sodium/Sulphadiazine Sodium/Sulphathiazole Sodium 125g/125g/125g)

Indications

• Bacterial infections
• Urinary tract infections
• Respiratory tract infections
• Certain types of meningitis
• Toxoplasmosis

Dosage

Children: Refer to BNF for Children for specific dosing guidelines.

Adults: Refer to BNF for specific dosing guidelines.

Mechanism of action

Sulfadiazine acts as a competitive inhibitor of the bacterial enzyme dihydropteroate synthetase. This enzyme plays a key role in the metabolism of para-aminobenzoic acid (PABA), which is essential for folic acid synthesis in bacteria. By inhibiting this enzyme, sulfadiazine disrupts the production of folic acid, which is vital for bacterial growth and replication.

Pharmacodynamics

Sulfadiazine is classified as a sulfonamide antibiotic, which means it is bacteriostatic and acts by inhibiting bacterial growth. Sulfonamides are effective against a wide spectrum of bacteria, but resistance may develop. The mechanism involves the competitive inhibition of PABA in the folic acid metabolism pathway, which is critical for bacterial survival. While many bacterial strains are sensitive to sulfadiazine, some may show resistance, indicating that sensitivity to one sulfonamide generally implies sensitivity to others.

Pharmacokinetics

Sulfadiazine is well absorbed when taken orally, although parenteral administration is less common due to its alkaline properties that can irritate tissues. The drug distributes widely throughout body tissues and fluids, achieving high concentrations in pleural, peritoneal, synovial, and ocular fluids. Although it is not commonly used for meningitis treatment, it can reach therapeutic levels in the cerebrospinal fluid during meningeal infections. Its antibacterial effectiveness can be reduced in the presence of pus.

Contra-indications

• Hypersensitivity to sulfadiazine or other sulfonamides
• Severe liver or kidney impairment
• Pregnancy near term
• Infants under 2 months of age

Adverse effects

• Nausea
• Vomiting
• Skin rash
• Hematological reactions such as agranulocytosis or thrombocytopenia
• Hypersensitivity reactions including Stevens-Johnson syndrome
• Renal impairment

Interactions

• May enhance the effects of anticoagulants such as warfarin
• May interact with methotrexate, increasing toxicity
• May decrease the efficacy of oral contraceptives
• Probenecid may increase sulfonamide levels and risk of toxicity

Precautions

• Use with caution in patients with G6PD deficiency
• Monitor for signs of blood dyscrasias
• Ensure adequate hydration to prevent crystalluria
• Assess renal function before initiation

Pregnancy

Sulfadiazine should not be used during pregnancy, especially near term, due to potential risks to the fetus.

Breast-feeding

Sulfadiazine is excreted in breast milk. Caution is advised when administering to nursing mothers.

Storage

Store in a cool, dry place away from light. Keep out of reach of children.

Formulations

• Tablets
• Oral suspension
• Injectable solution

Indications

• Bacterial infections of the urinary tract
• Respiratory tract infections
• Certain skin infections
• Other infections caused by susceptible organisms

Dosage

Children: Refer to the BNF for Children for appropriate dosing based on the child's age and weight.

Adults: Refer to the BNF for specific dosing recommendations based on the type and severity of infection.

Mechanism of action

Sulfonamides, including sulphadimidine, inhibit the enzymatic conversion of pteridine and p-aminobenzoic acid (PABA) to dihydropteroic acid by competing with PABA for binding to dihydrofolate synthetase. This inhibition reduces the synthesis of dihydrofolate, which is required for the synthesis of tetrahydrofolic acid (THF). THF is crucial for the synthesis of purines and deoxythymidine monophosphate (dTMP), thereby inhibiting bacterial growth.

Pharmacodynamics

Sulphadimidine is bacteriostatic, meaning it inhibits bacterial growth by preventing the synthesis of dihydrofolic acid. This, in turn, decreases the synthesis of bacterial nucleotides and DNA, effectively limiting the ability of bacteria to reproduce and proliferate within the host.

Pharmacokinetics

Sulphadimidine is well absorbed from the gastrointestinal tract and reaches peak plasma concentrations within a few hours after administration. It is distributed widely throughout body tissues and fluids, including the central nervous system. The drug is metabolized in the liver and excreted primarily via the kidneys in the urine, with a half-life that can vary based on patient factors such as renal function.

Contra-indications

• Hypersensitivity to sulfonamides
• Severe liver or kidney disease
• Porphyria
• Pregnancy at term

Adverse effects

• Rash
• Nausea
• Vomiting
• Diarrhea
• Hematological reactions such as agranulocytosis and aplastic anemia
• Hepatotoxicity
• Renal toxicity

Interactions

• May enhance the anticoagulant effect of warfarin
• May interact with methotrexate, increasing its toxicity
• May decrease the efficacy of oral contraceptives

Precautions

• Use with caution in patients with G6PD deficiency
• Monitor renal function regularly during prolonged therapy
• Use cautiously in patients with asthma or other allergic conditions

Pregnancy

Not recommended in pregnancy, especially during the third trimester due to potential risks to the fetus.

Breast-feeding

Use with caution, as it may pass into breast milk and affect the nursing infant.

Storage

Store in a cool, dry place away from direct light.

Formulations

• Tablets
• Oral suspension

Indications

• Urinary tract infections
• Gastrointestinal infections
• Bacterial infections susceptible to sulfonamide antibiotics

Dosage

Children: Refer to the BNF for Children for appropriate pediatric dosing guidelines. Dosing in children is often weight-based and must be tailored to the individual patient.

Adults: Refer to the BNF for specific dosing guidelines. Typical adult dosages may vary based on the severity and type of infection being treated.

Mechanism of action

Sulphathiazole interferes with the utilization of p-aminobenzoic acid (PABA) in the biosynthesis of tetrahydrofolic acid in susceptible bacteria. It acts as a structural analog of PABA, competitively inhibiting the enzyme dihydropteroate synthase. This inhibition prevents the formation of dihydropteroic acid, a precursor to tetrahydrofolic acid, thereby reducing the levels of tetrahydrofolate, which is essential for bacterial nucleic acid synthesis.

Pharmacodynamics

Sulphathiazole's bacteriostatic action relies on its ability to inhibit folic acid synthesis, which is crucial for nucleic acid production in bacteria. The effectiveness of sulphathiazole can be reduced in the presence of blood or purulent exudates, which may contain components that interfere with its antibacterial activity. It is important to note that sulphathiazole only affects microorganisms that synthesize their own folic acid and does not impact animal cells or bacteria that can utilize folate precursors.

Pharmacokinetics

Sulphathiazole is well absorbed from the gastrointestinal tract and distributes widely throughout the body, including into body fluids and tissues. It undergoes hepatic metabolism and is primarily eliminated via the kidneys. The half-life of sulphathiazole can vary, generally ranging from 6 to 12 hours, depending on the individual's renal function and other factors.

Contra-indications

• Hypersensitivity to sulfonamides
• Severe hepatic or renal impairment
• Porphyria

Adverse effects

• Rash
• Nausea
• Vomiting
• Diarrhea
• Hematological reactions such as leukopenia and thrombocytopenia
• Stevens-Johnson syndrome
• Toxic epidermal necrolysis

Interactions

• May enhance the effects of anticoagulants such as warfarin
• May interact with methotrexate, increasing toxicity
• Antidiabetic agents may have increased hypoglycemic effects
• May reduce the effectiveness of oral contraceptives

Precautions

• Use with caution in patients with renal impairment
• Monitor for signs of blood dyscrasias
• Assess for potential allergic reactions in patients with a history of sulfa drug allergies
• Consider potential interaction with other medications

Pregnancy

Not recommended during pregnancy due to potential risks to the fetus, including kernicterus.

Breast-feeding

Use with caution as it may pass into breast milk and affect the nursing infant.

Storage

Store in a cool, dry place, protected from light.

Formulations

• Tablets
• Suspension

Mechanism of action

Sulfadiazine is a competitive inhibitor of the bacterial enzyme dihydropteroate synthetase. This enzyme is needed for the proper processing of para-aminobenzoic acid (PABA) which is essential for folic acid synthesis. The inhibited reaction is necessary in these organisms for the synthesis of folic acid.

Pharmacodynamics

Sulfadiazine is a sulfonamide antibiotic. The sulfonamides are synthetic bacteriostatic antibiotics with a wide spectrum against most gram-positive and many gram-negative organisms. However, many strains of an individual species may be resistant. Sulfonamides inhibit multiplication of bacteria by acting as competitive inhibitors of <i>p</i>-aminobenzoic acid in the folic acid metabolism cycle. Bacterial sensitivity is the same for the various sulfonamides, and resistance to one sulfonamide indicates resistance to all. Most sulfonamides are readily absorbed orally. However, parenteral administration is difficult, since the soluble sulfonamide salts are highly alkaline and irritating to the tissues. The sulfonamides are widely distributed throughout all tissues. High levels are achieved in pleural, peritoneal, synovial, and ocular fluids. Although these drugs are no longer used to treat meningitis, CSF levels are high in meningeal infections. Their antibacterial action is inhibited by pus.

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.

Pharmacodynamics

Sulfamethazine 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). Sulfamethazine is bacteriostatic in nature. Inhibition of dihydrofolic acid synthesis decreases the synthesis of bacterial nucleotides and DNA.

Mechanism of action

Sulfonamides are usually bacteriostatic in action. Sulfonamides interfere with the utilization of p-aminobenzoic acid (PABA) in the biosynthesis of tetrahydrofolic acid (the reduced form of folic acid) cofactors in susceptible bacteria. Sulfonamides are structural analogs of PABA and appear to interfere with PABA utilization by competitively inhibiting the enzyme dihydropteroate synthase, which catalyzes the formation of dihydropteroic acid (a precursor of tetrahydrofolic acid) from PABA and pteridine; however, other mechanism(s) affecting the biosynthetic pathway also may be involved. Compounds such as pyrimethamine and trimethoprim, which block later stages in the synthesis of folic acid, act synergistically with sulfonamides. Only microorganisms that synthesize their own folic acid are inhibited by sulfonamides; animal cells and bacteria which are capable of utilizing folic acid precursors or preformed folic acid are not affected by these drugs. The antibacterial activity of the sulfonamides is reportedly decreased in the presence of blood or purulent body exudates. /Sulfonamides/ The sulfonamides are structural analogs of para-aminobenzoic acid (PABA) and competitively inhibit an enzymatic step (dihydropterate synthetase) during which PABA is incorporated into the synthesis of dihydrofolic acid (folic acid). Because dihydrofolate synthesis is reduced, the levels of tetrahydrofolate (folinic acid) formed from dihydrofolate diminish. Tetrahydrofolate is an essential component of the coenzymes responsible for single carbon metabolism in cells. Acting as antimetabolites to PABA, sulfonamides eventually block, in a complex fashion, several enzymes. These enzymes include those needed for the biogenesis of purine bases; for the transfer of desoxyuridine to thymidine; and for the biosynthesis of methionine, glycine, and formylmethionyl-transfer-RNA. This results in suppression of protein synthesis, impairment of metabolic processes, and inhibition of growth and multiplication of those organisms that cannot use preformed folate. The effect is bacteriostatic, although a bactericidal action is evident at the high concentrations that may be found in urine.