SULFRAN VET POWDER

Indications

• Urinary tract infections
• Respiratory tract infections
• Gastrointestinal infections
• Pneumocystis pneumonia
• Toxoplasmosis
• Certain skin infections

Dosage

Children: Refer to the BNF for Children for dosing guidance, as pediatric dosing should be determined based on age and weight.

Adults: Refer to the BNF for specific dosing recommendations, as dosage can vary based on the indication.

Mechanism of action

Sulfamethoxazole exerts its antimicrobial effect by competitively inhibiting the bacterial enzyme dihydropteroate synthase. This enzyme is crucial for the synthesis of folate, which is necessary for the production of nucleic acids. By blocking this pathway, sulfamethoxazole effectively starves bacteria of essential nutrients, leading to their growth inhibition and eventual death.

Pharmacodynamics

The pharmacodynamics of sulfamethoxazole involve its action as a bactericidal agent, especially in combination with trimethoprim. The combination enhances the effect by inhibiting two sequential steps in the folate synthesis pathway, leading to a synergistic effect that results in a broader antimicrobial spectrum and reduced resistance development.

Pharmacokinetics

Sulfamethoxazole is well absorbed from the gastrointestinal tract and achieves peak plasma concentrations within 2 to 6 hours after oral administration. It has a biological half-life of approximately 8 to 10 hours. The drug is extensively distributed in body tissues and fluids, including urine, and is metabolized in the liver primarily through acetylation and oxidation. Sulfamethoxazole is excreted mainly by the kidneys, with approximately 70% of the drug being eliminated as unchanged drug in the urine.

Contra-indications

• Severe renal impairment
• Hypersensitivity to sulfonamides
• History of acute porphyria
• Pregnancy at term

Adverse effects

• Rash
• Nausea
• Vomiting
• Diarrhea
• Headache
• Dizziness
• Hematological reactions (e.g., agranulocytosis, aplastic anemia)
• Stevens-Johnson syndrome
• Toxic epidermal necrolysis

Interactions

• May potentiate the effects of oral anticoagulants
• Increased risk of toxicity with methotrexate
• May reduce the effectiveness of oral contraceptives
• Caution with other drugs that may cause bone marrow suppression

Precautions

• Monitor renal function before and during treatment
• Use with caution in patients with G6PD deficiency
• Caution in patients with liver disease
• Assess for signs of hypersensitivity reactions

Pregnancy

Sulphamethoxazole is contraindicated in pregnancy at term due to the risk of kernicterus and other potential adverse effects on the fetus.

Breast-feeding

Sulphamethoxazole is excreted in breast milk; use with caution as it may cause kernicterus in newborns.

Storage

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

Formulations

• Tablets
• Suspensions
• Injectable solutions

Indications

• Bacterial infections
• Urinary tract infections
• Respiratory tract infections
• Prophylaxis of recurrent urinary tract infections

Dosage

Children: For children aged 6 weeks to 5 months: 4 mg/kg twice daily (max. 200 mg). For children 6 months to 5 years: 4 mg/kg twice daily (max. 200 mg). For children 6–11 years: 4 mg/kg twice daily (max. 200 mg). For children

Adults: 200 mg twice daily.

Mechanism of action

Trimethoprim is a reversible inhibitor of dihydrofolate reductase, an enzyme that catalyzes the formation of tetrahydrofolic acid from dihydrofolic acid. By inhibiting this enzyme, trimethoprim disrupts the biosynthesis of nucleic acids and proteins in bacteria, leading to their growth inhibition. The drug has a significantly higher affinity for bacterial dihydrofolate reductase compared to the mammalian enzyme, ensuring selective antibacterial activity.

Pharmacodynamics

Trimethoprim exerts its antimicrobial effects by disrupting bacterial nucleic acid synthesis. It is effective against various gram-negative bacteria and some coagulase-negative Staphylococcus species. Resistance can develop through mechanisms such as alterations to the bacterial cell wall or overproduction of the target enzyme. Monitoring for potential blood disorders is important during therapy, as rare adverse effects can occur.

Pharmacokinetics

Trimethoprim is well absorbed from the gastrointestinal tract and reaches peak plasma concentrations within 1-4 hours post-administration. It has a volume of distribution that suggests extensive tissue penetration, including into the lungs and kidneys, and is primarily excreted unchanged in the urine. The elimination half-life is approximately 8-10 hours, and dosing adjustments may be necessary in cases of renal impairment.

Contra-indications

• Severe renal impairment
• Known hypersensitivity to trimethoprim or any component of the formulation

Adverse effects

• Diarrhoea
• Nausea
• Headache
• Dizziness
• Fatigue
• Skin reactions
• Vomiting
• Anxiety
• Agranulocytosis
• Eosinophilia
• Photosensitivity reactions
• Thrombocytopenia
• Leukopenia
• Pseudomembranous colitis

Interactions

• Increases exposure to pramipexole
• Increases exposure to treprostinil
• Increases exposure to dopaminergic receptor agonists
• Increases concentration of antiepileptics
• Increases concentration of fosphenytoin
• Increases concentration of phenytoin
• Increases risk of haematological toxicity with azathioprine in renal transplant patients
• Increases concentration of digoxin
• Increases exposure to repaglinide

Precautions

• Caution in patients with renal impairment
• Caution in elderly patients (75 years and over)
• Monitor for signs of blood disorders such as sore throat, fever, and pallor
• Consider local antimicrobial susceptibility patterns before use

Pregnancy

Manufacturer advises avoidance due to potential fetal developmental toxicity observed in animal studies.

Breast-feeding

Manufacturer advises avoidance as trimethoprim is present in milk in animal studies.

Storage

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

Formulations

• Tablets
• Oral suspension
• Injection solution

Mechanism of action

Trimethoprim is a reversible inhibitor of dihydrofolate reductase, one of the principal enzymes catalyzing the formation of tetrahydrofolic acid (THF) from dihydrofolic acid (DHF). Tetrahydrofolic acid is necessary for the biosynthesis of bacterial nucleic acids and proteins and ultimately for continued bacterial survival - inhibiting its synthesis, then, results in bactericidal activity. Trimethoprim binds with a much stronger affinity to bacterial dihydrofolate reductase as compared to its mammalian counterpart, allowing trimethoprim to selectively interfere with bacterial biosynthetic processes. Trimethoprim is often given in combination with sulfamethoxazole, which inhibits the preceding step in bacterial protein synthesis - given together, sulfamethoxazole and trimethoprim inhibit two consecutive steps in the biosynthesis of bacterial nucleic acids and proteins. As a monotherapy trimethoprim is considered bacteriostatic, but in combination with sulfamethoxazole is thought to exert bactericidal activity. Trimethoprim is a bacteriostatic lipophilic weak base structurally related to pyrimethamine. It binds to and reversibly inhibits the bacterial enzyme dihydrofolate reductase, selectively blocking conversion of dihydrofolic acid to its functional form, tetrahydrofolic acid. This depletes folate, an essential cofactor in the biosynthesis of nucleic acids, resulting in interference with bacterial nucleic acid and protein production. Bacterial dihydrofolate reductase is approximately 50,000 to 60,000 times more tightly bound by trimethoprim than is the corresponding mammalian enzyme. To determine the incidence & severity of hyperkalemia during trimethoprim therapy, 30 consecutive patients with acquired immunodeficiency syndrome receiving high-dose (20 mg/kg/day) trimethoprim were studied; in addition, the mechanism of trimethoprim-induced hyperkalemia was investigated in rats. Trimethoprim increased serum potassium concn by 0.6 mmol/l despite normal adrenocortical function & glomerular filtration rate. Serum potassium levels >5 mmol/l were observed during trimethoprim treatment in 15 of 30 patients. In rats, iv trimethoprim inhibited renal potassium excretion by 40% & increased sodium excretion by 46%. It was concluded that trimethoprim blocks apical membrane sodium channels in the mammalian distal nephron. As a consequence, the transepithelial voltage is reduced & potassium secretion is inhibited. Decreased renal potassium excretion secondary to these direct effects on kidney tubules leads to hyperkalemia in a substantial number of patients being treated with trimethoprim-containing drugs.

Pharmacodynamics

Trimethoprim exerts its antimicrobial effects by inhibiting an essential step in the synthesis of bacterial nucleic acids and proteins. It has shown activity against several species of gram-negative bacteria, as well as coagulase-negative _Staphylococcus_ species. Resistance to trimethoprim may arise via a variety of mechanisms, including alterations to the bacterial cell wall, overproduction of dihydrofolate reductase, or production of resistant dihydrofolate reductase. Rarely, trimethoprim can precipitate the development of blood disorders (e.g. thrombocytopenia, leukopenia, etc.) which may be preceded by symptoms such as sore throat, fever, pallor, and or purpura - patients should be monitored closely for the development of these symptoms throught the course of therapy. As antimicrobial susceptibility patterns are geographically distinct, local antibiograms should be consulted to ensure adequate coverage of relevant pathogens prior to use.