SULFACHLORPYRIDAZINE SODIUM
Chemistry - Sulfachlorpyridazine sodium is listed as a short to intermediate-acting, low lipidsoluble sulfonamide antibacterial. It is reportedly very soluble in urine at usual pH's.
No information was located regarding the compatibility of sulfachlorpyridazine with other fluidsor agents.
Microorganisms that are usually affected by sulfonamides include some gram positive bacteria, including some strains of streptococci, staphylococcus, Bacillus anthracis, Clostridium tetani, C.perfringens and many strains of Nocardia. Sulfas also have in vitro activity against some gramnegative species, including some strains of Shigella, Salmonella, E. coli, Klebsiella, Enterobacter,
Pasturella and Proteus. Sulfas also have activity against some rickettsia, and protozoa(Toxoplasma, Coccidia). Unfortunately, resistance to sulfas is a progressing phenomenon andmany strains of bacteria that were once susceptible to this class of antibacterial are now resistant.
The sulfas are less efficacious in pus, necrotic tissue or in areas with extensive cellular debris.
Sulfas are well distributed throughout the body and some reach significant levels in the CSF.
Levels of the drugs tends to be highest in liver, kidney and lung, and lower in muscle and bone. Thesulfas can be highly bound to serum proteins, but the extent of binding is species and drugdependent. When bound to proteins the sulfa is not active.
Sulfas cross the placenta and may reach fetal levels of 50% or greater of those found in maternalserum. Sulfonamides also are distributed into milk.
Sulfonamides are both renally excreted and metabolized. Renal excretion of unchanged drugoccurs via both tubular secretion and glomerular filtration. Protein bound drug is not filtered by theglomeruli. Metabolism is performed principally by the liver, but extra-hepatic metabolism is alsoinvolved. Mechanisms of metabolism are usually acetylation and glucuronidation. The acetylatedmetabolites may be less soluble and crystallization in the urine can occur with some sulfonamides, particularly at lower pH. The serum half-life of sulfachlorpyridazine is approximately 1.2 hours incattle.
Oral sulfonamides can depress the normal cellulytic function of the ruminoreticulum, but thiseffect is generally temporary and the animal adapts.
Sulfas cross the placenta and teratogenicity has been reported in some laboratory animals whengiven at very high doses. They should be used in pregnant animals only when the benefits clearlyoutweigh the risks of therapy.
Too rapid intravenous injection of the sulfas can cause muscle weakness, blindness, ataxia andcollapse.
In dogs, keratoconjunctivitis sicca has been reported with sulfonamide therapy. Also, in dogs, bonemarrow depression, hypersensitivity reactions (rashes, dermatitis), focal retinitis, fever, vomiting andnonseptic polyarthritis have been reported.
Oral sulfonamides can depress the normal cellulytic function of the ruminoreticulum, but thiseffect is generally temporary and the animal adapts.
Because solutions of sulfonamides are usually alkaline, they can cause tissue irritation andnecrosis if injected intramuscularly or subcutaneously.
Antacids may decrease the oral bioavailability of sulfonamides if administered concurrently.
Drug/Laboratory Interactions - Sulfonamides may give false-positive results for urine glucosedeterminations when using the Benedict's method.
Storage, Stability, Compatibility
-The injection should be stored at room temperature and protected from light; avoid freezing. The oral suspension should be stored at room temperature; avoidfreezing. The oral boluses and powder should be stored at room temperature; avoid excessive heat(above 40°C/104°F).No information was located regarding the compatibility of sulfachlorpyridazine with other fluidsor agents.
Pharmacology - SULFACHLORPYRIDAZINE SODIUM
Sulfonamides are usually bacteriostatic agents when used alone. They are thoughtto prevent bacterial replication by competing with para-aminobenzoic acid (PABA) in thebiosynthesis of tetrahydrofolic acid in the pathway to form folic acid. Only microorganisms thatsynthesize their own folic acid are affected by sulfas.Microorganisms that are usually affected by sulfonamides include some gram positive bacteria, including some strains of streptococci, staphylococcus, Bacillus anthracis, Clostridium tetani, C.perfringens and many strains of Nocardia. Sulfas also have in vitro activity against some gramnegative species, including some strains of Shigella, Salmonella, E. coli, Klebsiella, Enterobacter,
Pasturella and Proteus. Sulfas also have activity against some rickettsia, and protozoa(Toxoplasma, Coccidia). Unfortunately, resistance to sulfas is a progressing phenomenon andmany strains of bacteria that were once susceptible to this class of antibacterial are now resistant.
The sulfas are less efficacious in pus, necrotic tissue or in areas with extensive cellular debris.
Uses, Indications
Sulfachlorpyridazine is indicated for the treatment of diarrhea caused orcomplicated by E. coli in calves less than one month of age or for the treatment of colibacillosis inswine. It is also used parenterally as a general purpose sulfonamide in adult cattle and other species.Pharmacokinetics - SULFACHLORPYRIDAZINE SODIUM
Very limited information is available on the specific pharmacokinetics for thisagent. In general, sulfonamides are readily absorbed from the GI tract of non-ruminants, butabsorption can vary depending on the drug, species, disease process, etc.. Food delays the rate, butusually not the extent of absorption. Peak levels occur within 1-2 hours in non-ruminant (andyoung pre-ruminant) animals. Adult ruminants may have significant delays before the drug is absorbed orally.Sulfas are well distributed throughout the body and some reach significant levels in the CSF.
Levels of the drugs tends to be highest in liver, kidney and lung, and lower in muscle and bone. Thesulfas can be highly bound to serum proteins, but the extent of binding is species and drugdependent. When bound to proteins the sulfa is not active.
Sulfas cross the placenta and may reach fetal levels of 50% or greater of those found in maternalserum. Sulfonamides also are distributed into milk.
Sulfonamides are both renally excreted and metabolized. Renal excretion of unchanged drugoccurs via both tubular secretion and glomerular filtration. Protein bound drug is not filtered by theglomeruli. Metabolism is performed principally by the liver, but extra-hepatic metabolism is alsoinvolved. Mechanisms of metabolism are usually acetylation and glucuronidation. The acetylatedmetabolites may be less soluble and crystallization in the urine can occur with some sulfonamides, particularly at lower pH. The serum half-life of sulfachlorpyridazine is approximately 1.2 hours incattle.
Contraindications, Precautions, Reproductive Safety
Sulfonamides are contraindicated in patients hypersensitive to them, thiazides, or sulfonylurea agents. They are also considered contraindicated in patients with severe renal or hepatic impairment and should be used with caution inpatients with diminished renal or hepatic function, or urinary obstruction.Oral sulfonamides can depress the normal cellulytic function of the ruminoreticulum, but thiseffect is generally temporary and the animal adapts.
Sulfas cross the placenta and teratogenicity has been reported in some laboratory animals whengiven at very high doses. They should be used in pregnant animals only when the benefits clearlyoutweigh the risks of therapy.
Adverse Effects, Warnings
Sulfonamides (or their metabolites) can precipitate in the urine, particularly in an acidic environment resulting in crystalluria, hematouria and renal tubule obstruction. Different sulfonamides have different solubilities at various pH's. Alkalinization of theurine using sodium bicarbonate may prevent crystalluria, but it also decreases the amount availablefor tubular reabsorption. Crystalluria can usually be avoided with most of the commerciallyavailable sulfonamides by maintaining an adequate urine flow. Normal urine pH in herbivores isusually 8 or more so crystalluria is not frequently a problem in those species. Sulfonamides canalso cause various hypersensitivity reactions or diarrhea by altering the normal gut flora.Too rapid intravenous injection of the sulfas can cause muscle weakness, blindness, ataxia andcollapse.
In dogs, keratoconjunctivitis sicca has been reported with sulfonamide therapy. Also, in dogs, bonemarrow depression, hypersensitivity reactions (rashes, dermatitis), focal retinitis, fever, vomiting andnonseptic polyarthritis have been reported.
Oral sulfonamides can depress the normal cellulytic function of the ruminoreticulum, but thiseffect is generally temporary and the animal adapts.
Because solutions of sulfonamides are usually alkaline, they can cause tissue irritation andnecrosis if injected intramuscularly or subcutaneously.
Overdosage, Acute Toxicity
Acute toxicity secondary to overdoses apparently occurs only rarelyin veterinary species. In addition to the adverse effects listed above, CNS stimulation and myelindegeneration have been noted after very high dosages.Drug Interactions
Sulfachlorpyridazine or other sulfonamides may displace highly proteinbound drugs, such as methotrexate, warfarin, phenylbutazone, thiazide diuretics, salicylates, probenicid and phenytoin. Although the clinical significance of these interactions isnot entirely clear, patients should be monitored for enhanced effects of the displaced agents.Antacids may decrease the oral bioavailability of sulfonamides if administered concurrently.
Drug/Laboratory Interactions - Sulfonamides may give false-positive results for urine glucosedeterminations when using the Benedict's method.