Sulfonamide
Sulfonamide is a functional group that is the basis of several groups of drugs, which are called sulphonamides, sulfa drugs or sulpha drugs. The original antibacterial sulfonamides are synthetic antimicrobial agents that contain the sulfonamide group. Some sulfonamides are also devoid of ant…
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How do sulfonamide antibiotics work?
Sulfonamides are the oldest and remain among the most widely used antibacterial agents in veterinary medicine, chiefly because of low cost and their relative efficacy in some common bacterial diseases. The synergistic action of sulfonamides with specific diaminopyrimidines renders these drugs much more effective than sulfonamides alone.
What are sulfonamides?
ELUSCatsEL: Sulfadiazine and trimethoprim injection is indicated in the treatment of bacterial infections, such as abscesses and wounds, caused by susceptible organisms.{R-8} Dogs: ELCANOrmetoprim and sulfadimethoxine tabletsEL are indicated in the treatment of skin and soft tissue infections caused by susceptible E. coli and Staphylococcus
How often do you give sulfonamides to dogs?
It is indicated for the treatment of bovine mastitis @500mg/quarter. It is added @13.2 mg/kg in milk replacer for prevention of colibacillosis in calves. In poultry it is effective against fowl typhoid S. typhimurium infection and mycoplasmosis. For …
Why are sulfonamides considered bacteriostatic?
Sulfonamides are some of the earliest used antibiotic drugs in both humans and animals. In the past, their availability and low cost made them popular options for treating many animal diseases, such as bacterial pneumonia, bacterial scours, coccidiosis and foot rot.
What are sulfonamide antibiotics used for?
Also referred to as sulfa drugs, sulfonamides are man-made antibiotics that are used to treat bacterial infections. If you are struggling with a UTI, bronchitis, pneumonia, or have an eye or ear infection that requires an antibiotic, your health care provider may prescribe you sulfonamides.Dec 28, 2021
What are sulfonamides used for in dogs?
The sulfonamides are commonly used to treat or prevent acute systemic or local infections. Disease syndromes treated with sulfonamides include actinobacillosis, coccidiosis, mastitis, metritis, colibacillosis, pododermatitis, polyarthritis, respiratory infections, and toxoplasmosis.
What infections do sulfonamides treat?
Sulfonamides, or "sulfa drugs," are a group of medicines used to treat bacterial infections. They may be prescribed to treat urinary tract infections (UTIs), bronchitis, eye infections, bacterial meningitis, pneumonia, ear infections, severe burns, traveler's diarrhea, and other conditions.Dec 1, 2015
What are the indications of sulfonamides?
Indications for SulfonamidesA broad spectrum of gram-positive and many gram-negative bacteria.Plasmodium. Symptoms and signs include fever (which may be periodic), chills, rigors, sweating, diarrhea, abdominal pain, respiratory distress, confusion... read more and Toxoplasma.
What are examples of sulfonamides?
Examples of sulfonamides includes sulfadiazine, sulfamethizole (brand name: Thiosulfil Forte), sulfamethoxazole (Gantanol), sulfasalazine (Azulfidine), sulfisoxazole (Gantrisin), and various high-strength combinations of three sulfonamides. Sulfa drugs kill bacteria and fungi by interfering with cell metabolism.
What is sulfonamides in pharmacology?
Sulfonamides or sulfa drugs are a class of antibiotics that target bacteria causing infections. These classes of drugs are generally broad-spectrum antibiotics that act on a wide range of bacterial types and are therefore employed in treating many kinds of bacterial infections.
What do sulfonamides target?
Sulfonamides target the enzyme dihydropteroate synthase (DHPS) that catalyzes a key step in microbial folate biosynthesis, the production of 7,8-dihydropteroate from para-aminobenzoic acid (pABA) and dihydropterin pyrophosphate (DHPP).Jul 17, 2018
What is the action of sulfonamides?
Sulfonamides. Although sulfonamides are bacteriostatic and act by blocking utilization of para-aminobenzoic acid (PABA) by bacteria, potential sulfonamides in more common use are bactericidal. Sulfonamides inhibit many gram-positive and some gram-negative organisms, including Pseudomonas spp.
Which adverse effect is most common with sulfonamides?
Skin reactions, from benign rash to potentially lethal toxidermias, are the most frequent ADRs to sulfonamides. Other major ADRs include acute liver injury, pulmonary reactions, and blood dyscrasias.
Why are sulfonamide selective to bacteria?
Mammalian cells lack dihydropteroate synthase and cannot synthesize folic acid. They are dependent on a nutritional supply of this vital compound. This is the basis for the selective action of sulfonamides on bacteria.Jan 10, 2014
Which sulfonamides are mainly used in treatment of eye infection?
Efficacy. Sulfacetamide is a sulfonamide antibiotic, that is used as a cream to treat skin infections and as eye drops to treat eye infections.
What are sulfonamides Slideshare?
The original antibacterial sulfonamides are synthetic antimicrobial agents that contain the sulfonamide group. Sulfonamide (also called sulphonamide, sulfa drugs or sulpha drugs) is the basis of several groups of drugs.
Why are sulfonamides used in veterinary medicine?
Sulfonamides are the oldest and remain among the most widely used antibacterial agents in veterinary medicine, chiefly because of low cost and their relative efficacy in some common bacterial diseases. The synergistic action of sulfonamides with specific diaminopyrimidines renders these drugs much more effective than sulfonamides alone.
Why are sulfonamides inappropriate for veterinary use?
The standard classification of short-, medium-, and long-acting sulfonamides used in human therapeutics is usually inappropriate in veterinary medicine because of species differences in disposition and elimination.
What is the classification of sulfonamides?
Probably the most common classification is based on water versus lipid solubility or duration of effect.
How often is sulfonamide given?
In most species, members of this large group are administered 1–4 times/day, depending on the drug, to control systemic infections caused by susceptible bacteria. In some instances, administration of the sulfonamide can be less frequent if the drug is eliminated slowly in the species being treated. Sulfonamides included in this class, depending on ...
Where are sulfonamides distributed?
Sulfonamides are distributed throughout all body tissues. The distribution pattern depends on the ionization state of the sulfonamide, the vascularity of specific tissues, the presence of specific barriers to sulfonamide diffusion, and the fraction of the administered dose bound to plasma proteins.
What are the names of the sulfonamides?
Sulfonamides included in this class, depending on the species, are sulfathiazole, sulfamethazine (sulfadimidine), sulfamerazine, sulfadiazine, sulfapyridine, sulfabromomethazine, sulfaethoxypyridazine, sulfamethoxypyridazine, sulfadimethoxine, and sulfachlorpyridazine.
How are sulfonamides metabolized?
Sulfonamides are usually extensively metabolized, mainly by several oxidative pathways, acetylation, and conjugation with sulfate or glucuronic acid. Species differences are marked in this regard. The acetylated, hydroxylated, and conjugated forms have little antibacterial activity.
What is the effect of sulfonamide on bacteria?
The combined and synergistic activities of the two agents in each type of potentiated sulfonamide produce antibacterial activity against a wide range of infections caused by gram-positive and gram-negative bacteria, some protozoa, and some anaerobes under certain conditions.{R-44} The minimum inhibitory concentrations against specific susceptible bacteria for each antibiotic are generally lowered when the antibiotics are administered in the potentiated sulfonamide combination. The resistance developed to the potentiated sulfonamides is lower than that to each individual agent;{R-20; 23} this is an important benefit because of the common resistance to sulfonamides and rapid development of resistance to diaminopyrimidines when used alone.{R-20} Cross-resistance between sulfonamides is considered complete and often occurs between pyrimidines, as well.{R-25; 94}
What is the role of sulfonamides in bacterial cells?
Sulfonamides—The sulfonamides are bacteriostatic antimicrobials that interfere with the biosynthesis of folic acid in bacterial cells; they compete with para-aminobenzoic acid (PABA) for incorporation into dihydrofolic acid.{R-20} By replacing the PABA molecule in dihydrofolic acid, they prevent formation of folic acid required for nucleic acid synthesis and multiplication of the bacterial cell.{R-94;101} Sulfonamides are effective only in cells that must produce their own folic acid; mammalian cells do not synthesize folic acid, but get it from outside sources.
Why are MICs of sulfonamides misleading?
Although the minimum inhibitory concentrations (MICs) of potentiated sulfonamides are important in determining therapeutic regimens, they can be misleading because the actual concentrations of drugs at the therapeutic site can be difficult to pinpoint at any one time. Trimethoprim goes rapidly into tissues, and sulfonamides often have measurable serum concentrations for longer periods. The ratio of sulfonamide to trimethoprim concentrations necessary at the site for efficacy may vary from the goal of 20 to 1, depending on the tissue and the local concentrations of other factors, such as thymidine.{R-24} Clinical efficacy also should be considered, once pathogen susceptibility has been determined.{R-24; 31}
How much sulfonamide is in milk?
Sulfonamides are distributed into milk, with 0.5 to 2% of the total dose found in the milk.{R-114; 115} For example, the milk-to-plasma concentration ratio for sulfadiazine and sulfadoxine was measured to be 0.5 in cows.{R-75; 82}
Where are sulfonamides metabolized?
Sulfonamides—Sulfonamides are metabolized primarily in the liver, but metabolism also occurs in other tissues. Biotransformation occurs by acetylation, glucuronide conjugation, and aromatic hydroxylation in many species.{R-94} The types of metabolites formed and the amount of each varies depending on the specific sulfonamide administered; the species, age, diet, and environment of the animal; the presence of disease; and, with the exception of pigs and ruminants, the gender of the animal.{R-105-108} N4-acetyl metabolites have no antimicrobial activity and hydroxymetabolites have 2.5 to 39.5% of the activity of the parent compound.{R-109} Metabolites may compete with the parent drug for involvement in folic acid synthesis. They have little detrimental effect on the bacterial cell, so their presence could decrease the activity of the remaining parent drug.{R-109} Sulfadiazine—Calves: Sulfadiazine is excreted primarily as unchanged drug in the urine; the percentage of unchanged drug excreted increases from 1 day of age to 42 days of age, changing from 22 to 50%.{R-79}
What is ElUSArthritis, bacterial (treatment)EL?
ELUSArthritis, bacterial (treatment)EL—Pigs: Sulfadoxine and trimethoprim injection is indicated in the treatment of bacterial arthritis caused by susceptible organisms.{R-13-15} Coccidiosis (prophylaxis)— Chickens: ELCANOrmetoprim and sulfadimethoxine Type A medicated articleEL{R-6} is indicated in the prevention of coccidiosis caused by susceptible Eimeria acervulina, E. brunetti, E. maxima, E. mivati, E. necatrix, and E. tenella. ELUSPyrimethamine and sulfaquinoxaline oral solution is indicated in the prevention of coccidiosis, caused by susceptible organisms.EL{R-17} ELCANPartridges, chukarEL: Ormetoprim and sulfadimethoxine Type A medicated article is indicated in the prevention of coccidiosis caused by susceptible Eimeria kofoidi and E. legionensis.{R-6; 125}
How cold should I store a sandpaper sandpaper?
Store below 40 ºC (104 ºF), preferably between 15 and 30 ºC (59 and 86 ºF), in a tight container, unless otherwise specified by the manufacturer. Protect from light.{R-22}
What is sulfonamide used for?
Sulfonamides are synthetic chemotherapeutic agents. They were in common use as antimicrobial drugs prior to the advent of antibiotics. Frequent development of cross drug resistance in bacteria isolated from animals has now-a-days reduced their clinical values.
What is the action of sulfonamides?
Mode of Action: Sulfonamides compete with paraaminobenzoic acid (PABA) for the catalytic site of the enzyme dihydropteroate synthatase (Woods, 1940) thereby inhibiting conversion of PABA to folic acid in bacteria. This action of sulfonamide is selective over bacteria without interfering animal cells.
How are drugs distributed?
Distribution of the drug, however, depends upon ionization of drug and barriers to diffusion vascularity of tissues. Drug distribution occurs by passive diffusion. Metabolism of drug affects its antibacterial toxic activity.
Where are sulfonamides excreted?
Sulfonamides are excreted as such or as metabolic products. They are eliminated in urine, faeces, bile, milk and sweat. Urine is the main source of their excretion.
How are sulfonamides metabolized?
Sulfonamides are metabolized in the body by acetylation, oxidation, conjugation with sulphate or glucuronic acid and cleavage of heterocyclic ring. Acetylated, hydroxylated and conjugated sulfonamides have less antibacterial activity. Acetylated drugs cause renal damage because of their insolubility.
Is nephrotoxicity toxic to animals?
A wide variety of side effects are produced. This may be allergic or toxic. Nephrotoxicity is common side effect. Renal damage is characterised by crystalluria, haematuria and obstruction of renal tubules. During therapy water should be readily available to animals to maintain adequate hydration to avoid occurrence of crystalluria.
Is sodium salt soluble in water?
Sodium salts are however easily soluble in water. The sulfacetamide is neutral in pH and is used to combat eye infections. The basic structure of sulfanilamide and PABA is given in Fig 25.1. The nitrogen of amino group at para position is designated as N 4 while nitrogen of So 2 NH 2 is designated as N 1.
Warnings
Milk taken from treated animals during treatment and within 96 hours after the latest treatment with this drug must not be used as food. Treated animals must not be slaughtered for use in food for at least 10 days after the latest treatment with this drug. This product must not be added to swine feeds.
Dosage and Administration
To reduce the development of antimicrobial resistance and maintain effectiveness, use this antibiotic prudently.
What is the NH2 group in sulfonamide antibiotics?
Sulfonamide antibiotics contain an SO2 -NH 2 group that gets metabolized to reactive, haptenic nitroso compounds in the liver. IgE-mediated reactions are infrequent, and most cases are due to T-cell–mediated reactions.
What are sulfa drugs?
The sulfonamides, known widely as sulfa drugs, were the first antibacterial agents and paved the way for the antimicrobial revolution in medicine. 7 Sulfonamide antibiotics such as sulfamethoxazole (SMX), sulfadiazine (SDZ), and sulfadimethoxine (SDM), potentiated by combination with either trimethoprim (TMP) or ormetoprim (OMP), inhibit two consecutive steps in bacterial folic acid synthesis.1 Folate is necessary for cells to synthesize nucleic acids, and in its absence cells are unable to divide. Folate is not synthesized in mammalian cells but is instead a dietary requirement. 1 This explains the selective toxicity of these agents to bacterial cells. 7
What is TMS antibiotic?
TMS antibiotics have a broad spectrum of activity and can be used to treat gram-positive and many gram-negative bacterial infections, as well as some protozoal infections . Enterococci are intrinsically resistant to TMS antibiotics. Many anaerobic bacteria are not treated successfully because despite in vitro susceptibility, the drugs are less active in tissues where anaerobes proliferate. TMS antibiotics are the treatment of choice for nocardiosis. They have also been used successfully for prevention of bacterial infections in dogs being treated with myelosuppressive chemotherapeutics such as doxorubicin. 49 Prophylactic protocols have selected for resistant bacteria in humans, 50 but this has not been reported in animals. TMS combinations are available as either trimethoprim-sulfadiazine or trimethoprim-sulfamethoxazole (the latter is a human medical preparation), which are used interchangeably. However, the veterinary formulation of trimethoprim-sulfadiazine is rarely available commercially, and most veterinarians rely on trimethoprim-sulfamethoxazole. No difference in activity between the two formulations has been documented, but this has never been evaluated. The primary difference between the formulations is that sulfadiazine is more water soluble and is excreted in the urine in an unchanged form. A similar formulation to the trimethoprim-sulfonamides for use in veterinary medicine is ormetoprim sulfadimethoxine, which has been used for the same indications as trimethoprim-sulfonamides. Doses for TMS combinations are listed in Table 8-10.
Can sulfonamides be tested?
Skin testing with sulfonamides lacks good predictive value. As with other drugs, graded challenges can be performed if the likelihood is low for true allergy. 39 Most experts believe that testing for sulfonamide allergy should be approached with caution because of the well-known propensity for these drugs to cause severe cutaneous adverse reactions.
What is the role of sulfonylureas in the release of endogenous insulin?
The sulfonylureas are thoughtto act by a variety of mechanisms to ultimately cause the release of endogenous insulin. Sulfonylureas may also enhance insulin receptor binding. 11 Chlorpropamide potentiates the effect of vasopressin in the renal tubules and may also stimulate vasopressin secretion. 1
Can HIV be treated with antibiotics?
In nonimmediate reactions with mild rashes, especially in HIV-positive individuals, the antibiotic can be continued (“treating through”) or readministered after a gradually increasing dosing protocol, with good success rates. 40 Such reactions are not IgE mediated. Furthermore, these so-called desensitization procedures may or may not truly induce drug tolerance and do require monitoring for more serious systemic involvement. These measures should not be pursued in patients with severe nonimmediate reactions and have not been studied in immunocompetent patients.
What are the symptoms of sulfonylurea toxicosis?
Clinical signs secondary to hypoglycemia of other causes have included ataxia, weakness, behavioral changes, and coma. 16 Four of 50 cats treated with 2.5 mg of glipizide twice daily developed jaundice, increased total bilirubin concentration, and liver enzymes within 4 weeks of starting treatment. Other adverse effects seen in this prospective study included anorexia and vomiting. Signs resolved within 5 days of discontinuing the glipizide. 19 Tolbutamide and tolazamide have positive inotropic and arrhythmogenic effects on the cardiovascular system of dogs. 20
What is sulfadimethoxine 40%?
Sulfadimethoxine Injection 40% is indicated for the treatment of bovine respiratory disease complex (shipping fever complex) and bacterial pneumonia associated with Pasteurella Spp. sensitive to sulfadimethoxine; neurotic pododermatis (foot rot) and calf diphtheria caused by Fusobacterium necrophorum (Sphaerophorus necrophorus), sensitive to sulfadimethoxine.
How long after slaughter can you give milk?
Milk taken from animals during treatment and for 60 hours (5 milkings) after the latest treatment must not be used for food. Do not administer within 5 days of slaughter.
What is sulfonamide used for?
They are derivatives of sulfanilic acid (p -aminobenzenesulfonic acid), and they are used for prophylactic and therapeutic treatment of infections caused by gram-positive and gram-negative bacteria and some protozoa (causative agents of malaria, toxoplasmosis, etc.).
What is the mechanism of action of sulfonamides?
Mechanism of Action. The sulfonamides inhibit the bacterial enzyme dihydropteroate synthetase (DPS) in the folic acid pathway, thereby blocking bacterial nucleic acid synthesis. Sulfonamides substitute for PABA, preventing its conversion to dihydrofolic acid. Alone, this action is considered bacteriostatic.
What is the role of sulfonamide in folic acid?
Sulfonamides inhibit dihydropteroate synthase (DHPS) which condenses pteroate and p-aminobenzoic acid (pABA) to form dihydropteroate from which folic acid is generated. The folic acid is an essential enzyme for bacteria which can synthesize it. The sulfonamide competes with pABA at the active site of the enzyme to act as an alternative substrate and produce pteroate-sulfonamide complex from which the bacteria cannot generate folic acid. Resistance to sulfonamide is associated with amino acid substitutions in DHPS enzyme which prevents the drug binding. The sulfonamide resistant S. aureus strains have chromosomally encoded genes producing amino acid substitutions in DHPS enzyme ( Hampele et al., 1997 ).
Where are sulfonamides found?
Highest tissue concentrations of sulfonamides plus metabolites are found in the liver and kidney of various food-producing species, but the rather high rate of sulfonamide-related violations in pig liver has decreased considerably over the past decades. View chapter Purchase book. Read full chapter. ...
Does trimethoprim inhibit tetrahydrofolic acid?
Trimethoprim inhibits the subsequent conversion of dihydrofolic acid to tetrahydrofolic acid by inhibiting dihydrofolic acid reductase. The combined activity of trimethoprim-sulfonamide as a result inhibits two successive steps in the folic acid pathway, producing a bactericidal effect. View chapter Purchase book.
Can sulfonamide cause hepatitis?
Sulfonamides can cause both acute and chronic toxic effects. The reactions are due to hypersensitivity and direct toxic effect. Anaphylactoid reactions have been reported with sulfonamides. Several adverse reactions have been reported after prolonged treatment including bone marrow depression, hepatitis, icterus, peripheral neuritis and myelin degeneration in the spinal cord and peripheral nerves, photosensitization, stomatitis, keratoconjunctivitis (Kahn, 2005).
What organs are affected by toxicity?
The most important organ affected in toxicity is the kidney. Animals with renal toxicity show elevated levels of blood urea nitrogen (BUN) and creatinine. In some animals sulfonamide crystals will be observed in the renal pelvis as a gross finding and kidneys may be gritty in texture when cut.
Regulatory Issues
- When used improperly, sulfonamides can be hazardous to human health. While many steps have been taken to ensure that the food supply is safe from toxic levels of sulfonamides, they remain a top concern. The FDA-CVM has established a tolerance of 0.1 part per million for negligible resid…
Drugs in Market Show Animals
- While drugs intended for medical purposes (such as antibiotics) and drugs used to enhance production (such as growth hormones) are approved for use in market show animals, some shows may not permit some medical drugs that are used as performance enhancers. Glucocorticoids such as dexamethasone may fall into this category. Other drugs that are not ap…
Acknowledgments
- The authors wish to thank M. Bailey, W. Kirkpatrick and B. Lawhorn for contributing to this publication.
References
- Ballentine, Carol. “Taste of Raspberries, Taste of Death.” U.S. Food and Drug Administration. June 1981. FDA Consumer Magazine. Last retrieved Dec. 2007 at http://www.fda.gov/oc/history/elixir. html. U.S. Food and Drug Administration. Center for Veterinary Medicine.” Guideline for Establishing a Safe Concentration.” Last retrieved Dec. 2007 at http://www.fda.gov/cvm/Guidanc…