Recommended
More Related Content
What's hot
What's hot (20)
Similar to Sulfa drug- Mechanism of action-Resistance mechanism
Similar to Sulfa drug- Mechanism of action-Resistance mechanism (20)
Recently uploaded
Recently uploaded (20)
Sulfa drug- Mechanism of action-Resistance mechanism
- 1. Sulfa Drug MOA & Resistance SUBMITTED BY HASNAIF MOHAMMAD MOSTAKIM SIFAT (01102132002) MICROBIOLOGY AND IMMUNOLOGY BANGLADESH UNIVERSITY OF HEALTH SCIENCES
- 2. Sulfa Drug Sulfa is found in a variety of medications, including antibiotics and nonantibiotics drugs. Sulfa drug, also called sulfonamide Antibiotics containing the sulfanilamide
- 3. History First observed in 1932 Clinical usage in 1935 Widely used drug during WW II Gerhard Domagk(para-aminobenzenesulfonamide)
- 4. Sulfonamides Broad spectrum Poor activity against anaerobes Bacteriostatic Sulfa allergic reaction Formation of crystalluria Give toxic metabolites
- 5. Chemical structure Sulfanilamide P-Aminobenzoic acid (PABA) sulfadiazine Sulfamethoxazole
- 6. Mechanism of action Interfering with the synthesis of Folic acid (folate) Microorganism synthesize Folate from PABA
- 7. P-aminobenzoic acid Dihydrofolic acid Dihydropteroate Synthase Sulfonamides (Compete with PABA) Tetrahydrofolic acid Dihyrofolate reductase Purines DNA
- 8. Resistance Over production of PABA Folic acid synthesizing enzyme with low affinity for sulfonamides Impair permeability to the sulfonamide Cross-resistance
- 9. Drug Synergism Cotrimoxazole: Co: for combination Trim: for trimethoprim Oxazole: for Sulfamethoxazole Trimethoprim and sulfamethoxazole at the ratio of 1:5
- 10. P-aminobenzoic acid Dihydrofolic acid Dihydropteroate Synthase Sulfonamides (Compete with PABA) Tetrahydrofolic acid Dihyrofolate reductase Purines DNA Trimethoprim Trimethoxibenzylpyrimidine
- 11. Advantages Expanded number of organisms inhibited Greater inhibition of BAC. growth Bactericidal Decreased resistance Decreased toxicity Hour 0 5 10 100 50 Numberofbacteria No drug Trimethoprim alone Sulfamethoxa zole alone Both drug
- 12. Thank you
Editor's Notes
- They are the first synthetic antibacterial agents. Good antibacterial activity mainly on gram +ve bacteria. The antibacterial effects of sulfonamides were first observed in 1932, when German bacteriologist and pathologist Gerhard Domagk noted the effects of the red dye Prontosil on Streptococcus infections in mice. It was later proved by French researchers that the active agent of Prontosil was sulfanilamide, or para-aminobenzenesulfonamide, a product of the body’s metabolism of Prontosil. By the 1940s sulfanilamide was a widely used drug. During World War II white sulfanilamide powders became standard in first-aid kits for the treatment of open wounds, and sulfanilamide tablets were taken to fight intestinal infections. Though the medicine was relatively safe, allergic reactions such as skin rashes, fever, nausea, vomiting, and even mental confusion were common. With the introduction of less-toxic derivatives and especially with the mass production of penicillin, its use declined.
- Inhibit both gram + and – bacteria, Nocardia sp, Chlamydia tracomatis, and some protozoa. Some enteric bacteria such as, Escherichia coli, Klebsiella pneumoniae, Salmonella, Shigella, and Enterobacter sp. Are also inhibited. Give toxic metabolites after the oxidation of the aromatic amine.
- Sulfonamides have structural similarity to Para-aminobenzoic acid (PABA). NH2 is responsible for pharmacodynamic property of drug. SO2-NH2 group (also called sulfonyl group) is responsible for pharmacokinetic property of drug.
- Sulfonamide-susceptible organisms, unlike mammals, cannot use exogenous folate but must synthesize it from PABA. This pathway is thus essential for production of purines and nucleic acid synthesis. As structural analogs of PABA (p -aminobenzoic acid), sulfonamides inhibit dihydropteroate synthase and folate production. so the bacteria can no longer grow and divide which gives time for the host immune system to destroy the bacterial cells.
- Sulfonamide-susceptible organisms, unlike mammals, cannot use exogenous folate but must synthesize it from PABA. This pathway is thus essential for production of purines and nucleic acid synthesis. As structural analogs of PABA (p -aminobenzoic acid), sulfonamides inhibit dihydropteroate synthase and folate production. so the bacteria can no longer grow and divide which gives time for the host immune system to destroy the bacterial cells.
- Dihydropteroate synthase with low sulfonamide affinity is often encoded on a plasmid that is transmissible and can disseminate rapidly and widely. Sulfonamide-resistant dihydropteroate synthase mutants also can emerge under selective pressure.
- resulting in marked enhancement (synergism) of the activity of both drugs. is bactericidal only 10% of the concentration is needed, compared to concentrations needed when each drug is used alone. The combination also has a broader spectrum of action and greatly reduces the emergence of resistant strains.