Sulfonamides, Trimethoprim, & Quinolones PDF

Sulfonamides, Trimethoprim, & Quinolones Asst. Prof. Zülfiye GÜL  ac!ds necessary for...

Sulfonamides, Trimethoprim, & Quinolones Asst. Prof. Zülfiye GÜL  ac!ds necessary for nucle!c ANA/RNA Fol!c Ac!d (V!tam!n Bg) - - Bacter!a ac!d para-am!nobenzo!e ac!d (PABA) efed!hydropter!c ac!d ↳ d!hydrofol!c d!hydrofol!e d!hydropter d!hydrofolate Synthetase reductase Synthetase Sulfenam!des tetrahydrofol!c sulfamethoxazole (SMX) Y · !nh!b!t ac!d · sulf!soxazole d!hydropteroate ↓ · sulfad!az!ne synthetase pur!nes/thymed!ne ag!ven perorally or !njected l!ver metabol!zed by a TMP/SMX nocard!a chlamyd!a, synerg!st!c - TRIMETHOPRIM reductase -bacter!c!dal (together) tract !nf. s!nh!b!ts d!hydrofolate traveler's < d!arhee ,pneumon!a,ur!nary apneumocyst!s g!rovec!! Fluoroqu!ondones * MRSA < !nh!b!ts DNA topo!somerase topo!somerase II (DNA gyrase) topo!somerace 11 2 breaks double strand * -floxac!n * gram negat!ve > - Not w!ron , Z!nc , calc!um d!sorder X No !n pregnant - cort!lage SULFONAMİDES Mechanism of Action & Antimicrobial Activity Gram-positive bacteria, such as Staphylococcus sp Gram-negative enteric bacteria such as Escherichia coli, Klebsiella pneumoniae, Salmonella, Shigella, Yükleniyor… Activity is poor against anaerobes. Pseudomonas aeruginosa is intrinsically resistant to sulfonamide antibiotics. - Yükleniyor… Resistance Mechanism - 1) cause overproduction of PABA A 2) cause production of a folic acid- synthesizing enzyme that has low affınity for sulfonamides - tr!metrop!m & cause production of a folic acid- synthesizing enzyme that has low - affınity for trimethoprim 3) impair- permeability to the sulfonamide  Clinical Uses a. Simple urinary tract infections—Oral (eg, triple sulfa, sulfisoxazole) V b. Ocular infections—Topical (eg, sulfacetamide) v c. Burn infections—Topical (eg, mafenide, silver sulfadiazine) ~ d. Ulcerative colitis, rheumatoid arthritis—Oral (eg, sulfasalazine) V e. Toxoplasmosis—Oral sulfadiazine plus pyrimethamine (a dihydrofolate reductase inhibitor) plus folinic acid) V Clinical Uses Trimethoprim can be given alone (100 mg twice daily) in acute urinary tract infections. Trimethoprim-sulfamethoxazole (TMP-SMZ) urinary tract infections respiratory, ear, and sinus infections caused by Haemophilus influenzae and Moraxella catarrhalis. In the immuno compromised patient, Aeromonas hydrophila prevention treatment of pneumocystis pneumonia An intravenous formulation pneumocystis pneumonia gram-negative sepsis. nocardiosis, a possible backup drug for cholera, typhoid fever, and shigellosis  Adverse. Reaction Hypersensitivity Allergic reactions, including skin rashes and fever, occur commonly. Exfoliative dermatitis and Stevens-Johnson syndrome have occurred rarely. 2. Gastrointestinal Nausea, vomiting, and diarrhea occur commonly. Mild hepatic dysfunction can occur, but hepatitis is uncommon. 3. Hematotoxicity Yükleniyor… granulocytopenia, thrombocytopenia, and aplastic anemia. Acute hemolysis may occur in persons with glucose-6-phosphate dehydrogenase deficiency. 4. Nephrotoxicity Sulfonamides may precipitate in the urine at acidic pH, causing crystalluria and hematuria. Drug Interactions Competition with warfarin and methotrexate for plasma protein binding transiently increases the plasma levels of these drugs. Sulfonamides can displace bilirubin from plasma proteins, with the risk of kernicterus in the neonate if used in the third trimester of pregnancy. FLUOROQUINOLONES Mechanism of Action & Antimicrobial Activity  Resistance Production of O efflux pumps or changes in porin structure (in gram-negative bacteria). - M tuberculosis, S aureus, and S pneumoniae Changes in the sensitivity of the target enzymes via point mutations in the antibiotic binding regions are also established to confer resistance against specific fluoroquinolones. gonococci. Clinical Use urogenital and gastrointestinal tracts infection gram-negative organisms, including gonococci, E coli, Klebsiella pneumoniae, C jejuni, Enterobacter, P aeruginosa, Salmonella, and Shigella species. Levofloxacin most organisms associated with community-acquired pneumonia, including chlamydiae, mycoplasma, and legionella species v Gemifloxacin and moxifloxacin - atypical pneumonia gents, and some anaerobic bacteria. Fluoroquinolones have also been used in the meningococcal carrier state, in the treatment of tuberculosis, and in prophylactic management of neutropenic patients. -  Gastrointestinal distress headache, dizziness, insomnia tendinitis and tendon rupture. children or pregnant women (may damage growing cartilage and cause arthropathy) v prolong the QTc interval. They should be avoided in patients with known QTc prolongation and those on certain antiarrhythmic drugs ~