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20 Cards in this Set
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Describe "Sulfonamides"
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Derivatives of PABA (ingredient in sunscreen), Prontosil as precursor, 1st agents used against bacteria
Described by Hildegard Domagk |
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List some diseases in which sulfonamides play important role
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Bronchitis, IBD, Otitis, PCP, Burns, UTI, Sinusitis
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BIOP BUS
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List some rapidly absorbed Sulfonamides
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Short acting: 4-8 hrs
Sulfisoxazole Sulfadiazine Intermediate Acting:12-18 hrs Sulfamethoxazole Long acting Sulfadoxine |
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List some poorly absorbed Sulfonamides
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Sulfasalazine used in IBD&RA
In GI it converted into 5-ASA and Sulfapyridine (revesible infertility due to change count&morphology) Pentasa: deliver to enter GI and small intestine Asacol: terminal ileum and beyond Olsalazine: a prodrug, couple to 5-ASA split by intestinal bacteria Rowasa: Rectal enema and suppositories, used for proctosigmoiditis |
OPRA drugs: Olsalazine, Pentasa, Rowasa, Asacol are formulated to be released at a specific GI location. They are poorly absorbed and active in intestinal lumen
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What are the uses of the following Sulfonamides: Sulfacetamide, Mafenide, Silver Sulfadiazine?
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Sulfacetamides: Ophthalmic infection like trachoma (Chlamydia)
Mafenide: for burns AE: Allergy,pain, Carbonic Anhydrase inhibition Silver Sulfadiazine: prevents infection of burnt surface and chronic ulcers with minimal allergy |
AE: for Mafenide
paracarboxybenzenesulfonamide is also CAI Stop Mafenide and infuse Sodium Bicarbonate to prevent acidosis. |
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What's the mechanism of action of Sulfonamides?
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Competitive inhibitors of Dihydropteroate Synthase, enz that add PABA to Dihydropteroic acid, as precursor of folic acid.
BACTERIOSTATIC effet. |
Sulfonamides are incorporated into a dysfunctional folate. they Bacteriostatic, means immune System is required to eliminate the infection.
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Describe Sulfonamides Kinetics
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Most of them are well absorbed from GI, moderate tissue penetration.
Biotrans/liver excr/Kidneys. Inactivation by acetylation They can cross placenta and produce antibact and toxic effect to the fetus. Decrease solubility in acidic urine, precipitation of metabolites or the drug, but higher conc. in urine provide usefulness in UTI |
In renal failure Biodegraded metabolites are toxic.
Slow vs fast acetylators |
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Therapeutic uses?
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Sulfisoxazole+Phenazoppyridine (Dye): UTI, Cystitis
Sulfadiazine+Pyrimethamine=Folonic acid+Hydration =DOC for Toxoplasmosis Short acting Sulfas: Norcardia, trachoma, LVG Sulfamethaxasole+Trimethoprim for UTI, RTI, PCP, Sulfadoxine+Pyrimethamine as prophylaxis in Malaria |
Sulfamethoxazole+Phenazopyridine for UTI
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How do bacteria resist Sulfonamides?
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Lowered affinity/sensitivity to Dihydropteroate Synthase
Incr. in PABA from external sources like procaine administration and pus, tissue breakdown Use preformed folic acid/alternative pathway for essential metabolites decrease permeability, less intrtacellular accumulation./ incr. acetylation |
1. Lowered sensitivity to the enz.
2. Increase usage of Paba from outside and alternative sources 3. Less permeability and fast acetylation |
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What are the AE of Sulfonamides?
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Hypersensitivity; Stevens Johnson Syndrome
Cross Sensitivity: w/ other drugs: Thiazides, oral Hypoglycimic drugs Crystalluria: low solubility of some types, Sulfadiazine used in AIDS for Toxo. Acute Hemolytic Anemia: pts w/ G6PD Deficiency kernicterus: in neonates&Prematures b/c they can displace bilirubin from binding site, premature BBB can allow passage of Sulf. Displacement of drugs like METHOTRAXATE, TOLBUTAMIDE, WARFARIN, Hydantoin, from plasma binding site, incr. of plasma level Drug interaction: Methenamines releases formaldehydes in acid media of urine, forming complex w/ sulf. |
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What's the struture of Trimethoprim? Use as?
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similar to folic acid, weak base that can get caught in acidic media, reaching high conc. in the prostate &vaginal fluid. excr. in urine mostly unchanged
SMZ-TMP (Co-trimoxazole) has a synergistic effect on blockage of Dihydrofolic acid and tetrahydrofolic acid synthesis. Same t1/2,SMZ-TMP ratio 5:1 |
Sequential blockage of Dihydropteroate Synthase and Dihydrofolate reductase
Leading to impaired Purine,pyrimidine and AA synthesis causing impaired DNA synthesis |
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What's the spectrum of activity of SMZ-TMP co-trimoxazole?
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No anearobic cpverage.
Effective against: E.coli, Salmonella and PCP, alternative to Doxycyclin and Streptomycin for NOCARDIA |
ESPN: Ecoli, Salmonella, PCP, Nocardia
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AE of SMZ-TMP/Co-trimoxazole?
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Megaloblastic anemia in folate deficient pt., Leukopenia, Thrombocytopenia
Transient Jaundice Skin rashes, exfoliative dermatitis in eldery |
TMP: Treat Marrow Poorly
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TMP/SMX clinical uses?
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TMP: Respiratory tract: Strep. Pneumonia, H. infl, otitis Media, Sinusitis, Bronchitis, Pneumonia
GIT: Ecoli, Salmonella, Shigella UTI, Prostatis, urethritis by ecoli SMX: AIDS-PCP |
T(Tree) Resp. tract
M (Mouth) GIT P (Pee) UTI SMX (Syndrome) AIDS-PCP |
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List other Antibacterial agents used in UTI
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Fluoroquinolones
Methenamine Mandelate Nitrofurantoin (SMZ-TMP) (Sulfonamides) |
FQ: aredivided in 4 generations
based on spectrum of actity |
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what are the 1st generation Quinolones?
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Nalidixic Acid (not used) & Norfloxacin
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narrow spec, for UTI
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2nd generation of Quinolones?
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Ciprofloxacin, Ofloxacin
Greater activity against G(-)bacteria, Gonococcal, Mycobacteria (atypical included) mycoplasma pneumonia |
Cipro & O (-FLOXACIN)
2,3,4 Gen have broa spec. |
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3rd Gen. of Q?
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Lomefloxacin, Gatifloxacin, Sparfoxacin
Greater acivity against G(+)cocci, some MRSA strain and Enterococci, less activity against G(-) |
Gati par(s) a Lome
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4th Gen. of Q?
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Moxifloxacin & Trovafloxacin
Broadest Spec. against ANAEROBES. |
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What's the mechanism of action of Quinolones?
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Inh. of Gyrase mediated by supercoiling of the DNA. Post antibiotic effect.
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Newwe Q are effective against G-,G+, and anearobic infection. that includes skin, soft tissues, RTI, GI infection.
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