Antibacterials
Terms
undefined, object
copy deck
- Describe "Sulfonamides"
-
Derivatives of PABA (ingredient in sunscreen), Prontosil as precursor, 1st agents used against bacteria
Described by Hildegard Domagk - List some diseases in which sulfonamides play important role
- Bronchitis, IBD, Otitis, PCP, Burns, UTI, Sinusitis
- List some rapidly absorbed Sulfonamides
-
Short acting: 4-8 hrs
Sulfisoxazole
Sulfadiazine
Intermediate Acting:12-18 hrs
Sulfamethoxazole
Long acting
Sulfadoxine - List some poorly absorbed Sulfonamides
-
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 - What are the uses of the following Sulfonamides: Sulfacetamide, Mafenide, Silver Sulfadiazine?
-
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 - What's the mechanism of action of Sulfonamides?
-
Competitive inhibitors of Dihydropteroate Synthase, enz that add PABA to Dihydropteroic acid, as precursor of folic acid.
BACTERIOSTATIC effet. - Describe Sulfonamides Kinetics
-
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 - Therapeutic uses?
-
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 - How do bacteria resist Sulfonamides?
-
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 - What are the AE of Sulfonamides?
-
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. - What's the struture of Trimethoprim? Use as?
-
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 - What's the spectrum of activity of SMZ-TMP co-trimoxazole?
-
No anearobic cpverage.
Effective against: E.coli, Salmonella and PCP, alternative to Doxycyclin and Streptomycin for NOCARDIA - AE of SMZ-TMP/Co-trimoxazole?
-
Megaloblastic anemia in folate deficient pt., Leukopenia, Thrombocytopenia
Transient Jaundice
Skin rashes, exfoliative dermatitis in eldery - TMP/SMX clinical uses?
-
TMP: Respiratory tract: Strep. Pneumonia, H. infl, otitis Media, Sinusitis, Bronchitis, Pneumonia
GIT: Ecoli, Salmonella, Shigella
UTI, Prostatis, urethritis by ecoli
SMX: AIDS-PCP - List other Antibacterial agents used in UTI
-
Fluoroquinolones
Methenamine Mandelate
Nitrofurantoin
(SMZ-TMP)
(Sulfonamides) - what are the 1st generation Quinolones?
- Nalidixic Acid (not used) & Norfloxacin
- 2nd generation of Quinolones?
-
Ciprofloxacin, Ofloxacin
Greater activity against G(-)bacteria, Gonococcal, Mycobacteria (atypical included) mycoplasma pneumonia - 3rd Gen. of Q?
-
Lomefloxacin, Gatifloxacin, Sparfoxacin
Greater acivity against G(+)cocci, some MRSA strain and Enterococci, less activity against G(-) - 4th Gen. of Q?
-
Moxifloxacin & Trovafloxacin
Broadest Spec. against ANAEROBES. - What's the mechanism of action of Quinolones?
- Inh. of Gyrase mediated by supercoiling of the DNA. Post antibiotic effect.