Pharm Block 2 (Sulfa drugs and quinolones)

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Pharm Block 2 (Sulfa drugs and quinolones)
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2010-11-30 19:56:21
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Pharm Block Sulfa drugs quinolones
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Pharm Block 2 (Sulfa drugs and quinolones)
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  1. What is the Structure of Sulfonamides?
    STRUCTURE

    -Weakly acidic

    -Resembles para-amino benzoic acid (PABA)
  2. What are the Available sulfa drugs?
    Sulfadiazine

    Sulfamethoxazole

    Sulfisoxazole
  3. What are the Sulfa drugs mechanism of action?
    Bacteriostatic inhibition of folic acid synthesis via action on Dihydropteroate synthetase
  4. What is the mechanism of action for microbial resistance?
    • -Decreased intracellular
    • accumulation of drug secondary to porin
    • mutations which decrease ability of drug to enter bacteria

    -Increased production of PABA

    -Decreased sensitivity of dihydropteroate synthetase (target) to sulfa
  5. What is sulfa often combined with?
    What does this do?
    What is another compo drug?
    • - Trimethoprim
    • -Inhibits a second enzyme (Dihydrofolate reductase) in folic acid synthetic
    • pathway

    -Cotrimoxazole - combination of TMP-Sulfa
  6. What is the Specrum of Sufa drugs?
    • Gram negative bacteria:
    • Neisseria meningitidis, E. coli $

    • Gram positive bacteria:
    • Strep pyogenes, Strep pneumoniae, some MSSA and MRSA $
    • Chlamydia (but not for neonate)
    • Nocardia
    • Toxoplasma $
    • Pneumocystis $
  7. What are the clinial uses of Sulfa drugs?
    Uncomplicated urinary tract infections (TMP – Sulfa methoxazole) $

    Otitis Media (TMP – Sulfamethoxazole) $

    Topical burn prophylaxis (Mafenide acetate – Sulfamylon) (Silver sulfadiazine)

    Ulcerative colitis (Salicylazosulfapyridine – Azulfidine)

    Toxoplasmosis (pyrimethamine added as second drug) $

    PCP prophylaxis and treatment (TMP – Sulfa) $

    • Enteric bacterial infections with cholera, salmonella, and shigella
    • Nocardia
    • Some MSSA and MRSA
    • Rheumatic Fever Prophylaxis
    • (in PCN allergic)
  8. What are some toxicities of the sulfa drugs?
    Hypersensitivity (Stevens-Johnson Syndrome) $

    GI (N & V) (Diarrhea)

    • Transaminase elevation, Severe hepato-toxicity in HLA-B 5701
    • positive recipients $

    • Neonatal hyperbilirubinemia with resultant kernicterus [cerebral palsey and deafness]
    • (contraindicated in late pregnancy) $

    Nephrotoxicity, Severe dysglycemia in elderly

    • Pancytopenia (bone marrow suppression);
    • Acute haemolytic anemia in G6PD
    • deficiency $

    Phototoxicity
  9. What are the 1st gen Quinolones?
    2nd gen?
    3rd?
    4th?
  10. Norfloxacin 1st Generation
    • __________________________________
    • Ciprofloxacin 2nd Generation
    • Ofloxacin 2nd Generation
    • ____________________________________
    • Levofloxacin 3rd Generation
    • Gatifloxacin 3rd Generation
    • ________________________________________
    • Moxifloxacin 4th Generation
    • Trovafloxacin 4th Generation
  11. What hinders the absorption of the quinolones?
    Oral absorption hindered by antacids
  12. what is the mechanism of action of the quinolones?
    -Bacteriocidal inhibition of DNA Gyrase topoisomerase II and IV

    -Exhibit post-antibiotic effects
  13. What is the MECHANISM
    OF RESISTANCE for the quinolones?
    • -Alteration of DNA gyrase (mutation of target enzyme
    • structure)
    • -Increased efflux
    • -Alteration of bacterial permeability to drug
  14. What is the spectrum of the quinolones?
    • Gram negatives, including:
    • pseudomonas, H. influenzae, morexella, salmonella, shigella, E.coli, campylobacter

    • Gram positive (especially
    • newest fluoroquinolones) including PCN resistant
    • Strep pneumonia

    Legionella, chlamydia, mycoplasma
  15. What are the clinical uses of the quinolones?
    Urinary tract infections; gonorrhea

    Enteric infections and Typhoid fever

    • Prostate infections $
    • Osteomyelitis
    • Soft tissue infections

    Respiratory infections; including those caused by atypical agents and sever CAP $

    Pseudomonas infections (resistance may develop rapidly)
  16. Common disease manifestation of the quinolones
    and major cause of hospitalization and death especially in aged and immune comprimised. What is it?
    what do you treat it with?
    -Community Acquired Pneumonia

    -Treatments: Levofloxacin or Moxifloxacin, Ceftriaxone and Azythro or Clarithromycin, Ampicillin/Sulbactrim and Clarithromycin
  17. what are some of the toxicitys of the quinolones?
    Older quinolones demonstrate serious neurotoxicity (seizures)

    Achilles tendon rupture in adults $$

    G.I. upset is common (5%)

    Increase QT interval

    NOT GENERALLY USED IN CHILDREN UNDER 18 YEARS OF AGE BECAUSE OF POSSIBLE ARTICULAR CARTILAGE INJURY

    CONTRAINDICATED IN PREGNANCY

    Headache (1%)

    Skin rash (phototoxicity), Eosinophilia (2%)

    Elevated hepatic enzymes (2%)

    • Trovafloxacin can be hepatotoxic
    • Candida overgrowth (superinfection)

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