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What is the Structure of Sulfonamides?
-Resembles para-amino benzoic acid (PABA)
What are the Available sulfa drugs?
What are the Sulfa drugs mechanism of action?
Bacteriostatic inhibition of folic acid synthesis via action on Dihydropteroate synthetase
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
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
- combination of TMP-Sulfa
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)
- Toxoplasma $
- Pneumocystis $
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
- Some MSSA and MRSA
- Rheumatic Fever Prophylaxis
- (in PCN allergic)
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 $
What are the 1st gen Quinolones?
Norfloxacin 1st Generation
- Ciprofloxacin 2nd Generation
- Ofloxacin 2nd Generation
- Levofloxacin 3rd Generation
- Gatifloxacin 3rd Generation
- Moxifloxacin 4th Generation
- Trovafloxacin 4th Generation
What hinders the absorption of the quinolones?
Oral absorption hindered by antacids
what is the mechanism of action of the quinolones?
-Bacteriocidal inhibition of DNA Gyrase topoisomerase II and IV
-Exhibit post-antibiotic effects
What is the MECHANISM
OF RESISTANCE for the quinolones?
- -Alteration of DNA gyrase (mutation of target enzyme
- -Increased efflux
- -Alteration of bacterial permeability to drug
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
What are the clinical uses of the quinolones?
Urinary tract infections; gonorrhea
Enteric infections and Typhoid fever
- Prostate infections $
- Soft tissue infections
Respiratory infections; including those caused by atypical agents and sever CAP $
Pseudomonas infections (resistance may develop rapidly)
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
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
Skin rash (phototoxicity), Eosinophilia (2%)
Elevated hepatic enzymes (2%)
- Trovafloxacin can be hepatotoxic
- Candida overgrowth (superinfection)