-
What is the Structure of Sulfonamides?
STRUCTURE
-Weakly acidic
-Resembles para-amino benzoic acid (PABA)
-
What are the Available sulfa drugs?
Sulfadiazine
Sulfamethoxazole
Sulfisoxazole
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What are the Sulfa drugs mechanism of action?
Bacteriostatic inhibition of folic acid synthesis via action on Dihydropteroate synthetase
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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
- pathway
- Cotrimoxazole - 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)
- Nocardia
- 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
- Nocardia
- 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 $
Phototoxicity
-
What are the 1st gen Quinolones?
2nd gen?
3rd?
4th?
-
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
- structure)
- -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 $
- Osteomyelitis
- 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
Headache (1%)
Skin rash (phototoxicity), Eosinophilia (2%)
Elevated hepatic enzymes (2%)
- Trovafloxacin can be hepatotoxic
- Candida overgrowth (superinfection)
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