Cephalosporin Drug

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CONTENTS

CEPHALOSPORINS

1)      Classification

2)      MOA

3)      AMS –of each generation

4)      ADRs

5)      Uses

6)      Preparations

ž  Semisynthetic antibiotics from Cephalosporin –C obtained from a fungus Cephalosporium

ž  Nucleus consists of a β-Lactam ring fused to a dihydrothiazine ring (7—ACA) 

MECHANISM OF ACTION

·      Beta lactam antibiotic interferes with synthesis of bacterial cell wall

·      Bacteria synthesise

                UDP-N-acetyl muramic acid pentapeptide [Park nucleotide]

                                                    &

                              UDP-N-acetyl glucosamine

                                                     

   Action of  cephalosporins

1.Attachment to target proteins of bacteria

2.Blocking transpeptidase of peptidoglcan of bacterial cell wall

3.Activation of autolytic enzyme of cell wall

CLASSIFICATION

    I^st  GENERATION

                                     Oral                   Parenteral

                                   Cephalexin       . Cefazolin

                                   Cefadroxil         . Cephalothin

.                                  Cephradine       . Cephaloridine       

II^st  GENERATION

                                   Oral                       Parenteral

                                Cefaclor                    Cefuroxime

                                Cefuroxime axetil     . Cefoxitin

III^st  GENERATION :

                                     Oral                    Parenteral

                                   Cefixime               Cefotaxime

                                   Cefpodoxime       Ceftriaxone

                                   Cproxetil               Ceftazidime

                                   Cefdinir                  Ceftizoxime

                                  Cefoperazone         

IV^th  GENERATION

                Parenteral:

                 . Cefepime

                 . Cefpirome    

                

   GENERATION  I

ANTIMICROBIAL  SPECTRUM

·         Mainly on G +ve

·         Weaker on G –ve

·         Strepto, Staph, gonococci, meningococci, C. diphtheriae, clostridia, actinomyces

·         E.coli, klebsiella, proteus,salmonella, shigella, H.influenza

  GENERATION  II

ANTIMICROBIAL  SPECTRUM

·         More active on G-ve org

·         Some member also on anaerobes

·         E.coli, Proteus, Klebsiella, Salmonella, shigella

·         Also on G+ve cocci

GENERATION  III

ANTIMICROBIAL  SPECTRUM

·         Mainly on G-ve enterobacteriaceae

·         Some on Pseudomonas

·         All are resistant to β-Lactamases

·         Less active on G+ve cocci

GENERATION  IV

·         Resistant to β-Lactamases

·         More potent on G+ve & some G-ve bact.

CEFIXIME

·         Highly active on Enterobacteriaceae, H.influenzae, Strep.pyogenes,Strep.pneumoniae, Gonococci, M.catarrhalis

·         Resistant to many β-Lactamases

·         Not  active on staph & pseudomonas

CEFTRIAXONE

·         Good CSF penetration

·         Longer acting

·         Salmonella, enterobacteriaceae.           .Bacterial meningitis

·         Hypoprothrombinemia, bleeding& diarrhoea.

   ADVERSE REACTION

1. Nephrotoxicity :

                     Cephaloridine –common

                    3^rd & 4^th G : rare

2. Bleeding :(cefoperazone.ceftriaxone)

                     Hypoprothrombinemia

                   Thrombocytopenia

                    Platelet dysfunction

                     Common in elderly, malnourished & debilitated persons,cancer and intra abdominal inf .   

3. Diarrhoea :

                   Alteration of microbial flora

                   Irritation of mucosa

                   Oral cephradine common

        4.    HS reactions :

                    Rashes

                    Rarely urticaria, asthma, angioedema & anaphylaxis

5. Disulfiram like reaction    : Cefoperazone
6. Pain(im), thrombophlebitis(i.v)
7. Neutropenia ,thrombocytopenia  :  Ceftazidime
8. GIT symptoms :      Nausea,Vommiting, epigastric distress

USES

  1.  Dental infections :

-        Alternative to penicillin / amoxicillin

o   Pencillin / amoxicillin resistant infection

-        Oral antibiotics are routinely employed in dentistry.

o   Parenetral ones are reserved for serious and fulminating infection

o   Ist & IInd generation are mainly used

o   Ist gn have high activity against gram +ve aerobic bacteric

o   IInd gn have high activity against oral anerobes

o   Orodental infection caused by Klebsiella

               

      Cephalexin & cephadroxil are alterrnative to amoxicillin for prophylaxis of local wound infection as well as bacterial endocarditis following dental surgery in predisposed patients

2.  RTIs      : Cefadroxil, Cephalexin, Cefixime, Ceftriaxone

3.  UTIs

4.  Skin & soft tissue infections  :  Cefadroxil, Cephalexin, Ceftriaxone

5.Mixed aerobic and anaerobic infections in cancer undergoing colorectal surgery

6.Septicaemias

7.Meningitis     : Ceftazidime, Ceftriaxone, Cefotaxime

8.   Surgical prophylaxis :  Ceftriaxone , Cefotaxime

9.   Gonorrhoea :  Ceftriaxone

10.   Typhoid : Cefixime, Ceftriaxone,Cefoperazone  

11.  Mixed aerobic /anaerobic   infections    : Cefuroxime

12. Hospital infections

     . Ceftizoxime

     . Cefepime, Cefpirome

13. Prophylaxis in neutropenic pts

              . Ceftazidime    

PREPARATIONS

1. Cephalexin:

       Cap: 125, 250, 500 mg

    

2. Cefodroxil :

       Cap : 125, 250, 500 mg

     

3. Cefazolin :

      Inj  : 0.25, 0.5, 1 g / vial

             : 6 -8 hrly       

4. Cefuroxime :

     Inj : 250, 750mg /vial

     Dose : 0.75 -1.5 g 8^thhrly

5. Cefuroxime axetil

      Cap : 125, 250, 500 mg

    

     Dose : 250 – 500 mg b.i.d