1. CEPHALOSPORINS VIJAY NAGDEV H.O.MU-I CMCH LARKANA

2. CEPHALOSPORINS A class of beta lactam antibiotics They were first isolated from cultures of cephalosporium acremonium

3. Mechanism of action Peptidoglycan layer is important for cell wall structural integrity The final step in synthesis of petidoglycan(Transpeptidation) is fascillitated by transpeptidases(pencillin binding proteins) Cephalosporins competitively inhibit PBP and disrupt synthesis of peptidoglycan These are bactricidal agents

4. Therapeutic uses Pharyngitis Tonsilitis Bronchitis Pneumonia UTI Skin and bone infections(cefazolin and ceftriaxone have good penetration into bone) Meningitis( 3rd generation cephalosporins) Surgical prophylaxis

5. Adverse effects Diarrhea,nausea,vomitting Pain and inflammation at injection site Pseudomembranous colitis Allergic reactions Disulfiram-like effect(cefamandole,cefoperazone)because these block oxidation of alcohol. Bleeding(cefamandole,cefoperazone,ceftriaxone)because these contain MTT side chain(anti vit-k effect) Seroconversion of direct coombs test from negative to positive.

6. Pharmacokinetics Except 1st and some of 2ndgeneration,allcephalosporins are adminsteredparentrally Well distributed in body fluids Crosses placenta and secreted in breast milk. Therapeutic levels in CSF are achieved only with 3rd generation cephalosporins 20-30% bound to plasma proteins 80-90% excreted unchanged in urine Elimination occurs through tubular secretion/glomerular filtration Cefoperazone and ceftriaxone are excreted through bile (can be administered in renal insufficiency)

7. CLASSIFICATION

8. GENERATIONS Cephalosporins are divided into five generation based largely on their Spectrum and Resistance to beta lactamases Each newer generation has increased activity against G-ve rods and decreased activity against G+vecocci

9. First generation

10. Therapeutic uses Pharyngitis Tonsilitis Otitis Pneumonia UTI Skin infections Bone infections (cefazolin) Surgical prophylaxis (cefazolin is drug of choice )

11. Dosage

12. 2ndgeneration

13. Therapeutic uses Upper RTI (weaker effect) Pneumonia UTI Skin infections Bone infections Gonorrhea Surgical prophylaxis(cefuroxime 1.5 G 1hour prior ) Meningitis (cefuroxime ; but less effective than 3rd generation )

14. Dosage

15. 3rd generation

16. Therapeutic uses Gonorrhea(single dose of ceftriaxone;1stline drug) Meningitis ( good penetration in CSF) Sepsis Typhoid (4G ceftriaxone/day for 2 days,then 2G/day for 2 days) Surgical prophylaxis UTI Intra-abdominal infections

17. Dosage

18. 4thgeneration

19. Therapeutic uses Upper RTI (weaker effect) Pneumonia UTI Skin infections Intra abdominal infections Febrile neutropenia

20. Dosage

21. 5th Generation CeftarolineFosamil

22. Ceftarolinefosamil On 29thoctober 2010 ceftaroline was approved by FDA(U.S food and drug administration ) It was added as 5th generation cephalosporin In phase III clinical trials it shown non inferior efficacy with same adverse effects to ceftriaxone.

23. Mechanism of action Same mechanism of action as for other generations While it can bind to and inhibit PBP-2A( PBP produced by MRSA) which is not inhibited by others.

24. Therapeutic uses Infections caused by MRSA CAP Skin infections

25. Pharmacokinectis and adverse effects Same as of other generations

26. THANKS