Cephalosporin Antibiotics

Definition
History
Chemistry
Properties
Classification & its Generation
Pharmacokinetics
Mechanism of action
Indication
Contraindication
Therapeutic use
Adverse effect
Resistance
Comparison with penicillin
Market preparation

1. A Presentation On Cephalosporin

2. Md. Ashraful Zaman Akash ID-131017 Asraful Islam Rayhan ID-131039 Md. Nazmus Sakib ID-131032 Sanzida Afroze ID-131004 Shamsunnahar Lipa ID-131021 Md. Rubel Haque ID-131024 Presented By……….

3. Outlines…… Definition History Chemistry Properties Classification & its Generation Pharmacokinetics Mechanism of action Indication Contraindication Therapeutic use Adverse effect Resistance Comparison with penicillin Market preparation...

4. Any  of a group of widely used  broad-spectrum antibiotics ,  originally isolated as  a  product   of fermentation  from the fungus  Cephalosporium acremonium are called Cephalosporins. Definition Cephalosporium acremonium Fig:

5. The first chemical compounds of the cephalosporin group were isolated from Cephalosporium acremonium , a cephalosporin-producing fungus, first discovered by Giuseppe Brotzu in 1948. The Cephalosporines are isolated from Cephalosporium species Prepared semisynthetically Giuseppe Brotzu (1895-1976) Italy. History:

6. It has a bicyclic system containing 4-membered -lactam ring fused to a six membered dihydrothiazine ring system . Nucleous of the most cephalosporin is 7-amino-cephalosporanic acid ( 7-ACA) . Possible modifications 7-Acylamino side chain 3-Acetoxymethyl side chain Substitution at C-7   Chemistry of Cephalosporin: 7-Aminocephalosporinic acid (7-ACA) Dihydrothiazine ring b -Lactam ring

7. Properties of cephalosporins Broad spectrum activity They are water soluble The molecular weight of cephalosporins is 400-450 Relatively stable to pH and temperature changes Nucleus of cephalosporin is 7-amino cephalos poranic acid Their activity is not reduced by serum

8. Range from very narrow spectrum to very broad spectrum nucleus Consists of dihydrothiazine ring fused to a β –lactam ring 7-aminocephalosporanic acid has been modified by addition of different side chains to create a whole family of cephalosporin antibiotics.

9. Classification of cephalosporins: According to generations Cephalosporins are following types… First Generation Second Generation Third Generation Fourth Generation Fifth Generation Sixth Generation

10. First Generation: Parenteral Drugs: Cefazolin Cephalothin Cephapirin Cephradine Oral Cephalexin Cephradine Cefadroxil

11. Most gram-positive cocci Strepto , Pneumo , Modest activity against E. coli, K. pneumoniae & Proteus mirabilis Exhibit good activity against gram-positive bacteria

12. Second Generation: Parenteral Drugs Cefamendole Cefonicid Cefoxidin Oral Drugs Cefaclor Cefuroxime axetil

13. Exhibit somewhat increased activity against gram negative organisms, but much less active than third generation agents . Less active against gram positive cocci & bacilli compared to first gen. drugs .

14. Third Generation: Parenteral Drugs Cefotaxime Cefriaxone Ceftazidime Cefoperazone Oral Drugs Cefixime Cefotaxime Cefdinir Cefpodoxime proxetil

15. Highly augmented activity against gram-negative organisms All are highly resistant to β -lactamases from gram negative bacteria . Some members of this group have enhanced ability to cross the blood-brain barrier eg . Ceftriaxone .

16. Fourth Generation: Parenteral Drugs: Cefepime Cefpirome Cefozopran

17. Highly active against G – ve organisms Effective against bacterial infections resistant to earlier drugs.

18. Ceftobiprole Ceftaroline Active against, g + ve cocci especially MRSA penicillin resistant S. pneumoniae and enterococci Fifth Generation:

19. Pharmacokinetics: Rout of administration: Oral Parenteral Distribution Body fluid Joint fluid Pleural fluid CNS Elimination Unchanged in urine Renal tubules Plasma Half-life: 1-4 hours mostly

20. Peptidoglycan layer is important for cell wall structure integrity of bacteria . The final step in synthesis of peptidoglycan ( Transpeptidation) is facilitated by transpeptidase ( PBP- Penicillin Binding Protein ) Cephalosporin comptitively inhibit PBP as it mimics the structure of D- Ala -D- Ala link to which PBP bind for cross-linking of peptidoglycan . As it disrupting the cross-linking process the cell wall will lose its strength which results in cell lysis . Mechanism of action:

21. MECHANISM OF ACTION:

22. By Flow Chart: Cephalosporin Act as transpeptidase enzyme Inhibit transpeptidation reaction Block peptidoglycine synthesis Activation of Autolytic enzyme Increase the permeability of cell membrane Cell explodes and lysed Death of microorganism

23. UTI Infection of gut Respiratory tract infection Boils, abscess Prophylaxis in surgery Biliary sepsis Person allergic to penicillin Indication..

24. Meningitis Gonorrhoea Infected burns Septicaemia Aspirin Pneumonia Mixed infection Tonsillitis

25. Contraindication: Renal failure Hepatic impairment Rheumatic fever These drugs are contraindicated in patient with known hypersensitivity to cephalosporin & penicillin . Lactating patient and anaerobic infections . Pregnancy & Breastfeeding

26. Therapeutic Uses: Extensively used & therapeutically important antibiotics Effective therapeutic & prophylactic agents

27. Adverse Effect.. Allergic reaction Anaphaylaxis Serum sickness Urticaria Skin rash Haemolytic anaemia etc.. GIT upset Nausia Vomiting Diarrhoea

28. Nephrotoxicity : Interstitial Nephritis Renal Tubular necrosis Others: Disulfiram-like reaction Local irritation after I/M injection Thromboflavitis after repeated I/V Bleeding tendency Eosinophilia and thrombocytosis Defect of newborn babies Pharyngitis ( Throat infection) Stillbirth or Miscarriage

29. Impermeability to the antibiotic. -to reach its site of action Alteration in PBPs -antibiotics bind with low affinity Elaboration of β -lactamases; that can hydrolyze the β -lactam ring and inactivate the cephalosporin ( most prevalent mech ) Resistance

30. Similarity : Both obtained from fungus Structural similarity Mechanism action ( Cell wall inhibitor ) Dissimilarity : Resistant to beta lactamase Antibiotic spectrum Precursor COMPARISON WITH PENICILLIN

31. Broad spectrum of activity Stability to Beta-lactamase Oral and parenteral preparations Widely accepted Treats ‘Day to Day’ as well as serious infections. High safety profile. Why Cephalosporin is used-

32. Extremely widely used :- Safe : Side effects specific to individual members of the family as well as the family as a whole Not necessarily cross reaction with penicillin hypersensitivity

33. Market Preparation Of Cephalosporin…

34. LORACEF (Square) Doses form: Dose: Suspension 125mg/5ml Capsule 500mg Drop 100mg/1ml

35. CLOBAC (Opsonin) -Dose: 100mg/1ml drop 125mg/5ml suspension -Price: 100ml bot: 180.00 MRP 15ml bot: 125.00 MRP

36. CEFLON (Eskayef) Doses form: Dose: Suspension 125mg/5ml Capsule 500mg Drop 100mg/1ml

37. CEFTICLOR (Renata) -Dose: 250mg & 500mg/capsule 125mg/5ml suspension 100mg/1ml drop -Price: 250mg x 12s pack: 252.00 MRP; 500mg x 12s pack: 456.00 MRP 100ml bot: 190.00 MRP 15ml bot: 125.00 MRP

38. References : Lippincott’s Illustrated Pharmacology , Champ P.C - Essentials of Medical Pharmacology , Tripathi K.D - Basic & Clinical Pharmacology , Katzung B.G. www . Wikipedia.com