CEPHALOSPORIN ANTIBIOTICS (1).pptx part 1 for pharmacy students 6th sem

Cephalosporin part 1 antibiotics for bpharma 6th sem

1. Name :- Zovia Ejaz Ahmad Rollno . :- B-VI-07

2. OUTLINES….. INTRODUCTION CHEMISTRY MECHANISM OF ACTION CLASSIFICATION FIRST GENERATION CEPHALOSPORINS SECOND GENERATION CEPHALOSPORINS THIRD GENERATION CEPHALOSPORINS FOURTH GENERATION CEPHALOSPORINS FIFTH GENERATION CEPHALOSPORINS ADVERSE EFFECTS USES

3. INTRODUCTION Cephalosporins are a group of semi- synthetic antibiotic Derived from Cephalosporin –C , obtained from a fungus Cephalosporium B- lactam antibiotic Wider spectrum of activity than penicillins Bactericidal

4. CHEMISTRY OF CEPHALOSPORINS

5. GENERAL MECHANISM OF ACTION Peptidoglycan layer is important for cell wall structure integrity of bacteria Final step in synthesis of peptidoglycan is facilitated by PBP Cephalosporins competitively inhibit PBP as it mimics the structure of D-Ala-D-Ala link to which PBP bind for crosslinking of peptidoglycan

6. Mechanism of action

7. CLASSIFICATION

8. FIRST GENERATION AGENTS First generation cephalosporins are very effective against gram+ve organisms. They are generally used in minor infections of the skin , respiratory & urinary tract infections. Examples of first generation cephalosporins include:- Cefazolin ; Cephalexin ; Cefadroxil ; Cephradine ; Cephalothin etc. They were developed in 1960s

9. 1. CEFAZOLIN SUMMARY:- Cefazolin  is a broad-spectrum cephalosporin antibiotic mainly used for the treatment of skin bacterial infections and other moderate to severe bacterial infections in the lung, bone, joint, stomach, blood, heart valve, and urinary tract. ANTIBACTERIAL SPECTRUM:- The antibacterial spectrum of cefazolin includes streptococci , staphylococci , Enterobacter , Klebsiella , E.coli etc.

10. Cefazolin MECHANISM OF ACTION :- It acts b y binding to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall, it inhibits the third and last stage of bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins. PHARMACOKINETICS :- absorption :- It is not absorbed from the GI tract hence it must be administered parenterally . Peak serum concentrations are attained 1-2 hrs post IM injection

11. CEPHAZOLIN volume of distribution :- approx 10 L Protein binding :- 74-86 % metabolism :- Not metabolized ROUTE OF ELIMINATION :- It is excreted unchanged in the urine. In the first six hours approximately 60% of the drug is excreted t1/2 (half-life) :- 1.8 hr following IV administration & 2 hr following IM administration USES OF CEFAZOLIN :- It is mainly used for the treatment of UTIs ; respiratory infections; Biliary tract infections ; Cellulitis ;infection caused by Gram + ve bacteria (MSSA); Pneumonia ;Bacterial Endocarditis etc.

12. Cefazolin Prescribed dosage of Cefazolin :- For infections with gram + ve bacteria :- 1-2 weeks :- 40 mg/kg/day IV/IM divided every 12 hourly >7 days :- 60mg/kg/day IV/IM divided every 8 hourly For infants & children :- 25-150 mg /kg/day IV/IM divided every 6-8 hourly ; do not exceed 6g /day Endocarditis prophylaxis :- 50 mg /kg IV/IM , 30-60 minutes before the procedure NO DOSE ADJUSTMENTS REQUIRED FOR RENALFAILURE

13. CEFAZOLIN Adverse effects of cefazolin :- Hypersensitivity , Anorexia , Diarrhoea , Fever , Leukopenia ,Nausea , vomiting,oral candidiasis etc. Interaction :- It shows Pharmacodynamic synergism. NOTE :- Cefazolin is used as an agent of choice for Surgical prophylaxis

14. 2 .CEPHALEXIN Cephalexin is effective when given orally Its antibacterial spectrum is same as that of other first generation drugs. It is less effective against penicillinase producing staphylococci ). It is a semisynthetic antibiotic drug MECHANISM :- It acts by inhibiting the cell wall synthesis by forming covalent bond with transpeptidase .

15. Cephalexin PHARMACOKINETICS :- Absorption :- Cefalexin is rapidly & almost completely absorbed from GIT with oral administration . Absorption is slightly reduced when taken with food, it can be taken without regard for meals. Peak levels of cefalexin occur about 1 hour of administration. Volume of distribution :- 5.2 -5.8 L Protein binding :- 10-15 % bound to serum proteins including serum albumin. Metabolism :- It is not metabolized in the body

16. CEPHALEXIN Route of elimination :- Cephalexin is over 90% excreted in the urine after 6 hours by glomerular filtration and tubular secretion , it is unchanged in the urine. T1/2 :- 49 minutes in fasted state & 75 minutes when taken with food USES :- It is mainly used for the treatment of Tonsilitis ; Pyoderma ; Pyelonephritis ; Cystitis ; Subcutaneous abcesses ; Dental infections ; Pneumonia . CONTRAINDICATIONS :- Cephalexin is contraindicated in patients with allergies

17. CEPHALEXIN PRESCRIBED DOSE :- For mild infection : 25-20 Po mg/kg/24 hours in 3-4 divided doses for 5-10 days Severe infection :- 50-100 PO mg/kg/24 hours in 3-4 divided doses for 10 days NO DOSE ADJUSTMENTS REQUIRED FOR RENAL /HEPATIC FILURE ADVERSE EFFECT :- Pseudomembranous colitis , dyspepsia, nausea, vomiting, diarrhoea , rash, urticaria , angioedema , pruritus etc. INTERACTION :- Decreases effect of BCG vaccine & Typhoid vaccine

18. 3 . CEPHRADINE Cephradine is a semi-synthetic first generation cephalosporin , which is effective when orally administered. MECHANISM OF ACTION :- It has mechanism of action similar to that of Cefalexin . It inhibits the 3 rd & last stage of bacterial cell wall synthesis by binding to specific penicillin binding proteins (PBPs ). Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as the autolysins ; it could be possible that Cephradine interferes with an autolysin inhibitor PHARMACOKINETICS :- Absorption :- It is absorbed rapidly and almost completely when administered orally

19. CEPHRADINE Volume of distribution :- 5L Protein binding :- 15 % Metabolism :- Not metabolized in the body Route of elimination :- Over 90 % of the drug is excreted unchanged in the urine within 6 hours. T1/2 :- 1-2 hours USES :- It is used for the treatment of Bacterial-sepsis ; Bloodstream infections ; Tonsils ; Laryngitis ; Respiratory tract infections ; UTIS etc CONTRAINDICATIONS :- should not be used in allergic patients.

20. CEPHRADINE PRESCRIBED DOSE :- For moderate infections : - 100-200 mg /day, divided into 2-4 doses per day. The maximum dose is 400mg/day For parenteral route :- 200-400 mg /kg , divided into 4 doses by IM injection. The maximum dose is 800 mg/kg For surgical prophylaxis :- 100-200 mg before surgery Dose for children ( susceptible infections ) :- 25-50 mg/kg/day divided into 2-4 doses For otitis media in children :- 75-100 mg/kg/day

21. CEPHRADINE ADVERSE EFFECTS :- Diarrhoea ; Hypersensitivity reactions such as skin rashes ; Blisters ;itching; joint pain ; angina ; nausea ; vomiting; dizziness; restlessness etc INTERACTIONS :- The risk of nephrotoxicity is increased when combined with cefpirome It decreases the effect ,if combined with anticoagulant drug If taken with alcohol ,it can show disulfiram like reactions.

22. 4. CEFADROXIL Cefadroxil is an analog of Cephalexin ,it is similar to it in many of its properties . It is generally used in respiratory tract infections & skin infections. MECHANISM OF ACTION :- Cefadroxil is bactericidal in nature as it inhibits the process of cross-linking in the bacterial cell wall synthesis. It is very effective for the infections caused by the gram + ve bacteria. It binds to PBP1a which leads to spheroplast formation ultimately leading to the lysis of the bacterial cell.

23. 4. CEFADROXIL PHARMACOKINETICS :- Absorption :- Cefadroxil is completely absorbed on oral administration; food does not interfere with its absorption. Volume of distribution :- 0.3 L/kg Protein binding:- About 28 % binds to plasma proteins Metabolism :- Not metabolized in the body Route of elimination :- Over 90% of the drug is excreted unchanged in the urine within 24 hours. T1/2 :- 1.5 hours 

24. 4. CEFADROXIL USES OF CEFADROXIL :- Cefadroxil is used for the treatment of respiratory tract infections ; Pyoderma ; Otitis media ; Pyelonephritis ; Cystitis ; Urethritis ; Endocarditis prophylaxis CONTRAINDICATIONS :- Cefadroxil is contraindicated in patients with known allergies to cephalosporins PRESCRIBED DOSAGE :- Oral dose :- 30 mg/kg/24 hours in 2 divided doses for 10 days . Maximum dose is 1g Endocarditis prophylaxis :- 50 mg/kg 1 hour before procedure (orally )

25. CEFADROXIL ADVERSE EFFECT :- Pseudomembranous colitis ,dyspepsia , nausea , vomiting , diarrhoea , rashes , angioedema , hepatic dysfunction, neutropenia , agranulocytosis , thrombocytopenia , serum sickness , arthralgia , etc INTERACTIONS :- It competitively inhibits renal tubular secretion when combined with Probenecid Dosage in renal impairment :- 20-50 mg/kg in normal renal function 10-20 mg/kg as in case of renal impairment

26. SECOND GENERATION CEPHALOSPORINS Second generation Cephalosporins are more active against some gram-negative organisms They are also active against some anaerobes They are more resistant to beta- lactamases & H.influenzae Examples include:- Cefamandole , Cefaclor,Cefoxitin etc.

27. 1.CEFAMANDOLE Cefamandole is a broad spectrum second generation drug , it is administered parenterally . It is generally formulated as a formate ester , cefamandole nafate . It is no longer marketed in the U.S MECHANISM OF ACTION :- cefamandole binds to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall, causing the inhibition of the third and last stage of bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins.

28. CEFAMANDOLE PHARMACOKINETICS :- Absorption :- It is poorly absorbed in the GIT , thus it is given parenterally . A 1g IM dose acheives a plasma concentration of 25-30 mg/L after 1 hour Volume of distribution :- It is widely distributed in the body tissues Protein binding :- 65-80 % Elimination :- Renal excretion , a small amount is also excreted in the bile ( 150-250 mg/L ) t ½ :- 50 -60 minutes (less than 1 hour )

29. CEFAMANDOLE USES :- It is widely used for the treatment of infections caused by H . Influenzae , Enterobacter , E.coli , Proteus , Klebsiella etc . It is mainly used for respiratory tract & soft tissue infections in infants & children. CONTRAINDICATIONS :- Clinical & microbiological failure in case of meningitis caused by H. influenzae is reported. Limited use to disease in which the development of sepsis not a concern. The safety & efficacy of this agent is not established for infants younger than 1 month

30. CEFAMANDOLE PRESCRIBED DOSE :- Usual adult dose for pneumonia :- 500 mg i n tramuscularly or IV every 6 hours. Usual Adult Dose for Skin or Soft Tissue Infection :- 500 mg intramuscularly or IV every 6 hours. Usual Adult Dose for Urinary Tract Infection :- Uncomplicated: 500 mg intramuscularly or IV every 8 hours. Complicated: 1 g intramuscularly or IV every 8 hours. Usual Adult Dose for Surgical Prophylaxis :- Preoperative: 1 to 2 g IV or intramuscularly 30 to 60 minutes prior to surgical incision.

31. CEFAMANDOLE Postoperative: 1 to 2 g IV or intramuscularly every 6 hours for 24 to 48 hours (72 hours for prosthetic arthroplasty ). Cesarean section: the initial dose may be administered just prior to surgery or immediately after the cord is clamped. Usual Pediatric Dose for Surgical Prophylaxis > 3 months: 50 to 100 mg/kg/day in divided doses IV or intramuscularly 30 to 60 minutes prior to surgical incision and every 6 hours for 24 to 48 hours. Renal dose adjustments are made in accordance to creatinine clearance .

32. CEFAMANDOLE ADVERSE EFFECTS :- Nausea and vomiting , Hypersensitivity   Anaphylaxis, maculopapular rash, urticaria , eosinophilia , and drug fever have been reported. Blood   Thrombocytopenia has been reported rarely. Neutropenia has been reported, especially in long courses of treatment.  INTERACTIONS :- Nephrotoxicity has been reported following concomitant administration of aminoglycoside antibiotics and cephalosporins . As with other broad-spectrum antibiotics, hypoprothrombinemia , with or without bleeding, has been reported rarely, but it has been promptly reversed by administration of vitamin K. 

33. CEFAMANDOLE When ingested with alcohol it shows disulfiram like reactions , that means the concentration of acetaldehyde rises which results in flushing , dizziness, nausea , vomiting , dilirium etc Carcinogenesis, Mutagenesis, Impairment of Fertility   Certain (beta)- lactam antibiotics containing the N- methylthiotetrazole side chain have been reported to cause delayed maturity of the testicular germinal epithelium ( during spermatogenesis )

34. 2. CEFUROXIME AXETIL Cefuroxime is a broad spectrum antibiotic , which is administered parenterally , Cefuroxime axetil ( prodrug ) is effective orally . It is resistant to beta lactamase enzymes Though it attains good conc. in the CSF it is not used in Meningitis. Effective against gram – ve bacteria, Citrobacter , Enterobacter ,pneumonia , Gonorrhoea etc MECHANISM OF ACTION :- It acts by binding to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall, it inhibits the third and last stage of bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins.

35. CEFUROXIME AXETIL PHARMACOKINETICS :- Absorption :- Absorbed from the gastrointestinal tract. Absorption is greater when taken after food (absolute bioavailability increases from 37% to 52%). Volume of distribution :- 11.1 -15.8 L / m(2) Protein binding :- 50% to serum protein Metabolism :- Body is not able to metabolize the drug Elimination :- eliminated unchanged in the urine T1/2 :- Cefuroxime has t ½ of about 70-80 minutes

36. CEFUROXIME AXETIL USES :- It is used in Pharyngitis , Pneumonia , Sinusitis , Otitis media , Skin infections , Gonorrhoea , Osteomyelitis , Lyme disease CONTRAINDICATIONS :- It is containdicated in patients with hypersensitivity /allergic reactions PRESCRIBED DOSE :- < 3 months :- Safety & efficacy is not established >3 months – 12 years :- 30 mg /kg/day in 12 hourly divided doses for 10 days (Maximum is 1g /day )

37. CEFUROXIME AXETIL Alternatively , 75-150 mg/kg/day IM/IV in 8 hourly divided doses for severe infections , do not exceed 6 g /day . Duraton varies with severity of the infection For >12 years :- 250-500 mg tablet every 12 hours for 10 days. For infants ( less than 4 weeks ) :- 100 -150 mg /kg /day divided 12 hourly IV NO hepatic dosage adjustments are recommended . ADVERSE EFFECTS :- Pseudomembranous colitis , nausea , vomiting, diarrhoea , rashes , urticaria , amgioedem , pruritis etc

38. CEFUROXIME AXETIL INTERACTION :- It increases the level of argatroban , bivalirudin , fondaparinux by anticoagulation .

39. 3. CEFACLOR Cefaclor is second generation cephalosporin ,administered orally It is very effective against H.influenzae , Proteus , E.coli , Moraxella MECHANISM OF ACTION :- It acts by binding to PBP 3 , thus inhibiting the cross-linking in the bacterial cell wall , ultimately causing lysis of the cell PHARMACOKINETICS :-

40. CEFACLOR Absorption :- Well absorbed after oral administration, independent of food intake. Volume of distribution :- 11L Protein binding :- 23.5 % Metabolism :- No appreciable biotransformation in liver (approximately 60% to 85% of the drug is excreted unchanged in the urine within 8 hours). Elimination :- Approximately 60% to 85% of the drug is excreted unchanged in the urine within 8 hours, the greater portion being excreted within the first 2 hours. T ½ :- 1.5 hours

41. CEFACLOR USES :- Tonsilitis , Rhinosinusitis , Otitis media , External otitis , Epiglottitis , Impetigo , Pyoderma , Gonococcal infections , Pyelonephritis , Cystitis CONTRAINDICATIONS :- It is contraindicated in patients with known allergy to cephalosporins PRESCRIBED DOSE :- 20 mg/kg/day in 3 divided doses . In severe infections , dose can be doubled

42. CEFACLOR ADVERSE EFFECTS :- Serum sickness , erythema multiforme , rashes , arthritis , diarrhoea , nausea , vomiting , hepatitis , jaundice , lymphatocytosis , leukopenia , hyperactivity , insomnia , dizziness , hallucinations . INTERACTIONS :- Probenicid :- prolongs the serum levels by slowing the rate of excretion by competitively inhibiting renal tubular secretion Warfarin :- Prolongs anticoagulant duration

43. 4. CEFOXITIN Cefoxitin is more active against anaerobes & is most active cephalosporin against B.fragilis It is generally used for treatment of lung abcesses , & pelvic inflammatory disease MECHANISM OF ACTION :- Cefoxitin mainly causes inhibition of the cell wall synthesis mainly inhibiting the cross linking of the peptide chains. PHARMACOKINETICS :- Absorption :- The drug is well absorbed post IV/IM infusion

44. CEFOXITIN Distribution :- It is widely distributed throughout the body with poor penetration Protein binding :- approx 30 % Metabolism :- Not metabolized in the body Elimination :- about 85 % of the drug is excreted unchanged in the urine T ½ :- Half life after an IV dose is 41 -50 minutes USES :- It is mainly used in lung abcesses , UTIs , Endometritis , Gonorrhoea , Peritonitis , Influenza , Pelvic cellulitis etc.

45. CEFOXITIN CONTRAINDICATIONS :- It is contraindicated in patients with known allergy to cephalosporins PRESCRIBED DOSE :- Uncomplicated infections :- 1g IV in 6-8 hours , maximum dose is 3-4 g Severe infections :- 2g IV in every 6-8 hours ; 6-8 g/day is maximum dose If used for surgical prophylaxis :- 1-2 IV Renal impairment :- Crcl ( 30-50 Ml/min ) : 1-2 g in 8-12 hours Crcl (10-30 ml / min ) : 1-2 g in 12-24 hours

46. CEFOXITIN ADVERSE EFFECTS :- High doses may cause CNS toxicity , pregnant women are associated with risk of miscarriage , Diarrhoea , Anaemia , Eosinophilia , Leukopenia etc. INTERACTIONS :- No major drug interactions are shown by Cefoxitin

47. THIRD-GENERTION AGENTS Third generation cephalosporins are highly resistant to beta- lactamases,have good activity against gram-negative organisms & anaerobes They cross the BBB , hence useful in Meningitis They can be life-saving in serious gram-negative infections & hence have replaced second generation agents.

48. 1 . CEFOTAXIME Cefotaxime is highly resistant to several beta- lactamases & it has a wide gram –negative coverage. It crosses the BBB & has been used successfully in the treatment of meningitis due to H.influenzae , S.pneumoniae , meningitis MECHANISM OF ACTION :- On parenteral administration cefotaxime show bactericidal property by inhibiting the cell wall synthesis PHARMACOKINETICS :- Absorption :- r apidly absorbed following intramuscular injection

49. CEFOTAXIME Distribution :- It is distributed throughout the body Metabolism :- a pproximately 20-36% of an intravenously administered dose of 14C-cefotaxime is excreted by the kidney as unchanged cefotaxime and 15-25% as the desacetyl derivative, the major metabolite. The desacetyl metabolite has been shown to contribute to the bactericidal activity. Two other urinary metabolites (M2 and M3) account for about 20-25%. They lack bactericidal activity. Elimination :- a pproximately 20-36% of an intravenously administered dose of 14C-cefotaxime is excreted by the kidney as unchanged cefotaxime and 15-25% as the desacetyl derivative, the major metabolite.

50. CEFOTAXIME T ½ :- 60-70 minutes USES :- It is mainly used for the treatment of Pneumonia , meningitis epiglottitis , pyoderma , pyelonephritis , subcutaneous abcess , pelvic inflammations , peritonitis CONTRAINDICATIONS :- It is contraindicated in patients with known allergy to cephalosporins PRESCRIBED DOSE :- < 12 years or <50 kg :- 50-200 mg/kg/day , IV/IM in 6-8 hourly divided doses for 7-14 days For meningitis :- 250 mg/kg/day in 6-8 hourly divided doses

51. CEFOTAXIME >12years or >50kg :- 1-2 g IV/IM every 8 hours for 7-14 days For meningitis :- 3g /day IV ADVERSE EFFECT :- Injection site inflammation , hypersensitivity reactions , colitis , diarrhoea , nausea , vomiting , pseudomembranous colitis INTERACTION :- If given alongwith aminoglycoside antibiotics , it shows increased risk of nephrotoxicity

52. 2. CEFTRIAXONE Ceftriaxone is a long-acting cephalosporin for IV / IM administration also it is one of the most commonly used agents for meningitis MECHANISM OF ACTION :- Ceftriaxone is bactericidal in nature as it causes inhibition of the bacterial cell wall synthesis , mainly by binding to PBP 3 . PHARMACOKINETICS :- Absorption :- Ceftriaxone is only given as an injection, either intramuscularly or intravenously. 11   Ceftriaxone is less than 1% bioavailable if given orally. 3

53. CEFTRIAXONE Distribution :- 5.78 to 13.5 L Protein binding : - Ceftriaxone is 95% protein bound Metabolism :- negligible Elimination :- about 33 % of the drug is excreted in the urine , the remainder is eliminated by bile secretion ( excretion by faeces ) T ½ :- 5.8 -8.7 hours USES :- Meningitis , typhoid , pneumonia , otitis media, pyelonephritis , pelvic infections , septicaemia , gonococcal infections etc

54. Ceftriaxone CONTRAINDICATIONS :- It is contraindicated in patients with known allergy to cephalosporins PRESCRIBED DOSE :- 50-100 mg/kg/day IV divided in 12 hourly doses for 7-14 days , maximum dose is 4 g / day In meningitis :- 100 mg/kg/day ADVERSE EFFECTS :- Injection site inflammation , rash , pruritis , otitis media , fever , eosinophilia , urticaria , colitis, diarrhoea etc INTERACTION :- Increased nephrotoxicity if taken with aminoglycoside antibotics

55. 3. CEFOPERAZONE Cefoperazone is particularly more effective against Pseudomonas whereas activity against other gram –negative bacteria is weaker It is not very useful for the treatment of meningitis as it does not penetrate the BBB as freely as compared to other 3 rd generation cephalosporins Cefoperazone fails to inhibit beta lactamase producing microbes MECHANISM OF ACTION :- It acts by inhibiting cell wall synthesis of bacteria by binding to PBP3

56. CEFOPERAZONE PHARMACOKINETICS :- Absorption :- It is well absorbed by intravenous or intramuscular administration Distribution :- well distributed throughout the body Protein binding :- 60 -70 % Elimination :- It is mainly excreted by the bile T ½ :- 1.5 -2 hours USES :- Respiratory tract infections caused by  S. pneumoniae ,  H. influenzae ,  S. aureus   Peritonitis and other intra-abdominal infections caused by  E. coli ,  P. aeruginosa , and anaerobic gram-negative bacilli (including  Bacteroides fragilis ).

57. CEFOPERAZONE Bacterial septicemia caused by  S. pneumoniae ,  S. agalactiae ,  S. aureus ,  Pseudomonas aeruginosa ,  E. coli ,  Klebsiella  spp.,  Klebsiella pneumoniae , Proteus species ( indole -positive and indole -negative),  Clostridium  spp. and anaerobic gram-positive cocci . Infections of the skin and skin structures caused by S. aureus Pelvic Inflammatory Disease, Endometritis , and Other Infections of the Female Genital Tract caused by N. gonorrhoeae , Peritonitis

58. CEFOPERAZONE CONTRAINDICATIONS : - It is contraindicated in patients with hypersensitivity PRESCRIBED DOSE :- 100 – 200 mg/kg/day in 2 divided doses IV/IM for 10-14 days ADVERSE EFFECT :- Anemia , bleeding , haemolytic anemia , leukopenia , bone marrow depression , dizziness , fever pain, chills , urticaria INTERACTIONS :- It produces disulfiram like reactions when taken with alcohol

59. 4. CEFIXIME It is orally effective with good activity against gram-positive cocci , H.influenzae , gonococci , & is highly effective against Enterobacteriaceae . It is mainly used in the infections of urinary , respiratory & biliary infections MECHANISM OF ACTION :- It shows bactericidal activity by causing inhibition of cross linking of peptide chains PHARMACOKINETICS :- Absorption :- With oral administration of cefixime , about 40%-50% is absorbed whether administered with or without food.  However, time to maximal absorption is increased approximately 0.8 hours when administered with food.

60. CEFIXIME Distribution :- Cefixime has a volume of distribution averaging 0.1 L/kg of body weight when administered orally Protein binding :- 65 % cefixime is bound to serum proteins Metabolism :- not metabolized in the body Elimination :- Approximately 50% of absorbed cefixime is excreted unchanged in the urine in 24 hours T ½ :- 3-4 hours USES :- UTIs , Diarrhoea , Enteric fever , other garm – ve infectionjs etc

61. CEFIXIME PRESCRIBED DOSE :- For children :- 8mg/kg/24hours orally in 1-2 divided doses IN TYPHOID :- 20 mg/kg/day in 2 divided doses for 14 days For adolescents & adults :- 400 mg/24 hours orally in 1-2 divided doses ADVERSE EFFECTS :- Pseudomembranous colitis , nausea , vomiting, diarrhoea , hypersensitivity , hepatic dysfunction , fever , thrombocytopenia , serum sickness , Stevens-Johnsons syndrome

62. cefixime INTERACTIONS :- No major drug or food interactions are shown by the drug

63. FOURTH GENERATION AGENTS Fourth generation Cephalosporins include – CEFPIME & CEFPIROME, active against a variety of gram+ve & gram- ve bacteria More resistant to many of the Beta- lactamases Both cefepime & cefpirome are administered parenterally , half –life is about 2 hrs , excreted through kidneys Cefepime attains high concentration in CSF while Cefpirome has good tissue penetrability.

64. USES FOURTH GENERATION CEPHALOSPORINS These agents are widely used in Specticaemia , nosocomia & other serious infections of the skin , urinary & respiratory tracts & infections in immunocompromised infections Cefepime – DOSE:- 1-2 gm IV q 8-12hr Cefpirome – DOSE:-1-2 g IM/IV q 12hrs

65. FIFTH GENERATION AGENTS Fifth generation cephalosporins include- Ceftaroline & Ceftobiprole These are anti-MRSA cephalosporins , both drugs are also effective against penicillin-resistant Streptococcus pneumoniae in addition to gram- ve microbes Used for mainly skin & respiratory infections Ceftobiprole is also effective against Pseudomonas DOSE:-600mg slow IV over 1 hour

66. ADVERSE EFFECTS

67. ADVERSE EFFECTS

68. USES CEPHALOSPORINS

69. USES