Cephalosporins - (First Generation)

CEPHALOSPORINS� (First Genertaion)

Introduction:
First discovered in 1945
A class of Beta Lactam Antibiotics
Are derivatives of 7-aminocephalosporanic acid
They were first isolated from Cephalosporium acremonium (fungus)

Structure:
Are Beta-lactam compounds

In which the beta-lactam ring is fused to a 6-membered dihydrothiazine ring, thus forming the cephem nucleus.

Mechanism of action:
They are Bactericidal agents by cell lysis.
Bind to the Penicillin-binding proteins (PBPs) on the bacterial cell membrane and inhibit cell wall synthesis.
Inhibit Peptidoglycan synthesis by inhibiting the transpeptidation reaction – failure of cross-linking of peptidoglycan.

Mechanism of resistance
Acquired resitance to cephalosporins could be due to:
Alternation of the PBPs (target protiens)
Impermeability to the antibiotic thus preventing it to reach it’s site of action.
Production of Beta lactamases by many bacteria that inactivate the drug.
Resistance developed by penicilinase produced by staphylococci (less than penicillin)

Classification of cephalosporins:
Based on their spectrum of activity, Cephalosporins can be broadly categorized into four generations.
1st Generation (Cefazolin, Cephalexin)
2nd Generation (Cefotetan, Cefoxitin)
3rd Generation (Cefoperazone, Cefixime)
4th Genertaion (Cefepime)

First Generation drugs:
Also called Narrow spectrum Cephalosporins
Include;
ORAL:
CEPHALEXIN
CEFADROXIL
CEPHRADINE
PARENTERAL:
CEFAZOLIN (prototype)
CEPHAPIRIN

Anti-baterial spectrum:
First generation cephalosporins are very active against gram positive cocci which include:
Pneumococci
Streptococci
staphylococci.
Against gram negative bacilli
E. coli
Klebsiella
Proteus
Active against most penicillin-susceptible anaerobes found in the oral cavity,
except those belonging to the Bacteroides fragilis (that are Gram-negative bacillus bacterium species, and an obligate anaerobe of the gut ) group.

Clinical uses:
For dental surgical prophylaxis (Cephalexin and Cefazolin)
Skin and bone infections (Cefazolin)
Pharyngitis
Tonsilitis
Otitis
Pneumonia
UTI 
Skin infections

Toxicity:
Diarrhea
Nausea
Vomiting
Abdominal discomfort
Headache
Fever
Rashes
Pruritis
Urticaria
Serum sickness like reaction
Disturbance in liver enzymes
Transient Hepatitis
Cholestatic jaundice
Eosinaphilia
Blood disorders
Antibiotic associated colitis (rare)

1. CEPHALOSPORINS (First Genertaion ) Presentation by: Dr. Almas Muhammad Arshad BDS (UOL). RDS, PGAGD

2. Introduction: First discovered in 1945 A class of Beta Lactam Antibiotics Are derivatives of 7-aminocephalospranic acid They were first isolated from Cephalosporium acremonium (fungus)

3. Structure: Are Beta- lactam compounds In which the beta- lactam ring is fused to a 6-membered dihydrothiazine ring, thus forming the cephem nucleus.

4. Structure:

5. Mechanism Of Action: They are Bactericidal agents by cell lysis . Bind to the Penicillin-binding proteins (PBPs) on the bacterial cell membrane and inhibit cell wall synthesis. Inhibit Peptidoglycan synthesis by inhibiting the transpeptidation reaction – failure of cross-linking of peptidoglycan .

6. Mechanism of Resistance: Acquired resitance to cephalosporins could be due to: Alternation of the PBPs (target protiens ) Impermeability to the antibiotic thus preventing it to reach it’s site of action. Production of Beta lactamases by many bacteria that inactivate the drug. Resistance developed by penicilinase produced by staphylococci (less than penicillin)

7. Classification: Based on their spectrum of activity, Cephalosporins can be broadly categorized into  four generations. 1 st Generation ( Cefazolin , Cephalexin ) 2 nd Generation ( Cefotetan , Cefoxitin ) 3 rd Generation ( Cefoperazone , Cefixime ) 4 th Genertaion ( Cefepime )

8. First Generation: Also called Narrow spectrum Cephalosporins Include ORAL CEPHALEXIN CEFADROXIL CEPHRADINE PARENTERAL CEFAZOLIN (prototype) CEPHAPIRIN

9. Anti-bacterial Spectrum: First generation cephalosporins are very active against gram positive cocci which include: Pneumococci Streptococci staphylococci. Against gram negative bacilli E. coli Klebsiella Proteus Active against most penicillin-susceptible anaerobes found in the oral cavity, except those belonging to the Bacteroides fragilis (that are Gram-negative bacillus bacterium species, and an obligate anaerobe of the gut ) group.

10. Cefazolin : Pharmacokinetics: Route of administration: Parentral PPB  70 – 86% Volume of distribution  9.2/1.73 sg.meter Half life  1.6 – 2.2 hours Renal Excretion  87%

11. Cntd .. Dosage: In mild disease: 250mg – 500mg after every 8 hours In Moderate to sever disease : 500mg – 1g after every 6 hours In most severe cases ( e.g Endocarditis , Septicemia) : 1g – 1.5g every 6 hours

12. Cephalexin : Pharmacokinetics: Route of administration: Oral Partially bound to plasma protiens . Half life : 60 mins It attains high concentration in the bile Excretion through the urine Dosage: In Adults  250mg – 1g every 6 – 8 hours In Children  25 – 1000mg/kg/day

13. Cephadroxil : Pharmacokinetics: Route of administration  Oral Half life  1.5 hours Metabolism  Unknown Absorption in GIT PPB  20% of drug binds to plasma protien . Can cross the placental barrier and also appear in the breast milk Excretion  90% through urine Dosage: 500mg – 1g after every 12 hours.

14. Cephradine : Pharmacokinetics: Route of administration  Oral and I/M Volume of distribution  0.29 +- 0.03l/kg PPB  Less than 10% Half life  0.7 hours (oral) and 2-3hrs (I/M) Dosage: In Adults  250mg – 4g/day (orally) In Children  25 -100mg/kg/day (I/M)

15. Cephapirin : Pharmacokinetics: Route  I/V Half life  0.36hrs Can cross the placental barrierand appear in the breast milk Dosage: 2 grams every 6 hours

16. Clinical Uses: For dental surgical prophylaxis ( Cephalexin and Cefazolin ) Skin and bone infections ( Cefazolin ) Pharyngitis Tonsilitis Otitis Pneumonia UTI  Skin infections

17. Toxicity: Diarrhea Nausea Vomiting Abdominal discomfort Headache Fever Rashes Pruritis

18. Cntd .. Urticaria Serum sickness like reaction Disturbance in liver enzymes Transient Hepatitis Cholestatic jaundice Eosinaphilia Blood disorders Antibiotic associated colitis (rare)

19. Thank You! Presentation by: Almas Muhammad Arshad (Roll#01) Qurat-ul-Ain Aslam (Roll#04) Naima Khalid (Roll#33) Iqra Rafi (Roll#83) Sana Kanwal (Roll#88)