Cephalosporins - (First Generation)

Cephalosporins - (First Generation)

• 2.
   First discoveredin 1945  A class of Beta Lactam Antibiotics  Are derivatives of 7-aminocephalospranic acid  They were first isolated from Cephalosporium acremonium (fungus)
• 3.
   Are Beta-lactamcompounds  In which the beta-lactam ring is fused to a 6-membered dihydrothiazine ring, thus forming the cephem nucleus.
• 5.
  They are Bactericidalagents 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.
   Acquired resitanceto cephalosporins could be due to: 1. Alternation of the PBPs (target protiens) 2. Impermeability to the antibiotic thus preventing it to reach it’s site of action. 3. Production of Beta lactamases by many bacteria that inactivate the drug. 4. Resistance developed by penicilinase produced by staphylococci (less than penicillin)
• 7.
   Based ontheir 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)
• 8.
   Also calledNarrow spectrum Cephalosporins  Include ORAL  CEPHALEXIN  CEFADROXIL  CEPHRADINE PARENTERAL  CEFAZOLIN (prototype)  CEPHAPIRIN
• 9.
   First generationcephalosporins 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.
   Pharmacokinetics: › Routeof 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.
   Dosage: › Inmild 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.
   Pharmacokinetics: › Routeof 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.
   Pharmacokinetics: › Routeof 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.
   Pharmacokinetics: › Routeof 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.
   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.
   For dentalsurgical prophylaxis (Cephalexin and Cefazolin)  Skin and bone infections (Cefazolin)  Pharyngitis  Tonsilitis  Otitis  Pneumonia  UTI  Skin infections
• 17.
   Diarrhea  Nausea Vomiting  Abdominal discomfort  Headache  Fever  Rashes  Pruritis
• 18.
   Urticaria  Serumsickness like reaction  Disturbance in liver enzymes  Transient Hepatitis  Cholestatic jaundice  Eosinaphilia  Blood disorders  Antibiotic associated colitis (rare)