CephalosporinBy: Faseeha Mudassir

Introduction

• Beta lactam antibiotics.

• Bactericidal.

• Safest antibiotics.

• Variable spectrum.

• Cell wall synthesis inhibitors.

• High therapeutic index.

Source

• Natural:

i. Cephalosporin C

ii. Cephalosporin P

iii. Cephalosporin N

• They may be synthetic.

• Cephalosporin C is produced by fungi Cephalosporium acremonium.

Chemistry

• Basic nucleus is 7 amino cephalosporinic acid (A.C.A).

• Composed of three parts.

i. Dihydrothiazine ring

ii. Beta lactam ring.

iii. Two side chains R and X

R changes in pharmacodynamics.

X changes in pharmacokinetics.

Classification of Cephalosporins

• Classified into 4 groups.

i. 1st generation

ii. 2nd generation

iii. 3rd generation

iv. 4th generation

i. 1st Generation

A. Oral: (DLR)

• Cefadroxil

• Cephalexin

• Cephradoxine

B. Parenteral: (PZ, TX)

• Cephapirin

• Cefazolin longest t1/2 among 1st generation.

• Cephalothin

• Cephaloxidine

Properties of 1st Generation

• Cannot cross BBB.

• Narrow spectrum antibiotics.

• Highly effective against Gram +ive bacteria and less effective against gram -ive bacteria.

• Highly sensitive to beta lactamases.

ii. 2nd Generation

A. Oral: (ACP L)

• Cefuroxime axetil

• Cefaclor

• Cefprozil

• Loracarbef

B. Parenteral (NMR S, TMX)

• Cefonicid

• Cefamandol

• Ceforanide

• Cefuroxime sodium

• Cefotetan

• Cefmetazole

• Cefoxitin

Properties of 2nd Generation

• Cannot cross BBB.

• Sensitive to beta lactamases.

• Intermediate spectrum.

• Moderately effective against Gram –ive as well as gram +ive bacteria.

iii. 3rd Generation

A. Oral: (TIP D)

• Ceftibuten

• Cefixime

• Cefpodoxime proxetil

• Cefdinir

• These cannot cross BBB.

B. Parenteral: (ST3 PML)

• Cefotaxime sodium

• Ceftriaxone longest half life among cephalosporins.

• Ceftizoxime

• Ceftazidime

• Cefoperazone cannot cross BBB.

• Moxalactam

• Latamoxef

Properties of 3rd Generation

• Can cross BBB except cefoperazone. So can be used in meningitis.

• Resistant to beta lactamases.

• Broad spectrum.

• Highly effective against Gram –ive and less effective against Gram +ive bacteria.

iv. 4th Generation

A. Parenteral: (P2)

• Cefepime

• Cefpirome

Properties of 4th Generation

• Can cross BBB.

• Broad spectrum.

• Highly resistant to beta lactamases.

• Highly effective against Gram –ive bacteria.

Pharmacokinetics

• Orally good absorption.

• Parenterally not well absorbed.

• 1st and 2nd generation cannot cross BBB where as 3rd and 4th generation except cefoperazone can cross BBB.

• Not well metabolized.

• Excretion through renal pathway except ceftriaxone and cefoperazone which are excreted through biliary pathway.

Pharmacodynamics

• Cell wall synthesis inhibitors.

• Bactericidal.

Antimicrobial spectrum1st, 2nd, 3rd, and 4th generations.

i. 1st Generation

SSPEK

• Streptoccal species:

a. Streptococcus pneumonia (lower respiratory tract infections)

b. S. pyrogens (pus infections)

c. S. mutans (dental infections)

d. S. viridans

e. S. agalactiae

Staphyloccal species:

a. Staphylococcus aureus

b. S. epidermidis

c. S. saprophyticus

• Proteus mirabilis

• E.coli

• Klebsiella pneumoniae

ii. 2nd Generation

• SSPEK

SH MB

• Serratia species

• Haemophilus influenza

• Moraxella catarrhalis

• Bacterioid fragilis

iii. 3rd Generation

• SSPEK

• SH MB

VPN S2

• Vibrio cholera

• Pseudomonas aeruginosa

• Neisseria species

• Shigella

• Salmonella typhae

iv. 4th Generation

• SSPEK

• SH MB

• VPN S2

• Hospital acquired nosocomial resistant infections.

Clinical Uses

• Respiratory tract infections (upper and lower RTIs)

• Urinary tract infections

• Bone and Joint infections (Septic arthritis, osteomyelitis)

• Mixed abdominal Infections

• Septicemia

• Hospital acquired nosocomial infections

Side Effects

• Hypersensitivity reactions (anaphylactic shock, rashes etc.)

• Bleeding tendency (antibiotics of 2nd generation such as cefamandol, cefotetan, cefmetazol and 3rd generation such as cefoperazone and moxalactam cause hypoprothrombinemia that results in bleeding)

• GIT disturbance (Nausea, Vomiting, Diarrhea)

• Disulfiram like reactions with some 2nd and 3rd generation cephalosporins leading to tachy cardia, flushing of face etc.

• Intramuscular injection causes severe pain.

• Intravenous injection sometimes cause phlebitis and thrombophlebitis.

Containdications

• Allergy

• Bleeding disorder

• Pregnancy