Changes

'''First Generation Cephalosporins''' - Cefalexin, Cefalonium

'''First Generation Cephalosporins''' - Cefalexin, Cefalonium, Cephapirin

* Active against gram positive organisms

* Active against gram positive organisms

* Active aginst many gram negatives. ''Pseudomonas'' species are resistant.

* Active aginst many gram negatives. ''Pseudomonas'' species are resistant.

'''Second Generation Cephalosporins''' - Ceftiofur

'''Second Generation Cephalosporins''' - Cefuroxime

* Very broad spectrum with very high activity against enterobacteriaeceae.

* Very broad spectrum with very high activity against enterobacteriaeceae.

* Struggle against the most difficult gram negative organisms

* Struggle against the most difficult gram negative organisms

'''Third Generation Cephalosporins''' - Cefoperazone

'''Third Generation Cephalosporins''' - Cefoperazone, Ceftiofur

* Very active against gram negatives, especially the hardier species, including ''Pseudomonas''

* Very active against gram negatives, especially the hardier species, including ''Pseudomonas''

* Less active against gram positives compared to other cephalosporins; Staphylococci and enterococci can be resistant.

* Less active against gram positives compared to other cephalosporins; Staphylococci and enterococci can be resistant.

'''Fourth Generation Cephalosporins''' - Cefquinome

'''Fourth Generation Cephalosporins''' - Cefquinome

* Very broad spectrum, only the very hardiest of gram negatives aren't susceptible. It is still active againts ''Pseudomonas''.

* Very broad spectrum, only the very hardiest of gram negatives aren't susceptible. It is still active against ''Pseudomonas''.

 

==Pharmacokinetic Considerations==

==Pharmacokinetic Considerations==

They are organic acids, hydrophilic and will ionise at physiological pH. They generally have poor oral bioavailability as they unstable in acid environments. They have a limited volume of distribution (0.2-0.3l/kg), this means the drug is mainly confined to plasma and interstitial space. As the are lipophilic they can't enter cells and won't cross the blood brain barrier, unless it is damaged. They have short half-lives of about 0.5 - 1.2 hours. They are readily excreted by the kidneys, via tubular secretion in the proximal convoluted tubule. This results in high concentrations of the drug in urine.  

They are organic acids, hydrophilic and will ionise at physiological pH. They generally have poor oral bioavailability as they unstable in acid environments. They have a limited volume of distribution (0.2-0.3l/kg), this means the drug is mainly confined to plasma and interstitial space. As the are hydrophilic they can't enter cells and won't cross the blood brain barrier, unless it is damaged. They have short half-lives of about 0.5 - 1.2 hours. They are readily excreted by the kidneys, via tubular secretion in the proximal convoluted tubule. This results in high concentrations of the drug in urine.  

Exceptions are:

Exceptions are:

* Cefalexin which is stable in acid and so suitable for oral dosing.

* Cefalexin which is stable in acid and so suitable for oral dosing.

* Ceforperazone is excreted in bile rather than in urine.

* Ceforperazone is excreted in bile rather than in urine.

==Side Effects and Contraindications==

==Side Effects and Contraindications==

* Very high doses has been known to result in nephrotoxicity.

* Very high doses has been known to result in nephrotoxicity.

* They can result in bleeding problems because of interference with the formation of vitamin K in the gut (esp Moxalactam).

* They can result in bleeding problems because of interference with the formation of vitamin K in the gut (esp Moxalactam).