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Mechanism of Drug Action of Penicillins and Cephalosporins:

Like all β-lactam antibiotics, penicillin and cephalosporin inhibit bacterial growth by
intriguing with a specific step in bacterial cell wall synthesis. This maintains cell
shape and prevents it from high osmotic pressure.

The cell wall is composed of cross linked polymer, peptidoglycan (polypeptide +

polysaccharide). The polysaccharide contains alternating amino sugars , N- acetyl
glucose amine and n-acetyl muramic acid. A five amino acid peptide is linked to N-
acetyl muramic acid sugar. This peptide terminates in D- alanyl-D- alanine, penicillin
binding proteins(PBP's) catalyze the transpeptidase reaction that removes terminal
alanine to forms a cross link with nearby peptide , which gives cell wall structure to
its rigidity.

β-lactam anti-biotics are structural analogue of D- Ala-D- Ala substrate and they are
covalently bound by PBPIS at active sites. After a β- lactam antibiotics have attached
to the PBP's at the active sites, the transpeptidation reaction is inhibited;
peptidoglycan synthesis blocked and cell dies.

Penicillin and cephalosporin are bactericidal, only if cells are actively growing and
synthesizing cell wall.

Pharmacokinetics of Penicillins.

Adsorption of orally administrated drugs differs greatly for different penicillin,

depending on part of acid stability and protein binding e.g. methcillin and
gastrointestinal absorption of nafcillin is erratic, so not suitable for oral
administration. But ampicillin and amoxicillin are acid stable and relatively well
absorbed producing serum concentrations in the rage of 4-8 µg /mL following a 500
mg oral dose.

Administration by intravenous route is preferred because of irritation and local pain

produced by the intramuscular injection of large doses. Serum concentration 30 min.
after an intravenous injection of 1g of pencillin is 20-50 µg/mL.

Only a fraction of total drug in serum is present as a free drug , its concentration is
determined by protein binding highly protein bound pencillins (e.g. nafcillin) produce
lower level of free drug in serum than less protein bound fraction is approximately
95% or more . Pencillins are widely distributed in body fluids and tissues. They are
polar molecule and concentration in cell is less than extra cellular fluid.

Penicillin concentrations in most tissues are equal to those in serum. Pencillin is

excreted into milk to level 3-15% of those present in serum. Penetration into eye and
nervous system is poor. However, in active inflammation of menings, as in bacterial
meningitis. Penicillin concentration of 1-5ug/mL cab be archived with a parental dose
of 18-24 million units. These concentrations are sufficient to kill pneumococci and

Penicillin is rapidly excreted by kidney into urine and small amount by other routes.
About 10% of renal excretion is by glomerular filtration and 90% by tubular
secretions. The normal half life of penicillin G is 30 min. and amoxicillin is 1 hour.
The dose must be adjusted according to dose being administrated if creatinine
clearance is 10 mL / min.

Pharmacokinetics of Cephalosporins:

Cephalexin, Cephradine, Cephalothin are absorbed from gut to a variable extent. After
oral doses of 500mg, serum levels are 15-20 µg/mL. Urine concentration is very high
but in most tissues levels are variable and generally lower than in serum. Excretion is
mainly by glomerular filtration and tubular secretions into the urine . In patients with
impair renal function, dosage must be reduced.