Structure:

Thiazolidine and beta-Lactam ring form nucleus. Side chain determine specificity

Mechanism:

G+ bacteria contain NAG and NAM. The peptide chains are cross-linked between 2 NAMs at the D-alanyl-D-alanine terminus by transpeptidase. PCN inhibits this enzyme preventing cross-linking and causing cell lysis.

Penicillinase Sensitive

Given has a IM/IV. Acid-labile so cant be given orally. Goes into CNS if meninges are inflammed

3 Forms

1. Aqueous (Pfizerpin) - solution for IM/IV
2. Procaine (generic) - suspenion for IM only. Local anesthetic that combines with PCN & slows absorption.  (Available with benzathine as Bicillin C-R, controled-release)
3. Benzathine (Bicillin L-A, long acting) - suspension of IM

90% eliminated by tubular secretion. Uric acid and probenicid compete for the same site and can increase PCN concentration.

Penicillinase Sensitive

acid stable (for oral use)

food interferes with absorption so take 1hr before eating

oral

Penicillinase Resistant Penicillins

S. Aureus that is resistant to this drugs are called Methicillin Resistant S. Auereus (MRSA)

Excreted by biliary and renal excretion (advantage in hepatic or renal disease)

Parenteral

Penicillinase Resistant Penicillins

S. Aureus that is resistant to this drugs are called Methicillin Resistant S. Auereus (MRSA)

Excreted by biliary and renal excretion (advantage in hepatic or renal disease)

Parenteral

Penicillinase Resistant Penicillins

S. Aureus that is resistant to this drugs are called Methicillin Resistant S. Auereus (MRSA)

Excreted by biliary and renal excretion (advantage in hepatic or renal disease)

Oral or IV

available with Sulbactam as Unasyn for IM/IV use

Sulbactam - beta-lactamase inhibitor

Unasyn is preferable for peritonitis due to Bacteroides fragiles

tablets, oral suspension, or pediatric drop.

Better oral absorption and half-life than ampicillin.

available with clavulanate (beta-lactamase inhibitor) called Co-amoxiclav

As an oral prep can be used for peritonitis after IV therapy to finish off infection. Not used for initial infection because because it is to slow when given orally

Also used for otis media & prophylaxis before dental procedure

Antipseudomonas PCN

parenteral

Antipseudomonas PCN

parenteral

same uses as timentin

Side Effects of Penicillins

• Hypersensitivity from metabolites acting as haptens. IgE mediated. Rashes, serum sickness, fever, Stevens-Johnson syndrome
• Diarrhea - kills normal flora
• superinfection - allows C. Difficile and Pseudomembranous collitis to grow out of control resulting in bloody diarrhea
• Increased risk of seizures if it gets through the BBB (needs to be inflammed) by acting as a GABA-A antagonist
  
• Decreased renal function increases risk - cleared through kidneys
• Jarisch-Herxheimer Reaction in patients with 2nd degree syphilic several hours after 1st injection (resolves spontaneously, treat with aspirin)