Beta Lactam Antibiotics

Possess beta-lactam ring in their nucleus include
- Penicillins
- Cephalosporins

 

Basic Structure Of Penicillin

Penicillins

- Possess beta-lactam ring and thiazolidine ring in their nucleus (6-APA : 6-amino penicillanic acid)
- Semi synthetic penicillins produced by altering the composition of the side chain attached to 6 APA nucleus
- Stability of penicillins against gastric acid and beta-lactamase varies among individual compounds

Classification Of Penicillins

- Natural penicillins : Penicillin G (Benzyl penicillin)Procaine penicillin G
Benzathine penicillin G
- Acid resistant penicillins :Phenoxymethyl penicillin (penicillin V)
Phenoxyethyl penicillin (phenethicillin
- Penicillinase-resistant penicillins :a) Acid Labile : Methicillin, Nafcillin, Cloxacillin, Dicloxacillinb) Acid resistant : Flucloxacillin

 

Classification Of Penicillins (Contd…)

- Penicillins effective against Gram-positive and some Gram-negative organisms: Ampicillin, Amoxycillin, Talampicillin, Pivampicillin
- Extended spectrum penicillins:
a) Carboxypenicillins : Carbenicillin, Ticarcillin
b) Ureidopenicillins : Piperacillin, Mezlicillin
c) Amidinopenicillins : Mecillinam, Pivmecillinam
- Penicillins with betalactamase inhibitors:
Amoxycillin-clavulanic acid
Ticarcillin-clavulanic acid

 

Mechanism Of Action Of Penicillins

* Bactericidal
* Inhibition of bacterial cell wall synthesis

 

Resistance

* Hydrolysis by beta lactamase breaks the beta lactam ring
* Important mechanism of resistance
* Beta lactamase producers include Staph. aureus, E. coli, H. influenzae, Neisseriae, etc.

 

Ampicillin

Broad spectrum penicillin, effective against gram-positive and gram-negative bacteria

 

Ampicillin - Antibacterial Spectrumsome important organisms

Absorption

* Absorbed following oral administration
* Peak 2 hours after oral dose; 1 hour after IM dose * Plasma levels persist for 6 hours

 

Distribution

* Well distributed in tissues / fluids
* Excreted unchanged in urine
* Good concentrations in bile
* Crosses blood-brain barrier when meninges are inflammed
* Crosses placental barrier and excreted in breast milk

 

Fate / Excretion

* Not metabolized in the body
* Excreted unchanged in urine
* Unabsorbed drug excreted in stools

 

Dosage & Administration

* Usual adult dose 250-500 mg 6 hourly orally / IM / IV. (Higher doses eg., 1 g 6 hourly for refractory infections)
* Children : 25 - 100 mg / Kg / day

Tolerability

* Well known for good tolerability
* Diarrhoea, skin rashes may occur
* Safe in pregnancy, lactation, children
* Contraindicated in hypersensitivity to penicillins

 

Indications

* Respiratory tract and ENT infectionseg, pharyngitis, tonsillitis, otitis media, sinusitis, bronchitis, pneumonia

- Good concentrations in respiratory tract and coverage of common organisms in RTI, eg, Streptococci and H. influenzae
- Good efficacy and tolerability; suitable for day-to-day respiratory infections

 

Indications (Contd…)

* Urinary tract infections« Excreted in urine in active form
- Covers E. coli and other organisms involved in UTI

* Biliary tract infections« Enterohepatic circulation; high concentrations in biliary tract
- Efficacy against salmonella; useful in typhoid carriers

 

Indications (Contd…)

* Meningitis
- Achieves adequate concentrations in CSF in the presence of inflamed meninges. Covers bacterial causes eg., E. coli, H. influenzae, Neisseria

* G. I. Infections / Enteric fever
- Effective against some strains of shigella & salmonella, but other drugs eg, fluoroquinolones may be preferred for these situations today

* Gonorrhoea
- Effective against non-beta lactamase - producing strains of Neisseria gonorrhoea
- 1g single dose

 

Amoxycillin

- Broad spectrum penicillin; similar to ampicillin
- OH group in chemical structure conferspharmacokinetic differences fromampicillin
- Superior G. I. absorption, with serum concentration double that with a similar dose of ampicillin

 

Amoxycillin Spectrum - Important Organisms

Pharmacokinetics

* Well absorbed orally; serum concentrations twice those with ampicillin
* Higher tissue concentrations than ampicillin
* Peak similar to ampicillin (2 hours) but levels persist longer (8 hours), hence t. d. s. administration
* Good concentrations in bile & urine; crosses placental barrier and excreted in breast milk
* Not metabolized in body; excreted unchanged in urine

Dosage and Administration

* Usual adult dose 250-50 mg 8hourly
* Children : 25 - 100 mg / Kg / day(Administered orally andparenterally)

 

Tolerability

* Well known for good tolerability
* Lower incidence of diarrhoea & rash than with ampicillin
* Safe in pregnancy, lactation, children
* Contraindicated in patients hyper sensitive to penicillins

 

 

Salient Features of Ampicillin & Amoxycillin

* Broad spectrum penicillins, similar spectra covering common gram positive and gram negative bacteria
* Effective by oral / parenteral routes
* Safety and good tolerability is well known
* Well distributed in the body
* Effective in RTI & ENT infections, UTI, biliary tract infections, G. I. Infections, enteric fever, meningitis, gonorrhoea
* Safe in pregnancy, lactation & in children
* Amoxycillin is better absorbed than ampicillin; achieves twice the serum concentrations of ampicillin
* Less diarrhoea, rash with amoxycillin