Beta Lactam Antibiotics

BETA LACTAM ANTIBIOTICS:

are the most popularly used antibiotics. They are  any antibiotic agent that contains a β-lactam chain in the molecular structure. Penicillin is the prototype drug and once was a cure for almost anything. Sir Alexander Fleming discovered Penicillin. It was a miracle discovery in history of Mankind.

Mechanism of Action:

–          Interfere with the synthesis of bacterial cell wall

–          Inhibit transpeptidases so that cross linking does not take place

–          When susceptible bacteria divide in the presence of it- cell wall deficient forms are produced resulting in the lysis of bacterial cell

–          Peptidoglycan cell wall is unique to bacteria and it is non toxic to man

–          Gram positive bacteria have higher susceptibility to PnG

Penicillin G (Benzyl Penicillin):

–          Narrow spectrum; gram positive

–          Majority of gram negative bacilli, M.tuberculosis, ricketsiae, chlamydiae, virus insensitive

–          Resistance:

1. Inherent: PBPs located deeper under lipoprotein where PnG is unable to penetrate
2. Penicillinase: opens the beta lactam ring
3. Penicillin tolerant but not penicillin destroying like pneumococci

–          Pharmacokinetics:

1. Acid labile: gastric acid
2. Low oral absorption and rapid and complete absorption from i.m site
3. Plasma t1/2  30 minutes
4. Poor CSF  and serous cavity penetration but increased in inflammation
5. Rapid renal excretion (GFR-10 % and rest tubular secretion)
6. Tubular secretion blocked by Probenecid: higher and longer lasting plasma concentration

–          Preparation and Dose:

1. Sodium Penicillin G injection
2. Repository Penicillin G injection
   1. Procaine Penicillin G
   2. Benzathine Penicillin G

–          Adverse Effects:

1. Local irritancy and direct toxicity: pain at im site, nausea, thrombophlebitis, mental confusion, muscular twitchings, convulsions, bleeding, hallucinations, CNS stimulation
2. Hypersensitivity: Urticaria, fever, wheezing, edema, serum sickness
3. Superinfections
4. Jarisch Herxheimer reaction

Semisynthetic Penicillins:

1. Acid resistant alternative: Phenoxymethyl penicillin (Penicillin V)
2. Penicillinase Resistant: Methicillin, Cloxacillin
3. Extended Spectrum:
   1. Aminopenicillin: Amoxycillin, Ampicillin, Bacampicillin
   2. Carboxypenicillin: Carbenicillin, Tircarcillin
   3. Ureidopenicillin: Poperacillin, Mezlocillin
   4. Beta- lactamase inhibitor: Clavulanic acid, Sulbactam, Tazobactam