Penicillin

Introduction

In our previous blog, we’ve discussed THE PRINCIPLES OF ANTIBIOTICS, so that you can get a basic idea about the chapter. Today we’ll talk about β-LACTAM ANTIBIOTICS.

β-LACTAM ANTIBIOTICS:

   Þ   β-lactam antibiotics are called so due to the presence of β-lactam ring in their structure.

    Þ  All of them i.e., Penicillin, Cephalosporin, carbapenem, and monobactams share a common mechanism of action (inhibition of synthesis of the bacterial peptidoglycan cell wall.

    Þ   Inhibited by the β-lactamase enzyme.

    Þ   Bactericidal in nature.

PENICILLIN:

    Þ   The Accidental Discovery:

       In 1928, while studying Staphylococcus variants in his laboratory, Sir Alexander Flemming observed a mold contaminating one of his cultures resulting in bacterial lysis. The broth in which the fungus was developed showed inhibitory effects on other microorganisms too. As the fungus belonged to the genus Penicillium, he named the antibiotic–Penicillin.

    In this context, he said, “One sometimes finds what one is not looking for. When I woke up just after dawn on Sept 28, 1928, I certainly didn’t plan to revolutionize all medicine by discovering the world’s first antibiotic, or bacteria killer. But I guess that was exactly what I did.”

        Þ   The chemical name of Penicillin is 6-amino penicillanic acid. It contains an acyl side chain, a β-lactam ring, and a thiazolidine ring in its structure.

                                           Fig 2: Chemical structure of penicillin

TYPES OF PENICILLINS:

1.  Penicillin G and Penicillin V:

• Penicillin V is more acid-resistant than Penicillin G. Therefore, Penicillin V is given orally and Pen G is given either IM or IV.
• They are highly active against sensitive strains of gram +ve cocci but resistance is a major problem as they are hydrolyzed by penicillinase / β-lactamase.
• USES: For Pneumococcal infections (S.pneumoniae ), pneumococcal pneumonia, Pen G is favored. Very effective in some strains of Streptococci and infections caused by them. The first line of treatment for Syphillis, Actinomycosis. Also used in clostridial infections (gangrene). 

2.     Penicillinase Resistant Penicillins:

• Resistant to hydrolysis by bacterial penicillinase enzyme. Ex: Cloxacillin, Methicillin (nephrotoxic), Oxacillin, Dicloxacillin, Nafcillin, etc.
• Not active against MRSA (Methicillin-Resistant Staphylococcus aureus)
• Active against most penicillinase-producing staphylococci.

3.     Aminopenicillins:

• Aminopenicillins, i.e., Amoxicillin, Ampicillin has activity against gram –ve bacterias too, hence they are different from others. They are destroyed by penicillinase (both gram+ve and gram –ve) so they must be given with β-lactamase inhibitors.
•  USES:

          I. Respiratory Tract Infections: Both are active against S.pyrogens, S.pneumoniae, H.influenzae. Amoxicillin is most active among all oral β-lactam antibiotics used against S.pneumoniae. Useful in Sinusitis, Otitis, Epiglottitis, chronic bronchitis.

          II.  Urinary Tract Infections: Uncomplicated UTIs caused by E.coli and Klebsiella can be treated by aminopenicillins. But the occurrence of resistance is higher nowadays.

          III.   Also used in acute bacterial meningitis for children caused by S. pneumoniae or Neisseria meningitidis.

4.   Antipseudomonal Penicillins:

• Caboxypenicillins – Carbenicillin, Ticarcillin, and Ureidopenicillins- Mezlocillin and Piperacillin come under this category.
• They are active against some strains of Pseudomonas aeruginosa.
• Piperacillin when combined with Tazobactam (β-lactamase inhibitor) shows the broadest spectrum of activity among penicillins. This has activity against methicillin-susceptible S. aureus, H. , B. fragilis, and most E. coli and Klebsiella. Piperacillin is only available for parenteral administration.

In the next blog, we will discuss about THE PENICILLINS AND THEIR BACTERIAL RESISTANCE. Till then make sure you subscribe to @A-Z pharmascience.