Penicillin | The First Antibiotic

Penicillin | The First Antibiotic

The accidental discovery of penicillin was done by Alexander Flemming in the year 1939 which was later cultured by Florey and Chain in the year 1945.
It was obtained from Penicillium notatum (now called Penicillium chrysogenum )
It is the first antibiotic to be used clinically.

Structure

Penicillium consists of two rings.

The side chains are attached through the amide linkages.

Mechanism of Penicillin

The bacterial cell wall is made up of peptidoglycan that protects the cell integrity, shape and prevents macromolecules from entering into the cell.
It has cross-linking chains of NAG(N-acetylglucosamine) and NAM (N- acetylmuramic acid) components covalently attached through small peptides
Peptidoglycan is continuously synthesized and remodelled during growth and division.
Therefore bacteria assemble them into a single macromolecule by synthesizing the peptidoglycan components.
The peptide cross-linkages are formed by the activity of specific enzymes called transpeptidases or Penicillin-Binding Proteins (PBPs).
Penicillin contains a four-membered beta-lactam ring inhibits the transpeptidase.
By mimicking the last two D-alanine residues of the peptide, penicillin is able to bind irreversibly the active site of the transpeptidase, preventing the enzyme from cross-linking the peptidoglycan strands.
This leads to cell lysis as there won’t be any formation of peptidoglycan and the cell is no more susceptible to osmotic stress.

Penicillin G

Penicillin G is a broad-spectrum beta-lactam naturally occurring penicillin which is also known as benzylpenicillin
Benzylpenicillin is more active against Gram-positive bacteria in particular cocci, such as staphylococci, pneumococci, and other streptococci, and bacilli, including Bacillus anthracis, Clostridium perfringens, and Corynebacterium diphtheriae, but less effective against Gram-negative bacteria.
The penicillin is less effective against Gram-negative bacteria as it has an additional outer membrane, which acts as a selective barrier against penicillin.
Also, some Gram-negative bacteria have acquired specific genes which encode for penicillinases (beta-lactamases) which inactivate penicillin by hydrolysis of the beta-lactam ring

Second Generation Penicillin

The Gram-positive strains later emerged a new strain producing penicillinases.
This lead to the discovery of second-generation penicillin called semi-synthetic beta-lactamase resistant penicillin.
Ex- Oxacillins, Methicillin, Dicloxacillin

Third Generation penicillin

The third generation penicillin is more effective against a wider group of Gram-negative bacteria including Haemophilus influenzae, Escherichia coli, Salmonella spp., and Shigella spp
This included broad-spectrum penicillins known as aminopenicillins
Ex- Amoxicillin and ampicillin
These have higher stability towards penicillinases.
This also includes carboxypenicillins and ureidopenicillins which is effective against Pseudomonas aeruginosa.

Administration

Penicillin G can be taken either intravenously or intramuscularly.
Penicillin G administration ensures a continuous low dose of penicillin over 2 to 4 weeks.
Penicillin G degrades more easily by stomach acid and has a bioavailability of less than 30%.

Adverse Effect

Penicillin G has adverse effects that include nausea, vomiting, diarrhea, rash, abdominal pain, urticaria, muscle spasms, fever, chills, muscle pain, headache, tachycardia, flushing, tachypnea, and hypotension

Toxicity

Penicillin has a small risk of toxicity compared to other biologically-active substances
The doses involve 5g/kg body weight intravenously to cause convulsions in a patient.

References