#penicillins(beta lactum antibiotics)

        PENICILLINS

Penicillin refers to a group of beta lactum antibiotics used in the treatment of bacterial infections caused by susceptible,usually Gram-positive organisms.

History:

       The discovery of penicillin is usually attributed to Scottish scientist sir Alexander Fleming in 1928,though others had earlier noted the antibacterial effects of penicillium .the development of penicillin for use as a medicine is attributed to the Adelaide born Nobel Laureate Howard Walter Florey .In march 2000, doctors of the San Juan de Dios Hospital in San Jose published manuscripts belonging to the Costa Rican scientist&medical doctor Clodomiro Picado Twiggy (1887-1944).The manuscripts explained Picado's experiences between 1915 and 1927 about the inhibitory actions of the fungi of genera penic.

Apparently clorito picado had reported his discovery to the Paris academy of sciences in Paris,yet did not patent it,even though his investigation had started years before Fleming's .

Fleming at his laboratory in St.mary's hospital in London,noticed a halo of inhibition of bacterial growth around  containment blue-green mold  staphylococcus plate culture.fleming concluded that the mold was releasing a substance that was inhibiting bacterial growth and lysing the bacteria.he grew a culture of the mold and discovered that it was a penicillium mold,now known to be penicillium notatum .Fleming coined the term "pencicillin" to describe the filtrate of a broth culture of the penicillium mold.Even in these early stages,penicillin was found to be most effective against Gram+be bacteria and ineffective against Gram-ve organisms and fungi.

The chemical structure of penicillin was determined by Dorothy Crowfoot Hodgkin

in the early 1940s, enabling synthetic production. A team of Oxford research scientists led by Australian Howard Walter Florey and including Ernst Boris Chain and Norman Heatley discovered a method of mass producing the drug. Chemist John Sheehan at MIT completed the first total synthesis of penicillin and some of its analogues in the early 1950s, but his methods were not efficient of mass production. Florey and Chain shared the 1945 Nobel Prize in medicine with Fleming for this work. Penicillin has since become the most widely used antibiotic to date and is still used for many Gram-positive bacterial infections.

Development from Penicillin: The narrow spectrum activity of penicillins, along with the poor activity of the orally-active Phenoxymethyl penicillin, led to the search for derivatives of penicillin which could treat a wider range of infections.

The first major development was Ampicillin, which offered a broader spectrum of activity than either of the original Penicillins. Further development yielded beta-lactamase resistant penicillins including Flucloxacillin, Dicloxacillin and Methicillin. These are ineffective against the Methicillin-resistant Staphylococcus aureus strains that subsequently emerged.

The line of true penicillins was the antipseudomonal penicillins, such as Ticarcillin and Piperacillin, useful for their activity against Gram-negative bacteria. However, the usefulness of the beta-lactam ring was such that related antibiotics, including the Mecillinams, the Carbapenems and most importantly, the Cephalosporins, have this at the center of their structures.

Mechanism of action:

B-lactam antibiotics work by inhibiting the formation of peptidoglycan crosses links in the bacterial cell wall. The B-lactam moiety of penicillin binds to the enzyme (transpeptidase) that links the peptidoglycan molecules in bacteria and this weakens the cell wall of the bacterium. In addition, the build-up of peptidoglycan precursors triggers the activation of bacterial cell wall hydrolysis which further digests the bacteria's existing peptidoglycan.when the bacterial lose their cell walls they are then called spheroplasts.

CLASSIFICATION;

Penicillins are also classified on many ways depending upon the nature and

spectrum of activity.

I. a) Natural (Biosynthetic) Penicillins: eg. Benzyl penicillin (Penicillin - G), 2-Pentenyl penicillin (Penicillin -F), 3-Pentenyl penicillin, n-Pentyl penicillin, n-Heptyl penicillin (Penicillin K), p-Hydroxy benzyl penicillin, (Penicillin- X), Phenoxymethyl penicillin. (Penicillin-V) and Zero allergy penicillin (Penicillin-O).

b) Semi-synthetic Penicillins: eg. Ampicillin, Amoxicillin, Methicillin, Nafacillin, Oxacillin, Cloxacillin, Dicloxacillin, Flucloxacillin, Carbenicillin, Ticarcillin, Piperacillin, Mezlocillin, Cyclacillin.

c) Penicillin Combination: eg. Benzathine penicillin, Procaine penicillin.

II. Based on Spectrum of Activity

a) Effective against Gram-positive bacteria: eg. Benzyl penicillin, Ampicillin,

Oxacillin.

b)Effective against Gram-negative bacteria: eg. Temocillin.

c) Broad spectrum penicillin: eg. Ampicillin, Amoxicillin, Carbenicillin.

d)Penicillinase resistant penicillin: eg. Methicillin, Nafacillin, Oxacillin, Cloxacillin, Dicloxacillin, Flucloxacillin.

e)Acid resistant penicillin: eg. Benzathine penicillin, Phenoxymethyl penicillin, Phenoxy ethyl penicillin, Phenoxy propyl penicillin.

[For knowledge purpose only]