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PENICILLINS
SANJIB KUMAR YADAV
M.PHARM(PHARMACOLOGY)
LECTURER, DEPARTMENT OF PHARMACY,
CHHINNAMASTA EDUCATIONAL ACADEMY,
RAJBIRAJ, NEPAL
Yadavsanjibkumar@gmail.com

HISTORICAL BACKGROUND
In 1928 ALEXANDER FLEMMING discovered penicillin
from the fungus Penicillium notatum.
Observed that colonies of S. aureus failed to grow in the
areas contaminated by Penicillium notatum.
He isolated the mould, grew it in a fluid medium and
found that it produced a substance capable of killing many
of the common bacteria that infect humans.
He coined the term PENICILLIN.
It was unstable and he was unable to purify.
FLOREY & CHAIN used Freeze drying &
Chromatography to isolate penicillin & shared the Noble
prize with Fleming.
In June 1941 penicillin was available to treat 10 patients.

INTRODUCTION
penicillin obtained by fermentation from Penicillium
notatum.
Now it is from a high yielding strain Penicillium
chrysogenum.
All penicillins consist of a sulfur containing thiazolidine
ring fused with beta lactum ring and acyl side chain.

CLASSIFICATION
 Natural penicillins
- penicillin-G
- procain penicillin-G
- benzathin penicillin-G
- penicillin-V
 Semisynthetic penicillins
A. penicillinase resistant penicillin
- oxacillin
- cloxacillin
- dicloxacillin
- flucloxacillin
- methicillin

B. Broad spectrum penicillins
- ampicillin
- amoxycillin
- bacampicillin
C. Beta-lactamase inhibitors
- clavulanic acid
- sulbactum
- tazobactum

MECHANISM OF ACTION
Interfere with synthesis of bacterial cell wall.
Bacterial Cell wall composed of peptidoglycan, it consist
of two amino sugars;
1)N-acetylmuramic acid (NAcM).
2)N-acetylglucosamine(NAcG).
Peptidoglycan residues are linked together peptide bridge
i.e. transpeptidation process by release of transpeptidase
enzyme, and sequence is also called as “Park nucelotide”,
This cross bridging provide neccessry strength to bacterial
cell wall.

β-lactum antibiotics inhibit the transpeptidase enzyme
so that cross-linking does not take place.
So, integrity of bacterial cell wall lost, due to High
osmotic pressure inside cell and low osmotic pressure
outside cell and leads to BRUST the cell wall.
Cause bacterial cell lysis which leads to bacterial cell
death.

Note: The bacteriocidal activity of penicillin is greater
against gram positive bacteria as compared with gram
negative bacteria.
Gram positive Gram negative

Gram positive bacteria having thick layer of
peptidoglycan surrounds the cytoplasmic membrane.
Such peptidoglycan layer is easily assessible to beta
lactum antibiotics.
Hence, inhibitation of transpeptidase enzyme is so
easier.

Gram negative having thin layer of peptidoglycan
sandwiched between the outer membrane and
cytoplasmic membrane.
Here, outer membrane consist of lipopolysaccharides
with narrow porin channels which function as barrier for
entry of beta lactum antibiotics especially for natural
penicillin.
However some penicillin with hydrophilic character e.g.
amoxycillin, ampicillin can diffuse significantly through
porin channel.

PHARMACOKINETIC
Well absorbed by oral administration but some are
inactivated by gastric acid i.e. penicillin-G , so it is
mainly given by IV/IM.
Distributed well, but 60% drugs are bind with plasma
protein.
Metabolized in liver.
 They are usually excreted by kidney through urine
and small amounts are excreted by biliary excretion.

ADVANTAGES
Have excellent tissue penetration .
Bactericidal against sensitive strains.
Relatively nontoxic.
Efficacious in the treatment of infections.
Inexpensive in comparision with other antibiotics.
Newer penicillin’s are resistant to stomach acid , such
as penicillin-V or a broader spectrum ,such as
ampicillin and amoxicillin.

DISADVANTAGES
Acid liability – most of these drugs are destroyed by
gastric acid.
Lack of activity against most gram negative organisms.
Short duration of action.
Many patients experience GI upset.
Painful if given intramuscularly.

Penicillin-G (Benzyl penicillin)
It is a narrow spectrum antibiotic, activity is limited
primarily to gram positive bacterias and few gram
negative bacterias.
Adverse effects:
 local irritancy
 nausea, vomiting, diarrhoea
 convulsion
 confusion
 glositis (inflammation of tongue)
 stomatitis (inflammation of stomach)
 myocardiatis (inflamation of myocardium)

 bronchial asthma
 hypersensitivity (1-10%, if patient is allergic to penicillin)
 superinfection
 jarisch- herxheimer reaction (in 2⁰ syphillis )
charracterized by
- shivering
- fever
- myalgia
- exacerbation of lesions
- even vascular collapse
due to sudden release of spirocheatal lytic product.

Therapeutic uses: in the treatment of
 Streptococcal Infections:
Pharyngitis, Otitis Media, Scarlet Fever
Rheumatic Fever, Subacute Bacterial Endocarditis
Pneumococcal Infections: Pneumonia
Meningococcal Infections: Meningitis
 Others:
Syphilis, diphtheria, tetanus, rat bite fever

Contraindication: hypersensitivity to penicillins
Precautions:
- history of allergy
- renal impairment
- pregnancy
- lactation
Dose: 1.2-2.4 g. QID by IM/IV.

Penicillin-V
It is differ from penicillin-G only it is acid stable, so
oral absorption is better.
Anti- bacterial spectrum of penicillin-V is identical to
penicillin-G, but it is less active against gonococci and
other gram – ve bacteria.
Also known as phenoxy methyl penicillin.
Therapeutic uses: in the treatment of,
- pharyngitis
- otitis media
- pneumonia
- rheumatoid arthritis

Adverse effects, contraindication, precaution:
same as penicillin-G
Dose: 250-500 mg. QID

Semisynthetic penicillins
Are produced by chemically combining specific side chains in
place of benzyl side chain.
 Penicillin G has…
1. Poor oral efficacy.
2. Susceptibility to penicillinase.
3. Not stable in gastric acid; rapidly broken down in stomach.
4. Narrow spectrum of activity.
5. Hypersensitivity reactions.

Penicillinase resistant penicillins
Some of the staphylococci produce an enzyme called
penicillinase which destroys penicillin and make the
drug inactive against them.
Several semisynthetic penicillins have been developed
which are penicillinase resistant and are effective even
against such organisms.
Therapeutic uses: in treatment of,
- staphylococcal infections
- burn wound

Adverse effects:
- nausea, vomiting, diarrhoea
- intrastitial nephritis
- dizziness
- anaphylaxis
Dose:
cloxacillin – 250-500 mg. QID

Broad spectrum penicillins
These are semisynthetic penicillins and active against
variety of gram +ve as well as gram –ve bacteria.
Ampicillin: it is active against all organisms sensitive to
penicillin-G, it is acid resistant and water soluble and
having less bioavailability than amoxycillin.
Amoxycillin: it is structural analogue of ampicillin, but
has got advantage over ampicillin i.e.
 better absorption from GIT.
 less incidence of superinfection and diarrhoea.

Therapeutic uses: it is use in treatment of,
- respiratory tract infection
- urinary tract infection
- billary tract infection
- intestinal infection
- bone and joint infection
- meningitis
- gonorrhoea
- typhoid fever
- otitis media
- H. pylori infection

Adverse effect:
- nausea, vomiting, diarrhoea
- abdominal pain
- nephropathy
- hypersensitivity
- superinfection
Contraindication: hypersensitivity to penicillin
Drug interaction: contraceptive pills
Dose: ampicillin- 0.5-2 g. QID
amoxycillin- 0.25-1 g. QID

Beta lactamase inhibitors
Beta lactamases are a family of enzymes produced by
many gram +ve and gram –ve bacteria that inactivate beta
lactum antibiotics by opening the beta lactum ring.
Therapeutic use: it is use in treatment of,
- skin and soft tissue infection
- urinary tract infection
- respiratory tract infection
- gonorrhoea
Adverse effect: same as amoxycillin
Dose: clavulanic acid- 125-500 mg. QID

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