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DR.SHAIKH UBEDULLA,(MBBS,MD,PGDCR,PGDPM)

ASSISTANT PROFESSOR,DEPT OF PHAMACOLOGY,

MMC.

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How an accidental discovery

changed the history of antibiotics!!!

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Sir Howard Florey and Ernst Chain

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The historical landmarks :

28th Sep 1928 Fleming observed the inhibitedgrowth of Staph aureus in the petri dishcontaminated with Penicillium notatum

fungus(Mold juice). 7th Mar 1929 he coined the term PENICILLIN

which is effective against scarlet fever, pneumonia,diptheria but not typhoid , paratyphoid.

1940 : Dr. Howard Florey & Ernst Chain firstpurified Penicillin.

1945 : Mass production started(world war 2) & all 3

got Nobel prize!!24 August 2012

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Chemistry

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Mechanism of action

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Classification

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PENICILLINS

NATURAL

PENICILLIG

SEMISYNTHETIC

ACIDRESITANT

PENICILLINASE RESISTANCE

EXTENDEDSPECTRUM

AMINO

PENICILLINS

CRABOXY

PENICILLINS

UREIDO

PENICILLINS

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PENICILLIN-G (BENZYL PENICILLIN)

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Spectrum of activity

COCCI :

1) Most Streptococci(except viridans)

2) Pneumococci3) Staphylococcus aureus

4) Neisseria gonorrhoeae(Gonococcus) , N .Meningitidis(Menigococcus)

BACILLI :

1) Bacillus anthracis

2) Corynebacteriumdiptheriae

3) Clostridium tetani ,welchii

4) Listeria

5) Spirochetes(Treponema pallidum ,Leptospira)

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Mechanism of resistance

Penicillinase enzyme

Altered in PBP

Loss of or altered porin channels Formation of biofilms

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Bacterial resistance

In generally, there are three main mechanism of -lactam antibiotics resistance.

(1) Nearly all bacteria can produce -lactamase after

contact with -lactam antibiotics. -lactamase caninactivate -lactam antibiotics through rupture the -lactam ring. Different microorganisms produce anumber of distinct -lactamase.

E.g. staphylococci.

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Bacterial resistance

(2) Many bacterial can alter PBPs with decreased

affinity for -lactam antibiotics. This can result in

failure of antibiotics binding to active sites.

E.g. MRSA

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Bacteria Resistance

(3) The concentration of antibiotics in target site is

too low because of lacking of porin protein, such us

OmpF and OmpC. This permeability block isparticularly seen in resistance gram-negative

bacteria that possess a complex outer layer.

Increased active antibiotics efflux which reduce the

drug in bacteria is the other reason for lowconcentration in target site.

E.g. Pseudomonas

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PHARMACOKINETICS

Less than 1/3 rd absorbed orally

Destroyed by gastric acid

Absorption from i.m. site is rapid & complete 60 % Plasma protein bound

Half life 30 mins

Very rapid excretion 90% Tubular secretion & 10 %

Glomerular filtration

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ADVERSE EFFECTS :

LOCAL :

Pain , Thrombophlebitis of vein , irritation.

CNS (High dose):

Confusion , Convulsion , Coma. HYPERSENSITVITY (10 %):

Rash,fever,urticaria,oedema,itching.

Anaphylaxis1-4/10000 pts, often fatal

History of Pen allergy is important

Scratch test / Intradermal test dose (2- 10 U) done first.

RENAL IMPAIRMENT

Dose adjustment is required

OTHERS

Superinfections , Jarisch

Herxheimer reaction24 August 2012

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Unitage of penicillin G

1 U of crystalline penicillin (sod.penicillin G) is equalto 0.6 mcg of standard preparation.

Thus 1 mg = 1667 U1 gm = 1.6 MU

1 MU = 0.6 gm

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Preparations of Penicillin G

Sod.Penicillin G (Crystalline penicillin) injection

Available in dry powder

0.5 -5 MU im/iv

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Preparations of Penicillin G

Procaine penicillin GFollowing deep intramuscular injection, it isslowly absorbed into the circulation andhydrolysed to benzylpenicillin thus it is used

where prolonged low concentrations ofbenzylpenicillin are required.

This combination is aimed at reducing the painand discomfort associated with a large

intramuscular injection of penicillin.

Fortified procaine penicillin G3 lac U procaine pen.+ 1 lac U sod.penicillin G

Rapid as well as sustain release24 August 2012

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Preparations of Penicillin G

Benzathine penicillin G

Intramuscular injection, and hydrolysed tobenzylpenicillin in vivo.

It is the drug-of-choice when prolonged lowconcentrations of benzylpenicillin are required

and appropriate, allowing prolonged antibioticaction over 24 weeks after.

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USES :

1. STREPTOCOCCAL INFECTIONS (Pharyngitis , Otitismedia , Scarlet fever , Rheumatic fever , SABE requirehigh dose)

2. PNEUMOCOCCAL INFETIONS (Lobar pneumonia)

3. MENINGOCOCCAL INFECTIONS

4. GONORRHOEA

5. SYPHILIS

6. DIPTHERIA

7. TETANUS & GAS GANGRENE

8. OTHERS (Anthrax, actinomycosis,Weilsdisease)

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PROPHYLACTIC USES :

RHEUMATIC FEVER :

Benzathine Penicillin 1.2 MU every 4 wks till 18yrsor 5 yrs after attack.

BACTERIAL ENDOCARDITIS :

Pts with valvular heart disease & during Dentalprocedures , Endoscopy , Catherterisation.

AGRANULOCYTOSIS PTS :

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