BETA-LACTAM ANTIBIOTICS• Beta-lactam antibiotics include

penicilin,cephalosporins,carbapenem and monobactams.

• All of them have a beta-lactam ring in their chemical,hence the beta-lactam antibiotics.

PENICILLINS Penicillin was the first antibiotic

developed and used clinically. It was discovered accidentally by

Alexander Fleming in one of the laboratories in london.

Initialy penicillin was obtained from the fungus penicillin notatum,but the yield was very low .

The present source of penicillin is the high-yielding chrysogenum

PENICILLINS

PENICILLINS

PENICILLINSDisadvantages of Penicilin G

1. It is sensitive to beta-lactamase-enzyme. which hydrolyse the beta-lactam ring.

2. It is sensitive to stomach acids.3. Narrow spectrum of activity.4. Possibility of anaphylaxis.5. Short duration of action.

PENICILLINS Beta-lactamase hydrolysis of

penicillin G.

PENICILLINS Mechanism of action. Beta-lactma antibiotic produce

bactericidal effect by inhibiting cell-wall synthesis in susceptible bacteria.

Bacterial cell wall is composed of peptidoglycan,a highly cross-linked structure that makes the cell wall rigid and also gives it stability.

The are three stages involved in the biosynthesis of peptidoglycan.

PENICILLINSMechanism of action. The third stage is inhibited by beta-lactam

antibiotics. Beta –lactam antibiotic inhibit transpeptidase

enzyme which is needed for the cross linking of peptidoglycans.

This result in autolysis which causes cell death.

Gram negative bacteria have lipopolysacchaide which limits the entry of penicillin.

PENICILLINS Penicillin derivatives for parenteral

use. Benzyl penicillin(Penicillin G) It reaches high plasma concentration Rapid onset of action used in servere

infections such as menigitis,endocardium,pnemonia.

PENICILLINS Procain penicillin G. Its a combination of benzyl penicillin and

procain(poorly water soluble anaeshetic). Moderate plasma concentration used in

mild infections,less painful because of the procaine component.

PENICILLINS Benzathine penicillin G It is a combination of banzathine and benzyl

penicillin. Benzathine is a poorly water soluble

compound it forms aqueous suspension. Both benzathine penicillin and procain penicillin

are called respiratory or depot penicillin. Slow onset of action with longest duration of

action. Used in syphilis and rheumatic fever

prophylaxis.

PENICILLINS methicillin

PENICILLINSmethicillin

Methoxy group blocks acces to beta-lactamases but not to transpeptidases

Actve against some penicillin G resistant strains(Staphylococcus aureus)

Binds less to transpeptidase compare to penicillin G

In active against gram negative bacteria Acid sensitive hence orally inactive

PENICILLINS Penicillin derivatives for oral route Phenoxymethyl penicillin(Pen V) It is the first oral penicillin

PENICILLINSOxacillin

PENICILLINS Oxacillin Resistant to beta-lactamase Acid resitant and orally active Actve against some penicillin G resistant

strains(Staphylococcus aureus) Binds less to transpeptidase compare to

penicillin G In active against gram negative bacteria

PENICILLINS Derivatives of oxacillin. Cloxacillin Better absorbed than oxacillin.

PENICILLINS Flucloxacillin Less bound to plasma protein,leading to

higher levels of free drugs.

PENICILLINSBroad spectrum penicillin. Ampicillin.

PENICILLINS Amoxacillin.

PENICILLINSBroad spectrum penicillin.Advantages Active against gram positive bacteria Acid resistant and orally active Non toxicDisadvantages Sesitive to beta-lactamases Poor absorption through the gut wall. Disruption of gut flora leading to diarrhoea

PENICILLINSResistance to penicillin. Presence of beta-lactamase enzyme. Transfer of beta-lactamases between

strains Mutated transpeptidase enzyme may be

present Cell wall may have a coat preventing

access to the cell(presence of LPS in gram negative bacteria).

PENICILLINS Adverse reaction. Penicillin are relatively safe.They may cause

hypesensitivity reaction such as skin rashes,uticaria,fever,dermatitis,joint pain.serum sickness or even acute anaphylactic reactions.

The symptoms of anaphylactic shock are servere hypotension,bronchospasm and laryngeal oedema.

Cross reactivity can occur among penicillin and also among the beta-lactams.

PENICILLINSTreatment of anaphylactic shock

1. Inj. Adrenaline 0.3-0.5ml 1:1000 solution intramascularly.

2. Inj. Hydrocortisone 200mg intravenously.3. Inj. Diphenhydramine 50-100mg i.m or i.v

PENICILLINS Precautions.

1. Before giving penicillin,history of previous administration and allergic history,if any must be noted.

2. In patient with history of asthma,allergy rhinitis,hay fever,etc,there is an increased risk of penicillin allergy,hence penicillin should be avoided in such cases.

PENICILLINS Precautions.

3. Sensitivity test should be performed by an intrdermal test (0.02ml of penicilling).Itching and erythema formation are watch for.A negative skin test does not ensure absolute safety.

4. Inj. Adrenaline and hydrocortisone should be kept ready before injecting penicillin to treat the anaphylactic reaction.

Other adverse effects are pain and sterile abscess at the site of i.m. injection.The prolonged use of i.v penicillin G may cause thrombophlebitis.

PENICILLINSJarish-herxheimer reaction. It is an acute exacerbation of sign and

symptoms of syphilis during penicillin therapy due to the release of endotoxin from the dead organisms.

The manifestation are fever,chills myalgia,hypotension,circulatory collapse,etc.It is treated with aspirin and corticosteroids

PENICILLINS

PENICILLINS Therapeutic uses.

1. Pnemococcal infections:in pnemonia mengitis or other serious infections,third-generation cephalosporin are drug of choice.

2. Streptococcal infections:Sinusitis,rheumatic fever,otitis media,etc are effectively treated with procaine penicillin G or benzathine penicillin

3. Syphilis:Penicillin G is the drug of choice for syphilis.

PENICILLINS4. Diphtheria:it is acute infection of upper

respiratory tract caused by C.diphtheriae.Patient sensitive to penicillin is treated with erythromycin.

5. Other infections:Gram positive bacillary infections are treated effectively with penicillin G.

6. Clostridium infections(Tetnus and gas gangrene);The main treatment is neutralisation of the toxin by using human tetnus immunoglobin.For gas gangrene ,penicilline G is the drug of choice.

PENICILLINS Therapeutic uses of

aminopenicllins(broad spectrum penicillin)

Upper respiratory infections Urinary tract infections:flouroquinolones

are preferred for emperical therapy in UTI infections.However for enterococcal UTI treated effectively with amoxillin.