- Penicillin
- Mechanism of action
- Mechanism of bacterial resistance
- Spectrum of activity
- Pharmacokinetics
- Precaution
- Therapeutic uses
- Limitations / drawbacks of PenicillinG
- Penicillin allergy/ adverse effects
- Semisynthetic penicillins
You will learn in this article above mentioned topics.
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PENICILLIN
Penicillin was the first antibiotic to be used clinically in 1941. It is a miracle that the least toxic drug of its kind was the first to be discovered.
It was originally obtained from the fungus Penicillium notatum, but the present source is a high yielding mutant of Penicillium chrysogenum.
The penicillin nucleus consists of fused thiazolidine and beta-lactum rings to which side chains are attached through an amide linkage.
Penicillin G is highly water soluble, it is stable in the dry state but solution deteriorates rapidly at room temperature.
MECHANISM OF ACTION
Beta-lactum antibiotics produce bactericidal effect by inhibiting cell wall synthesis in susceptible bacteria.
Bacterial cell wall is composed of peptidoglycan, which is highly cross linked structure that makes the cell wall rigid and also gives it stability.
There are three stages involved in the biosynthesis of peptidoglycan.
The third stage is inhibited by beta-lactum antibiotics. The mode of action of Penicillin is given below as flowchart.👇
MECHANISM OF BACTERIAL RESISTANCE
Bacteria develop resistance to beta-lactums mainly through the release of beta-lactumases, which hydrolyse the beta-lactum ring and inactivate them.
The other mechanism of resistance to beta-lactums are due to :
i) altered penicillin binding protein (PBPs)
ii) decreased penetration of the drug to its site of action.
SPECTRUM OF ACTIVITY
1. Bactericidal effect on Gram +ve cocci - Streptococci, Pneumococci. etc.
2. Bactericidal effect on Gram -ve Gonococci - Neisseria gonorrhea, Neisseria meningitis.
3. Bactericidal effect on Bacilli - Bacillus anthracis, etc.
4. Bactericidal effect on Trypanoma palladium.
PHARMACOKINETICS
Most of the orally administered penicillin G is destroyed by gastric acid.
Absorption of sod.PnG from i.m. site is rapid and complete. It is distributed mainly extracellulary; reaches most body fluids but penetration is serous cavities and CSF is poor.
About 60% is plasma protien bound.
It is little metabolized because of rapid excretion.
The plasma t 1/2 of PnG in healthy adult is 30 min.
Tubular secretion of PnG can be blocked by probenecid-higher and longer lasting plasma concentration are achieved.
Probenecid has also been shown to decrease the volume of distribution of Penicillins.
Also read something more about Antibiotics: 👇
Antibiotics • Classification • Antibiotics selection • Problems arise with use of Antibiotics • Why Combination of Antibiotics • Top 10 Antibiotics
Antibiotics • Classification • Antibiotics selection • Problems arise with use of Antibiotics • Why Combination of Antibiotics • Top 10 Antibiotics
PRECAUTION
- Before giving penicillin, history of previous administration and allergic manifestations, if any, must be noted.
- In patients with history of asthma, allergic rhinitis, hay fever, etc, there is an increased risk of Penicillin allergy, hence penicillin should be avoided in such cases.
- Sensitivity test should be performed by an Intradermal test. Itching, erythema and wheal formation are watched for a negative skin test does not ensure absolute safety.
- Inj. Adrenaline and hydrocortisone should be kept ready before injecting penicillin to treat the anaphylactic reaction.
THERAPEUTIC USES
1. Pneumococcal infections : In pneumonia, meningitis or other serious infections, penicillin G can be used as alternative of Cephalosporin if the organism is sensitive, it should be continued for 7 to 10 days.
2. Streptococcal infection : Pharyngitis, sinusitis, rheumatic fever, otitis media, celulitis, etc. are effectively treated with procaine penicillin G 6 lac units i,m, once daily for 10 days.
3. Meningococcal meningitis : penicillin G is effective by intravenously, it should be given only for confirmed cases.
4. Gonococcal infection : penicillin was the drug of choice for gonococcal infections. Because of the emergence of resistant organisms, penicillin are not preferred at present.
5. Syphilis : penicillin G is the drug of choice for syphilis. Treponema pallidum is very sensitive to penicillin and is killed at very low concentration of drug.
6. Diphtheria : it is acute infection of upper respiratory tract caused by C. diphtheriae. Penicillin G is used for this treatment for 10 days.
7. Clostridial infection : The main treatment is the neutralisation of toxin by using human tetanus immunoglobin. For gas gangrene, Penicillin G is the drug of choice.
LIMITATIONS / DRAWBACKS OF PENICILLIN G
1. Orally not very effective.
2. Short duration of action.
3. Narrow spectrum of antibacterial activity.
4. Destroyed by penicillinase enzyme.
5. Possibility of anaphylaxis.
PENICILLIN ALLERGY / ADVERSE EFFECT
Local irritancy and direct toxicity :
- Pain at i.m injection site, nausea on oral ingestion, and thrombophlebitis, of injected vein are dose related expression of irritancy.
- toxicity to brain can cause mental confusion, muscular twitching, convulsions and coma when very large dose is injected.
- bleeding has also occured due interference with platelets function.
- intrathecal injection of Penicillin G is no longer recommended because it has caused arachnoiditis and degenerative changes in spinal cord.
- accidental i.v. injection of procaine penicillin produces CNS stimulation, hallucination.
Hypersensitivity :
- Rash
- itching
- urticaria
- fever
- wheezing, angioneurotic edema, serum sickness, exfoliative dermatitis are less common.
- anaphylaxis is rare but may be fatal.
- Super infection
- Jarisch-Heixheimer reaction.
SEMISYNTHETIC PENICILLIN
Semisynthetic penicillins are produced by chemically combining specific side chains or by incorporating specific precursors in the mould cultures.
They are :
- Ampicillin
- Amoxicillin
- Dicloxacillin
- Nafcillin
- Cloxacillin
- Bacampicillin
- Piperacillin
- Carbenicillin
Ampicillin
- It is active against all organisms sensitive to PnG.
- Due to spread use resistance may develop.
Amoxicillin
It is a close congener of ampicillin, similar to it in all respects except:- Oral absorption is better.
- Incidence of diarrhoea is less.
Carbenicillin
- The special feature of this penicillin congener is its activity against pseudomonus aeroginisa and indole positive proteus which are not inhibited by PnG.
- Klebsiella and gram positive cocci are unaffected by it.
- It is inactive orally and is excreted rapidly in urine.
- High dose can cause bleeding, dose is - 1 to 5 gram every 4 to 6 hours.
Piperacillin
- This antipseudomonal penicillin is about 8 times more active than carbenicillin.
- It has good activity against klebsiella and is used mainly in neutropenic / immunocompromized patients having serious gram negative infections.
- Elimination t1/2 is 1 hr.
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