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Penicillin [Penicillin-G / Benzyl penicillin] - Coggle Diagram
Penicillin
[Penicillin-G / Benzyl penicillin]
Penicillin
[Penicillin-G / Benzyl penicillin]
MOA
Interfere synthesis of bacterial cell wall
Inhibit the transpeptidases - prevent cross linking of amino acids that form structure of cell membrane
binds at Penicillin-binding protein on the cell membrane
The binding of B-lactams - cell wall deficient (CWD) forms
CWD forms of bacteria swell and burst due to hyperosmotic interior
Bacterial cell wall - Peptidoglycan
rigid mechanical stability by its highly cross-linked lattice work structure
composed of glycan chains
linear strands of two alternating amino acids: N-acetyl glucosamide & N-acetyl muramic acid
glycan chains are cross-linked by peptide chains
Bacteria synthesis UDP-N-acetyl muramic acid pentapeptide (Park nucelotide) & UDP-N-acetyleglucosamine,
they are linked by splitting off the UDP
the cleavage of D-alanine of peptide is by
Transpeptidase
energy release is for establishment of cross linkages
Antibacterial spectrum
Narrow spectrum - Gram+ve bacteria
Cocci - Streptococci & Pneumococci
Staphylococcus aureus
has developed resistant
Gram-ve cocci -
Neisseria gonorrhoeae
&
N. meningitis
Gram+ve bacilli:
Highly sensitive -
Bacillus anthracis, Corynebacterium diptheriae, Clostridia, Listeria, Spirochetes
Bacteroides melaninogenicus
Anaerobes - Fusobacteria, Peptostreptococci, Eubacterium, Campylobacter, Prevotella, Porphyromonas
Moderate sensitive - Actinomyces israelii
Gram-ve bacilli - E. coli, Proteus
INSENSITIVE to: Mycobacterium in tuberculosis, rickettsiae, chlamydiae, protozoa, fungi, viruses
Bacterial resistance
Target enzymes and PBPs (penicillin-binding protein) are located deeper under lipoprotein barrier
PnG is unable to penetrate / having low affinity for PnG - MRSA
Production of penicillinase
Eg. Staphylococci, Gonococci, B. subtilis, E.coli, H. influenza
Penicillinase
narrow spectrum B-lactamase
opens B-lactam ring
inactivates PnG
Pharmacokinetics
Destroy by gastric acid - <1/3 of oral absorption
Infants & Elderly - large fraction of oral absorption due to lower gastric level
Sodium PnG IM injection - rapid and complete absorption
Peak plasma level - 30mins
Distributed in most body fluids
POOR penetration to serous cavity & CSF - but adequate to reach infected sites
60% plasma protein bound
little metabolization because rapid excretion
Preparation & Dose
Sodium PnG / Crystalline penicillin Injection
0.5-5 MU im/iv 6-12 hourly
Dosage forms: dry powder in vials to be dissolve in sterile water
Repository PnG injection
insoluble salts
given by deep im injection (never iv)
release PnG very slow
a. Benzathin PnG 0.6-2.4 MU im
administered every 2-4 weeks
Aqueous suspension
Extremely slow release - low Plasma conc.
For prophylactic purposes up-to 4 weeks
b. Procaine PnG injections 0.5-1 MU im
administered 12-24 hourly
Aqueous suspension
Lower but sustained plasma conc. for 1-2 days
Fortified procaine PnG injection
300000 U procaine penicillin & 100000 U sodium PnG
Rapid and sustained blood levels
Adverse effects
Hypersensitivity
Allergic diathesis individual prone to sensitivity
More common to paranteral than oral administration
Allergy reactions:
Rash
Itching
Urticaria
Fever
Wheezing
Angioneurotic edema
Serum sickness
Exfoliative dermatitis
Bronchospasm
Analphylaxis shock - rare but fatal
Topical use is highly sensitizing
Contact dermatitis
Eye ointment is banned
Eye solution of Gonococcal ophthalmia is approved
Superinfections
Jarisch-Herxeheimer reaction
Penicillin injected to syphilitic patient:
Shivering
Fever
Myalgia
Exacerbation of lesions
Vascular collapse
these are due to sudden release of spirochetal lytic products
it last for 12-72 hrs
does not recure
does not need interruption of therapy
Aspirin & Sedation - relief symptoms
Local irritancy & Direct toxicity
IM injection - Pain, Thrombophlebitis
Oral ingestion - Nausea
Intrathecal injection (not recommended):
Arachnoiditis
Degenerative changes in spinal cord
Very large doses (>20MU), specially to renal insufficient:
Brain toxicity
Mental confusion
Muscular twitching
Convulsions
Coma
Bleeding - interference with platelets
IV inj of Procain PnG:
CNS stimulation
hallucinations
convulsions
microembolism
Uses
Streptococcal infections - Pharyngitis, Tonsillitis, Otitis media, Scarlet fever, Rheumatic fever
Bacterial endocarditis: Streptococci viridans - high doses required in combination with Gentamicin
Pneumococcal infections - Pneumonia, Meningitis
Meningococcal meningitis
Gonnorrhoea
Syphilis - Benzathine penicillin
Diphtheria, Tetanus
Rare infections - Gas gangrene, Anthrax, Actinomycosis
Prophylactic uses:
Rheumatic fever - Benzathine penicillin
Surgical prophylaxis - in combination with Gentamicin
Agranulocytosis
Short-coming:
Poor oral efficacy
Susceptibility to penicillinase
Narrow spectrum of activity
Hypersensitivity reactions