This document provides information on beta-lactam antibiotics, specifically penicillins. It discusses the common structure and mechanism of action of beta-lactams through inhibition of bacterial cell wall synthesis. It then classifies and describes various types of penicillins, their mechanisms, uses, and adverse effects. It also covers pharmacokinetics, drug interactions, and resistance mechanisms for penicillin antibiotics.

1. Beta-Lactam Antibiotics
Dr. Ravi Mundugaru
Assistant Professor
Dept. of Pharmacology
DM WIMS, Wayanad

2. Β-Lactam antibiotics
• Share common structure and
mechanism of action
- Four membered β Lactam ring
- Inhibition of bacterial peptidoglycan cell
wall synthesis
• Penicillins, Cephalosporins,
Monobactams, Carbapenems and
Carbacephems.
Other cell wall synthesis inhibitiors
Vancomycin, teicoplanin

3. Penicillins
• Discovered by Alexander Flemings
• Natural penicillin obtained from
P.notatum/P.chrysogenum
Chemical structure

4. Classification
1. Penicillin G and congeners
- Benzyl penicillin (Penicillin G)-iv,im
- Phenoxymethyl penicilln
(penicillin V) oral
- Benzathine penicillin G-im
- Procaine penicillin G-im
Repository
penicillins
Oral penicillin

5. Classification
2. Penicillinase-resistant penicillins –
Methicillin (im,iv), cloxacillin (oral), oxacillin
(oral, im, iv), naficillin (oral, im, iv),
dicloxacillin (oral).
3. Extended spectrum penicillins
a. Aminopenicillins – ampicillin (oral, im, iv),
amoxicillin (oral), bacampicillin (oral)

6. Classification
b. Carboxypenicillin – carbenicillin (im, iv),
ticarcillin (im, iv)
c.Ureidopenicillin - pipericillin, mezlocillin
– im, iv
4. Lactamase inhibitors – clavulanic acid,
sulbactum, tozabactum.

7. Mechanism of action
• Inhibit bacterial growth by
interfering with a specific step
in bacterial cell wall synthesis.
• Binds to penicillin binding
protein, inhibits transpeptidase
and hence inhibits cross
linking of pedtidoglycan
residues
• Bactericidal with intense action
on dividing bacteria

8. Resistance
• Natural – lack of peptidoglycan cell wall
(mycoplasma)/cell wall impermeable to
drug
• Acquired
– β lactamase activity
- ↓ permeability to the drug
- Altered penicillin binding proteins-↓affinity
for β lactam antibiotic

9. Pharmacokinetics
• Penicillin G - destroyed by
gastric acid, given im/iv.
• Plasma half life 30 min
• Rapidly excreted by the
kidneys
• Probenecid blocks the renal
secretion of penicillin – higher
&long lasting plasma
concentration of the drug.

10. Pharmacokinetics
• Penicillin V, cloxacillin, ampicillin, and
amoxicillin are acid-stable and relatively
well absorbed
• Benzyl and procaine penicillins - delay
absorption - prolonged blood and tissue
concentrations (im)

11. Benzathine penicillin (Penicillin G)
• Antibacterial spectrum - narrow spectrum
gram positive cocci, bacilli and gram
negative cocci and spirochetes.

12. Preparations
• Sodium penicillin G (crystalline penicillin)
injection 0.5-5 MU im/iv 6-12 hrly
• Repository preparations (Depot
preparations)
- insoluble salts of penicillin G given only im
- Release penicillin G slowly
• E.g. Procaine penicillin G inj 0.5-1MU im
12- 24 hrly), Benzathine penicillin G 0.6-
2.4 MU im(2-4 weekly)

13. Therapeutic use
• Streptococcal infections – pharyngitis,
otitis, sinusitis, endocarditic, rheumatic
fever
• Dental infections- suppurative pulpitis,
pericoronitis, oral cellulitis, acute
necrotizing ulcerative gingivitis
(Streptococci viridans, Ekinella corrodens,
Peptostreptococcus, Actinomyces,
Fusobacteria, Porphyromonas, Prevotella,
Veillonella, Treponemes)

14. Therapeutic use
• Sensitive pneumococcal infections –
pneumonia, meningitis
• Meningococcal infections – meningitis
• Syphilis – procaine penicilline 1.2MU for
10 days/benzathine penicilline 2.4 MU
• Diphtheria
• Tetanus and gas gangrene
• Leptospirosis, anthrax, actinomycosis

15. Prophylactic use
• Decrease recurrence of rheumatic fever
• In patients with valvular heart disease before
any intervention to prevent bacterial
endocarditis
• Syphilis – prophylaxis for a contact

16. Penicillinase resistant
penicillin
• Side chains protect β-Lactam ring from
destruction by penicillinase
• Effective against Penicillinase producing
staphylococci
• Parenteral Naficillin and Methicillin –
vanconycin/ linezolid are used against
methicillin resistant staphylococcus aureus
• Oral/parenteral Cloxacillin – penicillinase
and acid resistant (0.25-0.5 g 6th hrly)

17. Extended-spectrum penicillins
• Semisynthetic ; effective against gram –ve
bacilli as well
Aminopenicillins
• Ampicillin – orally administered
• Wider antibacterial spectrum
• Bactericidal against gram positive and
gram negative organisms
• Inactive against β-Lactamase producing
organism
• Skin rashes, diarrhea, pseudomembrane
enterocolitis are the common adverse
effect

18. Aminopenicillins
• Amoxicillin – congener of ampicillin
• Oral absorption better
• Food does not interfere with absorption
incidence of diarrhea lower
• Dose - 250-500 mg three times daily
• A/E – nausea, epigastric distress,
diarrhoea, skin rash, urticaria

19. Therapeutic uses
• Bronchitis, sinusitis, otitis media
• Meningococcal meningitis
• Orodental abscesses
• Orodental infections
• Periodontal infections
• Subacute bacterial endocarditis –
amoxicillin/ampicillin +gentamicin
• Septicaemia

20. Antipseudomonal penicillins
Carboxypenicillin (carbenicillin,
ticarcillin) – active against
pseudomonas and proteus,
given parenterally
Ureidopenicillin (piperacillin,
mezlocillin) – active against
pseudomonas and klebsiella
• Antipseudomonal penicillins -
combined with
gentamicin/tobramycin to treat
serious pseudomonal infection.

21. β-Lactamase inhibitors
• β-Lactamase –inactivate β-Lactam
antibiotics
• Clavulanic acid, sulbactam, tozabactam has
β-Lactam ring, it inactivates β-Lactamase
hence preventing the destruction of β-
Lactam antibiotic
• No antibacterial activity of its own.

22. β-Lactamase inhibitors
• Amoxicillin +clavulanic acid combination
is available for both oral and parenteral
administration
• Sulbactam – semisynthetic β-
Lactamase inhibitor
• Given with ampicillin parenterally.
• Tozabactam – given along with
piperacillin

23. Adverse reaction
• Hypersensitivity reaction (skin
rashes, urticaria, fever,
bronchospasm, serum
sickness, exfoliative
dermatitis, anaphylaxis) –
penicilloyl moiety
• Local irritancy – pain;
thrombophlebitis; nausea;
confusion, convulsion, coma
Ampicillin,
amoxicillin
methicillin
Carbenicillin,
ticarcillin

24. Drug interaction
• Cholestyramine, colestipol, antacids may ↓the
absorption of oral penicillins
• Concurrent use of estrogen containing OCP with
ampicillin, amoxicillin, penicillin V may ↓
effectiveness of hormonal
contraceptive(Inhibition of enterohepatic
recycling of Ethenyl estradiol)
• Probenecid ↓ renal tubular secretion of penicillin
- ↑ serum levels and half life of Penicillin's