Pharmacology

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