The presentation include semisynthetic penicillin introduction and classification. Contents Semisynthetic penicillins- Introduction Classification Acid-resistant alternative to Penicillin G Penicillinase- resistant penicillins Extended spectrum penicillins

1. SEMISYNTHETIC
PENICILLINS
Anusha Shaji, B.Pharm, M.Pharm
Assistant Professor
Department of Pharmacology
Nirmala College of Pharmacy,
Muvattupuzha, Ernakulam

2. Contents
Semisynthetic penicillins- Introduction
Classification
Acid-resistant alternative to Penicillin G
Penicillinase- resistant penicillins
Extended spectrum penicillins

3. Semisynthetic Penicillins- Introduction
Produced by chemically combinig specific side chains (in place of benzyl side
chain of PnG)
or
by incorporating specific precursors in the mould culture.
Salts of Penicillin G (PnG): Procaine penicillin & Benzathine penicillin (not
semisynthetic penicillins)
The aim of producing semisynthetic penicillins has been to overcome the short
comings of PnG, which are:
1. Poor oral efficacy
2. Susceptibility to penicillinase
3. Narrow spectrum of activity
4. Hypersensitivity reactions

4. Classification
Semisynthetic
penicillins
Acid- Resistant
alternative to
Penicillin G
Penicillinase
resistant penicillins
Extended spectrum
penicillins
Example:
Phenoxymethyl –
Penicillin
(Penicillin V)
Example:
Methicillin
Cloxacillin
Dicloxacillin
1. Aminopenicillins: Ampicillin
Amoxicillin
Bacampicillin
2. Carboxypenicillins:Carbenicillin
3. Ureidopenicillins: Mezlocillin
Piperacillin
Beta Lactamase inhibitors
Clavulanic acid, Sulbactam, Tazobactam

5. 1. Acid Resistant Alternative to Penicillin G
Phenoxymethyl Penicillin (Penicillin V)
It differs from PnG only in that it is acid stable.
Oral absorption is better
Peak blood level is reached in 1 hour
Plasma half life- 30-60 min.
The antibacterial spectrum of penicillin V is identical to PnG.
It is used only for streptococcal pharyngitis, sinusitis, otitis media,
prophylaxis of rheumatic fever (when an oral drug has to be selected), less
serious pneumococcal infections and trench mouth.
Dose: 250-500mg
Infants: 60mg
Children: 125-250mg, given six hourly

6. 2. Penicillinase- Resistant Penicillins
Their use is restricted to the treatment of infections caused by penicillinase
producing staphylococci (except methicillin resistant Staph. aureus-MRSA)
Because these analogues have side chains that protect the beta- lactam ring
from attack by staphylococcal penicillinase.
It also patially protects the bacteria from the beta lactam ring
Nonpenicillinase producing organisms are much less sensitive to these
drugs than to PnG.
These drugs are not resistant to beta lactamase produced by gram negative
bacteria.

7. Methicillin
Highly penicillinase resistant but not acid resistant
Also an inducer of penicillinase production
Methicillin resistant Staph. aureus (MRSA) are insensitive to all penicillinase
resistant penicillins and to other beta lactams
It is also insensitive to erythromycin, aminoglycosides, tetracyclines etc.
The MRSA have altered PBPs → which do not bind penicillins
The drug of choice for these organism- Vancomycin/ linezolid.
Adverse Effects- Haematuria, albuminuria and reversible interstitial nephritis

8. Cloxacillin/ Dicloxacillin
It is highly penicillinase as well as acid resistant
More active than methicillin against penicillinase producing Staph., but not
against MRSA.
Pharmacokinetics
Completely but dependably absorbed from oral route (especially taken in
empty stomach)
Plasma protein bound (>90%)
Elimination by kidney and liver
Plasma half life- About 1 hour
Dose: 0.25-0.5 mg, orally every 6 hours
Another penicillinase resistant penicillin- Nafcillin

9. 3. Extended spectrum penicillins
These semisynthetic penicillins are active against gram negative bacilli.
Classification
1. Aminopenicillins: Ampicillin
Amoxicillin
Bacampicillin
2. Carboxypenicillins: Carbenicillin
3. Ureidopenicillins: Mezlocillin
Piperacillin
Aminopenicillins
This group has an amino substitution in the side chain.
Similar antibacterial spectra
None is resistant to penicillinase or to other beta-lactamases

10. Ampicillin
Active against all organisms sensitive to PnG
Due to widespread use, many of these have developed resistance
More active than PnG for Strep. viridans, enterococci and Listeria
Equally active for pneumococci, gonococcia and meningococci
Less active against other gram postive cocci
Pharmacokinetics
Not degraded by gastric acid
Oral absorption is incomplete but adequate
food interferes with absorption
Partly excreted in bile and reabsorbed
Excretion by kindney
Plasma half life- 1 hour

11. Uses
• Urinary Tract infections
• Respiratory tract infections
• Gonorrhoea
• Cholecystitis
• Subacute bacterial endocarditis
Adverse effects
 Diarrhoea is frequent after oral administration
 Rashes especially in patients with AIDS, EV virus infections & lymphatic
leukaemia
Drug interactions
• Hydrocortisone inactivates ampicillin if mixed in the iv solution
• Probenecid retards renal excretion of ampicillin

12. Carboxypenicillins
Carbenicillin
Active against Pseudomonas aeruginosa and indole positive Proteus
Less active against Salmonella, E.coli and Enterobacter
Carbenicillin is neither penicillinase resistant nor acid resistant
Pharmacokinetics
 Inactive orally
 Excreted rapidly in urine
 Plasma half life- 1 hour
 Used as sodium salt
 Dose: 1-2 mg i.m or 1-5 mg i.v every 4-6 hours
 At high doses → Cause bleeding → by interfering with platelet function

13. Ureidopenicillins
Piperacillin
Antipseudomonal penicillin
Eight times more active than carbenicillin
Active against Klebsiella, Enterobacteriaceae and some bacteroides.
Pharmacokinetics
 Elimination half life- 1 hour
 Use: treating serious gram negative infections in neutropenic or burn
patients.
 Dose: 100-150 mg/kg/day in 3 divided doses (max 16g/day) i.m or i.v
Mezlocillin
• Antipseudomonal penicillin
• Not available in India