Semisynthetic Penicillins

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 Example: Phenoxymethyl – Penicillin (Penicillin V) Example: Methicillin Cloxacillin Dicloxacillin 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 P lasma half life- 30-60 min. The antibacterial spectrum of penicillin V is identical to P nG . 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) B ecause 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 N onpenicillinase producing organisms are much less sensitive to these drugs than to PnG . T hese 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 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 L ess active against other gram postive cocci Pharmacokinetics Not degraded by gastric acid Oral absorption is incomplete but adequate food interferes with absorption P artly excreted in bile and reabsorbed Excretion by kindney P lasma 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 L ess 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