Alexander Fleming Microbes make antibiotics Extracted from Penicillin Notatum ORIGIN: moldy culture plate DRUG: Penicillin (1928) NOBEL: 1945 1.According to source: Antibiotic isolate from 3 type of microbs From Fungi: Penicillin From Penicillin Notatum . From Actinomycetes: Streptomycin From Streptomyces Griseus From Bacteria: Bacitracin From Bacillus Subtilis Inhibitors Of Bacterial Cell Wall Synthesis:Penicillin , Cephalosporine, Bacitaeacin,Cycloserine 2. Inhibitors Of Protien Synthesis: Aminogycoside,Tertacycline, Chloramphenicol, Macrolides, Lincosamide 3. Inhibitors Of Bacterial Cell Membrane Function Polymyxins, Nystatin, Amphotericine B. 4. Inhibitors Of Nucleic Acid Metabolism: Grisofulvine, Actinomycin

1. ANTIBIOTICS
Mr.Vijay Salvekar
Dept. of Pharmacology
GRY Institute of Pharmacy, Borawan

2. Alexander Fleming
– Microbes make antibiotics
Extracted from Penicillin Notatum
ORIGIN: moldy culture plate
DRUG: Penicillin (1928)
NOBEL: 1945

3. Definitions of Antibiotics
• OLD: An antibiotic is a chemical substance
produced by various species of microorganisms
that is capable in small concentrations of
inhibiting the growth of other microorganisms
• NEW: An antibiotic is a product produced by
a microorganism or a similar substance
produced wholly or partially by chemical
synthesis, which in low concentrations,
inhibits the growth of other microorganisms

4. Classification
1.According to source: Antibiotic isolate from 3
type of microbs
• From Fungi: Penicillin From Penicillin Notatum .
• From Actinomycetes: Streptomycin From
Streptomyces Griseus
• From Bacteria: Bacitracin From Bacillus Subtilis
For More Example Ref. Fsk Barar

5. 2. According to the mode of action
1. Inhibitors Of Bacterial Cell Wall Synthesis:Penicillin
Cephalosporine, Bacitaeacin,Cycloserine
2. Inhibitors Of Protien Synthesis:
Aminogycoside,Tertacycline, Chloramphenicol,
Macrolides, Lincosamide
3. Inhibitors Of Bacterial Cell Membrane Function
Polymyxins, Nystatin, Amphotericine B.
4. Inhibitors Of Nucleic Acid Metabolism: Grisofulvine
Actinomycin

6. 3. According to the Antibacterial Spectrum
1. NARROW: Penicillin , Streptomycin,
lincomycin, Polymyxin B,
Vincomycin
2.BROAD: Chloramphenicolo, Tertracycline,
Kanamycin, Cephalosporine,
Ampicillin,

7. From mold genus Penicillium - ‘miracle drug’ from
WWII
Bacteria die of cell lysis (breakdown)
Both ‘static’ & ‘cidal’ in nature
Antibacterial agents which inhibit bacterial
cell wall synthesis
Discovered by Fleming from a fungal colony
(1928)

8. Shown to be non toxic and antibacterial
Isolated and purified by Florey and Chain (1938)
First successful clinical trial (1941)
Produced by large scale fermentation (1944)
Structure established by X-ray crystallography(1945)
Full synthesis developed by Sheehan (1957)
Isolation of 6-APA by Beechams (1958-60)
- Development of semi-synthetic penicillins
Discovery of clavulanic acid and b-lactamase
inhibitors

10. I. PENICILLINS
A. FLEMING
(1881–1955)
•Penicillin G
- P. notatum
(1929)

11. Penicillium chrysogenum

12. Natural Penicillins{PCN}
Penicillin G, Penicillin V, Procaine, Bicillin
- Good gram +, fair gram - , good anaerobic
- PCN G = more effective IV or IM,
But painful d/t aqueous solution
- PCN V = PO; peak 2 - 4 hrs

13. Aminopenicillins (Broad Spectrum)
Amoxicillin (Amoxil), Ampicillin
(Omnipen), Bacampicillin HCL
(Spectrobid)
- Gram + & Gram -
- Costlier
- Inactivated by beta-lactamases = ineffective
against Staphylococcus aureus (staph. A)
- Amoxicillin = most prescribed PCN derivative
for adults & children

14. • Penicillinase - Resistant Penicillins
Methicillin , Nafcillin, Oxacillin
- Used to treat penicillinase-producing Staph A.
- Gram + , not effective against Gram –
- IV & PO

15. • Extended - Spectrum Penicillins
Carbenicillin , Mezlocillin, Piperacillin,
Ticarcillin, Ticarcillin-clavulanate
(Timentin) - IM & IV
- Broad spectrum - good gram (-)
fair gram (+)
- Good against Pseudomonas aeruginosa
- Not penicillinase resistant

16. Penicillin G
Penicillin G is one of the natural
penicillins.
It is an effective antimicrobial for the
treatment of infections due to
susceptible organisms.

17. Penicillium chrysogenum

18. D0SING INFORMATION
Adult dose:
oral therapy - 375 mg to 1 g divided 3 to 4
times daily.
IV - 300,000 units to 1.2 million units/day
divided every 3 to 4 h.
continuous intravenous infusions of 10 to
20 million units have been given over 20
h/day for several weeks.

19. Pediatric dose:
Pediatric oral doses are 25 to 50 mg/kg/day
divided every 6 to 8 h.
Pediatric Parenteral doses are 300,000 units
to 1.2 million units/day given every 3 to 4 h
Maximum of 50,000 units/kg/dose or 5
million units/dose and 30 million units/day.

20. MECHANISM OF ACTION
Penicillin G Inhibits Bacterial Cell Wall Synthesis By
Binding To One Or More Of The Penicillin-binding
Proteins (PBPs).
Penicillin G Inhibits The Final Transpeptidation
Step Of Peptidoglycan Synthesis In Bacterial Cell
Walls,
 Thus Inhibiting Cell Wall Biosynthesis.

21. www.uccs.edu/

22. Mur NAc
Glycopeptide
Polymer Mur NAc
Glycopeptide
Polymer
Glycopeptide
Polymer
D-Alanine
Transpeptidase

23. Penicillin Binding Proteins
TRanspeptidases
Carboxypeptidases
Endopeptidases
Penicillin

24. PHARMACOKINETIC
Bioavailability:
1. Oral: less than 30%.
2. Oral, penicillin G capsule, suspension: 65% to 80%.
3. Intramuscular, penicillin G: 72%.

25. • Distribution Sites
Total Protein Binding: 65%
Other Distribution Sites:
Bile.
Bone.
Cerebrospinal Fluid: Poor
• Metabolism
The Liver.
• Distribution Kinetics
Volume Of Distribution (Vd): 33 Liters

26. • EXCRETION
• Renal Excretion: 79% To 85%
• Other Excretion: Bile: Small Amounts
• HALF-LIFE
• In Normal Individual:20 To 50 Minutes.
• The Half-life Of Penicillin In The Presence Of Renal
Failure Is 1 To 10 Hours Depending On Degree Of
Renal Failure.

27. CAUTIONS
CONTRAINDICATIONS:
• History of anaphylaxis, accelerated (e.g., hives-
URTICARIA)
• serum sickness reaction to previous penicillin
administration.
PRECAUTIONS:
• Use with caution in patients with a history of
penicillin or cephalosporin hypersensitivity
reactions, atopic predisposition (e.g., asthma),
impaired renal function, or pre-existing seizure
disorder.

28. CAUTIONS cont’d
Adverse Reactions:
• Hemolytic Anemia.
• Eosinophilia.
• Granulocytopenia.
• Leukopenia.
• Neutropenia
• Agranulocytosis.
• Myocardial Infarction.
• Convulsions

29. DRUG-DRUG INTERACTION
• ACETYLCYSTEINE.
• AMINOGLYCOSIDES.
• CHLORAMPHENICOL.
• CHOLESTYRAMINE.
• CIMETIDINE.
• COLESTIPOL.
• ETHINYL ESTRADIOL.
• MESTRANOL.
• METHOTREXATE.
• TETRACYCLINE.

30. DRUG-FOOD COMBINATIONS
• Penicillin G is rapidly destroyed by
gastric acid (pH = 2).
• Enteric absorption is adversely affected
by food.
• Administer oral penicillin G at least 30
minutes prior or 2 hours after a meal

31. CLINICAL APPLICATIONS
The Drug Is Frequently Used For
• Streptococcal Infections -Pneumonia,
• Otitis Media, Meningitis,
• Septic Arthritis.
 Penicillin G Is Effective Against
• Neisseria Meningitides ,
• Clostridium Tetani,
• Corynebacterium Diphtheria,
• Treponema Pallidum

32. 30S: Aminoglycosides
30S: Tetracyclines
50S: Chloramphenicol
50S: Macrolides, Lincosamides
50S: Linezolide, Streptogramins
RifampicinPolymyxins
ANTIBIOTICS – mechanism of action
β-lactams, Glycopeptides