1. Lecture 2 By Prof. Dr. Mohammed Fahmy
Pharmacology-3
Lecture 2 By Prof. Dr. Mohammed Fahmy

2. Antibiotics
Chemical substances produced by various species of organisms that are capable of killing or inhibiting the growth of other microbes or cells

3. Classification of bacteria
1- Gram-positive
e.g., Staphylococcus & Streptococcus
Many peptidoglycan layers
Stain blue
2- Gram-negative
e.g., E. coli & Salmonella
Few peptidoglycan layers
Stain red

4. Classification of antibacterial drugs
A- According to spectrum
1- Narrow spectrum
e.g., Penicillin G & V
Effective against Gram +ve or Gram –ve
2- Broad spectrum
e.g., Ampicillin & Amoxicillin
Effective against Gram +ve and Gram –ve

5. B- According to effect on bacteria
1- Bacteriostatic
Inhibit growth
e.g., Tetracycline & Chloramphenicol
2- Bactericidal
Kill bacteria
e.g., Penicillins & Cephalosporins

6. C- According to mechanism of action
1- Cell wall synthesis inhibitors
e.g., Penicillins & Cephalosporins
2- Cell membrane synthesis inhibitors
e.g., Daptomycin & Polymixin B

7. 3- Protein synthesis inhibitors
e.g., Aminoglycosides & Tetracyclines
4- Nucleic acid synthesis inhibitors
e.g., Quinolones & Rifampicin
5- Folic acid synthesis inhibitors
e.g., Sulfonamides & Trimethoprim

8. Inhibitors of bacterial cell wall synthesis
Beta-lactam antibiotics Other antibiotics
Penicillins Vancomycin
Cephalosporins Bacitracin
Carbapenems
Monobactams

9. Penicllins Discovered by Alexander Fleming in 1928
Obtained naturally from penicillum mold and synthetically
Contain beta lactam ring which is essential for antibacterial activity

10. Mechanism of action 1- Bactericidal
2- Bind to specific penicillin binding protein (PBP):
Inhibit transpeptidase enzyme responsible for cross-linking of peptidoglycan cell wall synthesis
Activate autolytic enzyme (autolysin) Lysis of cell wall
3- Selectivity
Human cells have no peptidoglycan cell wall

11. Preparation of penicillins
1- Benzyl penicillin (Penicillin G)
Natural penicillin
The spectrum of activity includes most Gram-positive cocci
Has the following disadvantages:
- Destroyed by gastric acidity and must be given parenterally

12. - Inactivated by beta lactamase (not effective in β-lactamase secreting organisms e.g., S. aureus)
- Narrow spectrum (not effective against Gram negative bacilli e.g., E. coli)
- Short duration of action (6 hrs)

13. 2- Long acting penicillins G e. g
2- Long acting penicillins G e.g., Procaine penicillin G Benzathine penicillin G (Durapen) - Used in suspension form - Given I.M. only never I.V. 3- Phenoxymethyl penicillin (Penicillin V, Ospen) - Natural penicillin - Acid stable (given orally)

14. 4- Methicillin
- Beta lactamase resistant
- Effective against S. aureus
- Not used due to its nephrotoxicity
5- Acid & beta lactamase resistant penicillins
e.g., Oxacillin, Cloxacillin and Nafcillin
Effective against S. aureus

15. 6- Broad spectrum penicillins
e.g., Ampicillin & Amoxicillin (Hiconcil)
- Effective against Gram +ve & Gram –ve
- Not effective against Pseudomons & Klibsiella
Advantages of Amoxicillin over ampicillin
Better absorbed orally and not affected by food

16. Longer duration of action (8 hrs)
Less GIT disturbances & diarrhea
7- Extended spectrum penicillins
e.g., Carbenicillin & Piperacillin
- Broad spectrum + effective against Pseudomons & Klebsiella
ِ - Acid sensitive (Given parenterally)

17. Resistance to penicillins 1- Inactivation by beta-lactamases 2- Modification of PBPs can decrease penetration of the antibiotic through the outer cell membrane 3- The presence of an efflux pump can reduce the amount of intracellular drug

18. Pharmacokinetics of penicillins
1- Absorption
Absorption of most oral penicillins (except amoxicillin) is impaired by food
Should be given 1-2 hours before or after meals
2- Distribution
Widely distributed all over the body
Pass placenta, but not teratogenic
Cross BBB when inflammed as in case of meningitis

19. 3- Metabolism
Metabolized by the liver to penicillanic acid, penicillamine and penicilloic acid (allergenic metabolites)
4- Excretion
Most penicillins are excreted by the kidneys
Nafcillin is excreted mainly in bile
Probenecid blocks the active tubular secretion of penicillin, thus elevating its blood level

20. Therapeutic uses of penicillins
1- Streptococcal infections e.g., Tonsilitis, Otitis media & Sinusitis
2- Pneumococcal infections e.g., Pneumonia
3- Staphylococcal infections e.g.,
Abscess
4- Meningococcal infections e.g., Meningitis

21. 6- Diphtheria, tetanus and gas gangrene 7- Urinary tract infections
5- Gonorrhea and syphilis
6- Diphtheria, tetanus and gas gangrene
7- Urinary tract infections
8- Typhoid and paratyphoid fever
9- Prophylaxis of streptococcal infection in rheumatic fever

22. Side effects of penicillins
1- Hypersensitivity reactions
Occur in 20% of patients
Produced by degradation products especially penicilloic acid
Induce urticaria, angioedema and anaphylactic shock
Treated by adrenaline, cortisol and antihistaminic

23. 2- Diarrhea due to superinfection, especially after oral ampicillin
3- Convulsions may occur after intrathecal injection of penicillin
4- Nephritis with methicillin
5- Platelet dysfunction with carbenicillin

24. Beta-lactamase (penicillinase) inhibitors
Examples: Clavulinic acid, Sulbactam and Tazobactam
They protect penicillins from inactivation by β-lactamases secreted by some bacteria e.g., S. aureus & E. coli
They have no antibacterial activity

25. (Augmentin, E-Moxclav, Hibiotic)
Preparations:
1- Clavulinic acid + Amoxicillin (Oral)
(Augmentin, E-Moxclav, Hibiotic)

26. 2- Sulbactam + Ampicillin
(Oral, IM & IV)
(Unasyn)
3- Tazobactam + Piperacillin (IV)
(Tazocin)

27. Cephalosporins Isolated from cephalosporium fungus
Similar to penicillin in structure and mode of action
More resistant to β-lactamase than penicillin

28. Classification 1- First generation
Examples: Cephalexin (Keflex), Cephadroxil (Duracef), Cephradin (Velosef)
Active mainly against Gram +ve cocci
Active on some Gram –ve bacilli
Resistant to β-lactamase enzyme
Do not pass BBB (Not effective in meningitis)

29. 2- Second generation
Examples: Cefaclor (Ceclor), Cefamandole (Mandol), Cefuroxime (Zinacef, Zinnat)
Less active on Gram +ve than 1st generation
More active on Gram –ve than 1st generation
More resistant to β-lactamase than 1st generation
Do not pass BBB except cefuroxime

30. 3-Third generation
Examples: Cefotaxime (Claforan), Ceftriaxone (Rociphen), Cefoperazone (Cefobid), Ceftazidine (Fortum)
Less active on Gram +ve than 2nd generation
More active on Gram -ve than 2nd generation
More resistant to β-lactamase than 2nd generation
Pass BBB (useful in meningitis)

31. 4- Fourth generation
Examples: Cefepime (Maxipime), Cefpirome (Cefrom)
Similar to 3rd generation but highly resistant to β-lactamase

32. Therapeutic uses 1- Urinary tract infections, especially in pregnancy 2- Pneumonia 3- Septicemia 4- Meningitis 5- Sinusitis

33. Can be prevented by vitamin K
Adverse effects
1- Allergy and cross allergy with penicillin (10%)
2- Diarrhea and superinfections
3- Bleeding with Cefamandole and cefoperazone
Can be prevented by vitamin K
4- Severe pain after IM injection