This presentation was used to conduct theory class of BSN 1st year

1. Antimicrobial agents:
Specific Drugs
Dr. Pravin Prasad
M.B.B.S., MD Clinical Pharmacology
Lecturer, Lumbini Medical College
21 February, 2019 (9 Falgun 2075), Thursday

2. By the end of the class BSN 1st year
students will be able to:
Classify AMAs that act by inhibiting:
Protein synthesis
DNA gyrase
Explain the mechanism of action of
aminoglycosides, tetracyclines, macrolides and
fluoroquinolones
List the uses and adverse effect of
aminoglycosides, tetracyclines, macrolides and
fluoroquinolones

3. Protein synthesis inhibitor AMAs
Includes tetracyclines, aminoglycosides, macrolides,
chloramphenicol
Tetracyclines: broad spectrum antibiotics
Affects the formation of protein molecules from
the mRNA

4. Protein synthesis mechanism

5. 30S
50S
Protein synthesis mechanism
c1 c2 c3 c4 c5 c6 c7 c8 c9
P A
mRNA being read and protein being formed
mRNA
Ribosome complex
Nascent protein
chain
Acceptor sitePeptidyl site
mRNA codons
a4
a3
a2
a1

6. Protein synthesis mechanism
c1 c2 c3 c4 c5 c6 c7 c8 c9
P A
30S
50S a5a5
a4
a3
a2
a1
Chain Elongation

7. Protein synthesis mechanism
c1 c2 c3 c4 c5 c6 c7 c8 c9
P A
a4
a3
a2
a1
30S
50S
a5
Chain Elongation

8. Protein synthesis mechanism
c1 c2 c3 c4 c5 c6 c7 c8 c9
P A
a4
a3
a2
a1
30S
50S
a5
Chain Elongation

9. Protein synthesis mechanism
c1 c2 c3 c4 c5 c6 c7 c8 c9
P A
30S
50S
a4
a3
a2
a1
a5
Translocation

10. Protein synthesis mechanism
c1 c2 c3 c4 c5 c6 c7 c8 c9
P A
30S
50S
a4
a3
a2
a1
a5
a6

11. Mechanism of Action:
Aminoglycosides
1. Aminoglycosides: several sites of 30S and 50S subunits,
and their interface:-
Freeze initiation, interfere with polysome formation,
misreading of mRNA code

12. Mechanism of Action: Tetracycline
2. Tetracycline: 30S ribosome:-
Inhibit aminoacyl tRNA attachment to ‘A’ site

13. Mechanism of Action: Macrolides
4. Macrolides (Erythromycin) : 50S ribosome:-
Hinders translocation  ribosome cannot move ahead
 premature termination of peptide chain

14. Aminoglycosides
Always given parenterally
Are bactericidal
Mainly effective against gram-negative organisms
Narrow spectrum
Demonstrate post antibiotic effect
Bactericidal effect exerted even after fall in
plasma level of drug

15. Aminoglycosides
Obtained from
Streptomyces
Obtained from
Micromonospora
Streptomycin Gentamicin
Kanamycin Netilmicin*
Tobramycin Amikacin*
Neomycin
* = Semisynthetic products

16. Aminoglycosides: Uses
Streptomycin
Tuberculosis, Plague, Tularemia
Gentamicin
Pseudomonas, Proteus, Klebsiella infections:
•UTI, pneumonia, lung abscess, osteomyelitis,
middle ear infection, septicaemia
Meningitis by gram negative bacteria
Subacute bacterial endocarditis

17. Aminoglycosides: Uses
Amikacin
Tuberculosis, Hospital acquired infections
Neomycin
Topically in skin infections, burns, ulcers and
wounds, eye and ear infection
Orally in hepatic coma, preoperative gut
sterilization

18. Aminoglycosides: Adverse effect
Most common adverse effects:
Ototoxicity (permanent deafness, vestibular
dysfunction)
Nephrotoxicity
Neuromuscular blockade

19. Tetracyclines: Uses
Drug of Choice:
Rickettsial infection
•Spotted fever, Scrub typhus
Chlamydia infection
•Lymphogranuloma venerum, Trachoma
Mycoplasma pneumonia, Vibrio cholera
Brucellosis
Plague

20. Tetracyclines: Uses
Of adjuvant value:
Acne
Traveller’s diarrhoea
Protozoal infections:
•Chronic intestinal amoebiasis
•Malaria

21. Tetracyclines: Adverse effect
Nausea, vomiting, diarrhoea
Administer drug with food
Hepatotoxicity, renal toxicity
Fanconi’s syndrome
Phototoxicity
Depress bone growth, brittle and staining of teeth
Suprainfections

22. Macrolides
Includes:
Erythromycin, Roxithromycin, Clarithromycin,
Azithromycin
Narrow spectrum
Aerobic gram positive bacteria
Gram negative bacteria (few)
Erythromycin, Clarithromycin: significant drug
interaction

23. Macrolides: Uses
Atypical pneumonia
Whooping cough
Strep. and Staph.
Infections
Diphtheria
Syphilis and gonorrhoea
Campylobacter
gastroenteritis
Tetanus
Anthrax

24. Macrolides: Adverse effects
Hepatitis with cholestatic jaundice
Epigastric distress, nausea, vomiting, diarrhoea
Allergic reactions
Cardiac arrhythmia
Reversible impairment
Azithromycin lesser side effects

25. DNA gyrase inhibitor AMAs
DNA gyrase:
Present in gram negative bacteria
Nicks the DNA  introduces negative supercoils
reseals the nicked ends
Necessary for DNA replication
Topoisomerase IV
Present in gram positive bacteria
Analogous to DNA gyrase of gram negative
bacteria

26. DNA gyrase inhibitor AMAs
Includes Quinolones and Fluoroquinolones (FQs)
Classification of FQs
First generation Second Generation
Ciprofloxacin Levofloxacin
Norfloxacin Moxifloxacin
Ofloxacin Gemifloxacin
Pefloxacin Prulifloxacin
Lomefloxacin
Sparfloxacin

27. Fluoroquinolones: Mechanism of
Action
Inhibits:
DNA gyrase enzyme and topoisomerase IV
enzyme present in gram negative and gram
positive bacteria respectively
Damaged DNA formed  digested by
exonucleases
Bacterial cell death occurs

28. Ciprofloxacin: Uses
Mainly used for gram negative infections
Urinary tract infection
Bacterial gastroenteritis
Typhoid
STI: Gonorrhoea, Chancroid (as alternative drugs)
Bone, soft tissue, gynaecological and wound
infections

29. Ciprofloxacin: Uses
Atypical pneumonia, Anthrax, Tuberculosis
Gram negative septicaemia
Meningitis
Prophylaxis of infection in neutropenic/cancer and
other susceptible patients
Topically in conjunctivitis due to gram negative
bacteria

30. Ciprofloxacin: Adverse effects
Generally safe, withdrawal required in 1.5% cases
Tendinitis and tendon rupture
Hypersensitivity
Gastro-intestinal
•Nausea, vomiting, bad taste DIARRHOEA
Central Nervous System
•Headache, impairment in concentration and
dexterity
•Tremors, seizures

31. Any queries?
Please revise your classes
Next class:
Antiviral agents and Antifungal agents
Thank you.