Pharmacology of Tetracyclines and Chloramphenicol

1. Tetracyclines , Glycylcyclines
and
Chloramphenicol
Dr KG Bandekar
MD Pharmacology

2. Tetracyclines , Glycylcyclines
and
Chloramphenicol
• Broad Spectrum antibiotics
• Bacteriostatic
• Inhibit Protein Synthesis

3. Tetracyclines

4. Source
• Actinomycetes (Fungus) present in Soil

5. Classification : Source
Natural
• Chlortetracycline
• Oxytetracycline
• Tetracycline
• Demeclocycline
Semisynthetic
• Doxycycline
• Minocycline
• Methacycline

6. Classification : duration of action
• Short acting (t1/2- 6-10 hr)
– Tetracycline
– Oxy tetracycline
– Chlor tetracycline
• Intermediate acting (t1/2-12-16 hr)
– Methacycline
– Demeclocycline
• Long acting (t1/2- 18-24 hr)
Doxycycline
Minocycline
Tigecycline

7. Pharmacokinetics : ADME
Absorption
1. Food :
interferes absorption of all except Doxycycline
2. Chelating effect :
(Stable insoluble unabsorbable complex with
metal ions : Ca+2 / Mg+2 / Al +3 /Fe+2 : Milk/
curd/ Antacids / Fe preparations)

8. PK
3. F (Bioavailability)
60% for shorter acting/older
(Incompletely absorbed from gut)
90-95 % for Doxycycline & Minocycline

9. Distribution (Vd)
• High
• Goes to tissues
• Liver / bone & teeth

10. Excretion
• Mainly renal EXCEPT
Doxycycline
• Doxycycline – feces
• Clinical imp –
• RF X all except Doxycycline and Minocycline

11. PD
• Mechanism of action
• t-RNA to A site of 30 S Ribosome
• A site of 30 S ribosome
• 30 S ribosome
• Inhibit Protein synthesis
• Bactriostatic

12. Mechanism of Action (MOA)
• Active transport in bacteria
Tetracycline
Active transport
Bacteria
Bacterial
Ribosome

13. MOA
• Binds to 30 S unit of bact ribosome
• Inhibits binding of t-RNA to A site of 30 S unit

15. MOA

16. Why are they not affecting host ?
1. TC do not bind to mammalian 40 S or 60 S
2. Carrier involved in Active transport of TCs is
absent in host mammalian cells.

17. Resistance
1. Decreased influx
2. Increased Efflux by Active Transport
(Pumping Out of Drug)
3. Reduced access of drug to the ribosome
(ribosome protection proteins)
4. Inactivation of Drug by elaboration of
enzymes

18. Spectrum
• Broad spectrum

19. Uses
• First choice / drug of choice
1. Rickettsial infn
2. Chlamydial infn
3. Relapsing fever
4. Plague prophylaxis
5. LGV (lymphogranuloma venerum)
6. GI (granulaoma inguinalae)

20. ADR
1. Super infections
2. GI side effects
3. Psedomembranous colitis
Contd…

21. PK
3. F (Bioavailability)
60% for shorter acting/older
(Incompletely absorbed from gut)
90-95 % for Doxycycline & Minocycline

22. ADR
4. In Children < 8 yrs – dentition abnormality
5. Teratogenic : ‘Foetal tooth enamal dysplasia’
& affects foetal bone growth
Contd…

23. Distribution (Vd)
• High
• Goes to tissues
• Liver / bone & teeth

24. ADR
6. Expired Tetracyclines : Fanconi’s like
syndrome
(Fanconi’s syndrome : Proximal convoluted
tubule damage – no absorption of many
molecules)
Contd…

25. ADR
7. Phototoxicity : Demeclocycline > Doxy
8. Vestibular damage : Minocycline
9. Diabetes insipidus : Demeclocycline

26. Glycylcyclines
• Tigecycline
• Derivative of minocycline
• MOA similar to tetracyclines
• More resistant to efflux mechanism – less
resistance

27. Chloramphenicol

28. PK
• Completely absorbed after oral ingestion.
• Plasma t½ of is 3–5 hours in adults
• Primarily conjugated in Liver

29. MOA
• Bactriostatic
• Inhibit protein synthesis
• 50 S ribosome
• Inhibition of peptidyl transferase

30. MOA

31. Use
• Rarely used due to toxicity
1. Intraocular infections –
Given systemically : It is the preferred drug for
endophthalmitis caused by sensitive bacteria.
2. Topical preparations for Eye & Ear use:
Conjunctivitis, external ear infections
0.5–5.0% is highly effective.
Topical use on skin or other areas is not
recommended because of risk of sensitization

32. ADR
1. Bone marrow depression
A. Idiosyncratic reaction (rare):- (1: 30,000 to
40,000) Aplastic anaemia, agranulocytosis,
thrombocytopenia or pancytopenia
unpredictable, but serious, often fatal.
B. Dose dependent- manifested as Anaemia,
Leucopoenia, thrombocytopenia – reversible
on stopping the drug. (Due to Inhibition of
Mammalian Mitochondrial Protein Synthesis)

33. ADR
2. Gray baby syndrome – (especially in premature)
 Stops feeding
 Vomiting
 Hypothermia
 Hypotonia
 Abdominal distensiion
 Cyanosis
 followed by cardiovascular collapse and death.

34. MCQ
• Drug with high degree of photosensitivity?
a) Tetracycline
b) Minocycline
c) Doxycycline
d) All are equally photosensitive

35. MCQ
• Which of the following can be used in Renal
failure without dose adjustment
a) Demeclocycline
b) Oxytetracycline
c) Doxycycline
d) Tetracycline

36. MCQ
• Which of the tetracycline is used in SIADH
a) Minocycline
b) Doxycycline
c) Demeclocycline
d) Tetracycline

37. Thank you!