This document summarizes broad spectrum antibiotics tetracyclines and chloramphenicol. It describes the classification, mechanisms of action, antimicrobial spectrum, resistance, pharmacokinetics, adverse effects and therapeutic uses of tetracyclines. It also summarizes the mechanism of action, antimicrobial spectrum, resistance, pharmacokinetics, adverse effects and therapeutic uses of chloramphenicol. Both antibiotics are bacteriostatic, have broad spectra, can cause bone marrow toxicity and are enterohepatically circulated.

1. BROAD SPECTRUM ANTIBIOTICS
 TETRACYCLINES
 CHLORAMPHENICOL

3.  Tetra cyclines have four cyclic ring
 Produced by genus Streptomyces

4. Tetracycline divided into:
a) Naturally occurring:
Tetracycline
Oxytetracycline
Chlortetracycline
Demeclocycline
b) Semisynthetic occurring:
Doxycycline
Meclocycline
Methacycline
Minocycline
Lymecycline
Rolitetracycline

5. CLASSIFICATION OF TETRACYCLINES
 GROUP I :
(6-10hr)
 GROUP II :
(12-13hr)
GROUP III :
(18-20hrs)
Chlortetracycline
Tetracycline
Oxytetracycline
Demeclocycline
Methacycline
Doxycycline
Minocycline

6. Mechanism of Action
BACTERIOSTATIC
1. Drug enter by :
 Active Transport (+Ve)
 Porin channels (-Ve)
Enter into periplasmic place
Protein Carrier system
Inner cytoplasmic membrane
Binds to 30s ribosome
Inhibits attach of aminoacyl t RNA to “A”site
Inhibition of protein synthesis

7. ANTIMICROBIAL SPECTRUM
 G +ve Bacilli :
* Clostridia
* Corynebacteria
* B. Anthracis
* P. acnes
 G –ve Bacilli :
* V. Cholerae
* H. ducryi
* Y. pestis
* Brucella
* H. pylori
* Y. enterocolitica
 G +ve Cocci :
* Streptococci
* Staphylococci
 G –ve Cocci :
* N. gonococci
* N. meningococci

8. ANTIMICROBIAL SPECTRUM cont…
 Rickettiae
 Chlamydiae
 Mycoplasma
 Actinomyces
 Spirochetes
 Entamoeba
 Plasmodia

9. RESISTANCE
1. Active transport Mechanism
2. Pumping Out of Drug
√
3. Protective Protein – Microorganism
4. Complete Cross Resistance
5. Partial Cross Resistance

11. PHARMACOKINETICS
 ABSORPTION :
* Group I & II – Incomplete; Empty Stomach
* Group III – Complete
* Chelating Property
 DISTRIBUTION :
* Liver, Spleen, Bones & Teeth, cross Placenta
 EXCRETION :
* Group I & II – Kidney (70-75%)
* Group III – Bile & Faeces
- Enterohepatic Circulation (Doxy)
* All Tetracycline – Milk
* Mino- saliva and tears

12. ADVERSE EFFECTS
1. LOCAL IRRITANCY (IM)
2. HEPATOTOXICITY
(preg., Inc. blood urea levels)
3. NEPHROTOXICITY (I &II)
4. TOXICITY TO TEETH & BONES
5. PHOTOSENSITIVITY –III
(Sun burn, Doxy)

13. ADVERSE EFFECTS
cont…
6.
VESTIBULAR TOXICITY –III
7.
SUPERINFECTION
8.
HYPERSENSITIVITY
9.
Pseudotumor cerebri (Adults) & Bulging
(acc.lipid cells of inner ear)
fontanelles
10. DIABETES INSIPIDUS LIKE CONDITION
(Mino, Anti ADH action)

14. THERAPEUTIC USES

FIRST CHOICE DRUG :
1. Venereal Diseases
2. Chlamydieal Infections
3. Brucellosis (with streptomycin)
4. Atypical Pneumonia
5. Plague prophylaxis
6. Cholera
7. Rickettseial Infections (Doxy)
8. Relapsing Fever (Doxy)

15. THERAPEUTIC USES

SEACOND CHOICE DRUG :
 To Penicillin
* Tetanus * Anthrax *Actinomycosis
 To Cotrimoxazole : E. coli infection
 To Streptomycin
: Tulaeremia
 To Ciprofloxacin
: Gonorrhoea &
Syphilis
 Azithromycin
: Chlamydial Infection

16. THERAPEUTIC USES
cont…
 MISCELLANEOUS CONDITION :
1. Amoebiasis
2. Malaria
3. Acne
4. COPD
 MINOCYCLINE:
1. Meningococal meningitis
2. Community Acquired Pneumonia
3. Chronic Intestinal Amoebiasis

17. Glycylcyclins
 Synthetic deriv. of Minocyclines
 Potent than Mino
 Effect Gm +ve, -Ve, aerobes,
Anaerobes, resistant tetracyclines
 Same mech, resistance

18. CHLORAMPHENICOL

19. CHLORAMPHENICOL
MECHANISM OF ACTION :
 Inhibits Protein Synthesis
: 50 s Ribosomes (Inhibit formation
of peptide bond)
 High Doses : Inhibits Mammalian
Mitochondrial Protein Synthesis

20. ANTIMICROBIAL SPECTRUM
 BACTERIOSTATIC
 BACTERIOCIDAL – H. influenzae
 BROAD SPECTRUM as TETRACYCLINES
Additional Spectrum:
 HIGHLY ACTIVE– Salmonella
 MORE ACTIVE
-
H. influenzae, B. pertusis,
Klebsiella & Anaerobes
 LESS ACTIVE
–
G+ve cocci, Spirochetes.
 INACTIVE
–
Entamoeba & Plasmodia

21. RESISTANCE
1. Transfer of R Factor
2. Formation of Acetyl Transferase
3. Decreased Permeability
4. Lowered Affinity of Bacterial
Ribosome

22. PHARMACOKINETICS
 Oral Absorption
: Complete
 Distribution
: CSF, Bile, Synovial Memb
Milk, Placenta.
 Metabolism
: Conjugation in Liver
 Excretion
: Unchanged in Urine

23. ADVERSE EFFECTS

24. ADVERSE EFFECTS
1. Bone Marrow Toxicity
 Non Dose Related (3-4g/day for 1-2week)
Inhibition of mitochondrial enzymes
 Dose Related
 Aplastic Anaemia
 Thrombocytopenia
 Agranulocytosis
1. Gray Baby Syndrome
2. Superinfection
3. Irritative Effects

25. THERAPEUTIC USES
1. H. Influenza Meningitis
2. Anaerobic Infections
3. Enteric Fever
4. Intraocular Infection
5. As Second Choice Drug :
 To Tetracycline : Cholera, Brucelosis, etc.
 To Erythromycin: Whooping Cough
 To Penicillin
: Meningitis
 To Cotrimoxazole : Shigella Dysentry

26. IMP
 All undergoes enterohepatic circulation
 CI in pregnancy and ,8 ye.old
 Outdated lead to Fanconi’s syndrome
( Renal tubular acidosis)
 Minocyclines cause dose dependent
vestibular toxicity
 Tetracycline's posses anti anabolic
effects