1. TETRACYCLINES Broad spectrum antibiotics

2. SOURCE Streptomyces aureofaciens (Chlortetracycline)
Streptomyces rimosus (Oxytetracycline)
Tetracycline Semisynthetic derivative of chlortetracycline
Semi synthetic derivatives (All others)

3. STRUCTURE
Tetracycline Consist of four fused rings with a system of double bonds arranged cyclically. Different members differ in substitutions at these rings.
They are close congeners of polycyclic
Naphthacenecarboxamide.

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5. Glycyclines New group of tetracycline derivatives.
Synthetic analog of tetracyclines
Tigecycline

6. CLASSIFICATION Natural I. Based upon source Chlortetracycline
Demeclocycline a mutant strain of Streptomyces aureofaciens
Oxytetracycline

7. b. Semi-synthetic Tetracycline Clomocycline Methacycline Lymecycline Doxycycline Minocycline

8. Based on Duration of Action.
A. Short-acting hrs
Chlortetracycline
Oxytetracycline
Tetracycline
Clomocycline

9. B. Intermediate-acting ( 10 – 14 hrs )
Methacycline
Demeclocycline
Lymecycline
C. Long-acting (16 – 18 hrs)
Doxycycline
Minocycline

10. PHARMACOKINETICS Oral absorption 30% for chlortetracycline
70% for tetracycline, oxytetracycline, demeclocycline
95-100% for doxycycline and minocycline
Absorption is more in fasting state

11. Tigecycline is administered intravenously no oral absorption.
Absorption of drug occurs mainly in upper small intestine and is impaired with
Food
Divalent cations Ca++, Mg++, Fe++ , Zn++ or Al+++
Dairy products
Antacids (Al+++ and Mg++)
Multivalent cations
Alkaline pH

12. 40-80% bound by serum proteins
Distributed widely to tissues (urine and prostate) and body fluids except for cerebrospinal fluid.
Minocycline reaches very high concentration in tears and saliva----useful for eradication of meningococcal carrier state
Cross the placenta to reach fetus
Excreted in breast milk----damage growing bones and teeth.

13. Undergo enterohepatic circulation

14. Mechanism of Action
Broad-spectrum bacteriostatic antibiotics that inhibit protein synthesis
Enter microorganisms in part by passive diffusion through the hydrophilic channels and in part by an energy dependent process of active transport

15. MOA

16. MECHANISM OF ACTION
I. Tetracyclines inhibit bacterial protein synthesis at ribosomal level as follows:-
Bind reversibly to 30 S subunit of the bacterial ribosome .
Block binding of aminoacyl tRNA to the acceptor site on mRNA- ribosomal complex.
Addition of AA to growing peptide is prevented.
Protein synthesis is inhibited.
II. Also interfere with oxidative phosphorylation, glucose oxidation, bacterial respiration and cell permeability

17. MECHANISM OF BACTERIAL RESISTANCE TO TETRACYCLINES
Decreased intracellular accumulation of
tetracyclines due to either impaired influx
or Increased efflux by an active transport
protein pump.
Interfere with tetracyclines binding to the
ribosome by bacterial proteins covering
30 S ribosomal subunits.

18. Note:- The most important of these is
3. Enzymatic inactivation of tetracyclines.
Note:- The most important of these is
presence of Bacterial Efflux Pump.

19. Spectrum of Activity Broad spectrum antibiotic
1. Rickettsiae
2. Chlamydia spp
3. Mycoplasma pneumoniae
4. Ureaplasma
5. Vibrio cholerae
6. Spirochetes
7. Helicobacter pylori
Brucella
9. Actinomycetes
10. Streptococci
11. Staphylococci
12. Gonococcus
13. H. influenzae
14. Plasmodium falciparum
15. Meningococci
16. E.histolytica
17. Mycobacterium marinum
18. Coxiella burneti
19. Leptospira
20. Pseudomonas pseudomalii

20. THERAPEUTIC USES Respiratory Tract Infections: S. pneumoniae, H
THERAPEUTIC USES Respiratory Tract Infections: S.pneumoniae, H.influenzae Mycoplasmal infections Primary atypical pneumonia. Skin and soft tissue infections: Methicillin resistant S.aureus Acne Act by inhibiting propionibacteria, reside in sebaceous follicles and metabolize lipids into irritating free fatty acids .

21. Intra-abdominal infections: Tigecycline has activity against Enterobacteriaceae and gram negative anerobes. GI Infections: Traveler's diarrhea Sexually Transmitted diseases: C. trachomatis, gonococcal urethritis, pelvic inflammatory diseases: endometritis, salpingitis, parametritis or peritonitis. Acute epididymitis in men.

22. b. Plague, Brucellosis, Tularemia, with Aminoglycosides.
4. Bacillary infections
a. Cholera
b. Plague, Brucellosis, Tularemia, with Aminoglycosides.
Rickettsial Infections:
Rocky Mountain spotted fever, recrudescent epidemic typhus , murine typhus and Q-fever.
Spirochetal infections
Lyme’s disease, Relapsing fever.
Protozoal infections
Amoebic Dysentery, Falciparum Malaria.

23. Eradication of Meningococci (Minocycline) From Menigococcal carriers
Eradication of Meningococci (Minocycline) From Menigococcal carriers. Eradication of H-pylori in duodenal & Gastric Ulcers along with specific ulcer therapy. Community acquired pneumonia

24. Inappropriate secretion of ADH. causing ch hyponatraemia
Inappropriate secretion of ADH. causing ch hyponatraemia. Demeclocycline produces unresponsiveness to ADH thus correcting hyponatraemia
Anthrax : Doxycycline is indicated for prevention or treatment of anthrax.
Atypical Mycobacterial infections caused by Mycobacterium marinum.

25. Acute treatment and for prophylaxis of leptosporiasis, relapsing fever (B.recurrentis) and Lyme disease (B. burgdorferi)

26. ADVERSE EFFECTS Effect on Bony structures & teeth (calcified tissues)
Deposition in growing / newly formed bones or
teeth, when given in pregnancy ,lactation or children below 8 yrs.
Fluorescence, Discoloration of teeth (yellowish changing into permanent brownish discoloration & Enamel dysplasia, inhibition of primary dentition, pitting, caries and malformation of cusps / crowns.
Deformity / Growth inhibition of Bones

27. 2. GIT adverse effects a. Due to irritation: Epigastric burning and distress, Nausea ,vomiting , Anorexia & Diarrhea. b. Due to Superinfection (by proteus, pseudomonas, enterrococci, candida spp, C. difficle) C. difficle Pseudomembranous enterocolitis leading to malabsorption and vitamins deficiency; treated by Vancomycin 250mg 6 hourly orally or Metronidazole mg TDS

28. Hepatic toxicity
With large doses or small doses during pregnancy given I/V
Oxytetracycline and tetracycline are least hepatotoxic
Renal toxicity
Tetracyclines may aggravate azotemia in patients with renal disease.

29. Local tissue toxicity.
Photosensitivity with Demeclocycline
Vestibular reactions with Minocycline (dizzziness, ataxia, nausea and vomitting)
Pseudotumor cerebri (increase intracranial pressure in young infants)
Thrombophlebitis.
Decreased protein synthesis with high doses (anti-anabolic effect) resulting in renal damage.

30. Disturbance of bone marrow with long – term therapy, causing leucocytosis, atypical lymphocytes and thrombocytopenic purpura
Fanconi-like syndrome (nausea, vomiting, polyuria, polydipsia, proteinuria, acidosis, glycosuria and aminoaciduria).