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
9. RESISTANCE
1. Active transport Mechanism
2. Pumping Out of Drug
√
3. Protective Protein – Microorganism
4. Complete Cross Resistance
5. Partial Cross Resistance
10.
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)
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
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
Notes de l'éditeur
Cessatin, bulging fontanelles= unossified space or soft spot lying between cranial bones of the skull of the foetus.
I & II food retards absorption.
Ca+2, Mg+2, Fe+2, Al+3, milk chelating action
Tulaeremia= plague like infectioucs. Transmitted by bite of an infected tick or blood sucking insect. Transmeted through Water/ uncooked food
Gray baby syndrome – Abdominal distension, progressive cyanosis ,hyptohermia– occurs due to cannot adequently conjugation, slow rate of flomerular filtration
Gray baby syndrome – Abdominal distension, progressive cyanosis ,hyptohermia– occurs due to cannot adequently conjugation, slow rate of flomerular filtration