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TETRACYCLINES:-
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Tetracyclines are the drugs comes under the broad spectrum of the antibiotics. which contains the four cyclic ring in it's structure.
Tetracyclines are generally use in  treatment of urinary tract infection,respiratory tract and also in intestine.

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Tetracycline resistance - 2 mechanism how bacteria developed resistance to tetracycline

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1)GOODMAN & GILMAN'S ,THE
PHARMACOLOGY BASIS OF THERAPEITICS ,10TH EDITION .
PAGE NO 1245.
2)TEXT BOOK OF PHARMACOLOGY BY F.S.K. BARAR
3)ESSENTAIL OF MEDICAL PHARMACOLOGY BY K.D. TRIPATHI.
TETRACYCLINES

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tetracyclines, classificatin, mechanism of action, clinical uses

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->common side effect:-
-vomiting
-diarrhoea
-nausea
-sour throat
-skin photo sensitivity
-stomatitis
->rare side effect:-
-abdominal pain
-headache
-loss of apetite.
-visual changes
-yellow skin
-pigmentation on skin
1)GI side effect:-
-GI side effects includes the
-anorexia
-black hairy tongue
-glossitis
-diarrhoea
-nuasea
-dysphagia
2)RENAL side effect:-
-generally occurring in patients having renal diseases.
3)DERMATOLOGIC SIDE EFFECT :-
-exfoliative dermatitis
-nail decoloration
-photosenstivity
-erethamatous rashes
4)MUSCULOSKELETAL side effect:-
-decrease in skeleton growth rate.
-In adult tooth declaration.
-tetracycline deposits into ca conating tissue.
5)NERVOUS SYSTEM side effect:-
-intracranial hypertension.
-blur  vision
6)HEMATOLOGIC side effect:-
-thrombocytopenia
-neutropenia
7)HEPATIC side effect:-
-increase level of liver enzyme.

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The growth of bacteria which can be inhibitaed by the antibiotics like tetracycline by stopping the protein synthesis. They have been widely used as therapeutic agent. In such bacteria usually the tetracycline concentrating mechanism becomes less effective or the bacteria acquire capacity to pump it out.Another mechanism is plasmid mediated synthesis of "protection" protein which protects the ribosomal binding site from tetracycline .Elaboration of tetracycline in activating enzyme is unimportant mechanism of tetracycline.Due to widespread use of tetracycline resistance has become common in gram positive bacteria like cocoa,E.coli, and many others.
(*)The 3 mechanism of resistance have been identified .
1)Tetracycline efflux
2)ribosome protection
3)tetracycline modification
1)Tetracycline efflux is achieved by export protein from major facilitator superfamily.
In gram negative bacteria the export protein contain 12 transmembrane  fragments whereas in Gram positive bacteria export protein contain 14 transmembrane fragments.
2)Ribosome protection mediated by the soluble protein
which shares the homology with the GTPase participating in protein synthesis.
(*)MECHANISM:-
tetracycline inhibit the growth by inhibiting the translation .
It binds to the 16s parts of the 30s ribosomal subunit and prevent the aminoacyl tRNA from binding to the site of ribosome
Inactivation is the rarest type of the resistance where acetyl group is added to the molecule ,causing  inactivation of the drug .The mechanism of action of the tetracycline resistance gene on artificial plasmid pBR322.
six classes of ribosomal protection  have been found ,all  with high sequence  homology ,suggesting common evolutionary ancestor .
(*)THE POSSIBLE MECHANISM OF ACTION OF THESE PROTECTIVE  PROTEIN INCLUDES :-
1)Blocking the tetracycline from the binding to the ribosomes.
2)binding to the ribosomes & distorting the structure to still allow t-rna binding while tricyclic is bound .
3)binding to the ribosomes and dislodging  tetracycline.

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Diaz, Mauesha Flores, Kim Manlapaz, Kathleen