Tetracyclines are a class of broad-spectrum antibiotics produced by soil microbes. They work by inhibiting bacterial protein synthesis by binding to the 30S ribosomal subunit. While originally effective against many pathogens, resistance has grown. Tetracyclines are used to treat conditions like pneumonia, cholera, and certain infections when the causative organism is unknown. They have side effects like phototoxicity, liver damage, and interference with bone and tooth development.
Tetracyclines are a class of broad-spectrum antibiotics produced by soil microbes. They work by inhibiting bacterial protein synthesis by binding to the 30S ribosomal subunit. While originally effective against many pathogens, resistance has grown. Tetracyclines are used to treat conditions like pneumonia, cholera, and certain infections when the causative organism is unknown. They have side effects like phototoxicity, liver damage, and interference with bone and tooth development.
Tetracyclines are a class of broad-spectrum antibiotics produced by soil microbes. They work by inhibiting bacterial protein synthesis by binding to the 30S ribosomal subunit. While originally effective against many pathogens, resistance has grown. Tetracyclines are used to treat conditions like pneumonia, cholera, and certain infections when the causative organism is unknown. They have side effects like phototoxicity, liver damage, and interference with bone and tooth development.
LECTURE:08(29-04-2020) UNIT:II (TETRACYCLINES) CONTENTS 1.INTRODUCTION 2. ANTIMICROBIAL SPECTRUM 3. CLASSIFICATION 4. MECHANISM OF ACTION 5. ADVERSE EFFECTS 6. USES 7. RESISTANCE 1.INTRODUCTION These are a class of antibiotics having a nucleus of four cyclic rings. First tetracyclin was introduced in 1948 Bacteriostatic Broad-spectrum antibiotics They inhibit protein synthesis Obtained from soil actinomycetes. All tetracyclines are slightly bitter solids Aqueous solutions are unstable. It contrasted markedly from penicillin and streptomycin ( the other two antibiotics available at that time) in being active orally and in affecting a wide range of microorganisms-hence called ‘broad spectrum- antibiotic. In gram-negative bacteria tetracyclines diffuse through porin channels. 2. ANTIMICROBIAL SPECTRUM When originally introduced, tetracyclines inhibited practically all types of pathogenic microorganisms except fungi and viruses. 1. Cocci: All gram-positive and gram- negative cocci were originally sensitive. 2. Most gram-positive bacilli 3. Sensitive gram-negative bacilli 4. spirochetes 5. All rickettsiae and chlamydiae 6. Mycoplasma 7. Protozoa 3. CLASSIFICATION This class has following members 1. Tetracycline 2. Oxytetracycline 3. De-methyl-chlor-tetracycline (demeclocycline) 4. Doxycycline 5. Minocycline 6. Tigecycline 4. MECHANISM OF ACTION Tetracyclines inhibit protein synthesis by binding to 30S ribosomes in susceptible organism. Ribosomes are the protein factory(Kitchen) of the organisms where proteins are synthesize . Ribosomes have two sub-units: 1. Smaller sub-unit (30 S) 2. Larger sub-unit (50 S) 50 S sub-unit has two sites 1. Peptidyl (P) 2. Acceptor (A) Protein synthesis is start from 30 S sub-unit by the m-RNA. The initiation complex of mRNA starts protein synthesis and polysome formation. When nacent peptide chain is formed it will transported to the (p)-site of 50 S ribosome. Next amino-acid is transported to the acceptor (A) site of the ribosome by its specific tRNA. Tetracycline binds to 30S ribosome and inhibit aminoacyl tRNA attachment to the ‘A’ site. 4. MECHANISM OF ACTION 5. ADVERSE EFFECTS 1.Irritative effects 2. Organ toxicity Liver damage Kidney damage Phototoxicity Teeth and bones (Chelate gets deposited ) Anti-anabolic effect increased intra cranial pressure Diabetes insipidus Vestibular toxicity 3. Hypersensitivity 4. Super infection 5. Superinfection 6. USES 1. Empirical therapy: TC are often employed when the nature and sensitivity of the infecting organism cannot be reasonably gussed. 2. TC are the first choice of drugs: i. Atypical pneumonia ii. Cholera iii. Brucellosis iv. Plague v. Rickettsial infections 3. TC are the second choice of drugs: ○i. To penicillins for tetanus, anthrax ○Ii. To ceftriaxone for gonorrhoea ○Ii. To ceftriaxone for syphilis in patients allergic to penicillin 4. other situations in which TC may be used are: ○i. Amoebiasis ○UTI ○Adjuvant to quinine 7. RESISTANCE Incomplete cross resistance is seen among different members of tetracycline group. Resistance develops slowly in a graded manner 1. tetracycline concentrating mechanism becomes less efficient 2. bacteria acquire capacity to pump it out 3. Plasma mediated synthesis of a ‘protection’ protein which protects the ribosomal binding site from tetracycline.