Tetracyclines - Jan 2024 for Students PDF

TETRACYCLINES & GLYCYLCYCLINES Dr. VINODHINI, B.Pharm, M.Sc,Ph.d, D.Acu, PGDITM, PGDBI Department of Pharmacology SRM Dental College, Ramapuram TETRACYCLINES GLYCYLCYCLINE MECHANISM OF ACTION BACTERIOSTATIC MECHANISM OF RESISTANCE  ANTIMICROBIAL SPECTRUM G...

TETRACYCLINES & GLYCYLCYCLINES Dr. VINODHINI, B.Pharm, M.Sc,Ph.d, D.Acu, PGDITM, PGDBI Department of Pharmacology SRM Dental College, Ramapuram TETRACYCLINES GLYCYLCYCLINE MECHANISM OF ACTION BACTERIOSTATIC MECHANISM OF RESISTANCE  ANTIMICROBIAL SPECTRUM Gram - positive bacteria Staphylococcus aureus Methicillin resistant Staphylococcus aureus Streptococcus pneumoniae – (Pneumococcus) Bacillus anthracis Erysipelothrix rhusiopathiae  ANTIMICROBIAL SPECTRUM Gram negative bacteria - aerobes Moraxella catarrhalis Neisseria gonorrhoeae (Gonococcus) Escherichia coli Klebsiella pneumoniae Acinetobacter Haemophilus influenzae Haemophilus ducreyi  ANTIMICROBIAL SPECTRUM Gram negative bacteria - aerobes Brucella Yersinia pestis Yersinia enterocolitica Francisella tularensis Vibrio cholerae Pasteurella multocida Klebsiella granulomatis  ANTIMICROBIAL SPECTRUM Gram negative bacteria - aerobes Streptobacillus moniliformis Legionella pneumophila Burkholderia pseudomallei Campylobacter jejuni  ANTIMICROBIAL SPECTRUM Gram positive bacteria - anaerobes Peptostreptococcus anaerobius Peptostreptococcus magnus Clostridium tetani Clostridium perfringens Clostridium septicum  ANTIMICROBIAL SPECTRUM Clostridium novyi Clostridium histolyticum Propionibacterium acnes  ANTIMICROBIAL SPECTRUM Gram negative bacteria - anaerobes Helicobacter pylori  ANTIMICROBIAL SPECTRUM SPIROCHETES Leptospira icterohaemorrhagiae Treponema pallidum Borrelia burgdorferi Borrelia recurrentis ANTIMICROBIAL SPECTRUM RICKETTSIAE Rickettsia - rickettsi, conorii, akari, typhi Coxiella burnetti ACTINOMYCETES Nocardia asteroids Actinomyces israelli ANTIMICROBIAL SPECTRUM Mycobacteria Mycobacterium leprae Mycobacterium fortuitum, abscessus, chelonae, marinum, ulcerans Chlamydiae Chlamydia trachomatis, psittaci, pneumoniae ANTIMICROBIAL SPECTRUM PARASITE - PROTOZOA Plasmodium falciparum Entamoeba histolytica Dientamoeba fragilis Balantidium coli PARASITE - FILARIAL WORM - NEMATODE Wucheriria bancrofti  ROUTE OF ADMINISTRATION Doxycycline Oral Intravenous / Infusion Topical - subgingival gel Minocycline Oral Intravenous / Infusion Topical - subgingival gel, microspheres Intra pleural Tetracycline Oral Intravenous / Infusion Topical - subgingival fibres,eye/ear -ointment,drops Intrapleural Demeclocycline Oral Oxytetracycline Oral Intravenous / Infusion Topical – eye/ear ointment, drops - skin ointment, cream Tigecycline Intravenous infusion Subgingival gel Subgingival fibres  Therapeutic uses Chronic Periodontitis Subgingival gel and microspheres are inserted into the periodontal pockets during scaling and root planning. – Doxycycline, Minocycline Doxycycline – Subantimicrobial, low dose 20mg twice daily  Subgingival fibres inserted into periodontal pockets.  Therapeutic uses 2. Bacterial infections Cholera, Brucellosis, plague Leptospirosis , Tularemia, Bartonellosis Non gonococcal urethritis, cervicitis, epididymitis Gonorrhea MRSA, Acne – SDD- 40mg twice daily  Therapeutic uses Peptic ulcer disease due to H.pylori - Tetracycline In Syphilis, tetanus, gas gangrene, actinomycosis – if patients are hypersensitive to Penicillins.  Therapeutic uses Chlamydial infections - FIRST CHOICE Lymphogranuloma venereum, nonspecific urethritis, cervicitis, epididymitis. Pelvic inflammatory disease Inclusion conjunctivitis, trachoma Pneumonia Psittacosis  Therapeutic uses Mycobacterium infections - Leprosy – Minocycline - Nontuberculous or atypical Mycobacterium marinum & fortuitum infections Doxycycline, Minocycline  Rickettsial infections - Rocky mountain spotted fever, murine typhus, Q fever, rickettsialpox, african tick bite fever. Protozoal infections Chloroquine resistant falciparum malaria. – Doxycycline, Tetracycline Balantidiasis – Tetracycline Adjunct to amoebicide in severe amoebic dysentery due to Entamoeba histolytica and in Dientamoeba fragilis infections. – Tetracycline Filarial worm infection Lymphatic filariasis – Doxycycline  NON ANTIMICROBIAL USES Sclerosing agent, given intrapleural to control pleural effusion in metastatic tumours. - Minocycline, Tetracycline Treatment of chronic hyponatremia associated with the syndrome of inappropriate antidiuretic hormone secretion (SIAD) – Demeclocycline  Prophylactic uses Brucellosis Doxycycline + Rifampin Plague Doxycycline / Tetracycline + Aminoglycoside Weil’s disease - Doxycycline, Tetracycline Chloroquine resistant falciparum malaria - Doxycycline  TIGECYCLINE THERAPEUTIC USES 1. COMPLICATED SKIN AND INTRA ABDOMINAL INFECTIONS CAUSED BY STAPHYLOCOCCUS AUREUS AND MRSA. 2. LEGIONELLA,KLEBSIELLA & ACINOBACTER INFECTIONS. 3.ANAEROBIC INFECTIONS CAUSED BY BACTERIOIDES, PEPTOSTREPTOCOCCUS,PRO PIONIC BACTERIUM & FUSOBACTERIUM SPECIES. ADVERSE DRUG REACTIONS Teeth - TERATOGENICITY CONTRAINDICATED IN PREGNANCY - TOOTH DISCOLOURATION - ENAMEL HYPOPLASIA - PIGEMENTATION TOOTH DISCOLOURATION  TOOTH DISCOLOURATION Between mid pregnancy to 4-6 months of postnatal period - deciduous anterior teeth affected by tetracyclines are discoloured yellow or brownish gray, which is pronounced at the time of eruption and become more brownish after exposure to light.Enamel hypoplasia and caries may also occur.  TOOTH DISCOLOURATION Between 2 months to 5 years of age - discolouration and pigmentation of the permanent teeth may occur. Children up to 12 years , may be susceptible to this adverse effects.  Bone May interfere with bone growth Nails Discoloration and onycholysis  CHLORAMPHENI COL AMOXICILLIN AMPICILLIN Suprainfections THIRD GENERATION CEPHALOSPORINS - Oral candidiasis - Vulvovaginitis and pruritus ani - Diarrhea - Pseudomonas,Proteus - Pseudomembranous enterocolitis due to clostridium difficile  NSAIDS AMINOGLYCOS NEPHROTOXICITY IDES AMPHOTERICI NB Renal dysfunction Systemic accumulation of tetracyclines  Increased blood urea  Increased phosphate level  Increased excretion of nitrogen  Loss of sodium and acidosis  HEPATOTOXICITY NIMESULIDE HALOTHANE ISONIAZID PYRAZINAMIDE RIFAMPIN ERYTHROMYCIN ESTOLATE INCREASE IN LIVER ENZYMES AND FATTY CHANGES IN LIVER OCCURS, ESPECIALLY IN PREGNANCY AND HEPATIC INSUFFICIENCY.  GIT NAUSEA , VOMITING, IRRITANT DIARRHEA EPIGASTRIC BURNING, OESOPHAGITIS AND PANCREATITIS OESOPHAGEAL ULCERS ODYNOPHAGIA  VESTIBULAR TOXICITY DIZZINESS, VERTIGO, ATAXIA, NAUSEA AND VOMITING MAINLY WITH MINOCYCLINE & DOXYCYCLINE PHOTOTOXICITY PATIENTS SHOULD AVOID DIRECT EXPOSURE TO SUNLIGHT OR UV LIGHT  DIABETES INSIPIDUS DEMECLOCYCLINE INHIBITS THE ACTION OF VASOPRESSIN CAUSING REVERSIBLE NEPHROGENIC DIABETES INSIPIDUS POLYURIA, POLYDIPSIA AND WEAKNESS  FANCONI SYNDROME - NEPHROTOXIC CAUSED BY OUTDATED AND DEGRADED TETRACYCLINES SYMPTOMS – POLYURIA, POLYDIPSIA, PROTEINURIA, ACIDOSIS, GLYCOSURIAAND AMINOACIDURIA  INTRACRANIAL HYPERTENSION IN INFANTS JARISCH – HERXHEIMER REACTION IN RELAPSING FEVER TREATED WITH TETRACYCLINES HYPERSENSITIVITY - UNCOMMON DRUG AND FOOD INTERACTION  THEREFORE ANTACIDS, IRON PREPARATIONS, MILK AND DAIRY PRODUCTS SHOULD NOT BE COADMINISTERED TETRACYCLINES  CHLORAMPHENICOL BACTERIOSTATIC MECHANISM OF ACTION Inhibits protein synthesis by binding with 50S ribosome. SPECTRUM - Gram positive and gram negative bacteria  Mechanism of resistance Oral, Intravenous Topical – eye solution ,ointment, ear drops  ADVERSE DRUG REACTIONS BONE MARROW DEPRESSION - DOSE RELATED - REVERSIBLE DECREASED IRON UTILISATION, RETICULOCYTOPENIA, ANAEMIA, LEUCOPENIA,THROMBOCYTOPENIA. - UNRELATED FORM - IRREVERSIBLE – SEVERE APLASTIC ANAEMIA, BLEEDING  SUPRAINFECTION GREY BABY SYNDROME  HYPERSENSITIVITY REACTIONS OTHERS - NAUSEA , VOMITING,DIARRHOEA, STOMATITIS, GLOSSITIS  THERAPEUTIC USES ENTERIC FEVER BACTERIAL MENINGITIS SEVERE ANAEROBIC INFECTIONS TYPHUS & SPOTTED FEVER  EYE & EAR INFECTIONS OTHERS - ANTHRAX , SEVERE GASTROENTERITIS, GAS GANGRENE, GRANULOMA, INGUINALE, LISTERIOSIS, PLAGUE,PSITTACOSIS, TULAREMIA PROBIOTICS  PROBIOTICS 1.LACTOBACILLUS SPECIES L.acidophilus L.sporogens L.rhamnosus L.salivarius L.plantarum L.brevis  L.fermentum L.helveticus L.delbrueki L.casei  2. BIFIDOBACTERIUM SPECIES B.longum B.bifidum B.infantis B.breve B.adolescentis 3.OTHER SPECIES Saccharomyces boulardii Streptococcus thermophilus  POSTULATED MECHANISMS ANTIMICROBIAL ACTIVITY COLONIZATION RESISTANCE  IMMUNE EFFECTS - CYTOKINE EXPRESSION - STIMULATION OF PHAGOCYTOSIS - SECRETION OF IgA ANTIMUTAGENIC EFFECTS ANTIGENOTOXIC EFFECTS  THERAPEUTIC USES 1.DIARRHEA - ANTIBIOTIC ASSOCIATED DIARRHEA - INFECTIOUS DIARRHEA - NOSCOMIAL DIARRHEA - RADIATION INDUCED DIARRHEA - Clostridium difficile DIARRHEA - HIV / AIDS DIARRHEA - ENTERAL FEEDING - ASSOCIATED DIARRHEA 2.LACTOSE INTOLERANCE 3.IRRITABLE BOWEL SYNDROME 4. INFLAMMATORY BOWEL DISEASE - ULCERATIVE COLITIS - Crohn’s disease 5.H.pylori infections 6.Pancreatitis 7.Pouchitis 8.Colon cancer