Antimicrobial Agents 4: Tetracyclines and Chloramphenicol PDF

Antimicrobial agents 4: Broad spectrum antibiotics – Tetracyclines and Chloramphenicol; Antifungal drugs Dr. Nazmun Nahar Alam AIMST University Specific Learning outcomes At the end of the lecture, students should be able to List the broad spectrum antibiotics. List different tetracyclines. State th...

Antimicrobial agents 4: Broad spectrum antibiotics – Tetracyclines and Chloramphenicol; Antifungal drugs Dr. Nazmun Nahar Alam AIMST University Specific Learning outcomes At the end of the lecture, students should be able to List the broad spectrum antibiotics. List different tetracyclines. State the mechanism of action, therapeutic uses, adverse effects and contraindications of demeclocycline, minocycline and doxycycline. State the mechanism of action, therapeutic uses, adverse effects and contraindications of chloramphenicol. Classify anti-fungal drugs based on their efficacy against cutaneous fungal infections and systemic fungal infections. State the mechanism of action, indications and adverse effects of anti-fungal drugs: fluconazole, ketoconazole, nystatin, griseofulvin, terbinafine, amphotericin B and flucytosine. State the treatment of candidiasis. Dr. Nazmun Nahar Alam Broad spectrum antibiotics Broad spectrum antibiotics have an antimicrobial spectrum which includes some gram-positive and some gram-negative organisms, as well as certain rickettsia, protozoa, and chlamydia. Example: Tetracycline Quinolone Chloramphenicol Carbapenem Azithromycin Dr. Nazmun Nahar Alam Tetracycline Characteristics: ❖ Broad spectrum of activity ❖ Bacteriostatic antibiotic Dr. Nazmun Nahar Alam Tetracycline Classification of Tetracycline (According to plasma half life) A) Short acting (6- 10 hours) – Chlortetracycline Oxytetracycline Tetracycline B) Intermediate acting (16-18 hours) – Demeclocycline Methacycline C) Long acting (18- 24 hours ) – Doxycycline Minocycline Dr. Nazmun Nahar Alam Tetracycline Mechanism Of action : Tetracycline reversibly binds to 30S subunit of bacterial ribosome blocking the binding of aminoacyl-tRNA to the acceptor site on the mRNA ribosome complex. This prevents addition of amino acids to the growing peptide. Dr. Nazmun Nahar Alam Tetracycline T- Tetracycline C-Chloramphenicol M-Macrolide Dr. Nazmun Nahar Alam Tetracycline Pharmacokinetics ▪ Route - Oral, IV, topical. ▪ Frequency of administration - BD. ▪ Oral absorption of demeclocycline is incomplete & impaired when given with milk or antacids due to complex formation. Minocycline & doxycycline are completely absorbed even when given with food & have long half-lifes, given OD or BD. ▪ Cross placenta, accumulate in bone, dentine & enamel of unerupted teeth of fetus. ▪ Minocycline – significant concentration in saliva, tears. ▪ Doxycycline is excreted primarily via bile. Hence, can be given to patients with kidney dysfunction. Other tetracyclines mainly undergoes urinary excretion (avoided in renal impairment patients) Dr. Nazmun Nahar Alam Tetracycline Spectrum Gram+ve and Gram-ve bacteria such as pneumococci, gonococci, some strains of beta haemolytic streptococci, H. influenzae, including certain anaerobes. Chlamydia, mycoplasma, spirochetes, rickettsia, protozoa etc. Ineffective against pseudomonas. Doxycycline, minocycline, tigecycline have wider spectrum. Dr. Nazmun Nahar Alam Tetracycline Indications: Chlamydial infections (Psittacosis, trachoma, pelvic inflammatory disease) Atypical Pneumonia (Mycoplasma pneumoniae) Dr. Nazmun Nahar Alam Tetracycline Indication : Continue… Rickettsia infections (Q fever, typhus) Plague, brucellosis Acne Cholera Combination therapy in peptic ulcer disease(H. Pylori ). Malaria (Doxycycline) Dr. Nazmun Nahar Alam Tetracycline Adverse effects: GI - abdominal pain, diarrhoea, nausea, vomiting. Should be taken with water while standing to avoid oesophageal ulcers. CNS- dizziness, increase in intracranial tension Photosensitivity Hepatotoxicity – especially in pregnant women. Superinfection Fanconi syndrome (impaired renal tubular reabsorption) following intake of outdated preparations. Nephrogenic diabetes insipidus with demeclocycline Dr. Nazmun Nahar Alam Tetracycline Adverse effects: When given to children below 8 year, tetracyclines get deposited in teeth causing yellow discoloration & increased susceptibility to caries. Also deposited in bones resulting in stunted growth. When given to pregnant women, they cross placenta, get deposited in the bones of the foetus with similar consequences as above. Dr. Nazmun Nahar Alam Tetracycline Demeclocycline Antagonises ADH in the nephron. Effective in excess, inappropriate secretion of ADH. Minocycline Long acting tetracycline given twice a day. Excellent absorption, less effect on intestinal flora. High concentration in tears & saliva, eradicates meningococcal carrier state. Vestibular toxicity (dizziness, imbalance and falls) is common Dr. Nazmun Nahar Alam Tetracycline Doxycycline Tetracycline of choice for most indications because it is generally well tolerated, can be given OD / BD. Completely absorbed in GI, hence, less effect on intestinal flora, its absorption is not significantly affected by food. No hepatotoxicity. Excreted by non-renal routes, safest for extra-renal infections in renal failure. Tigecycline Effective in infections due to tetracycline resistant gram-positive and gram-negative organisms. Dr. Nazmun Nahar Alam Tetracycline Contraindications: ▪ Pregnant & lactating mothers ▪ Children below 8yrs ▪ Impaired liver and renal function. Drug interactions: Dairy products, antacids, iron reduces absorption of tetracycline by chelation. * Widespread resistance to tetracycline limits their clinical use Dr. Nazmun Nahar Alam Chloramphenicol Characteristics: Broad spectrum of activity Bacteriostatic antibiotic Due to serious toxicity it is a reserve antibiotic, only for serious life threatening infections when benefits outweigh risks. Spectrum: Gram-positive, gram-negative, rickettsia, anaerobes etc. P. aeruginosa is resistant Dr. Nazmun Nahar Alam Chloramphenicol Mechanism of action: Binds reversibly to 50S subunit of bacterial ribosome. Inhibits transpeptidation reaction and thus inhibition of protein synthesis. Dr. Nazmun Nahar Alam Chloramphenicol Dr. Nazmun Nahar Alam Chloramphenicol Pharmacokinetics: Routes: oral, parenteral, topical routes. Absorbed well, distributed well into tissues & CSF. Dr. Nazmun Nahar Alam