Antimicrobials Lecture by Dr Muhammad Al-Shorbagy - GMU PDF

Antimicrobials C. Quinolones, Folic Acid Antagonists, and Urinary Tract Antiseptics Dr Muhammad Al-Shorbagy Professor of Pharmacology & Toxicology www.gmu.ac.ae COLLEGE OF PHARMACY...

Antimicrobials C. Quinolones, Folic Acid Antagonists, and Urinary Tract Antiseptics Dr Muhammad Al-Shorbagy Professor of Pharmacology & Toxicology www.gmu.ac.ae COLLEGE OF PHARMACY By the end of this session, the student will be able to: Understand the mechanism of action of different members of quinolones, folic acid antagonists & urinary antiseptics. Explain the resistance mechanisms for quinolones, folic acid antagonists & urinary antiseptics. Describe the pharmacokinetics descriptors for quinolones, folic acid antagonists & urinary antiseptics Understand common adverse effects and contraindications to quinolones, folic acid antagonists & urinary antiseptics 2 Overview Members 3 I. FLUOROQUINOLONES Mechanism of action Most bacterial species have two distinct type II topoisomerases: ü DNA gyrase: breaks double- strand DNA and introduces negative supercoils. ü Topoisomerase IV: separates daughter chromosomes once replication is completed. Fluoroquinolones bind to these enzymes and interfere with DNA ligation ➜ chromosomal breaks ➜ cell lysis. Main target for gram-negative (DNA gyrase) and gram-positive (topoisomerase IV). 4 I. FLUOROQUINOLONES Spectrum Generation Fluoroquinolone Spectrum First Nalidixic acid Moderate G-ve Second Ciprofloxacin Expanded G-ve Mild G+ve Third Levofloxacin Expanded G-ve Moderate G+ve Fourth Moxifloxacin Expanded G-ve Improved G+ve Gemifloxacin Delafloxacin Resistance mechanisms 1. Altered target binding: mutations in bacterial genes encoding DNA gyrase or topoisomerase ➜ alter target site structure and reduce binding efficiency of fluoroquinolones. 2. Decreased accumulation: i) ⤋ membrane permeability or ii) efflux pumps. 3. Fluoroquinolone degradation: can be acetylated ➜ inactive. 5 I. FLUOROQUINOLONES Pharmacokinetics Absorption: bioavailable orally, but reduced absorption occurs if co- ingested with sucrulfate, aluminum, and magnesium-containing antacids, zinc or iron supplements as well as calcium preparations. Distribution: Distribute well to tissues and body fluids, to bone, urine, and CSF. Elimination: most are excreted renally, so need dose adjustment in renal impairment. Adverse reactions Tendinitis 1 month) 20 THANK YOU 21