Antimicrobialagents.pdf
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This document discusses quinolones, a class of synthetic antimicrobial compounds. It begins by introducing nalidixic acid, the first quinolone, and describes its mechanism of action by inhibiting bacterial DNA gyrase. The document then discusses the development of more potent fluoroquinolones in the 1980s, which have additional fluorine substitutions. Various generations of fluoroquinolones are classified based on their chemical structure. The mechanism of action, pharmacokinetics, adverse effects, interactions and therapeutic uses of fluoroquinolones are summarized.
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Antimicrobialagents.pdf
- 1. Presented By- Md Shariq Ansari B.Pharm, Final year Roll No- 1455250020
- 2. ANTIMICROBIAL: These are the agents that kills the microorganisms or inhibits their growth. Antimicrobial can be grouped according to the (i) Microorganisms- i.e. Antibiotics against Bacteria, Antifungal against Fungi. (ii) Function- Microbicidal, Microbiostatics. ANTIBIOTICS: These are the substance produced by microorganisms, which selectively suppress the growth or kill the microorganisms at very low concentration. SOURCE OF ANTIBIOTICS: FUNGI BACTERIA ACTINOMYCETES Penicillin's (penicillium notatum) Polymyxin B Aminoglycosides Cephalosporin's (cephalosporium) Tyrothricin Chloramphenicol Griseofulvin (penicillium gresiofuloum) Bacitracin Erythromycin Cholistin Tetracycline
- 3. QUINOLONES INTRODUCTION: Synthetic antimicrobial compounds having quinolone structure (active moiety). Bactericidal, broad spectrum antibiotics. Primarily active against gram-negative bacteria. Most widely used because of their relative safety, their availability in both orally and parenterally and their favorable pharmacokinetics. HISTORY: The first member Nalidixic Acid was introduced in mid-1960s has usefulness limited to UTI and G.I.Tract infections because of low potency and high frequency of bacterial resistance.
- 4. In 1980s by fluorination of the quinolone structure at position no 6 & piperazine substitution at position 7 resulted in derivatives called fluoroquinolones. CHEMISTRY:
- 5. NALIDIXIC ACID (1) It is active against gram negative bacteria especially coliforms:- E.coli Proteus Kleibseilla Enterobacter Shigella Psuedomonas ( Except) (2) It acts by inhibiting bacterial DNA gyrase PHARMACOKINETICS: - Orally absorbed, high plasma protein binding and partly metabolized in liver. - t½ is about 8 hrs. - Therapeutic concentrations attained in urine & gut lumen are lethal to common urinary pathogens & diarrhoea causing coliforms. Bactericidal antibiotic
- 6. ADVERSE EFFECTS: - G.I. disturbance and rashes mostly occurs. - Headache, vertigo, visual disturbance are the most common adverse effects. CONTRAINDICATIONS: - It is contraindicated in infants. USES: - It is primarily used as an Urinary antiseptic. - Nitrofurantoin should not be given concurrently – Antagonism occurs. - In the treatment of Diarrhoea caused by coliforms. Norfloxacin /ciprofloxacin preferred.
- 7. FLUOROQUINOLONES INTRODUCTION: These are quinolone antimicrobials having one or more fluorine substitutions. Fluorination of quinolone structure at position 6 & piperazine substitution at position 7 resulted in derivatives called fluoroquinolones. High potency. Broad spectrum antimicrobial activity. Slow development of resistance. Better tissue penetration . Good tolerability. Used for wide variety of infectious diseases
- 8. HISTORY: - The first generation fluoroquinolones was introduced in 1980s, have one fluoro substitution. - In 1990s, compounds with additional fluoro group and other substitution have been developed- further exceeding antimicrobial activity to gram-positive cocci and anaerobes. CLASSIFICATION: First generation Second generation Levofloxacin Lomefloxacin Moxifloxacin Sparfloxacin Gemifloxacin Prulifloxacin Norfloxacin Ciprofloxacin Ofloxacin Pefloxacin
- 9. MECHANISM OFACTION Quinolones target bacterial DNA gyrase & topoisomerase IV. Gram negative bacteria - DNA Gyrase Gram positive bacteria - Topoisomerase IV Double helical DNA Two strands must separate to permit DNA replication / transcription “over winding” / excessive positive supercoiling of DNA in front of point of separation. Inhibit protein synthesis. DNA Gyrase - introduces negative supercoils into DNA (checks mechanical hindrance). DNA Gyrase has (A & B subunit). A subunit - strand cutting function of DNA gyrase. A subunit reseals the strand.
- 10. Quinolones - Bind to A - subunit with high affinity & interfere with strand cutting & resealing function. - Prevent replication of bacterial DNA during bacterial growth & reproduction. - finally bacterial cell death occurs .
- 14. PHARMACOKINETICS Rapid oral absorption. High tissue penetrability. CSF & aqueous levels are low Excreted in urine. Urinary & biliary concentrations are 10-50 fold higher than in plasma. Excreted in urine. Metabolized by liver should not be used in hepatic failure, except Pefloxacin & moxifloxacin.
- 15. Adverse effects Hypersenstivity; rashes including photosensitivity. Tendonitis & tendon rupture. Generally safe Nausea, vomiting, abdominal discomfort, bad taste CNS: headache, dizziness, rarely hallucinations, delirium. & seizures have occurred predominantly in patients receiving theophylline or NSAIDs. .QTc prolongation. Sparfloxacin. Gatifloxacin. Moxifloxacin. Cautious use in patients who are taking drugs that are known to prolong the QT interval . tricyclic antidepressants . Phenothiazine. class I anti-arrhythmics
- 16. INTERACTION - NSAIDs may enhance CNS toxicity of FQ’s Seizures reported. Antacids, Sucralfate, Iron salts reduce absorption of FQ,s THERAPEUTIC USE 1. Urinary tract infection 2. Gonorrhea 3. Typhoid 4. Bone, soft tissues and wound infections. 5. Respiratory infections 6. Tuberculosis
- 17. Ceftriaxone Most reliable Fastest acting bactericidal drug for enteric fever. i.v 4g daily 2 days. 2g daily till 2 days after fever subsides. Bone, joint, soft tissue & wound infections. Skin & soft tissue infections. joint infections