4. The lecture in points 1- quinolones general information. 2-Fluoroquinolones action , side actions & interactions . 3-Fluroquinolones group members in detail . 4-Fluroquinolones in the clinical use . 5-Practical tips . 6-Rapid review . 7- Test yourself .
6. Quinolones and fluoroquinolones Quinolones include nalidixic acid the old member of quinolones and the fluroquinolones . The older drug, nalidixic acid, is a nonfluorinatedquinolone, and is not effective against systemic infections. Its use in the treatment of urinary tract infections (UTIs) is limited due to the rapid emergence of resistant strains. The fluoroquinolones in the Egyptian market are collected in the following slide .
7.
8. Other quinolones There are other types of fluroquinolones not available in Egypt include Enoxacin , pefloxacin , clinafloxacin , grepafloxacin and trovaflaxacin .
12. Mechanism of action Quinolones inhibit bacterial DNA gyrase(important for coiling DNA) and topoisomerase (required to segregate DNA to daughter cells). Rapidly cidal , with concentration-dependent killing.
13. Spectrum of fluroquinolones All of the fluoroquinolones are bactericidal. In general, they are effective against gram-negative organisms such as the enterobacteria, pseudomonas organisms, Haemophilusinfluenzae, Moraxellacatarrhalis, Legionella, Chlamydia and mycobacteria except for M- aviumintracellulare complex. They are effective in the treatment of gonorrhea but not syphilis. Though active against some gram-positive organisms, they should be avoided in the treatment of pneumoccal or enterococcal infections. Their activity against anaerobes is poor. If used prophylacticallybefore transurethral surgery, they lower the incidence of postsurgical UTIs .
14. Quinolones dosage Oral doses in adults are 200–400 mg every 12 hours for ofloxacin . 400 mg every 12 hours for norfloxacin and pefloxacin . 250–750 mg every 12 hours for ciprofloxacin. 500-750 mg once daily for levofloxacin .
15. Main side effects nausea and anorexia. allergic reactions (most common with gemifloxacin; less common with other quinolones). Arthropathy and tendonitis. May damage cartilage. Not routinely recommended in children. Gatifloxacin can cause hypo- or hyperglycemia. Moxifloxacin prolongs the QT interval. Nephrotoxicity: Crystalluria has been reported in patients receiving excessive doses (3-4 times normal). Phototoxicity: Patients are advised to avoid excessive sunlight .
16. Interactions with quinolones Antiacids & minerals :- Decrease gastrointestinal absorption of ciprofloxacin, norfloxacin, enoxacin (and probably other quinolones).{ quinolones interact with compounds containing multivalent cations (Mg ++, AI +++, Ca++ ,Fe ++ ,Zn++).} Sucralfate:- Reduced gastrointestinal absorption of ciprofloxacin, norfloxacin, and probably other quinolones warfarin, cyclosporine and caffeine :- Ciprofloxacin, ofloxacin and enoxacin increase thier serum levels . Theophylline:- Ciprofloxacin , enoxacin, and, to a lesser extent, norfloxacin inhibit theophylline metabolism; levofloxacin, lomefloxacin, ofloxacin, and sparfloxacin appear to have little effect.
17. Contraindications Fluoroquinolones should be avoided in pregnancy, in nursing mothers and in children under 18 years of age, since articular cartilage erosion (arthropathy) occurs in immature experimental animals. patients with CNS disorders, such as epilepsy, should be treated cautiously with these drugs.
19. Ciprofloxacin Ciprofloxacin has an excellent gram-negative spectrum . Ciprofloxacin is the most potent quinolone for P. aeruginosa. ciprofloxacin is one of the primary antibiotics recommended for treatment of urinary tract infections. It concentrates in the prostate and is recommended for treatment of prostatitis. For gonococcalurethritis, it is a useful alternative to ceftriaxone. Ciprofloxacin is effective against many systemic infections with the exception of serious infections caused by methicillin-resistant Staphylococcus aureus (MRSA), the enterococci and pneumococci. Ciprofloxacin has been used effectively for traveler’s diarrhea most commonly caused by enterotoxigenicE. coli and Shigella. It is the drug of choice for Salmonella typhi (typhoid fever), Ciprofloxacin is an alternative to more toxic drugs, such as the aminoglycosides . It may act synergistically with B-Iactams .
20. Norfloxacin This agent is effective against both gram-negative (including Pseudomonas aeruginosa) and gram-positive organisms in treating complicated and uncomplicated UTIs and prostatitis, but not in systemic infections.
21. Ofloxacin Like norfloxacin, ofloxacin is primarily used in the treatment of prostatitis due to E. coli and of sexually transmitted diseases (STDs) with the exception of syphilis. It may be used as alternative therapy in patients with gonorrhea. It has some benefit in the treatment of skin and lower respiratory tract infections.
22. Lomefloxacin and enoxacin Lomefloxacin and enoxacin are useful in the treatment of UTIs and bronchitis caused by Haemophilusinfluenzae or Moraxellacatarrhalis. Lomefloxacin is not effective against pseudomonalbacteremia.
23. New fluoroquinolones Compared with ciprofloxacin, new compounds show increased activity against gram-positive organisms, Gatifloxacin, clinafloxacin, trovafloxacin and moxifloxacin show increased activity against anaerobes, compared with ciprofloxacin. Serious toxicities include phototoxicity (particularly with sparfloxacin), and prolongation of the QTc interval (seen with sparfloxacin and grepafloxacin).
24. تابعوا معنا برنامج Easy pharmacology فقط مع مشروع تطوير الصيدلى العربى وانتظروا المزيد
26. Uses of fluoroquinolones Urinary Tract Infections & Prostatitis The fluoroquinolones are more efficacious than trimethoprim–sulfamethoxazole for the treatment of urinary tract infections and for the treatment of prostatitis caused by sensitive bacteria. For chlamydialurethritis/cervicitis, a 7-day course of ofloxacin or sparfloxacin is an alternative to a 7-day course with doxycycline or a single dose of azithromycin .
27. Uses of fluoroquinolones Sexually Transmitted Diseases A single oral dose of a fluoroquinolone such as ofloxacin or ciprofloxacin is effective treatment for sensitive strains of N. gonorrhoeae, but increasing resistance to fluoroquinolones has made ceftriaxone the first-line agent. Bone, Joint, and Soft Tissue Infections the fluoroquinolones in combination with an agent with antianaerobic activity are a reasonable choice for diabetic foot infections . the fluoroquinolones have been used for the treatment of chronic osteomyelitis .
28. Uses of fluoroquinolones Respiratory Tract Infections The major limitation to the use of quinolones for the treatment of community-acquired pneumonia and bronchitis was the poor activity against S. pneumoniae and anaerobic bacteria. Many of the newer fluoroquinolones, including gatifloxacin and moxifloxacin, have excellent activity against S. pneumoniaeand have shown efficacy comparable to b-lactam antibiotics. The fluoroquinolones have activity against the rest of the common respiratory pathogens .
29. Uses of fluoroquinolones Gastrointestinal and Abdominal Infections Shigellosis is treated effectively with either ciprofloxacin or azithromycin . For traveler’s diarrhea (frequently caused by enterotoxigenic E. coli), the quinolones are equal to trimethoprim–sulfamethoxazole in effectiveness .
31. Practical tips For moxifloxacinand sparfloxacin , take with each oral dose a full glass of water to prevent crystal formation in the urine . Ofloxacinto be taken on empty stomach (1 hour before or 2 hours after food ) Gatifloxacin cause dizziness so , avoid driving operation or machinery . Levofloxacin , ofloxacin , gatifloxacin , ciprofloxacin anddnorfloxacin require dosage adjustment in renal insufficiency because they are renally eliminated . But moxifloxacin don’t require .
32. Practical tips Avoid co-administration of quinolones with antiacids – multivitamins – calcium preparations (osteocare preparations)– iron preparations (anemia preparations)– and zinc preparations (antioxidant preparations ) ,if necessary ,take them after quinolones by 2 hours at lest. The dose of caffeine , cyclosporin , theophylline & warfarin should be adjusted when they are taken with quinolones .
34. Rapid review Quinolones inhibit bacterial DNA gyrase and topoisomerase . fluoroquinolones are bactericidal. In general, they are effective against gram-negative organisms and some gram-positive . But, poor active against anaerobic except the newer generations which have wider spectrum for gram-positive and anaerobes . The main side effects of quinolones are nausea ,anorexia ,Arthropathy , Nephrotoxicity and Phototoxicity .
35. Rapid review The dose of most quinolones is twice daily . But the newer generations are used once daily . Quinolones interact with Antiacids , minerals ,Sucralfate , warfarin, cyclosporine ,Theophylline and caffeine. Fluoroquinolones are contraindecated in pregnancy, nursing mothers and in children under 18 years . ciprofloxacin is recommended for treatment of urinary tract infections , traveler’s diarrhea , prostatitis, typhoid fever . Levofloxacin , moxifloxacin and gatifloxacin are called risperatory quinolones because they are active against different types of pneumonia .
36. قال تعالى (ألم يأن للذين ءامنوا أن تخشع قلوبهم لذكر الله ) القسم الاسلامى .
38. Test yourself Which is right :- 1- ciprofloxacin is the drug of choice for gonococcal urethritis . 2- lomefloxacin is the most effective agent for pseudomonal bacteremia. 3- moxifloxacin show increased activity against anaerobes, compared with ciprofloxacin . 4- norfloxacin is the better quinolones for systemic infections .
39. Test yourself The active ingredient of Tavanic is :- 1- ciprofloxacin . 2- levofloxacin . 3- gatifloxacin . 4- moxifloxacin .
40. Test yourself The dose Norfloxacin is :- 1- 200 mg once daily . 2- 400 mg twice daily . 3- 400 mg once daily . 4- 200 mg twice daily .
41. Test yourself All the following are right about ciprofloxacin except :- 1- it is used forShigellosi . 2- it can be used for gonococcal urethritis . 3- it can be used for traveler diarrhea . 4- it can be used for S. pneumoniae .
42. Resources Drugs&Drugs-2ed . Infectious Diseases A Clinical Short Course . Drug – Drug Interactions . Goodman & Gilman’s Manual of Pharmacology and Therapeutics . LippincottIllustratedReviews_Pharmacology2ed . LippincottIllustratedReviews_microbiology . Pharmacology for the Health Care Professions . Master 2008 .
43. الحمد لله الذى بنعمته تتم الصالحات مع تحيات برنامج Easy microbiology? مشرف البرنامج د. محمد نصار مدير القسم العلمى د.محمد عبد الرحمن المشرف العام د.محمد نصار
