Quinolones

Slides on quinolones focusing on Ciprofloxacin drug

1. Quinolones Ngaahule Phadziri 28846060 Paballo Shiri 25699881 Siyabonga Mashiane 29760097 Azwidali Nekokwane 28731220

2. Quinolones(Fluoroquinolone) Quinolones are a drug class of chemotherapeutic antibacterial agents Founding drug class was Nalidixic acid Was later Oxolinic Acid which was synthesized in 1970s to form second generation Fluoroquinolones( clinical use) Diverse group of antibiotics Active against aerobic organisms

3. Ciprofloxacin Belongs to the fluoroquinolones class Is an antibacterial prescription medicine Effective in treating bacterial infection ranging from urinary tract infection to lower respiratory tract infection

4. Preparations of Ciprofloxacin Immediate release tablets Oral suspension Ophthalmic solution (eye drops) Extended release tablets Otic solution (ear drops) Injectable use

5. Routes of administration Enteral route: Oral - Solid (Tablets) -Liquid (Suspension) *Cipro tablets should not be split, crushed, or chewed Parenteral route: Intravenous infusion ( Injected directly to the veins) -400 mg for 60 minutes -200mg for 30 minutes Ophthalmic route: Eyes Otic route: Ear

6. Indication Used to treat infections caused by bacteria such as: Respiratory tract infections -Bronchitis -Pneumonia Urinary tract infections -Bladder infection -Kidney infection Gastro intestinal infection -Bacterial diarrhoea Sexually transmitted diseases - Gonorrhea Bone and joint infections Bacterial ear and eye infections

7. Dosage General dosage for immediate-release Cipro is 250–750 mg every 12 hours for up to 14 days. Cipro dosage depends on factors such as Age Children under 17: 10–20 mg/kg every 12 hours for 7- 21 days. *<750mg every 12 hours. Drug form and strength *Tablets: 250mg, 500 mg, 750 mg *Powder for oral suspension: 250 mg and 500 mg *Extended-release tablets (Cipro XR): 500 mg and 1,000 mg Type and severity of condition *Respiratory infections: 500–750 mg every 12 hours for 7-14 days *Bone & joint: 500–750 mg every 12 hours for 4-8 weeks *Diarrhea by infection: 500 mg every 12 hours for 5- 7 days *Severe UTI: Use cipro XR 1,000 mg once daily for 7-14 days.

8. Spectrum of activity Cipro is a broad-spectrum antibiotic. This means it is effective against different types of bacteria. Fluoroquinolones have expanded activity against gram-positive cocci and gram-negative activity of intracellular organisms such as Chlamydia, Mycoplasma and mycobacteria Also effective against G aerobic bacteria

9. Pharmacodynamics of Ciprofloxacin Ciprofloxacin inhibits DNA gyrase hence stopping bacteria replication Gyrase is the primary targeted enzyme by Ciprofloxacin Steps: Mechanism of Action Fluoroquinolone bind at the ligation site of the DNA gyrase Physically block gyrase enzymes from binding with the substrate This causes substrate complex Inability for double strand DNA to unwind; therefore blocking transcription Prevention of bacterial protein synthesis

10. Pharmacokinetics of Ciprofloxacin Absorption: Has a high bioavailability in both oral and parenteral form Preferred drug due to 70% bioavailability in these forms No significant loss by first pass metabolism Distribution: Non highly binding drugs Great distribution within body fluids and tissue Even able to reach bones and placenta when orally ingested Elimination: Renal based After it is metabolised 40-50% of unchanged cipro is found in urine Traces of the drug found in bile

11. Serious complications Hallucinations Photosensitivity Musculoskeletal disorders in pediatric patients Development of drug resistant bacteria Anxiety,depression and suicide

12. Adverse reactions Increase the risk of tendinitis and tendon rupture Hypoglycemia Dysmenorrhea It may worsen muscle weakness in patients who have myasthenia gravis Nerve damage

13. Key aspects of Clinical Management Assessment This involves the collection of information on patients likely to affect drug therapy. This information is used for individual medicine regimen. Forms the basis for the basic medical background of the patient. Planning This step involves the expected outcomes of drug therapy. Long and short term goals of the therapy. Focus is on health promotion and rehabilitation and health education. Benefits or the drug therapy are outlined.

14. Key aspects of Clinical Management cont. Implementation This involves putting the health care plan into action. Interventions are implemented. Medicines are administered as prescribed. Evaluation This involves assessing the patient's status in relation to those outlined whilst planning. Governs future direction of healthcare plans according to expected outcomes and actual outcomes

15. Drug resistance and alternative Overuse or misuse of ciprofloxacin because of a widespread availability of generic versions of ciprofloxacin. After the introduction of generic ciprofloxacin in the market, an increase in consumption of ciprofloxacin was observed. In another study, it was reported that the resistance of isolated E. coli obtained from patients with UTI increased proportionally with the use of quinolones.

16. Drug resistance and alternative cont. The following alternatives should be provided in the event of drug resistance: Trimethoprim Levofloxacin Ampicillin

17. Public health considerations · There has been e merging resistance. This resistance is especially problematic for Pseudomonas aeruginosa and Staphylococcus aureus. This potential problem underscores the importance of the physician being familiar with the appropriate clinical applications of these useful antibiotics. · There are several circumstances in which resistance has limited therapeutic use. · There is concern that expanded use of quinolones for treatment of respiratory tract infections may pose a risk for development of resistance in S. pneumoniae. · The use of fluoroquinolones in food animals has led to the emergence of fluoroquinolone-resistant Campylobacter and of Salmonella with reduced susceptibility to fluoroquinolones. · Antibiotic effects on early pregnancy.

18. Conclusion Ciprofloxacin has been shown to be a safe and effective antibiotic in the treatment of a wide variety of bacterial infections. Although there are some side effect and adverse reactions it has proven to be effective in the reduction of a wide range of bacterial infections. We believe a priority for both the pharmaceutical industry and regulatory authorities should be to prevent fluoroquinolone misuse and development of antibiotic resistance.

19. Reference List Aldred, K. J., Kerns, R. J., & Osheroff, N. (2014). Mechanism of quinolone action and resistance. Biochemistry , 53 (10), 1565–1574. Healthline. (2018). Ciprofloxacin . Retrieved from https://www.healthline.com/health/cdi/cipro Naeem, A., Badshah, S. L., Muska, M., Ahmad, N., & Khan, K. (2016). The Current Case of Quinolones: Synthetic Approaches and Antibacterial Activity. Molecules (Basel, Switzerland) , 21 (4), 268. doi:10.3390/molecules21040268 National Institute of Neurological Disorders and Stroke. (2019). Myasthenia Gravis Fact Sheet. Retrieved from: www.ninds.nih.gov FDA. (2005). CIPRO. Retrieved from https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/019537s057,020780s019lbl.pdf Singh,A., Bhat, T.K., Sharma, O.P,. (2011). Clinical Biochemistry of Hepatotoxicity. Journal of Clinical Toxicology, 4 (1),1-19 Sharma, D., Patel, R.P., Zaidi, S., Sarker, M., Lean, Q., Ming, L.C. (2017). Interplay of Quality of Ciproflofaxin and Antibiotic Resistance in Developed Countries. Frontiers of Pharmacology, 8 (546), 1-10.