sulfonamides and quinolones nursing.pptx

Pharmacology,4th semester bsc nursing ,

1. Sulfonamides & Quinolones Dr .Elizabeth Paul Junior Resident Department of Pharmacology

2. History

3. Classification

4. 0000000000000000000 a Dapsone PAS Pyrimethamine Proguanil Methotrexate Trimethoprim

5. Mechanism of action Sulfonamides – Structural analogue of PABA Competitive reversible inhibition of dihydropteroate synthase Prevent bacterial synthesis of purines & pyrimidines

6. A Absorbed orally D Cross BBB,accumulates in prostatic fluid M Acetylation in liver Acetylated metabolite is inactive:A /E Less soluble in acidic urine E Renal excretion Pharmacokinetics

7. Alternate pathway affinity Mechanism of resistance

8. ADR Hypersensitivity reactions ,Steven Johnson syndrome,Hemolysis in G6PD Deficient patients

9. Kernicterus-Premature infants

10. B BM suppression I insoluble in urine K kernicterus A agranulocytosis S SJS ,rash H hemolysis in G6PD

11. t1/2 -10 hours High fraction acetylated - Crystalluria FDC with Trimethoprim Sulfamethoxazole

12. High plasma protein binding-longest acting Sulfadoxine – Pyrimethamine combination in malaria,pneumocystis pneumonia and toxoplasmosis Sulfadoxine

13. A /c uncomplicated UTI Nocardiosis Chancroid Lymphogranuloma Therapeutic uses

14. Topical use Sodium sulfacetamide ophthalmic solution / ointment -- bacterial conjunctivitis -- adjunctive in trachoma Mafenide acetate Silver sulfadiazine Local action Sulfasalazine } Infection on burn surfaces Sulfasalazine – local action in colon Inflammatory bowel disease & Rheumatoid arthritis Therapeutic uses….

15. Cotrimoxazole

16. sulfamethoxazole + trimethoprim Rational fixed dose drug combination Optimum synergy obtained Concentration ratio 20:1 Dose ratio 5:1

17. Nearly same half life 2 bacteriostatic drugs produce bactericidal action when combined Wider antibacterial spectrum MIC of each component can be reduced 3-6 times Trimethoprim enters many tissue-has larger volume of distribution Delays development of antibiotic resistance Rationale of Combination

18. Sulfonamides Trimethoprim r Mechanism of Action Sequential blockade of folate metabolism

19. Additional organisms : Pneumocystis jiroveci Salmonella typhi Serratia Klebsiella Yersinia Antibacterial Spectrum

20. UTI Uncomplicated cystitis-160/800 mg BD X 3days Complicated pyelonephritis – 14 days prostatitis Bacterial RTIs Acute otitis media GI Infections Therapeutic uses

21. Pneumocystis jiroveci : DOC High dose therapy -: one DS tablet 4 times/day For 2-3 weeks Prophylaxis :one DS tablet OD STD Chancroid Lymphogranuloma Nocardiosis Therapeutic uses

22. Quinolones

23. Quinolones Synthetic Antimicrobials Quinolone structure 1⁰ active against Gram - ve bacteria Newer compounds → inhibits Gram + ve bacteria

24. History NALIDIXIC ACID Byproduct of chloroquine synthesis

25. Nalidixic Acid Bactericidal SPECTRUM: Gram negative → Coliforms ( except Pseudomonas) Inhibits bacterial DNA gyrase A=ORAL D=High PPB M =liver E= kidneys Dose: 0.5 – 1gm TDS/QID Low potency Modest blood and tissue levels Restricted spectrum ↑bacterial resistance

26. Adverse effects Contraindications Uses G.I Upset Rashes Neurological toxicity Phototoxicity Infants G6PD deficiency UTI Diarrhoea

27. Fluoroquinolones Fluorination at 6 th position Piperazine substitution at 7 th position 1 st Generation 2 nd Generation 1980s 1990s Extended antimicrobial activity Metabolic stability High potency Expanded spectrum Slow development of resistance Better tissue penetration Good tolerability

28. Classification Second Generation : LEVOFLOXACIN MOXIFLOXACIN GEMIFLOXACIN PRULIFLOXACIN LOMEFLOXACIN SPARFLOXACIN First Generation : NORFLOXACIN CIPROFLOXACIN OFLOXACIN PEFLOXACIN

29. Structure

30. Mechanism of Action

31. Gram Positive Bacteria Topoisomerase IV enzyme Nicks & seperates Daughter DNA strands Mechanism of Action

32. Mechanism of Resistance

33. Antibacterial spectrum Gram negative bacteria E.Coli , Klebsiella,Proteus,Salmonella , Shigella , Enterobacteria,Camphylobacter jejuni,Neisseria . Gram positive bacteria Staphylococcus,Streptococcus . Intracellular bacteria are also inhibited Chlamydia,Mycoplasma,Mycobacterium ( M.tuberculosis ) Ciprofloxacin is more active against Pseudomonas aeruginosa Anaerobes Ofloxacin Gatifloxacin Gemifloxacin Moxifloxacin

34. Pharmacokinetics Well absorbed orally ↑ Oral Bioavailability Widely distributed - Pefloxacin ↑ CSF levels Predominantly excreted by kidney Food interferes with Absorption of Ciprofloxacin 100% BA for Pefloxacin & Levofloxacin Pefloxacin , Sparfloxacin , Moxifloxacin Dose ↓hepatic failure

35. Pharmacokinetics Duration Of Action: max - Sparfloxacin 20 hrs Plasma half life: Ist generation – 3 to 8 hrs Gatifloxacin / Gemifloxacin – 8 to 10 hrs Moxifloxacin – 10 to 12 hrs Levofloxacin, Lomefloxacin , Ofloxacin → excreted unchanged in Urine Dose ↓ renal failure

36. Therapeutic Uses Urinary tract infections Norfloxacin 400 MG BD Ciprofloxacin 500 mg BD MOXIFLOXACIN → Not approved Prostatitis Norfloxacin Ciprofloxacin Ofloxacin Levofloxacin 3 days → Uncomplicated cystitis 5-7 days → Uncomplicated pyelonephritis 4-6 weeks

37. Therapeutic Uses Sexually T ransmitted Diseases Chlamydial urethritis Chlamydial cervicitis Gonorrhoea Ciprofloxacin ( no longer used d/t resistance ) Chancroid 3 day course of Ciprofloxacin 500 mg BD 7 day courseof Ofloxacin / Levofloxacin

38. Therapeutic Uses GI & Abdominal infections Ciprofloxacin Norfloxacin Ofloxacin Levofloxacin Ciprofloxacin Enteric fever ( S.typhi ) Ofloxacin HIV Pt’s Traveller’s Diarrhoea (1-3 days) Ciprofloxacin ●Prophylaxis for Traveller’s Diarrhoea ●Reduces stool volume Ofloxacin / Ciprofloxacin/ Levofloxacin with Metronidazole → Intra abdominal infections Ciprofloxacin 750mg BD for 10 days Ofloxacin 400mg BD Levofloxacin 500mg OD/BD

39. Therapeutic Uses Respiratory Tract Infections Levofloxacin Moxifloxacin Gemifloxacin Oral Cipro / Oflox Cystic Fibrosis Bone, Joint, Soft tissue Infections Chronic osteomyelitis Diabetic Foot Community Acquired Pneumonia & URI Respiratory quinolones

40. Therapeutic Uses Prophylaxis & treatment of Anthrax and Tularemia Mycobacterial infections MDR TB – Levofloxacin, Moxifloxacin Leprosy – Ofloxacin Atypical MB – Sparfloxacin Conjunctivitis , gm (-) ve meningitis & septicaemia Pts with granulocytosis & neutropenia

41. Adverse Effects GI Adverse effects Nausea, Vomiting (3%-17%), C.difficle colitis CNS Adverse effects Headache, Dizziness (1%-11%) Hallucinations, Seizures, Delirium ( rare)

42. Adverse Effects Musculoskeletal Effects Achilles Tendon Rupture Metabolic Effects Hypoglycemia

43. Adverse Effects QT Prolongation Torsades de pointes CVS Adverse Effects Skin Adverse Effects Photosensitivity

44. Black Box Warning Tendinitis Tendon rupture Peripheral neuropathy CNS effects Exacerbation of myasthenia gravis

45. Contraindications Pregnancy Children

46. Drug Interactions Divalent & Trivalent Cations , Antacids, Sucralfate Theophylline, Warfarin, Caffeine NSAIDS Reduces systemic Bioavailability of FQs Ciprofloxacin inhibits metabolism → Toxicity Displaces GABA from its receptors → Neurologic side effects Cautiously used in Pts on Class III & Class IA antiarrythmics → QT Prolongation

47. Ciprofloxacin Most potent first generation agent Active against gram - ve bacteria & enterobacteria Gram + ve bacteria inhibited at higher doses Bioavailability → 70% Potent Enzyme inhibitor Oral Dose: 250-750mg I.V Dose: 200-400mg BD Theophylline Warfarin Sulfonylureas