Respiratory Tract infections

1. Respiratory Tract infections

2. PROF. AzzAELMedany Department of pharmacology

3. Objectives of the lecture • At the end of lecture , students should be able to understand the following: • Types of respiratory tract infections • Antibiotics commonly used to treat respiratory tract infections and their side effects. • Understand the mechanism of action, pharmacokinetics of individual drugs.

4. The respiratory tract

5. Classification of respiratory tract infections • Upper respiratory tract infections (URTI) • Lower respiratory tract infections (LRTI)

6. URTI • Rhinitis- inflammation of the nasal cavity • Sinusitis- inflammation of sinuses • Pharyngitis- inflammation of the pharynx,uvula, tonsils • Laryngitis- inflammation of the larynx • Laryngotracheitis- inflammation of the larynx & trachea • Tracheitis- inflammation of trachea • Otitis media- inflammation of middle ear

7. The path of air

8. LRTI • Bronchitis Acute Chronic Acute exacerbation of chronic bronchitis • Pneumonia Community -acquired Hospital-acquired

9. LRTI,s • Are more costly to treat and generally more serious than URTI,s

10. Causes of URTI,s • Viruses ( over 200 different types have been isolated ) • Bacteria , mainly Group A streptococcus & H. influenzae

11. Causes of LRTI,s Bacteria mainly: • Streptococcus pneumoniae • Haemophilusinfluenzae • Moraxellacatarrhalis

12. Lines for treatment of respiratory tract infections • Analgesics ( NSAIDs) • Nasal decongestant • Vitamin C • Drinking plenty of fluids • Antiviral • Antibiotics

13. Antibiotics First-line treatment ( given for 3-10 days) • For the treatment of moderate to severe infections • Broad spectrum penicillins • Trimethoprim-sulfamethoxazole • Tetracyclines ( doxycycline )

14. Antibiotics ( continue) Second-line treatment • Used in allergic patients to drugs of first –line or in antibiotic –resistant organisms • Macrolids • Cephalosporins • Fluoroquinolones

15. Penicillins

16. Mechanism of action • Inhibits bacterial cell wall synthesis Bactericidal

17. Pharmacokinetics Given orally or parnterally Not metabolized in human. Relatively lipid insoluble. Excreted mostly unchanged in urine. Half-life 30-60 min ( increased in renal failure).

19. Broad- spectrum penicillins • Amoxicillin • Ampicillin Acts on both gram –positive & gram- negative bacteria Destroy by β-lactamase enzyme produced by certain bacteria

20. β-Lactamase inhibitors Such as : • Clavulanic acid • Sulbactam • Tazobactam • Themselves have no antibacterial activity. • They inactivate β-lactamase enzyme

21. β-Lactamase inhibitors (continue) • Given in combination with β -lactamase sensitive antibiotics : • Amoxicillin/clavulanic acid (augmentin ) • Ampicillin/ sulbactam

22. Therapeutic uses • Upper respiratory tract infections • Lower respiratory tract infections

23. Cephalosprins

24. Mechanism of action • Inhibit bacterial cell wall synthesis Bactericidal

25. Classification

26. 1st Generation Cephalosporins Cephalexin • Given orally • Effective against Gram positive bacteria & to some extent to Gram-negative • Effective in upper respiratory tract infections

28. 2nd Generation Cephalosporins Cefuroximeaxetil (zinnat) • Effective mainly on Gram –negative bacteria . • Given orally

30. 3rd Generation Cephalosporins Ceftriaxone / Cefotaxime • Not susceptible to hydrolysis by β-lactamase. • Effective against gram-negative bacteria • Given by intravenous route • Effective in treatment of pneumonia caused by β-lactamase producing bacteria

31. Pharmacokinetics of cephalosporins Given parnterallyor orally Relatively lipid insoluble Excreted Mostly unchanged in the urine. Half-life 30-90 min (increased in renal failure)

32. Adverse effects of cephalosporins

34. Mechanism of action Inhibit protein synthesis by binding to the 50 S subunit of the bacterial ribosomes Bacteriostatic Bactericidal at high concentration

35. Clarithromycin • Stable to stomach acidity • Inhibits cytochrome P-450 system • Metabolized in liver to active metabolite (antibacterial activity) • Half-life 6-8 hours

36. Azithromycin Rapidly absorbed from GIT Food delays absorption Stable against gastric acidity Undergo some hepatic metabolism ( inactive ) Biliary route is the major route of elimination Only 10-15% excreted unchanged in the urine Half- life ( 3 days) Advantage over clarithromycin 1- Once daily dosing 2- No effect on cytochromeP- 450

37. Adverse effects

40. Mechanism of action Inhibit DNA synthesis by inhibiting DNA Gyrase enzyme

41. CIPROFLOXACIN Antibacterial spectrum Mainly effective against G – bacteria ** Not effective against G+ and anaerobes

42. Pharmacokinetics • Well absorbed orally ( available i.v ) • Di & tri- valent cations interfere with its absorption • Concentrates in many tissues, esp. kidney, prostate, lung & bones/ joints • Poorly crossing BBB • Excreted mainly through the kidney • Half-life average 3 hrs

43. Gatifloxacin • Is a new fluoroquinolones • Has extended gram-positive activity • Given once daily • 1st line treatment of LRTI • It is effective against community acquired pneumonia

44. Adverse effects of fluoroquinolones • Nausea , vomiting & diarrhea • CNS effects – confusion, insomnia, headache, dizziness & anxiety. • Damage growing cartilage • Phototoxicity (avoid excessive sunlight )

45. Contraindications • Adolescents ( under 18 years ) • During pregnancy • Breast feeding women

46. Clinical Uses

47. THANK YOU