Anti-Infective Agents Cholinergics Surface Tension Reducing Agents Nicotine Replacement Therapy

1. Anti-Infective AgentsCholinergicsSurface Tension Reducing AgentsNicotine Replacement Therapy Module G

2. Topics for Discussion • Anti-infective agents • Antibacterial • Antitubercular • Antiviral • Antifungal • Antiprotozoal • Parasympathomimetics (cholinergics) • Surfactant Agents • Nicotine Replacement Therapy

3. Terminology • Antibiotic: Substance that kills microorganism growth. • Pathogen: Disease causing microorganism. • Empiric: Therapy that is started based upon on experience and precedent in the observation and treatment of disease. • Normal flora: Organisms found in various parts of the body living symbiotically. • Aerobic: Requires oxygen to survive. • Anaerobic: Does not require oxygen to survive.

4. Terminology • Gram Stain: Laboratory test used to determine if an organism is gram-positive or gram-negative. • C & S: Culture and sensitivity. Determines the organism present in the culture and the antibiotic to which it is sensitive (susceptible to). • Bacteriostatic: Inhibits replication of microorganisms and prevents growth. Does not kill bacteria. • Bacteriocidal: Kills the bacteria. • Broad spectrum vs. Narrow spectrum

5. Classes of Anti-infective Agents

6. Classes of Antibiotics

7. Antibiotics • Beta Lactams • penicillins • cephalosporins (4 generations) • Broader coverage with each generation. • Aminoglycosides • tobramycin • Vancomycin • MRSA • Protein Synthesis Inhibitors • macrolides • tetracyclines • Folate Inhibitors • metronidazole

8. tobramycin • Antibiotic used to treat pneumonias associated with cystic fibrosis (p. 286). • Pseudomonas aeruginosa • Trade Name is Tobi • Dosage: • 300 mg/5 mL unit dose vial • Give one vial BID • 28 days on, 28 days off • Very viscous solution • Administer a bronchodilator prior to giving Tobi. • Bronchospasm common side-effect.

9. Pari LC Plus Nebulizer • Tobi needs to be delivered with Pari LC Plus nebulizer • Flowrates should be set at 10 – 12 L/min

10. colistimethate • Brand Name: Colymycin, Colistin • Alterative to Tobi in drug-resistant strains of Pseudomonas. • From a group of antibiotics known as polymyxins and is similar to polymyxin B. • Supplied as a powder that needs to be reconstituted. • Has been identified to produce bronchospasm in some patients. • May require pre-treatment with a bronchodilator. • Dose: • Children less than 2 years of age: 1 MU twice daily. • Children older than 2 years of age & adults: 2 MU twice daily

11. Antibiotics and Pneumonias Page 281

12. Anti-Viral Agents • A virus is an obligate parasite. • Kill the organism, risk killing the host. • RNA Viruses • Influenza • Polio • HIV • Rabies • Encephalitis • DNA • Adenovirus Respiratory Disease • Papilloma warts • Herpes Simplex • Epstein-Barr Mononucleosis

13. Anti-Viral Agents • Anti-Prototozoal Agents • pentamidine • Used to treat Pneumocystis carinii pneumonia (PCP) – Organism may be a virus, may be a protozoa. • Anti-viral Agents • ribavirin • Used to treat Respiratory Syncytial Virus

14. ribavirin • Trade Name: Virazole • Antiviral Drug given with SPAG nebulizer • Used to treat Respiratory Syncytial Virus (RSV), influenza A and B and herpes simplex • Bronchiolitis and pneumonia. • RSV virus affects all children by age 3. • Use of ribavirin has decreased dramatically over the past 5 years.

16. Environmental Exposure • In animal studies, ribavirin has been found to be • Mutagenic • Carcinogenic • Teratogenic • Embryocidal • Pregnant women or women thinking of becoming pregnant should avoid exposure

17. ribavirin • American Academy of Pediatrics recommends ribavirin to ONLY be given for children with RSV and: • Congenital Heart Disease • Bronchopulmonary Dysplasia • Immunodeficient patients (cancers, AIDS, malnutrition) • Infants requiring mechanical ventilation • Premature infants or infants less than 6 weeks

18. RESPIRATORY SYNCYTIAL VIRUS IMMUNE GLOBULIN INTRAVENOUS – RSV-IGIV (1996) • Trade Name: RespiGam • Indications • Indicated for the prevention of serious lower respiratory tract infection with RSV in children under 24 months of age. • RSV-IGIV is a sterile liquid formulation of immunoglobulin G (IgG) containing antibody to RSV • Administration is by IV

19. RSV Virus • Supportive Care • Hydration • Oxygen • Bronchodilators • Most Commonly seen in Winter Months • November – March • Handwashing is the most effective way to interrupt the spread of RSV

20. Anti-Fungal Infections • Fungi include mushrooms, yeasts & molds. • Fungal infections occur in immunocompromised patients. • Common examples include athlete's foot, ringworm. • Histoplasmosis capsulatum, Aspergillosis, Blastomycosis, & Candida albicans (oral thrush). • Key agents • amphotericin B • nystatin • IV administration. Given experimentally by aerosol. • No approval from FDA

21. NON-AEROSOLIZED ANTI-INFECTIVE DRUGS ANTI-TUBERCULOSIS AGENTS • The standard approach to treating tuberculosis (TB) today consists of multiple first line drugs for a period of either 6 or 9 months. • First line drugs are: • Rifapentine • Isoniazid • Rifampin • Ethambutol • Pyrazinamide • Streptomycin used to be a front-line drug, but has been replaced by Rifapentine.

22. NON-AEROSOLIZED ANTI-INFECTIVE DRUGS ANTI-TUBERCULOSIS AGENTS • 9 Month approach • Isoniazid and Rifampin are given for 9 months and in an initial 2 to 8 week period these two drugs are supplemented with one of the other first line drugs. • 6 Month approach • Four drugs are used for 2 months followed by 4 months of Isoniazid and Rifampin. • There is an association of TB and HIV infection. • Along with the disturbing increase in the number of TB cases in conjunction with AIDS, there has been an emergence of drug resistant strains of TB. The cure rate is poor in this subset.

23. lidocaine • Trade Name: Xylocaine • Effect: Anesthetic • Indications • Aerosolized prior to bronchoscopy • Topically as nasal spray/jelly prior to intubations • Anesthetize area prior to chest tube insertion, (thoracentesis)

24. lidocaine • Dosage for nebulization – Use SVN • 2% solution; 20 mg/mL; 3-7 mL total volume • 4% solution; 40 mg/mL; 3-7 mL total volume • Nasal Spray • 2% solution • Jelly for lubricating ET tubes • 2%

25. Nicotine Replacement Therapy • What: • Nicotine Replacement Therapy should be used as part of a comprehensive smoking cessation program. • Why: • Smoking kills 440,000 Americans each year and debilitates ½ of all long-term smokers. • Tobacco dependence is a powerful addiction. • Tobacco relapses are high (5 attempts?). • Who: • Fagerstrom Test for Nicotine Dependence. • Figure 13-4, Page 256 • When: • Best time is when they are in the hospital.

26. Nicotine Replacement Therapy • Nicotine Transdermal System • Habitrol • Nicoderm • Nicotrol • ProStep • Nicotine Gum • Nicorette • Nicotine Nasal Spray • Nicotrol • Other (Non-NRT) • bupropion (Zyban, Wellbutrin) • Vareniciline (Chantix)

27. Nicotine Replacement Therapy • Nicotine stimulates the cholinergic receptor site • Nicotinic Receptor Sites • Autonomic and Somatic Nervous System • Involuntary and voluntary skeletal muscle systems • Nicotine directly affects brain cells • Increases alertness • Euphoria • Cognitive performance

28. Other Agents • bupropion (Zyban, Wellbutrin) • Antidepressant usually used to treat major depressive disorders and season affective disorders. • Also decreases urge to smoke; mechanism is unclear. • vareniciline (Chantix) • Mechanism of action is to partially block the a4-b2 nicotinic receptor in the brain. • Within 10 to 20 seconds of a single puff from a cigarette, nicotine attaches to this receptor. • The receptor, in turn, triggers large increases in dopamine, which rewards the smoker with a pleasurable sensation.

29. Nicotine Replacement Therapy • Precautions/Instructions • Replacement formulas DO contain nicotine. • Side effects can occur if using replacement formulas with tobacco. • Transference of nicotine dependency can occur. • Replacement formulas should be gradually withdrawn and stopped within 3 months. • HCW should avoid handling nicotine products. • varenicline and bupropion: Mood swings even after drug has been stopped; some instances of suicide ideation have been associated with Chantix. • Questionable whether Chantix had direct influence or not.

31. methacholine • Trade Name: Provocholine • Used in Pulmonary Function Lab • Methacholine Challenge Test • Bronchoprovocation Test • Used to test for hypersensitive airways • Parasympathomimetic • Induces bronchospasm

32. methacholine Challenge Test • Used for patients with normal pulmonary functions • Chronic cough • Recurrent respiratory infections • History of wheezing • Have crash cart in the room • Be prepared to administer a fast acting bronchodilator (metaproterenol)

33. Surfactant Agents • Ethyl Alcohol • Used in the treatment of pulmonary edema • Alcohol breaks the bubbles and decreases the surface tension of the exudate • Lack of approved clinical use • Efficacy is not well established • Dosage: 30 – 50% 3-5 mL of a 40% solution by aerosol or direct instillation down ET tube

34. Exogenous Surfactants • Natural Surfactants • Surfactants from natural sources with addition or removal of certain molecules • Survanta, Calfactant, Poractant Alfa • Artificial Surfactants • Surfaxin (?) • Synthetic Natural – genetic engineering; cloning gene of natural surfactant • None present

35. Beractant • Trade Name: Survanta (1991) • Mixture of bovine (cow) lung extract to which DPPC (lecithin) has been added • Watch ventilator settings after administration • O2 can increase, over-ventilation, hypocarbia • Administered down ET tube

36. New Surfactants • Calfactant (Infasurf) • Bovine Extract • Poractant Alfa (Curosurf) • Porcine Extract