Respiratory Pharmacology Week 5 Anticholinergics and Mucolytics

1. Respiratory PharmacologyWeek 5Anticholinergics and Mucolytics

2. Anticholinergic Agents • Only effective if bronchoconstriction exists due to cholinergic activity • USED FOR COPD PATIENTS only • May also be used for asthmatics during an attack

3. Anticholinergic Agents • In combination with beta-agonist in patients with COPD on regular treatment regimen who require additional bronchodilation • If you give Spiriva, you DO NOT also give Atrovent. Spiriva given QD • http://www.youtube.com/watch?v=KYS3-Kp672Y

4. Anticholinergic Agents • Adverse effects • Dry mouth • Cough • EXTREMENLY RARE SYSTEMIC SIDE EFFECTS AS IT DOES NOT CROSS BLOOD BRAIN BARRIER • Nervousness • Headache, dizziness

5. Anticholinergic Agents • Adverse effects • Pharyngitis • Dyspnea

6. Atrovent • “Back door bronchodilator” that is used in conjunction with a front door bronchodilator such as Albuterol or Xopenex. • It works by opening up the air passages in your lungs by preventing cholinergic responses. • It is not to be used alone for treating an acute attack of breathing problems, as it takes some time to work and is usually given as a maintenance drug that excels the use of Albuterol or Xopenex for people with COPD. • Ipratropium is only for inhalation by mouth through an inhaler device or for inhalation by a nebulizer.

7. Atrovent • Generic Name: Iprtropium Bromide • Trade Name: Atrovent • Classification: Anticholinergic agent • How it works: It relaxes airway muscles by impacting neurotransmitters sent to the autonomic nervous system, a process different than how beta-agonist drugs act. Sometimes given in addition to shorter-acting bronchodilator therapy, if the shorter-acting meds are not doing enough. Tends to have longer-lasting effect than beta-agonist drugs. • Delivery Device: As an aerosol used in a nebulizer or as a DPI as SPIRIVA®HandiHaler® (tiotropium bromide inhalation powder) • Doses: Unit dose is 0.5 mg or 0.02%, usually mixed with Albuterol or Xopenex. • Side Effects: Fever, infection, headache, skin rash or hives, swelling of lips, tongue or face, vomiting, cough, blurred vision, dry mouth • Contraindications/Percautions- If the following exist take precaution when initiating treatment:

8. Combo Drugs • Albuterol and Atrovent • DuoNeb (Nebulizer solution) • Combivent (MDI)

9. Anticholinergic Agents

10. Mucus controlling drugs • The general term for medications that are meant to affect mucus properties and promote secretion clearance is “mucoactive.” These include expectorants, mucolytics, mucoregulatory, mucospissic, and mucokineticdrugs • Mucoactivemedications are intended either to increase the ability to expectorate sputum or to decrease mucus hypersecretion

11. Expectorants • Expectorants are defined as medications that improve the ability to expectorate purulent secretions. • Medications that increase airway water or the volume of airway secretions, including secretagoguesthat are meant to increase the hydration of luminal secretions (eg, hypertonic saline or mannitol) and abhesivesthat decrease the adhesivity of secretions and thus unstick them from the airway (eg, surfactants).

12. Mucolysis • Mucolysis is the breakdown of mucus. • Mucolysis is needed in diseases in which there is increased mucus production: • Cystic Fibrosis • COPD • Bronchiectasis • Respiratory Infections • Turberculosis

13. Mucolysis • These diseases result in a marked slowing of mucus transport • Changes in properties of the mucus • Decreased ciliary activity • Both • http://www.nebraskamed.com/health-library/3d-medical-atlas/237/mucolytics

14. Mucolytics • Acetylcysteine • sodium bicarbonate (NaHCO3) • Dornasealfa • Pulmozyme

15. Airway Anatomy

16. Mucus Layer • Gel (1 to 2 mm): Gelatinous and sticky (flypaper) • Sol (4 to 8 mm): Watery, Cilia in this layer • Total layer thickness: 5 to 10 mm thick • Surface Epithelial Cells • Pseudostratified ciliated columnar • Surface goblet cells (6,800/mm2) • Serous cells – Sol layer • Clara cells – Unknown function (enzymes?) • Submucosal Gland • Bronchial Gland

17. Mucus Layer • Bronchial Gland • Found in submucosa • Found down to terminal bronchioles • Parasympathetic control (Vagus nerve) • Provide the majority of mucus secretion • Total volume 40 times greater than goblet cells

18. Mucus vs. Sputum • Mucus is the total secretion from mucous membranes including the surface goblet cell and the bronchial glands. • Sputum is the expectorated secretions that contains mucus, as well as oropharyngeal and nasopharyngeal secretions (saliva).

19. Mucociliary Escalator • Mucosal Blanket • Sol layer • Gel layer • Cilia • 200 per cell • 6 mm in length • Beat 1000/min • Move mucus 2 cm/min • Paralyzed by cigarette smoke

20. Function of Mucociliary Escalator • Protective function • Remove trapped or inhaled particles and dead or aging cells. • Antimicrobial (enzymes in sol/gel) • Humidification • Insulation (prevents heat and moisture loss) • NOTE: No cilia or mucus in lower airways (respiratory bronchioles on down) • Mucus also protects the epithelium from toxic materials.

21. Structure and Composition of Mucus • Composition • 95% water • Need for water intake to replenish • Mucus doesn’t easily absorb water once created • 3% protein and carbohydrates • 1% lipids • Less than 0.3% DNA

22. Structure and Composition of Mucus • Glycoprotein • Large (macro)molecules • Strands of polypeptides (protein) that make up the backbone of the molecule • String of amino acids • Carbohydrate side chains • Chemical bonds “hold” mucus together • Intramolecular: Dipeptide links • Connect amino acids • Intermolecular: Disulfide and Hydrogen bonds • Connect adjacent macromolecules

24. Mucus Production • Normal person produces 100 mL of mucus per 24 hour period • Most is reabsorbed back in the bronchial mucosa • 10 mL reaches the glottis • Most of this is swallowed • Mucus production increases with lung disease

25. Increased Mucus Production • Smoking • Environmental irritants • Allergy • Infections • Genetic predisposition • Foreign bodies

26. Increased Mucus Production • ­ Viscosity of mucus • ¯ Ciliary effectiveness • ­ Mucus plugs • ­ Airway Resistance • ­ Infections • Obstructed bronchioles leads to atelectasis

27. Diseases that Increase Mucus Production • Chronic Bronchitis • Asthma • Cystic Fibrosis • Acute Bronchitis • Pneumonia • Also some drugs (anticholinergics, antimuscarinics)

28. Factors that Impair Ciliary Activity • Endotracheal tubes • Temperature extremes • High FiO2 levels • Dust, Fumes, Smoke • Dehydration • Thick Mucus • Infections

29. Facilitation of Mucus Clearance • Provide adequate hydration • Increase fluid intake orally or IV • Remove causative factors • Smoking, pollution, allergens • Optimize tracheobronchial clearance • Use Mucolytics • Reduce Inflammation

30. Dairy Intake • No evidence to support the common belief that drinking milk increases the production of mucus or phlegm and congestion in the respiratory tract • There is a loose cough associated with milk intake

31. Secretion Management • Increase the depth of the sol layer • Water • Saline • Expectorants • Alter the consistency of the gel layer • Mucolytics • Improve ciliary activity • Sympathomimetic bronchodilators • Corticosteroids

32. Bland Aerosols • “Dilutes” mucus molecule • Also known as wetting agents • Function may be more of an irritant than a wetter • Types • Sterile & Distilled Water • Humectant • Dense aerosols and asthmatics • Normal (isotonic) Saline • Hypertonic Saline • Increase mucus production • Hypotonic Saline

33. Expectorants • Iodides • Unclear function • SSKI (Saturated Solution of Potassium Iodide) • Guifenesin • At high doses, stimulates bronchial gland secretion • Robitussin • Not typically given by RTs

34. Cough Suppressants • Vagal stimulation causes a cough. • Irritation of pharynx, larynx, and bronchi lead to a reflex cough impulse. • If the cough is dry and non-productive, it may be desirable to suppress its activity. • Cough suppressants depress the cough center in medulla • Narcotic preparations (codeine) • Non-Narcotic preparations (dextromethorphan) • Nebulized Xylocain • Caution in patients with thick secretions.

35. Function of Mucolytics • Weakening of intermolecular forces binding adjacent glycoprotein chains • Disruption of Disulfide Bonds • Alteration of pH to weaken sugar side chains of glycoproteins • Destruction of protein (Proteolysis) contained in the glycoprotein core of proteolytic enzymes • Breaking down of DNA in mucus

36. Function of Mucolytics • Disruption of Disulfide Bonds • acetylcysteine breaks the bonds by substituting a sulfhydril radical –HS

37. Function of Mucolytics • Alteration of pH • Sodium Bicarbonate 2% NaHCO3 solutions are used to increase the pH of mucus by weakening carbohydrate side chains • Can be injected directly into the trachea or aerosolized (2-5 mL)

38. Function of Mucolytics • Proteolysis • Dornase alfa (Pulmozyme) • Attacks the protein component of the mucus

39. Hazard of Mucolytics • The problem with all three mucolytics is that they destroy the elasticity of mucus while reducing the viscosity. • Elasticity is crucial for mucociliary transport. • The patient must be able to cough adequately to remove the mucus.

40. acetylcysteine • Indications • Mucolytic by aerosol or direct instillation into the ET tube. • Given orally to reduce liver injury with acetaminophen (Tylenol) overdose. • Mix with cola or given by NG tube.

41. Mucomyst • Draw up with a syringe and instill into nebulizer

42. Acetylcysteine • Indicated for treatment of accumulated airway secretions • Chronic obstructive pulmonary disease • Bronchiectasis • Acute tracheobronchitis

43. Acetylcysteine • Used to treat or prevent liver damage in acetaminophen overdose (patient drinks it) • Reduces viscosity of mucus by substituting sulfhydryl group for disulfide group

44. Acetylcysteine • May be directly instilled during bronchoscopy to remove mucus plugs • Normal dosage via SVN: 3 – 5 ml

45. Acetylcysteine • Side effects • Airway obstruction secondary to rapid liquefaction of secretions • Disagreeable odor (rotten eggs) • Nausea • Rhinorrhea • Bronchospasm

46. Acetylcysteine • Discard 96 hours after opening, usually refrigerated • Should not be administered in the presence of thin secretions • ALWAYS GIVE WITH A BRONCHODILATOR

47. Dosage of acetylcysteine • Concentration • 10% or 20% • Dosage • 3-5 mL of a 20% solution TID or QID • Maximum dose 10 mL • 6-10 mL of a 10% solution TID or QID • Maximum dose 20 mL • 1-2 mL of a 10% or 20% for direct instillation

48. Hazards of acetylcysteine • Bronchospasm • Asthma – may be a problem during an acute asthma attack. • Anecdotal; lack of evidence • If used with asthma, use 10% and mix with a bronchodilator (preferably a short-acting agent). • Increase mucus production • Be prepared to suction a patient who cannot cough or who is intubated.

49. Hazards of acetylcysteine • Do not mix with antibiotics in the same nebulizer (incompatible). • Nausea & Vomiting • Disagreeable odor (smells like rotten eggs) due to the hydrogen sulfide. • Open vials should be used within 96 hours to prevent contamination.

50. sodium bicarbonate • Weak base. • Increasing the pH of mucus weakens the polysaccharide chains. • Available as 1.4%, 5%, and 7.5% solutions. • Dosage: 2-5 mL of a 2.5% solution Q4-Q8. • Mix 5% solution with equal volume of sterile water. • Can be irritating (especially the 5 & 7.5% solutions).