Respiratory system lecture for MBBS, Nursing.pptx

Respiratory system for MBBS and Nursing

1. Respiratory System Dr. Mohammed Munaf

2. Drugs Used In Cough Bronchial Asthma COPD

3. COUGH Protective reflex Expulsion of a. Respiratory secretions b. Foreign particles 1. Productive Cough 2. Nonproductive Cough

4. 1. Productive Cough Excessive sputum. 1. Chronic bronchitis. 2. Bronchiectasis. Expectorants

5. 1. Productive Cough Productive cough should not be suppressed (i) Accumulation of mucus in LRT can interfere with gaseous exchange (ii) Productive cough removes the unwanted material thus helping the body to remove the respiratory infection.

6. 2. Nonproductive Cough Serves no useful purpose. Increases discomfort to the patient. Antitussive ( tussis in latin means cough)

7. DRUGS FOR COUGH

8. 1. Pharyngeal demulcents They act by increasing the flow of saliva, the best natural demulcent. Soothes the throat & reduces afferent impulses from the inflammed or irritated pharyngeal mucosa. Lozenges, cough drops, linctuses containing syrup, glycerine, liquorice.

9. 2. Expectorants ( Mucokinetics ): Secretion Enhancers: Expectorare in latin means to drive from the chest. Increase the production of demulcent- respiratory tract fluid that covers & protects the irritated mucosa.

10. 2. Expectorants ( Mucokinetics ): Secretion Enhancers: a. Direct - Guaiphenesin b. Reflex - Ammonium chloride Ipecacuanha c. Direct/ Reflex - Potassium iodide

11. 2. Expectorants ( Mucokinetics ): Secretion Enhancers: a. Directly acting agents: Guaiphenesin Increase the volume of bronchial secretions in the respiratory tract. Facilitates removal of secretion by Ciliary action & coughing.

12. 2. Expectorants ( Mucokinetics ): Secretion Enhancers: b. Reflex agents: Ammonium chloride, Ipecacuanha Gastric irritants which reflexly enhance bronchial secretion. Gastric irritation results in nausea.

13. 2. Expectorants ( Mucokinetics ): Secretion Enhancers: c. Direct/ Reflex - Potassium iodide Acts both directly & reflexly . Increases the respiratory secretion. Prolonged use can affect thyroid function.

14. 2. Expectorants ( Mucokinetics ): Mucolytics Bromhexine Ambroxol Acetylcysteine Carbocysteine ( carbocisteine )

15. 2. Expectorants ( Mucokinetics ): Mucolytics Depolymerise the mucopolysaccharides & break the network of fibres in tenacious sputum. Alters the structure of mucus to decrease its viscosity. Facilitates removal of mucus by ciliary action or expectoration.

16. Bromhexine Derivative of the alkaloid vasicine obtained from Adhatoda vasaca . Potent mucolytic & mucokinetic . Converted to ambroxol , active metabolite. Depolymerises the mucopolysaccharides in the mucus directly as well as by liberating lysosomal enzymes.

17. Bromhexine Adverse effects: a. Rhinorrhoea b. Gastric irritation Productive cough. Highly bitter Tablet may be preferred over syrup. Dose: 8 mg tds Available: tablet, elixer

18. Ambroxol Active metabolite of bromhexine . Similar to bromhexine . Productive cough Given orally or by inhalation Dose: 15-30 mg tds

19. Acetylcysteine Opens disulphide bonds in mucoproteins of the sputum reducing its viscosity. Given by aerosol. SE are common and hence not preferred. DOC in paracetamol poisoning.

20. Pancreatic dornase Deoxyribonucleoprotein is a major component of the purulent respiratory tract secretions. It is a deoxyribonuclease obtained from beef pancrease .. Breaks the deoxyribonucleic acid(DNA) into smaller parts thus making the secretion thin & less vicid . Administered by inhalation

21. Steam inhalation Humidifies the sputum associated with respiratory mucosa. Reduces irritation & helps in easier expectoration of sputum.

22. ANTITUSSIVE (Cough Centre Suppressants) 1. Centrally acting agents. Act by inhibiting cough centre in the medulla.   Codeine, Pholcodeine Noscapine Dextromethorphan 2. Peripheral: Benzonatate

23. Adjuvant antitussives 3. Antihistamines: Chlorpheniramine Diphenhydramine 4. Bronchodilators: Salbutamol Terbutaline

24. Cough suppressants a. Centrally acting agents. Act by inhibiting cough centre in the medulla. b. Peripherally acting agents. Decrease the sensitivity of the receptors in the respiratory tract.

25. Codeine Opium alkaloid More selective for cough centre. Acts on u opiod receptor & suppresses cough in subanalgesic doses. Suppresses cough for about 6 hours.

26. Codeine Abuse liability low. Avoided in pts with bronchial asthma since it is a respiratory depressant. Constipation & drowsiness commonest AE. Dry irritant cough dose:10mg BD or TDS Available as tablet & linctus

27. Noscapine Opium alkaloid It depresses cough Devoid of analgesic, drowsiness & addiction liability. Headache, nausea Release histamine & can produce bronchoconstriction in asthmatics. Dry unproductive cough (tablet & syrup)

28. Dextromethorphan Synthetic opioid compound d isomer has selective antitussive action. l isomer is analgesic. Acts centrally to elevate the threshold of coughing. Does not depress mucociliary function . Devoid of constipating & addicting actions. Dry cough.

29. Benzonatate Local anaesthetic Acts peripherally by anaesthetizing the stretch receptors in the respiratory passages, lungs & pleura.

30. Antihistaminics Added to antitussive formulations. 1. Sedative effects. 2. Decrease nasal secretion. Treat cough caused by postnasal drip associated with allergic rhinitis.

31. Bronchodilators Bronchial hyper-reactivity 1. Cough 2. Bronchoconstriction Improve the effectiveness of cough in clearing secretions by causing bronchodilatation.

32. Sympathomimetic decongestants Pseudoephedrine Phenylephrine Phenylpropanolamine (PPA) Use of cough mixture containing PPA has been Banned as it can cause haemorrhagic shock.

33. Drugs which induce cough ACEI Beta blockers Inhaled corticosteroid

34. Specific treatment approaches to Cough URTI/ LRTI - Appropriate antibiotics Pulmonary TB - Anti TB drugs Pulmonary eosinophilia - DEC ACEI - Substitute ACEI by Losartan Post viral cough - no specific treatment Asthmatic cough

35. Conclusion 1. Cough serves the useful purpose of clearing the respiratory tract. 2. Cough should not be suppressed in patients with productive cough. 3. Use of antitussives in sedated or debilitated patients may prove dangerous. 4. Cough suppressants should be kept out of reach of small children, as poisoning with them has been reported.

36. Bronchial Asthma Asthma means to “stay awake in order to breathe” or “difficulty in breathing”. Asthma is a chronic inflammatory disease in which the patient suffers from reversible episode of airway obstruction due to bronchial hyper-responsiveness.

37. Etiology of Bronchial Asthma a. Genetic b. Environmental

38. Bronchial Asthma a. Increased resistance to airflow. b. Contraction of airway smooth muscle. c. Excessive secretion. d. Inflammatory cell infiltration.

39. Types of asthma 1. Extrinsic type: associated with exposure to a. specific allergen ( pollen or house dust mite). b. nonspecific stimulus s/as chemical irritant or exercise. 2. Intrinsic type: With wheezing, breathlessness in absence of allergen.

40. Bronchial asthma 1. Acute attack 2. Chronic asthma

41. Chronic asthma Step 1: Mild intermittent asthma Infrequent symptoms Day time symptoms < 2days/week Nocturnal awakenings < 2 nights/month

42. Step 2:Mild persistent asthma Day time symptoms > 2days/week Nocturnal awakenings > 2 nights/month

43. Step 3 Moderate persistent asthma Symptoms do not abate. Daily > 1 night a week.

44. Step 4 Severe persistent asthma Continual during day frequent at night.

45. Acute severe asthma (Status asthmaticus ) Acute attack of severe asthma. Attack of BA is prolonged with severe intractable wheezing. URTI is the most common precipitant. Life threatening. Patient has to be hospitalised.

46. Classification of drugs

47. Bronchodilators Selective β 2 agonists Mainstay of treatment MOA 1. Stimulates β 2 receptor on the bronchi bronchodilatation 2. Stimulates β 2 receptor on the mast cell which inhibits release of bronchoconstricting chemical mediators from mast cells. 3. Inhibits microvascular leakage. 4. Increases mucociliary activity.

48. Salbutamol ( Albuterol ) & Terbutaline Rapid acting short lasting drug. Inhaled drug produces bronchodilatation within 5 mins & action lasts for 4-6 hrs. Highly selective β 2 agonist. Cardiac SE are less prominent. Selectivity is increased by inhaling.

49. Dosage forms of salbutamol Metered dose inhaler Dry powder inhaler Nebulizer Injection Oral tablets Oral syrups

50. Inhaled β 2 agonists 1. Effective 2. Easy to use 3. Rapid in onset 4. Dose required is less. 5. Without Systemic SE

51. Nebulized β 2 agonists Higher dose as compared to MDI. Reserved for patients unable to coordinate inhalation from MDI. Device is expensive & because of its size not easily portable.

52. Salbutamol Oral administration undergoes high first pass metabolism. DOA is longer 4-6 hours Frequent SE

53. Indication 1. Acute attack of asthma or COPD. 2. Step 1: Mild intermittent asthma S/N be used on regular schedule. Down regulation of β 2 receptors. Safe during pregnancy. 2. Premature labour.

54. DOSE 1. Salbutamol MDI 100 mcg/puff 1-2 puffs every 4-6 hrly . Oral 2-4 mg oral Nebulisation 2.5 mg 0.25 -0.5 mg im / sc 2. Terbutaline 250 mcg /puff 1-2 puffs 4-6 hourly. Oral 5mg

55. Salmeterol Long acting selective β 2 agonist. Duration of action 12 hours. More lipophilic easily dissolves in the smooth muscle membrane & attains high concentration in this cells. Slow onset of action. Dose: 25 mcg /puff, 2 puffs BD.

56. Formoterol Long acting selective β 2 agonist. Duration of action12 hours. Faster onset of action. Dose 12 mcg BD by inhalation.

57. Bambuterol Inactive prodrug of terbutaline. Action prolonged for 24 hrs.

58. Indication Moderate to severe persistent bronchial asthma in combination with ICS. Nocturnal asthma. Exercise induced asthma.

59. Adverse Effects 1. Tremors direct stimulation of β 2 receptors in skeletal muscle. 2. Tachycardia stimulation of β 1 receptor in heart. 3. Hypokalemia β 2 receptor stimulation of K+ entry into the skeletal muscle.

60. Glucocorticoids Long term controller medications in asthmatics. Not bronchodilators. 1. Decreases bronchial hyperreactivity. 2. Decreases influx of inflammatory cells into the lung. 3. Decrease release of mediators from macrophages & eosinophils. 4. Decreases microvascular leakage.

61. Corticosteroid 1. Improves Severity of symptoms. 2. Decreases frequency of exacerbations. 3. Improves quality of life.

62. Systemic Corticosteroid 1. Acute severe asthma Intravenous: hydrocortisone hemisuccinate Rapid onset of action. 2. Severe Persistent asthma. Start with prednisolone 20-60 mg daily. Attempt dose reduction. Shift to inhaled steroid.

63. Systemic Corticosteroid Oral steroids are given as a single dose in the morning because this coincides with the normal diurnal increase in plasma cortisol & produces less adrenal suppression than if given in divided doses or at night.

64. Systemic Corticosteroid Calcium supplements & vitamin D to prevent bone mineral loss. Rapid discontinuation after long term use may ppt adrenal insufficiency.

65. Inhaled steroid Beclomethasone dipropionate Budesonide Fluticasone Flunisolide Ciclesonide Mometasone

66. Inhaled steroids 1. Glucocorticoids with high topical & low systemic activity. 2. Not curative Effective only so long as they are taken.

67. Inhaled steroids 1. First line agents for all patients with persistent asthma. 2. Maximum responses may not be seen for months. 3. Spacer + mouth washing after MDI use decreases local SE.

68. Inhaled steroids Recommended for pts with persistent /s. Control inflammation. Facilitate long term prevention of symptoms. Reduce the need for oral glucocorticoids. Minimize acute occurrence. Prevent hospitalizations.

69. DOSES Beclomethasone 50 mcg,100 mcg, 200 mcg /puff Fluticasone 100 – 250 mcg BD

70. Inhaled steroids Adverse Effects 1. DYSPHONIA atrophy of vocal cords following laryngeal deposition of steroids. 2. Oral candidiasis 3. Cough

71. Corticosteroid + β 2 agonist 1. Corticosteroid potentiate the effect of β 2 agonists & prevent & reverse β 2 desensitization in airways. 2. β 2 agonist enhances the action of GR, resulting in increased nuclear translocation & enhances binding of GR to DNA.

72. Corticosteroid + β 2 agonist Fluticasone + Salmeterol Budesonide + Formoterol

73. Methyl Xanthines 1. CAFFEINE 2. THEOPHYLLINE 3. THEOBROMINE

74. Methyl Xanthines Medium potency bronchodilators. a. Inhibition of PDE accumulation of cAMP bronchodilatation b. Blockade of adenosine receptors. Adenosine causes bronchoconstriction & histamine release

75. Pharmacological Actions 1. Bronchodilatation . 2. Cardiac stimulation. 3. Vasodilatation. 4. CNS stimulation 5. Gastric acid secretion 6. Diuresis

76. Theophylline Well absorbed orally. Well distributed crosses placenta & secreted in milk. Kinetics changes from first to zero order. Plasma concentrations can increase disproportionately with dose. Eliminated in urine.

77. Theophylline Sustained release preparations are available. Produce therapeutic levels for 12 hrs. Advantages of SR theophylline Less frequent drug administration. Less fluctuation in blood levels. Effective for nocturnal bronchospasm.

78. Adverse Effects Theophylline has a narrow Therapeutic index. 1. GIT : dyspepsia. 2. CNS: insomnia, headache & restlessness. 3. CVS: high doses cardiac arrhythmias.

79. Drug interactions a. Induce theophylline metabolism. Phenytoin Rifampicin Phenobarbitone b. Inhibit theophylline metabolism Erythromycin Cimetidine Ciprofloxacin

80. Indication 1. Bronchial asthma & COPD a. Bronchodilatation b. Decreases release of inflammatory mediator c. Improves mucociliary clearance. d. Stimulates respiratory centre. 2. Apnoea in premature infant.

81. Theophylline 1. Adjunct to ICS in persistent asthma. 2. Inexpensive 3. Orally. 4. TDM

82. Aminophylline Complex of theophylline + ethylenediamine . Readily liberates theophylline in body. Acute severe attack of asthma not responding to β 2 agonists. Dose: 250-500 mg over 20 mins IV slowly.

83. Aminophylline Rapid IV injection may cause collapse & death Due to hypotension & arrhythmias. Watch out for Convulsions.

84. Etophylline Derivative of theophylline. Used along with theophylline for chronic persistent asthma.

85. Doxophylline Long acting oral methyl xanthine. Does not interfere with sleep. d/n increase gastric secretion. Dose 400 mg OD

86. Anticholinergics Ipratropium Tiotropium Oxitropium

87. Anticholinergics 1. Modest potent bronchodilators. 2. Block the action of acetylcholine on M3 receptor in bronchial smooth muscle. 3. Unlike atropine does not depress mucociliary clearance. 4. Decreases mucus secretion. 5. Less drying effect on mucus So does not form mucus plug.

88. Anticholinergics Act on the larger airways which receive vagal innervation. Quaternery compound. Poorly absorbed from bronchial mucosa into systemic circulation. D/N exhibit unwanted anticholinergic SE. D/N cross BBB no CNS SE.

89. Anticholinergics Gradual onset & late peak: 60-90 mins . Adjunct to β 2 agonists in acute severe asthma Benefit to pts with coexistent heart disease, in whom the use of xanthines & β 2 agonists may be dangerous.

90. Anticholinergics More effective in COPD than asthma. Parasympathetic tone is the major reversible factor in COPD.

91. Adverse Effects 1. Dryness of mouth. 2. Bitter taste. 3. Scratching in trachea.

92. Anticholinergics 1. Ipratropium short acting 20 μ g & 40 μ g/puff metered dose inhaler. 2 puffs 3-4 times daily. 2. Tiotropium long acting anticholinergic drug Once daily as DPI Combination of inhaled Ipratropium with β 2 agonist produces more marked & longer lasting bronchodilatation

93. Leukotriene Antagonist Leukotrienes are: LTC4 & LTD4 a. Powerful mediators of inflammation. b. Stimulate bronchoconstriction. c. Stimulate mucus secretion. d. Decrease mucociliary clearance.

94. Leukotriene Antagonist 1.Selectively & competitively block cys LT1 rs . ZAFIRLUKAST MONTELUKAST PRANLUKAST 2.Specific inhibitor of 5 LOX Inhibits Synthesis of LT. ZILEUTON

95. Leukotriene Antagonist MOA Block cysteinyl LT1 Rs . Bronchodilatation . Reduces sputum eosinophil count. Suppresses bronchial inflammation & hyperreactivity .

96. Zafirlukast Montelukast 1. Food decreases BA. 2. t 10hrs. 3. Dose 20 mg BD 1 hr before or 2 hrs after meals.   1. Food D/N affect BA. 2. t1/2 3-6 hrs but has Longer DOA 3. Dose 10 mg OD

97. Adverse Effects Headache. Rashes. Churg-strauss syndrome vasculitis with eosinophilia.

98. Indication Adjunct to ICS in patients with persistent asthma. Aspirin induced asthma.

99. Zileuton Specific inhibitor of 5 LOX enzyme. Inhibits formation of LTs. Limitations 1. Short DOA. 2. Hepatotoxicity

100. Mast cell stabilizers 1. Sodium cromoglycate ( cromolyn sodium) 2. ketotifen 3. Nedocromil sodium

101. Mast cell stabilizers Do not cause bronchodilatation . a. Prevent the release of chemical mediators by decreasing degranulation of mast cells. b. Chemotaxis of inflammatory cells is inhibited c. Reduces bronchial hyperreactivity .

102. Sodium cromoglycate ( cromolyn sodium) Not absorbed orally. Administered as an aerosol through MDI or nebulizer. 1 mg / dose 2 puffs 4 times a day. Takes 2-4 weeks for the beneficial effect to develop.

103. Adverse Effects Bronchospasm. Throat irritation. Cough.

104. Indication 1. Adjunct in the prophylaxis of allergic disorder. a. Rhinitis b. Conjunctivitis c. Bronchial asthma. 2. Prevention of exercise induced bronchospasm.

105. Nedocromil sodium Poorly absorbed from GIT. Maintenance therapy in patient with mild to moderate chronic bronchial asthma. Allergic conjunctivitis & allergic rhinitis.

106. Ketotifen H1 receptor antagonist & mast cell stabilizer. Drowsiness, dry mouth. 1. Chronic prophylaxis of asthma 2. Atopic dermatitis 3. Conjunctivitis 4. Urticaria .

107. Stepwise approach for chronic asthma Step 1 Mild intermittent asthma Infrequent symptoms <= 2 days a week, <=2 nights a month. Inhaled SA β 2 agonist on an as needed basis.

108. Step 2 Mild persistent asthma Nocturnal awakenings. Day time symptoms >2days a week > 2 nights / month Low dose inhaled steroids, mast cell stabilizers &/ leukotriene modifiers. Theophylline could be added.

109. Step 3 Moderate persistent asthma Symptoms do not abate. Daily > 1 night a week. Low to medium dose inhaled steroid +LABA. Leukotriene modifier, sustained release theophylline could be added.

110. Step 4 Severe persistent asthma Continual during day frequent at night. High dose inhaled steroids & LABA. Oral glucocorticoids could be added. For acute symptoms use salbutamol.

111. Acute severe asthma (Status asthmaticus ) Acute attack of severe asthma. Attack of BA is prolonged with severe intractable wheezing. URTI is the most common precipitant. Life threatening. Patient has to be hospitalised.

112. Acute severe asthma (Status asthmaticus ) High flow humidified oxygen inhalation. Nebulized salbutamol 2.5- 5 mg + Ipratropium bromide 0.5 mg intermittent inhalations driven by oxygen. Salbutamol/ Terbutaline 0.4 mg im / sc may be added, since inhaled drug may not reach smaller bronchi due to severe narrowing / plugging.

113. Acute severe asthma (Status asthmaticus ) Hydrocortisone hemisuccinate 100mg IV stat, Followed by 100- 200 mg 4-8 hrly infusion. Aminophylline 250-500 mg over 20 mins IV slowly. Correct dehydration & acidosis. Antibiotics for infection.

114. Drugs which causes bronchospasm NSAIDs Beta blockers Cholinergic drugs d tubocurarine Morphine

115. COPD Characterised by the presence of airflow obstruction due to chronic bronchitis or emphysema. Cigarette smoking is the most important cause.

116. Treatment 1. Smoking caessation Nicotine replacement transdermal patch, gum, lozenge, inhaler or nasal spray. Bupropion 2. Oxygen therapy 3. Inhaled bronchodilator Ipratropium Tiotropium SABA LABA

117. COPD Ipratropium is preferred to SABA 1. Parasympathetic tone is the major reversible factor in COPD. 2. Longer DOA 3. Absence of sympathomimetic SE

118. COPD 4. Corticosteroids ICS + LABA Reduces the frequency of COPD exacerbation. 5. SR Theophylline