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In the Name of Allah, The Most Beneficent and

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Presentation on theme: "In the Name of Allah, The Most Beneficent and"— Presentation transcript:

1 In the Name of Allah, The Most Beneficent and
The Most Merciful

2 To speak a kind workd is charity. (For which,
Hadith Shareef To speak a kind workd is charity. (For which, One deserves a reward from allah). (Bukhari) 2

3 A PROMISE IS A KIND OF DEBT
Hadith Shareef A PROMISE IS A KIND OF DEBT (AND SHOULD, THEREFORE, BE KEPT). (Tirmidhi )

4 The weak can never forgive; forgiveness
saying The weak can never forgive; forgiveness is the attribute of the strong.

5 Drug treatment of Bronchial Asthma

6 Asthma Chronic asthma Severe Acute asthma (Status Asthmaticus)

7 Clinical Manifestations
Dyspnea – difficulty breathing Wheezing Chest tightness Cough – chronic cough may be the only symptom Sputum production

8 Precipitating Factors - Triggers
Viral infections – especially with infants and young children Allergies GERD Cigarette smoke Smoggy air – smoke from fires Windy weather – hot and dry Santa Ana winds

9 Pathophysiology Broncho-constriction or bronchospasm
Spasm aggravated by inflammation, mucosal edema and excessive mucus Mast cells release substances that cause inflammation and constriction Acute reaction to some trigger – reversible with treatment

10

11 Hyper-inflated Lungs in Asthma

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13 Drugs used for treatment of Bronchial Asthma Classification
Bronchodilators A. Sympathomimetics i.  and  adrenoceptor Agonists Adrenaline Ephedrine ii.  (1 + 2) adrenoceptor Agonists Isoprenaline Orciprenaline iii. 2 Adrenoceptor Agonists Salbutamol Terbutaline Fenoterol Remiterol

14 V. Anti-IgE monoclonal antibodies Omalizumab
B. Methylxanthines Aminophylline Theophylline Choline Theophylline C. Muscarinic Antagonists Ipratropium Bromide Tiotropium II. Corticosteroids Hydrocortisone Prednisolone Betamethasone Beclomethasone Mast cell stabilizers Na Chromoglycate (Cromolyn) Nedocromil Ketotifen (H1 Blocker) IV. Leukotriene Receptors inhibitors & 5-lipoxygenase Antagonist Montelukast Na Zafirlukast Zileuten V. Anti-IgE monoclonal antibodies Omalizumab

15 Sympathomimetic agents
M.O.A: 1. They act on 2 receptors in airway s. muscles.  Stimulate adenyl cyclase  cAMP in airway tissue Relaxation of smooth muscle →Brochodilatation 2. Mediator release is prevented 3. Microvascular leakage is prevented. 4. Mucociliary transport. Epinephrine: (1:1000) 0.4 ml sol sub/cut OR 320µg/ puff Ephedrine: oral admin, longer duration of action but less potent Isoproterenol: by inhaler

16 2 selective Drugs Potent and effective Bronchodilators effective after inhalation, s/c administration and orally. Inhalation:- Delivery of drugs by inhalation results in greatest effect with least systemic effects or toxicity. Aerosol deposition depends upon i. Particle size --- optimal size 2 – 5 µm 80 – 90% is deposited in month or pharynx --- Particle under 1 – 2 µm in size remain suspended and may be exhaled ii. Pattern of breathing (Tidal vol. and rate of air flow) deposition can be  by holding the breath in inspiration. iii. Geometry of the airways.

17

18 Drugs used are Albuterol Metaproterinol by inhalation orally
Drugs used are Albuterol Metaproterinol by inhalation orally. Terbutaline --- Inhalation, Tab, s/c Inj Bitolterol --- By inhalation only. Salmeterol and formoterol --- long acting / 12 hrs by inhalation, as metered dose inhalers Bronchodilatation is maximum by 30 Min. DOA is 2 – 3 hrs. Orally – one Tab 2 – 3 times / day. s/c Inj mg only Terbutaline given in severe asthma as emergency treatment Repeated inj. can cause cumulative effect. Fomoterol & Salmeterol:- Newer agents highly lipid soluble & they dissolve in s. muscle cell membrane, this acts as slow release depot so DOA is longer – 12 hrs. They are given by inhalation. Toxicity:- In general 2 selective agonists are safe a effective Bronchodilators when given in doses that do not cause systemic effects. 1. skeletal muscle tremor 2. nervousness 3. weakness

19 Advantages of inhalation
1. quicker local absorption 2. prompt action 3. lesser systemic effects

20 Albuterol - Nebulizer

21 Muscarinic Antagonists
MOA:- They competitively inhibit effect of Ach on muscarinic receptors. In the airway Ach is released from vagal N. ending it causes: Action on M2 rec in Bronchial smooth mus. Inhibition of Adenylyl cyclase Contraction of smooth muscles Action on M3rec in Bronchial mucous glands Formation of IP3 & DAG Secretion of mucous These effects are blocked so there is bronchodilatation and  mucous secretion.

22 Prep. Used : Ipratropium bromide Dose: 1 mg ē Particle size 1 – 1.5µ
They are effective bronchodilators and can cause bronchodilation ē out causing  H.R ipratropium aerosol has localised action Bronchodilation is equal to 2 agonists. DOA: 5 hrs Dose: 1 mg ē Particle size 1 – 1.5µ Adverse effects:- Ipratropium Bromide:-

23 1. Pts. Intolerant to inhaled 2 agonists
Clinical uses: They are effective bronchodilators. Although they partially reverse provoked bronchoconstriction they are of value in 1. Pts. Intolerant to inhaled 2 agonists 2. In pts. Of chronic obstructive pulmonary disease (COPD) 3. In acute severe asthma addition of Ipratropium enhances effect of 2 agonist albuterol. 4. Investigative tools for studying P. sympath pathway in Bronchomotor response.

24 Anti-IgE monoclonal antibodies
Omalizumab (Monoclonal antibody)

25 Glucocorticoids Hydrocortisone Dexamethasone Prednisolone
Beclomethasone Budesonide Flunisolide Fluticasone Momatasone Triamcinolone Ciclesonide Used since 1950 for Br. Asthma precise MOA in Br. Asthma exactly was not known. If given for sometime :- They  Br. Hyper reactivity. They  air way caliber  asthmatic attacks. MOA:- Potentiation of effect of  agonists. Inhibition of Arachidonic acid   LTs: ie; a PG Most Important MOA is :- Inhibition of eosinophilic mucosal inflammation if asthmatic airways. They inhibit cytokinins which initiate inflammation, Provoked by antigen inhalation or viral infection. Hydrocortisone Dexamethasone Prednisolone

26 In mild disease AEROSOL is used urgent treatment is given when:
Clinical Use:- The clinical trails have shown efficacy of corticosteroids in Asthma but still there is controversy over indication as when to start corticosteroids & in what dosage schedule. Chronic use results in severe adverse effects oral and Parentral corticosteroids are only given as urgent treatment. In mild disease AEROSOL is used urgent treatment is given when:

27 With bronchodilators no adequate improvement.
Worsening of symptoms despite maintenance R/. R/ is started ē oral dose 30 – 60 mg Prednisone daily dose or I/V – 1 mg / kg of Methyl Prednisolone every 6 hrly. After improvement dose is gradually decreased over 7 – 10 days.

28 Cromolyn Sodium and Nedocromil Sodium
These drugs prevent mast cell degranulation. Used for Prophylaxis of Br. Asthma. Source: Synthetic Chemistry: Stable and Extremely insoluble salts. Ph. Kinetics:

29 Mechanism of Action Alteration in delayed chloride channels in the cell membrane and inhibiting their activation. So inhibition of nerve cells – Inhibition of cough To reduce the accumulation of I.C Ca++ induced by antigen in sensitized mast cells. Inhibition of mast cell degranulation in lungs: Early response to antigenic challenge is inhibited. Inhibition of Eosinophils, Monocytes & Neutrophils: Inhibition of late response.

30 Pharmacological Actions
Primarily Prophylactic Human bronchoalveolar mast cells are most sensitive. i. Inhibit both exercise antigen induced asthma. ii.Chronic use may reduce overall bronchial reactivity iii.Bronchial smooth muscles are not relaxed but broncho- constriction is prevented due to decreased bronchial reactivity.

31 Therapeutic Uses Cromolyn: Used at all ages
Nedocromil: Not below 12 years. For prophylaxis of Br. Asthma due to: Exercise. Aspirin Occupational allergens like wood dust. Other unavoidable allergens. Allergic rhinitis & Hay fever. Systemic Mastocytosis.

32 Administration and Dosage
By inhalation: In adults by metered dose inhaler 2.4 mg 4 times daily ii. In children aerosol of 1% solution. Nasal spray Eye Drops

33 Adverse Effects Mainly localized Throat irritation Cough
Dryness of mouth Chest tightness and wheezing

34 Ketotifen Recently introduced prophylactic agent. MOA:
Inhibits release of histamine and other mediators from the mast cells. Sustained inhibitory effect on H1-receptors. Given orally (1-2mg B.D) with food. It decreases Number, Severity and duration of asthmatic attacks. Adverse Effects: Drowsiness.

35 Leukotrienes inhibitors
A. leukotriene pathway inhibitors 5-lypoxygenase inhibitor zileutin B. leukotriene receptors antagonists Zafirlokast Montelukast

36 Methylxanthines Aminophylline Theophylline Theobromine Caffeine Absorption: Well from GIT when given orally absorption of rectal suppositories is unreliable. Absorption depend upon the type of preparation used. Microcrystalline: Complete and rapid absorption. Sustained Release: Therapeutic level for 12 hrs.

37 Mechanism of Action 1. At higher conc. Inhibition of phospho- diestrase which causes increased concentration of IC cAMP which lead to smooth muscle relaxation and decreases Histamine release. 2. Inhibition of adenosine cells surface receptors which causes increased concentration of IC cAMP. 3. Low doses inhibit. The late response.

38 Pharmacological Actions CNS: Low & Moderate Doses Specially caffeine mild cortical arousal increase alertness deferral of fatigue. In Sensitive individuals one cup of coffee (100 mg caffeine) causes nervousness insomnia. High Doses: Nervousness, Tremors. At very High Doses: Medullar stimulation & convulsions In pt taking high doses of aminophylline- Nervousness & tremors occur as side effect.

39 CVS Effects: They have +ve chronotropic & +ve inotropic effect on heart. Low Doses: Due to inhibition of adenosine receptors At High Conc: PDE inhibition Very High Conc: Impaired sequestration of Ca++ by SR in sensitive individuals a few cups of coffee can cause cardiac arrhythmias. In general high doses of methylxanthines are toxic. B.V: In larger doses. Vascular smooth muscle is relaxed vasodilatation (except in cerebral B.Vessels) In ordinary doses or consumption of coffee etc usually TPR incr. due to catecholamines. Blood Viscosity and blood flow is improved. Mech. is not well defined. (pentoxyfylline a dimethylxanthine used in intermittent claudication.)

40 GIT: Increase gastric sec and other digestive enzymes. Effect on kidney. Weak diuresis due to increase G.F.R & decreased tub reabsorption. On bronchial smooth muscles. The Major Effect due to direct action on smooth muscle of bronchial tree is bronchodilatation. Inhibition of release of histamine: from lung tissue due to antigens – so broncho-constriction is prevented. Effect on Muco-cilliary transport is unknown.

41 On Skeletal Muscles: increases strength, reversal of fatigue of diaphragm.

42 Adverse Effects of Theophylline Related to increasing plasma Conc.
Tremors Insomnia Restlessness Arrhythmia Accidental over dosage- Death

43 Status Asthmatics” Now known as “Acute Severe Asthma”, patient is unable to utter a complete sentence, condition potentially life threatening. The patient usually adopts a upright posture fixing shoulder girdle to assist accessory muscle of respiration.

44 Notice the look of patient
Pulse rate > 120 / min Resp rate > 25 / min PEF % Cyanosis Perspiration Notice the look of patient

45 Arterial Blood gases: Status asthmaticus Often accompanied by
un-productive cough, worsening the dyspnoea. (Peak flow <50%) central cyanosis Tachycardia, >120/min, Arterial Blood gases: 1. Increased CO2 tension (Normal 5-6Kpa). 2. Severe hypoxaemia (<8kPa) even if O2 Inhalation started. 3. Decreased pH or Increased H+

46 Pulsus paradoxus, sweating, usually are the accompanied features. On Percussion, note is hyper-resonant On Auscultation, air entry decreased or “Silent Chest” is ominous sign, inspiratory, expiratory High pitched rhonchi may be present

47 2. To restore pulmonary function.
Management Aims: To avoid mortality. 2. To restore pulmonary function. 3. To prevent relapse.

48 Life Threatening Features:
Can’t Speak. Central Cyanosis. Exhaustion (Respiratory muscle fatigue), confusion, decreased Sensorium. Bradycardia. Silent Chest. Un-recordable Peak Flow.

49 1. Oxygen inhalations ( highest available conc. Should be used
1. Oxygen inhalations ( highest available conc. Should be used. Arterial blood Pa O2 of > Pa be maintained.) 2. β2 agonist (nebulization) Salbutamol 2.5 – 5 mg Terbutaline mg Repeat after 30 min if needed or continuous nebulization of aerosolized Albetrol. 3. Systemic steroids: I/V Hydrocortisone 200mg or oral prednisolone mg

50 IF FEATURES PERSIST 4. Ipratropium bromide 0.5 mg added to nebulization of Beta 2 agonist. 5. Aminophylline 250 mg i/v diluted in 20ml 0f 5% dextrose is given in bolus over 20 minutes (very slowly). Subsequently 500mg Aminophylline diluted in 5% D/W infusion over next 3 hrs. The patients who are not already on aminophylline or β2 agonist terbutaline or salbutamol 250μg i/v over 10 min can be given.

51 6. in selected cases even adrenaline 0. 5-0
6. in selected cases even adrenaline mg sub/cutaneously can be considered. 7. Assisted Ventilation may be considered for those who are not responding (IPPR) by endotracheal intubation. (Coma, Resp. Arrest, Exhaustion, Determination of arterial blood gases)

52 Subsequently: 1. Continue O2 Inhalations.
2. Orally Prednisolon 30-60mg /day OR 3. I/V 200mg Hydrocortisone Hemisuccinate 6hly (In more ill) If good response with Initial β2 nebulization. Repeat it 4hly. 4. Rehydrate patients, as usually they are dehydrated and have decreased B.P.

53 Drug Reactions CIMETIDINE incr. plasma level of aminophylline ERYTHROMYCIN same VERAPAMIL same BENZODIAZEPINES can lead to sedation and are contraindicated. Beta Blockers …….. Extremely contraindicated.

54 Monitoring Treatment:
PEF recording after min. Repeat arterial blood gases measurements. Repeat pH or H+. Measure Serum levels of theophylline? If treated with Aminophylline. (Maintain µmol)

55 Adverse Effects of Drugs
Summary Adverse Effects of Drugs 1. Beta Agonists Palpitations/Tachycardia. Tremors. Sweating. 2. Aminophylline Anxiety. Arrhythmia. Insomnia. Palpitations. 3. Ipratropium Dryness of Mouth. Blurred Vision. Palpitations. 4. Adrenaline Hypertension. Tremors. Palpitation. Arrhythmia. Angina pectoris

56 The End

57 Jazak Allah o Khair, kaseeran kaseera


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