Bronchodilators

bronchodilators

1. BRONCHODILATORS Dr.ZIKRULLAH

2. Bronchodilators Drugs used to relieve bronchospasms associated with respiratory disorders Includes: Adrenoceptor agonists Selective β 2 -agonists & other adrenoceptor agonists Antimuscarinic bronchodilators Xanthine derivatives Leukotriene antagonist 2

3. Adrenoceptor agonists ( i ) Selective beta 2 agonists Stimulate beta 2 receptors in smooth muscle of the lung, promoting bronchodilation , and thereby relieving bronchospasms 4

4. Drug Formulation Dosage Adult Child Salbutamol Oral tablet 8 mg twice daily 4 mg twice daily Inhaler (MDI), 100mcg/dose 100-200mcg up to three to four times daily Same as adult Syrup, 2mg/5ml 4 mg three to four times daily 1-2 mg three to four times daily ( ≥2 yr) Terbutaline Oral tablet (S.R) 5-7.5 mg two times daily - Inhaler 500mg / dose ( Turbuhaler) 500 mcg up to four times daily - Inhaler 250mg / dose (MDI) 250-500mcg up to 3-4 times daily, .04mg/kg sc Same as adult 6 Short-acting β -2 agonists

5. Drug Formulation Dosage Adult Child Formoterol Inhaler 4.5mcg / dose (Turbuhaer) 4.5-9 mcg once or twice daily Same as adult Inhaler 9mcg / dose (Turbuhaer) Salmeterol Inhaler 25mcg / dose (MDI) 50-100 mcg twice daily Same as adult 50 mcg / dose (Accuhaler) 50 mcg twice Same as adult 7 Long-acting β -2 agonists

6. SIDE EFFECTS OF β2 AGONISTS Tremor ( β2- receptors in skeletal muscles) Tachycardia (reflex tachycardia and direct stimulation of β2- receptors in the heart) Transient decrease in arterial oxygenation (relaxation of compensatory pulmonary vascular vasoconstriction in areas of decreased ventilation) Acute metabolic responses ( hyperglycemia , hypokalemia , hypomagnesemia , not present with chronic treatment) Lactic acidosis

7. Drug-Drug Interactions

8. (ii) Other adrenoceptor agonists Less suitable & less safe for use as bronchodilators because they are more likely to cause arrhythmias . Adrenaline (epinephrine) injection is used in the emergency treatment of acute allergic and anaphylactic reactions 12

9. Antimuscarinic bronchodilators Blocks the action of acetylcholine in bronchial smooth muscle, this reduces intracellular GMP, a bronchoconstrictive substances. Used for maintenance therapy of bronchoconstriction associated with chronic bronchitis & emphysema 13

10. Drug Formulation Dosage Adult Child Ipratropium Inhaler 20 mcg / dose (MDI) 20-80 mcg three to four times a day 20-40 mcg three to four times a day ( ≥6yrs) Tiotropium Inhaler 18 mcg /dose 18 mcg daily Not recommended in children and adolescents 14

11. Adverse effects : Dry mouth Nausea Constipation Headache 15

12. Combination Therapy Ipratropium+albuterol ( DuoNeb ®, generic) [0.5 mg+3 mg# per 3 ml] 3 ml 6 times per day

13. Xanthine Derivatives Main xanthine used clinically is theophylline Theophylline is a bronchodilator which relaxes smooth muscle of the bronchi, it is used for reversible airway obstruction One proposed mechanism of action is that it acts by inhibiting phosphodiesterase , thereby increasing cAMP , leading to bronchodialtion 17

14. Drug Formulation Dosage Adult Child Theophylline Tablet 200 / 300 mg (S.R.) 200 – 300 mg twice daily 10 mg / kg (( ≥ 2yrs) twice daily Capsule 50 / 100 mg (Slow release) 7-12 mg/ kg / day in two divided doses 10-16 mg / kg / day in two divided doses (9–16yrs) 13-20 mg / kg / day in two divided doses (30 months – 8 yrs) Syrup 80 mg / 15 ml 25 ml q6h 1 ml / kg (Max 25 ml) q6h ( ≥ 2yrs) Aminophylline Injection 25 mg / ml 10 ml 500 mcg / kg / hr IV infusion, adjust when necessary 1 mg / kg /hr (6 months – 9 years) 800 mcg / kg /hr (10 – 16 yrs) IV infusion, adjust when necessary 18

15. Adverse effects : Toxicity is related to theophyline levels (usually 5-15 µg/ml) 20-25 µg/ml : Nausea, vomiting, diarrhea, insomnia, restlessness >30 µg/ml : Serious adverse effects including dysrhythmias , convulsions, cardiovascular collapse which may result in death 20

16. Bronchodilators are sympathomimetics and commonly interact with volatile anesthetics to cause cardiac arrhythmias . Aminophyllin commionly interact with halothane. It is advisable to wait 13 hrs (approx 3 half lives)after the last dose of aminophyllin before using halothane for an asthmatic patient. Use of another anaesthetic ( enflurane , isoflurane , sevoflurane ) decreases this problem The combination of Theophyllin and ketamine may predispose the patient to seizures . 21

17. Corticosteroids 1.Used for prophylaxis of chronic asthma 2.Suppressing inflammation Decrease synthesis & release of inflammatory mediators Decrease infiltration & activity of inflammatory cells Decrease edema of the airway mucosa 3.Decrease airway mucus production 4.Increase the number of bronchial beta 2 receptors & their responsiveness to beta 2 agonists 22

18. Drug Formulation Dosage Adult Child Beclomethasone Inhaler 50 mcg / dose (MDI) 200 mcg twice daily / 100mcg three to fours times daily Up to 800 mcg daily 50 – 100 mcg two to four times daily Inhaler 250 mcg / dose (MDI) 500 mcg twice daily / 250 mcg four times daily Not recommended 23

19. Drug (Cont’d) Formulation Dosage Adult Child Budesonide Inhaler 50 mcg / dose (MDI) 200 mcg twice daily Up to 1.6 mg daily 50 – 400 mcg twice daily Up to 800 mcg daily Inhaler 200mcg / dose (MDI) Inhaler 100 mcg / dose (Turbuhaler) 200-800 mcg once daily in evening Up to 1.6 mg daily in two divided doses 200-800 mcg daily in two divided doses / 200-400 mcg once daily in evening (<12 yrs) Inhaler 200 mcg / dose (Turbuhaler) Inhaler 400 mcg / dose (Turbuhaler) 24

20. Drug (Cont’d) Formulation Dosage Adult Child Fluticasone Inhaler 25mcg / dose (MDI) 100 – 1000 mcg twice daily 50-100 mcg twice daily (4-16 yrs) Inhaler 50 mcg / dose (MDI) Inhaler 125 mcg / dose (MDI) Inhaler 250 mcg / dose (MDI) Inhaler 50 mcg / dose (Accuhaler) Inhaler 100 mcg / dose (Accuhaler) Inhaler 250 mcg / dose (Accuhaler) 25

21. Adverse effects Inhaled corticosteroids: Candidiasis of the mouth or throat Hoarseness Can slow growth in children Adrenal suppression may occur in long-term, high dose therapy Increases the risk of cataracts 26

22. Perioperative systemic steriods should be administered to the patients of bronchial asthma if symptoms persist and PEFR and FEV1 is less than 80% of predicted. HPE suppression should be assumed to be present in the patients who have received systemic steroid for more than 3 weeks in the past six months. These should receive stress dose coverage( inj Hydrocot 100 mg iv 8 hrly with rapid tapering after 24 hrs. 27

23. Anaesthetics bronchodilator Halothane Sevoflurane Isoflurane Desflurane Enflurane Propofol

24. Cromoglycates Stabilise mast cells & prevent the release of bronchoconstrictive & inflammatory substances when mast cells are confronted with allergens & other stimuli Only for prophylaxis of acute asthma attacks 29

25. Drug Formulation Dosage Adult Child Cromoglycate Na Inhaler (1 mg & 5mg/dose) 10 mg four times daily, may be increased to six to eight times daily Same as adult Nebuliser solution 10 mg / ml 2 ml 20 mg four times daily, may be increased six times daily Same as adult Nedocromil Sodium Inhaler 2 mg / dose (MDI) 4 mg two to four times daily Sames as adult (>6 yrs) 30

26. Adverse effects Transient Bronchospasm A selective β 2 agonist such as salbutamol or terbutaline may be inhaled a few minutes beforehand Others: coughing, throat irritation 31

27. Leukotriene receptor antagonists Act by suppressing the effects of leukotrienes , compounds that promote bronchoconstriction as well as eosinophil infiltration, mucus productions, & airway edema Help to prevent acute asthma attacks induced by allergens & other stimuli Indicated for long-term treatment of asthma 32

28. Dosage: Montelukast (5 & 10 mg tablets) Adult: 10 mg daily at bedtime Child: (2-5yrs) 4 mg daily at bedtime (6-14yrs) 5 mg daily at bedtime 33

29. Adverse effects : GI disturbances Hypersensitivity reactions Restlessness & headache Upper respiratory tract infection Manufacturer advises to avoid these drugs in pregnancy & breast-feeding unless essential 34

30. Thank you 35