Bronchodilators sympathomimetics

bronchodilators- sympathomimetics.

1. DR. FIROZ A HAKKIM MD RESPIRATORY MEDICINE BRONCHODILATORS

2. SYMPATHOMIMETICS NON- SELECTIVE EPINEPHRINE (ADRENALINE) EPHEDRINE ISOPRENALINE ORCIPRENALINE SYMPATHOMIMETICS β2 - SELECTIVE SALBUTAMOL TERBUTALINE BAMBUTEROL FENOTEROL REPROTEROL PIRBUTEROL SALMETEROL EFORMOTEROL METHYLXANTHINES THEOPHYLLINE AMINOPHYLLINE CHOLINE THEOPHYLLINATE HYDROXYETHYL THEOPHYLLINE THEOPHYLLINE ETHANOLATE OF PIPERAZINE ANTICHOLINERGICS ATROPINE METHONITRATE IPRATROPIUM BROMIDE TIOTROPIUM BROMID E BRONCHODILATORS

3. In use for thousand of years Ephedra equisetina - used in ancient china Modern sympathomimetics Are derivatives or analogues Based on structure of Epinephrine (adrenaline) SYMPATHOMIMETICS

4. They are both alpha and beta adrenergic agonist that acts as a neurotransmitter in the sympathetic nervous system, Alpha receptor being predominantly stimulatory (vasoconstriction) and beta receptor predominantly inhibitory ( relaxation of smooth muscle in the respiratory tract, vasculature and uterus) SYMPATHOMIMETICS

5. Are non selective or poorly selective and are more likely to produce unwanted effects ( tachycardia, cardiac stimulation) Adrenaline – alpha + beta 1 + beta 2 agonist Ephedrine – alpha + beta 1 + beta 2 action Isoprenaline – beta 1 + beta 2 agonist Non selective sympathomimetics

6. The beta agonist produce bronchodilatation by stimulating beta 2 receptors situated in the smooth muscle of the bronchial tree, from the trachea down to the terminal bronchioles. This activates the enzyme adenyl cyclase , facilitating the conversion of ATP to cyclic AMP and resulting in the relaxation of smooth muscles in the bronchial wall. It also involves the activation of protein kinase with a reduction in ionic calcium concentration in bronchial smooth muscle Mechanism of action

7. Other beneficial non bronchodilator effects include enhanced mucociliary transport, diminished release of histamine and other chemical mediators of asthma from mast cells, inhibition of cholinergic neurotransmission and a possible increased ventilatory response to hypercapnia and hypoxia

8. Administration inhalation Oral medication Parenteral medication

9. Preferred route is inhalation from MDI 10 % of fraction leaving device reaches lungs, remaining impacting in oropharynx and being swallowed Systemic side effects are generally insignificant in comparison to oral administration Rapid onset of action compared with same drug taken orally Onset of 3-6 min, 80% bronchodilatation in 5 min. Reaching peak in 30- 60 min, effect wearing off over 3-6 hr. Inhalation

10. If unable to manage inhaled therapy Slow onset of action , produce bronchodilatation after about 30 min and reaching a peak at 1-2 hr Oral medication

11. In severe exacerbations Onset of action is rapid, occuring within a few minutes and peak effect reached sooner than inhalation , duration of action being 4 hrs Parenteral medication

12. When swallowed may undergo conjugation in gut wall as well as in liver Relatively small quantities of these drugs are excreted unchanged by the kidneys and dosage modification is unnecessary in renal insufficiency Slightly penetrate the blood brain barrier and also cross placenta so that oral medication is perhaps better avoided in pregnancy. Metabolism and excretion

13. Principal dose limiting adverse effect of beta agonist is Skeletal muscle tremors, particularly affecting hands. Muscle cramps, tachycardia ( reduced peripheral vascular resistance, vasodilatation occuring as a result of stimulation of receptors in vascular smooth muscle) Metabolic effects like hypokalemia , brought about by stimulation of pancreatic beta 2 receptors , resulting in increased insulin release and an intracellular potassium shift Non specific effects – dryness of mouth, nausea , vomiting Adverse effects

14. Paradoxical bronchoconstriction occuring after patients have taken beta 2 agonist by pressurized MDI or nebulization , are unusual and may be by drug or the constituent of propellant or physical charecteristics like temperature , ph , osmolality . May worsen ventilation – perfusion mismatch in short term.may arise if pulmonary vessels that were previously reflexly constricted in response to local hypoxia are dilated by beta 2 receptor stimulation so that blood is shunted into areas of lung still relatively poorly ventilated. This can be overcome by administration of oxygen as a routine.

15. Drug oral dose Iv bolus Iv infusion MDI Neb solution salbutamol 4mg tds 250µg 5µg /min initialy then 3 – 20µg/ min 100-200 µg 2.5- 5 mg terbutaline 5mg bd 250- 500 µg 1.5- 5 µg/ min 250- 500 µg 5-10 mg salmeterol 25-50µg formoterol 12- 24µg Dosage

16. To relieve wheeze To prevent or reduce wheeze in patients with exercise induced asthma Long acting bronchodilators may also be useful as a single dose before bedtime for patients who continue to experience nocturnal wheeze despite otherwise optimal treatment Adrenaline ( epinephrine ) given to patients developing bronchospasm , serious upper airway narrowing, hypotension with collapse ( bee or wasp sting) (dose 3-5 ml of 1 : 10000 iv) Use in respiratory medicine

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