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Pharmacology of Asthma Name: Rehan Aftab Email: ra1720@ic.ac.ukOBJECTIVES: • Be able to recognize signs and symptoms of asthma • Describe the pathophysiology of asthma • Explain the mechanism of action of drugs used to treat asthma • Recognise the side effects and contraindications of these drugs • Be aware of the treatment pathway for asthmaWhat is asthma? • Chronic inflammatory airway disease with variable REVERSIBLE airway obstruction , hyperresponsive airway and bronchial inflammation • Often linked with a family history of atopy (genetic tendency to develop allergic disease)Pathophysiology of asthma • Involves a type 1 hypersensitivity reaction which is IgE mediated • Presence of eosinophils and mast cells • Type 2 T helper cells produce cytokines such as IL-4, IL-5 and IL-13 st • Upon 1 exposure to allergens an individual become sensitised • Then when they encounter the allergen again IgE crosslinking on mast cells surface causing them to degranulate and release inflammatory mediators • Inflammation causes airway constriction, hypersecretion and a narrowed lumenPathophysiology of asthmaSigns and symptoms Symptoms: • Wheeze • Dyspnoea • Cough • Chest tightness • DiurnalvariationTreatment of asthmaShort Acting Beta Agonists Examples:Salbutamol, terbutaline Target:Beta-2 receptor Location:Bronchial smooth muscle Effect: Smoothmusclerelaxation and dilatation of theairwaysSABA Contraindications • Beta-2 agonistsshould be used with caution in people with: • Hyperthyroidism — beta-2 agonistsmay stimulatethyroid activity. • Diabetes mellitus — thereis a rare risk of ketoacidosis(especially after intravenous beta-2 agonistadministration).Additional blood glucose commenced.tsare recommendedwhen treatmentwitha beta-2agonist is • Cardiovascular disease (includinghypertension) — beta-2agonists may cause an increased riskof arrhythmias and significantchanges toblood pressure and heart rate. • Susceptibilityto QT-intervalprolongation. • Hypokalaemia — plasma potassiumconcentrationmay be reducedby beta-2 agonists (particularly high doses). • Convulsive disorders.SABA side effects • Palpitations/agitation • Tachycardia Salbutamolis nottotally • Arrhythmias specific for beta-2! • Hypokalaemia(at higher doses) Nebulisers • In emergency situations nebulisers are typically the best way of administering salbutamol.Spacers Onlyabout20% of inhaleddrugs actuallyreach the lungsto have the desired effects. Thisiswhy spacersare useful especiallyfor patientswithpoor inhalertechnique.Inhaled Corticosteroids Examples: Fluticasone, Mometasone,Budesonide Target: Glucocorticoidreceptor Location:Eosinophils Effect: Decreasedinflammatory cells and decreasednumberof cytokines ICS Side Effects Local vs systemic Local: Systemic: • Sore throat • Growth retardation in children • Hoarse voice • Hyperglycaemia • Opportunistic oral infections • Decreased bone mineral density • Immunosuppression • Effects on moodLeukotriene receptor antagonist Examples: Montelukast, Zafirlukast Target: CysLT1 receptor Location:Eosinophils, mastcells and airways smoothmusclecells Effect: Decreaseseosinophil migration, bronchoconstriction and inflammation-induced oedemaLTRA side effects Mild: Serious: •Diarrhoea • Mood changes •Fever • Anaphylaxis •Headaches •Nausea or vomitingSBA 1: Q1: Which of the following drugs can worsen asthma symptoms? A. Paracetamol B. Acetaminophen C. Budosenide D. Aspirin E. ZafirlukastSBA 1: Q1: Which of the following drugs can worsen asthma symptoms? A. Paracetamol B. Acetaminophen C. Budosenide D. Aspirin E. ZafirlukastA note on NSAIDsSBA 2: Q2: Which of the following drugs should not be given to someone with asthma? A. Propranolol B. Omeprazole C. Budosenide D. Aspirin E. ZafirlukastSBA 2: Q2: Which of the following drugs should not be given to someone with asthma? A. Propranolol B. Omeprazole C. Budosenide D. Aspirin E. ZafirlukastSBA 3: Q3:A 27-year-old lady presents to the GP with white patches in her mouth and a loss of taste. She has a PMH of asthma which she manages with salbutamol and a new drug which she started recently. Which of these drugs could be causing her symptoms? A. Salmeterol B. Isoniazid C. Inhaled beclometasone D. Oral prednisolone E. Oral montelukastSBA 3: Q3:A 27-year-old lady presents to the GP with white patches in her mouth and a loss of taste. She has a PMH of asthma which she manages with salbutamol and a new drug which she started recently. Which of these drugs could be causing her symptoms? A. Salmeterol B. Isoniazid C. Inhaled beclometasone D. Oral prednisolone E. Oral montelukastSBA 4: Q4 : A 27-year-old lady presents to the GP with worsening symptoms of asthma despite being on salbutamol. What is the most appropriate initial management of this patient? A. Prescribe inhaled corticosteroid B. Check inhaler technique C. Prescribe LABA D. Prescribe LAMA E. Prescribe LTRASBA 4: Q4 : A 27-year-old lady presents to the GP with worsening symptoms of asthma despite being on salbutamol. What is the most appropriate initial management of this patient? A. Prescribe inhaled corticosteroid B. Check inhaler technique C. Prescribe LABA D. Prescribe LAMA E. Prescribe LTRASBA 5: Q5 : Which interleukin promotes eosinophil survival? A. IL-1 B. IL-4 C. IL-5 D. IL-9 E. IL-13SBA 5: Q5 : Which interleukin promotes eosinophil survival? A. IL-1 B. IL-4 C. IL-5 D. IL-9 E. IL-13SUMMARY: What is asthma? Drug administration • Chronic inflammatory airway disease • Nebulisers are used in emergencies which is REVERSIBLE • Spacers may be easier for children to • Linked with atopy use and to ensure more of the drug reaches the target site Pathophysiology Treatment of asthma • inflammatory mediators which cause • Salbutamol is first line bronchoconstriction • Then add ICS • Then add LTRA (according to NICE)THANK YOU! Please fill in the Feedback form! Name: Rehan Aftab Email: ra1720@ic.ac.uk