BMS2047 Pharmacology - On Demand Lecture 5 Asthma PDF

Inflammation and Antiinflammatories Dr Penny Lympany [email protected] 28AY04 Asthma Lecture bite 5 Asthma FEV1: Forced expiratory volume in one second Early phase bronchospasm prevents further allergen entry Late phase inflammation is when recruitment & activation of immune cells occurs. Figur...

Inflammation and Antiinflammatories Dr Penny Lympany [email protected] 28AY04 Asthma Lecture bite 5 Asthma FEV1: Forced expiratory volume in one second Early phase bronchospasm prevents further allergen entry Late phase inflammation is when recruitment & activation of immune cells occurs. Figure 28.1 Rang & Dales Pharmacology (2016) 8th Edition Role of T cells in asthma MHC: major histocompatibility complex, Class II. Both eosinophils and mast cells use IgE antibody as a system to detect allergen. Figure 28.2 Rang & Dales Pharmacology (2016) 8th Edition Role of T cells in asthma MHC: major histocompatibility complex, Class II. Both eosinophils and mast cells use IgE antibody as a system to detect allergen. Figure 28.2 Rang & Dales Pharmacology (2016) 8th Edition Stages of Asthma and mediators Figure 28.3 Rang & Dales Pharmacology (2016) 8th Edition Changes in bronchiolar structure Figure 28.4 Rang & Dales Pharmacology (2016) 8th Edition Bronchodilators β2agonists: salbutamol, salmeterol (longacting) ↓mast cell release too but bronchodilator effect more important first choice drugs inhalation usually oral/iv too tremor, tachycardia (β1) Muscarinic receptor antagonists e.g. ipratropium inhalation – few side effects Symptomatic relief Methylxanthines e.g. theophylline oral, long action nausea, headache, insomnia common arrythmia, convulsions in overdose LTC4/D4 antagonists e.g. montelukast oral weak antiinflammatory activity too few side effects Bronchiolar Smooth Muscle M ATP ↑ Ca2+ cAMP PDE CONTRACTION AMP Parasympathetic innervation Little sympathetic innervation but lots of β2 receptors Sensory nerves → parasympathetic reflex → release of ACh Also → release of peptides from sensory nerves → bronchoconstriction Other Treatments M antagonists (H1 antagonists) β2 LT antagonists agonists M ATP ↑ Ca2+ CONTRACTION cAM P PD E AMP MeX Prophylactic anti-inflammatory drugs Steroids e.g. beclomethasone first choice drugs inhaled or oral slow-acting (3-7 days) side effects - oral candidiasis, sore throat, hoarseness systemic - as before Sodium cromoglicate ▪ mechanism unclear mast cell stabiliser? decreases sensory nerve stimulation? ▪ inhalation only - powder ▪ weak, not effective in all patients ▪ slower - several weeks ▪ no side effects - cough from powder Don’t forget to:  Check out the case study  Look at the covid question and start to brainstorm how you would approach it. We will be looking at this next week in the tutorial sessions.  Spend time reflecting on your week, what questions you have and have you been productive with your time. To post on the discussion board click here References GENERAL: Rang & Dales Pharmacology (2016) 8th Edition, Elsevier. Neal (2016) Medical Pharmacology at a Glance 8th Edn (especially for revision) IN MORE DETAIL: Serhan, C., Chiang, N. & Van Dyke, T. (2008). Resolving inflammation: dual anti-inflammatory and pro-resolution lipid mediators. Nat Rev Immunol 8, 349–361 https://doi.org/10.1038/nri2294 Ricciotti E, FitzGerald GA. (2011) Prostaglandins and inflammation. Arterioscler Thromb Vasc Biol. 31(5):986-1000. doi: 10.1161/ATVBAHA. Smith FG, Wade AW, Lewis ML, Qi W. (2012) Cyclooxygenase (COX) Inhibitors and the Newborn Kidney. Pharmaceuticals (Basel) 5(11):1160-76. doi: 10.3390/ph5111160. Murdoch JR, Lloyd CM. (2010) Chronic inflammation and asthma. Mutat Res. 690(1-2):24-39. doi: 10.1016/j.mrfmmm.2009.09.005. Farzam, K., Sabir, S. & O'Rourke, M.C. Antihistamines https://www.ncbi.nlm.nih.gov/books/NBK538188/