BMS2047 Pharmacology - On demand Lecture 2 histamine and steroids.pdf

Inflammation and Antiinflammatories Dr Penny Lympany [email protected] 28AY04 Histamine & Steroids Lecture Bite 2 Histamine Histamine Physiological process Derived from Histidine, found in: Mast Cells Basophils Neutrophils Secretion by slow release is physiologically important for gut, cardiova...

Inflammation and Antiinflammatories Dr Penny Lympany [email protected] 28AY04 Histamine & Steroids Lecture Bite 2 Histamine Histamine Physiological process Derived from Histidine, found in: Mast Cells Basophils Neutrophils Secretion by slow release is physiologically important for gut, cardiovascular and lung function. Mass degranulation activated in response to activated antibody leads to anaphylaxis → mass drop in blood pressure Histamine Receptors H1 receptor activation ▪ bronchoconstriction ▪ contraction of gut ▪ vasodilation & ↑vascular permeability, dec. bp ▪ stimulation of sensory nerves and release of peptide mediators in periphery → vasodilation H2 receptor activation ▪ gastric acid secretion ▪ heart rate G protein H3 - presynaptic nerve terminals H4 - mast cells Histamine release Local Itching Redness Swelling Oedema Headache Vasodilation Bronchoconstriction Vomiting Diarrhea Systemic Huge Vasodilation Bronchoconstriction and spasm Treated with Beta adrenoceptor agonists Antihistamines H1 receptor antagonists Older (can pass BBB) ▪ Promethazine, chlorpheniramine ▪ Also anti muscarinic- sedative effects Newer ▪ Loratadine, fexofenadine ▪ Reduced and muscarinic, don’t pass BBB Uses: anti allergy, sedation, cough/cold remedies, antiemetic Side effects: Dry mouth, blurred vision, sedation Steroids Steroids Glucocorticoids Prednisone, Beclametasone Gene expression changes Decrease PLA2 activity Decrease COX expression Side effects diabetes osteoporosis peptic ulcers immunosuppression adrenal suppression altered appearance – gain weight on face and trunk, wasted limbs mental disturbance topical - skin atrophy, hair growth Stop and Pause If you need to revise (or have not yet come across) nuclear receptor action then please check out these recordings from last semester: Cholesterol and its functions (19 minutes) Types of DNA Binding domains part 2 (21 Minutes) Effects of multi-protein complexes (20 Minutes) Learning outcome: Explain how nuclear receptors can both enhance or reduce gene expression 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/