Pharmacology SDL Flashcards
Lara Marr goes out for a curry with her boyfriend to celebrate their one-year anniversary. Midway through the meal she feels a ticking sensation in her throat and her eyes start watering.
She feels her tongue swelling and her breathing becomes increasingly difficult.
Her boyfriend notices and he also becomes worried when he sees a rash begin to appear on her face. He starts to panic when her breathing becomes a loud wheeze, and she starts to talk incoherently.
He asks the restaurant to call for an ambulance immediately.
What do these symptoms suggest, and why?
Differential – Anaphylactic shock
Rapid development of symptoms
Tongue swelling, rash, conjunctiva sensitivity - inflammation
Difficulty breathing, wheeze – bronchoconstriction
Talking incoherently – Potential poor cerebral perfusion, drop in blood pressure
Potentially life-threatening – think about ABC
What do you think has happened to Lara?
Rapid nature of onset of symptoms, inflammatory in nature (tongue swelling, rash)
Decrease BP, raised HR, increased RR, increased temp
All indicate anaphylactic shock – serious, requires immediate treatment
Cause of symptoms=Histamine release from mast cells
How do you explain the changes to her respiratory systems?
Histamine acts through H1 receptors (Gq receptors) on airway smooth muscle to produce bronchoconstriction—> difficulty in breathing, wheeze
How do you explain the changes to her cardiovascular systems?
Histamine acts on H1 receptors (Gq) on endothelium, increasing NO and vasodilatation – decreases TPR
Also increases endothelium permeability–> fluid loss from plasma into interstitial space–> decreases blood volume–> BP drops
H1 receptor stimulation on sensory nerves causes rash
Baroreflex stimulation + histamine acts on H2 receptors (Gs receptors) in heart, which increase HR
Increased venous return due to gravity
Increase preload, increased cardiac output (Starling’s law)
Increase in cardiac output will help maintain blood pressure
and blood flow to end organs and tissue
Why were adrenaline, chlorphenamine, hydrocortisone, and salbutamol given, and why in that order?
Adrenaline: rapidly acts at B2-adrenoceptors (Gs) on airway sm–> bronchodilation, helps breathing difficulties
Also acts at a1-adrenoceptors (Gq) on vsm to increase vasoconstriction –-> increase TPR, BP and BF to end organs
Chlorphenamine – Block histamine acting at H1 and H2
Hydrocortisone – reduce gene expression of pro-inflammatory and increase expression of anti-inflammatory agents
Reduces delayed hypersensitivity reaction by other agents released from mast cells
Salbutamol - B2 agonist, additional intervention to increase bronchodilation
How does this treatment relate to pharmacological and physiological antagonism?
Adrenaline produces physiological antagonism – producing physiological symptoms that reverse histamine actions
Chlorphenamine produces pharmacological antagonism – directly blocking the actions of histamine
why not treat with NSAIDs?
These agents block COX and PGs/TXA production,
no effect on histamine-mediated responses!!!
What are RAST tests?
RAST – Radioallergosorbent test – add patient’s serum to dish coated with allergen, then add radiolabelled/fluorescent IgE to bind to patient’s IgE that is bound to allergen
Greater the signal the greater the IgE present and the greater the allergic reaction to that allergen
outline, step-by-step and using mechanisms associated with hypersensitivity reactions, how Lara eating nuts in a curry led to her symptoms and her hospitalisation
Nuts + plasma proteins = large molecular weight HAPTEN which is strongly immunogenic
HAPTEN is recognised by APCs and presented on MHC, activating CD4 T cells
IL-2 release and receptor expression – Generates Th0
IL-4 release and receptor expression – Generates Th2
Activates B cells, makes memory + plasma cells that release IgE
IgE binds to Mast cells by Fc portion of antibody, priming them
Next exposure to nuts: Allergen binds to IgE, mast cells crosslink, release of histamine and other agents e.g., PGD2/LTC4 – histamine (rapid), other agents (delayed) inflammatory response
