Immunopharmacology of hypersensitivity and allergy

• What are the common sources of allergens?

  - inhaled materials

  - injected materials

  - ingested materials

  - contacted materials
• What are some important things to keep in mind when managing patients with allergy?

  Check comorbidities, risk factors, compliance and or treatment administration

  See if on other drugs

  Is treatment going to be okay longterm

  Make sure its really an allergy
• What are some risks in managing patients with allergy?

  Short term (exacerbation)

  Long term (remodelling)

  Risks due to comorbiditis

  Side-effects from treatment
• What is allergic rhinitis?

  Inflammation of the nasal mucosa
• What are the clinical symptoms of allergic rhinitis?

  Nasal discharge (rhinorrhea)

  Sneezing

  Congestion

  Itching
• How do people acquire allergic rhinitis?

  Sensitised for the first time. Makes IgE which sits on the mast cell so next time it will recognise and the antibody will attack. The mast cells is already "charge" with histamine and mast cell will release histamine which causes allergy
• What is the first line of case for general practitioners in rhinorrhoea, itchy nose and nasal blockage?

  Anti-histamine (anti-H1)

  Nasal corticosteroid
• What is the treatment in specialist care that is only used with caution in a restricted manner?

  Oral corticosteroids

  Also specialist care:

  Allergen immunotherapy

  Surgery
• What is the pharmacological management of allergic rhinitis in children?

  Education and avoidance should be the first line approach

  Treatment requires a stepwise approach
• What should you used for symptoms of allergic rhinitis?

  Anti-H1

  Histimanic
• What should you used for symptoms of nasal congestion, failure of previous tx and difficult to treat AR?

  Nasal corticosteroid
• What should you used for severe AR, not responder to previous step?

  Nasal corticosteroid and nasal antihistamine

  with steroids ONLY WITH CAUTION
• What is the long term relief of allergic rhinitis?

  Immunotherapy
• What are some histamine receptors?

  Allergic inflammation

  Gastric acid secretion

  Neurotransmission

  Immunomodulation
• How do you get allergic inflammation?

  Alteration of vascular permeability --> extravasation --> oedema --> adhesion molecules --> inflammatory cell migration
• What is anti-histamines for allergy also known as?

  H1 receptor antagonsits
• What are the problems with first generation H1 receptor antagonists?

  Cross blood brain barrier and cause drowsiness and sedation
• What are some examples of first generation H1 receptor antagonist?

  Diphenhydramine (Benadryl), chlorphenamine (Piriton)
• What are the characteristics of first generation H1 receptor antagonist?

  Short-acting
• What are the side effects of first generation H1 receptor antagonist?

  Can have anti-muscarinic activity which causes dry mouth and suggested neurological effects long term
• Why don't second generation H1 receptor antagonists not cause drowsiness?

  Do NOT cause blood brain barrier so do not cause drowsiness
• What are some examples of second generation H1 receptor antagonist?

  Cetirizine, loratadine (claritin)
• What are some characteristics of second generation H1 receptor antagonist?

  Long-acting
• What are some side effects of second generation H1 receptor antagonist?

  Fewer so therefor okay for chronic treatment whereas first generation antihistamines are not
• What is the most effective single therapy for persistent allergic rhinitis?

  Glucocorticoid nasal spray
• Do corticosteroids have side effects?

  Minimal side effects if locally administered. Systemic glucocorticoids not recommended due to systemic side effects
• What are glucocorticosteroids at low dose vs high dose?

  Anti-inflammatory at low doses

  Immunosuppressive at higher doses
• How should you start dosing?

  Start with highest dose to achieve symptomatic control then step down approach
• What are the first generation agents of glucocorticosteroids?

  Beclomethasone, budesonide
• What are the second generation agents of glucocorticosteroids?

  Fluticasone propionate, ciclesonide
• What is the difference of first and second generation?

  Second generation have lower bioavailability and therefore fewer side effects
• Up to how many patients with allergic rhinitis are estimated to have concurrent asthma?

  40%
• Drug treatment of asthma depends on?

  On severity and local control
• What are the two types of control?

  Immediate symptomatic relief

  Asthma control
• What are the immediate symptomatic relied?

  Short acting B2-agonist inhaler (eg.albuterol)

  Combination low dose B2-agonist plus corticosteroid inhaler
• What are the asthma control?

  Depending on severity, dose regularly or as needed with combinations of inhaled short-/long-acting B2-agonist +/- inhaled corticosteroid

  Can add on leukotriene receptor antagonist, and antibiotic for severe cases
• What are the key cells of Pharmacological management of asthma?

  Eosinophils
• What are the key mediatory of pharmacological management of asthma?

  Cytokines that expand eosinophils (eg, IL-4, IL-5)

  IgE

  Leukotrienes
• What are some biologics useful in asthma?

  Anti-IgE (omalizumab/xolair), anti-IL4-Ra (dupilumab/dupixent blocks both IL-4 and |L-13 signalling), anti-IL-5

  Leukotriene receptor antagonists are also useful
• What is type I hypersensitivity?

  Cell bound antibody (IgE) + circulating antigen (allergen).

  The cross linking causes mast cell activation which makes histamine