Drugs and Allergy Flashcards
What is an allergy?
An autoimmune disorder (hyper immune response to allergens)
Maladaptive immune system response creating memory to antigens
What are the key immune cells involved in allergic reactions?
Immediate: IgE, mast cells, basophils
Late phase: All the immediate ones, Eosinophils, dendritic cells, T-cells (Th1 and 2) and B cells
What are mast cells?
Immune system cells in the tissues that store histamine, interleukins, proteoglycans (heparin-platelet activating factor) and various enzymes in their granules
What causes degranulation of mast cells? What does degranulation cause?
Upon stimulation of allergen. Degranulation causes increased blood flow and permeability of blood vessels (inflammation, swelling, increased heart rate, constricted pupils), contraction of smooth muscles (airways), increased mucus production and fluid secretion
What occurs during the initial response to the allergen?
Initial exposure: Allergen bind to IgE on mast cell, releases IL-4 and TNFalpha which activates Th2 to release IL-4 and cause plasma cells to become IgE
Subsequent exposure: Allergen binds to dendritic cell which causes CD4+ cells to activate Th2 to activate B cells to form IgE
Where are mast cells not present?
Epidermal cells, CNS and gastric mucosa
What do histamines and prostaglandins cause?
Tickling, itchiness, nose rubbing and the allergic salute
What do histamines and leukotrienes cause?
Sneezing, runny nose, post nasal drip, throat clearing
What do histamine, leukotrienes, bradykinin and platelet activating factor cause?
Nasal congestion, mouth breathing, stuffy nose (mucosal edema) and snoring
Where are eosinophils and basophils found?
In the blood
Basophils also have IgE
Also release leukotrienes, proteins, platelet activating factor
What is histamine?
An autocoid used for self relief using NO, prostaglandins, serotonin, bradykinin that is stored in tissue mast cells and blood basophils
What is histamine released by?
Anitgens, allergic responses (immediate hypersensitivity), drugs, morphine, succinylcholine, radio contrast media, insect venoms, phsyical factors (scratching, cold)
What does the H1 receptor cause?
The target of classic antihistamines. Causes increased nasal and bronchial secretion, bronchoconstriction, constriction of GI smooth muscle (cramping, diarrhea), itching and pain
What does the H2 receptor cause?
Gastric acid secretion
What do the H1 and H2 receptors cause?
Reduced blood pressure and triple responses on the skin (red, wheal, flare)
What do the H3 receptors cause?
Negative feedback to inhibit neurotransmitters
What do the H4 receptors cause?
Chemotaxis of mast cells, esoinophils and neutrophils
What is the triple response of histamine on the skin?
Red area at the site of injection (vasodilation)
Wheal replaces red area (edema)
Bright read flare (indirect vasodilation from axonal reflex)
Negative control, positive control (with histamine), compare allergen testing to controls
What occurs in allergic rhinitis?
Rhinorrhea, plugged nasal passages, itching, tearing, fatigue, headache
Can be seasonal or perennial
Occurs more in those with asthma
How do antihistamines work?
Block the H1 receptor to decrease itching, vascular permeability, bronchial secretions, relax bronchial smooth muscle and decrease the cough receptor stimulation
What is the pharmacotherapy for allergic rhinitis?
Antihistamines, intranasal glucocorticoids (fluticasone), leukotriene modifiers (montelukast), decongestants (phenylephrine), mast cell stabilizers (cromolyn sodium), anticholinergic (ipratropium), anti-IgE therapy (omalizumab) and systemic steroids
What are some examples of antihistamines?
1st gen: chlorpheniramine, diphenhydramine,
2nd gen: certizine, loratidine
3rd gen:fexofenadine ,azelastine
What else can be used to treat allergic rhinitis?
Avoidance and allergen specific immunotherapy
What are the additional effects of 1st generation antihistamines?
Non-histamine blockage actions such as sedation, atropinic and antiemetic, problems with cognition, learning and memory, psychomotor
What are the additional effects of 2nd and 3rd generation antihistamines?
Prevent mast cell release of mediators that cause inflammation
No sedation
Don’t get through BBB as easily
What can be combined with an antihistamine?
A decongestant such as phenylephrine and pseudoephedrine
How should antihistamines be given?
Best given before an anticipated allergic reaction
What are the drug interactions with antihistamines?
Metabolized by CYP3A4 (grapefruit juice may block metabolism)
Why might IV antihistamine not be helpful?
Because the action is immediate and by the time a patient gets to the hospital, it may not be helpful anymore
What should be used in severe allergic rhinitis?
Intranasal glucocorticoid (fluticasone), effective for nasal and ocular symptoms (itching, sneezing, discharge, congestion) 7 days (OD) to become maximally effective, increasing dose will only increase side effects, not benefits
What dosage forms does azelastine come as?
Intranasal (rapid) and eyedrops
What are the potential effects of intranasal glucocorticoids?
Effect on growth, bone density, cataract formation and intraocular pressure
How do corticosteroids work?
Block phospholipase A2 and protein synthesis (to make COX-1 and 2)
What is a leukotriene receptor antagonist used with?
Normally used with an antihistamine or intranasal glucocorticoid
What is phenylephrine?
An alpha 1 agonist that causes increased vasoconstriction and reduced nasal swelling
Replacing pseudoephedrine
Use for 3 days at most, otherwise rebound congestion
What are the side effects of decongestants?
Insomnia, nervousness, headache, palpitations, hypertension and urinary retention
Intranasal application will reduce these side effects
What is a mast cell stabilizer?
Inhibits mast cell degranulation and release of mediators
Less effective, must be given before exposure but almost no local/systemic toxicity
How can an anticholinergic (ipratropium) help?
Reduces mucus secretion with no effect on inflammation (no relief of sneezing, itching or congestion)
Useful if primary symptom is nasal discharge
What are the adverse effects of ipratropium?
Atropinic (dry mucus membranes, urinary retention)
Caution in glaucoma and prostatic hypertrophy
How can an anti-IgE antibody (omalizumab) help?
Will selectively bind to IgE and prevents IgE from binding to cells and reduces free IgE in serum
How does allergen specific immunotherapy work?
Administer increasing doses of a solution of allergens over 3-5 years to which a patient is shown to be sensitive (subcutaneous or sublingual)
Dose until fewer symptoms with natural exposure (weekly, monthly)
What are the indications for immunotherapy?
IgE in the serum or skin sensitivity to the allergen, poor pharmacotherapy response or side effects, patient preference
When should immunotherapy be avoided?
Severe asthma, cardiovascular disease, high dose beta blocker, pregnancy (initiation)
