9 - Drugs & Allergy Flashcards
What is an allergy?
- Inflammatory disorder
- Maladaptive immune system response creating memory antigens
What are the key cells involved in allergic reactions?
- Mast cells
- Basophils
- Eosinophils
- Dendritic cells
- T-cells (Th 1 and 2)
- B-cells
- Plasma cells
What are mast cells?
- Tissue cells of immune system found in loose connective tissue, organs, vasculature, nerves, skin, respiratory tract, etc
- Not present in epidermal cells, CNS, or gastric mucosa
- Store histamine, interleukins, proteoglycans (ex: heparin), and various enzymes in their granules at cytoplasm
- Granules released upon stimulation of allergen (degranulation)
What happens when mast cell granules are released?
- Increased blood flow and permeability of blood vessels
- Contraction of smooth muscles
- Increased mucous production and fluid secretion
What is the effect of degranulation on the GI tract?
Expulsion of contents (diarrhea, vomiting)
What is the effect of degranulation on airways?
- Congestion and blockage of airways (wheezing, coughing, phlegm)
- Swelling and mucous secretion in nasal passages
What is the effect of degranulation on blood vessels?
- Increased fluid in tissues causing increased flow of lymph to lymph nodes
- Increased cells and protein in tissues
- Increased effector response in tissues
What allergy symptoms are caused by histamine and prostaglandins?
- Tickling
- Itchiness
- Nose rubbing (allergic salute)
What allergy symptoms are caused by histamine and leukotrienes?
- Sneezing
- Runny nose
- Post nasal drip
- Throat clearing
What allergy symptoms are caused by histamine, leukotrienes, bradykinin, and platelet activating factor?
- Nasal congestion
- Stuffy nose
- Congested airway => snoring
Where is histamine stored?
Tissue mast cells and blood basophils
What can cause cells to release histamine?
- Antigens (immediate hypersensitivity)
- Drugs (morphine, succinylcholine)
- Insect venoms
- Physical factors (scratching, cold)
Which histamine receptor is most important in allergic disorders?
H1
What does activation of the H1 receptor cause?
- Gastric and respiratory smooth muscle contraction
- Vasodilation
- Increased vascular permeability
- Itching
- Increased bronchial secretions and viscosity
What does activation of the H2 receptor cause?
Gastric acid secretion
What is the main function of H3 receptors?
Neurotransmitter control
What is the main function of H4 receptors?
Immune response regulation
What does activation of H1 and H2 receptors cause?
- Reduced BP
- Skin vasodilation
What is the response when the skin is pricked w/ an allergen?
- Red area at site of injection (vasodilation)
- Wheal replaces red area (edema)
- Bright red flare, indirect vasodilation (axonal reflex)
What is the pharmacotherapy for allergic rhinitis?
- Antihistamines
- Intranasal glucocorticoids
- Leukotriene modifiers
- Decongestants
- Mast cell stabilizers
- Anticholinergics
- Anti-IgE therapy
What will H1 receptor blockage cause?
- Decreased itching
- Decreased vascular permeability
- Decreased bronchial secretions
- Relaxation of bronchial smooth muscle
- Decreased cough receptor stimulation
What are some additional effects of antihistamines?
- 1st gen have non-histamine blockage actions, like sedation, atropinic, and anti-emetic
- 2nd and 3rd gen prevent mast cell release of mediators that cause inflammation
How can antihistamines be administered?
- Oral
- Intranasal
- IV (only used later in anaphylaxis but benefit questionable)
How are antihistamines metabolized?
CYP P450 system
What are indications for antihistamines?
- Mild to moderate allergic rhinitis
- Best for exudative allergies
- Seasonal rhinitis
Which 2nd gen antihistamine can be given to children?
Cetirizine
What are indications for fluticasone?
- Nasal and ocular sx (itching, sneezing, discharge, congestion)
- Severe sx
- Most effective for prevention and tx
What is the dosing for fluticasone?
Once daily, produces a plateau of dose response curve
What are side effects of fluticasone?
- Epistaxis
- Normal SE of oral glucocorticoids (bone density, cataract formation, intraocular pressure)
What is the difference between leukotrienes and prostaglandins?
- Leukotrienes mediate bronchiole constriction, mucous secretion, and inflammation of airway
- Prostaglandins mediate pain, fever, and inflammation
Which drug is a leukotriene receptor antagonist?
Montelukast
Are intranasal glucocorticoids more effective than leukotriene receptor antagonists?
Yes
What effect does montelukast have?
Modest relief of congestion, itching, and discharge
Are leukotriene receptor antagonists normally used alone?
No, normally used w/ antihistamine or intranasal glucocorticoid
What is phenylephrine?
- Decongestant
- Alpha 1 receptor agonist
What symptoms does phenylephrine help w/?
Only congestion
What is phenylephrine often given w/?
Antihistamine
What are side effects of phenylephrine?
- Insomina
- Nervousness
- Headache
- Palpitations
- Hypertension
What is an important usage warning for phenylephrine?
Only use for a max of 3 days b/c can cause rebound congestion
What is the function of cromolyn sodium?
Inhibits mast cell degranulation and release of mediators
Can mast cell stabilizers be given after exposure to the allergen?
No, must be given before exposure
What is the function of ipratropium?
Reduces mucous secretion, but no effect on inflammation
When are anticholinergics useful for allergic rhinitis?
If primary symptom is nasal discharge
What are side effects of ipratropium?
- Dry mucous membranes, urinary retention
- Caution in glaucoma and prostatic hypertrophy
What is omalizumab?
Anti-IgE antibody
What are indications for immunotherapy?
- IgE in serum or skin sensitivity to allergen (cat, pollen, dog)
- Poor pharmacotherapy response or SE
- Px preference
When should immunotherapy be avoided?
- Severe asthma
- CV disease
- High dose beta adrenergic receptor blocker
- Do not initiate during pregnancy
Immunotherapy is thought to be as effective as _____
Intranasal glucocorticoids
