Drugs and Allergy

Question 1

What is an allergy?

Answer 1

An autoimmune disorder (hyper immune response to allergens)

Maladaptive immune system response creating memory to antigens

Question 2

What are the key immune cells involved in allergic reactions?

Answer 2

Immediate: IgE, mast cells, basophils

Late phase: All the immediate ones, Eosinophils, dendritic cells, T-cells (Th1 and 2) and B cells

Question 3

What are mast cells?

Answer 3

Immune system cells in the tissues that store histamine, interleukins, proteoglycans (heparin-platelet activating factor) and various enzymes in their granules

Question 4

What causes degranulation of mast cells? What does degranulation cause?

Answer 4

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

Question 5

What occurs during the initial response to the allergen?

Answer 5

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

Question 6

Where are mast cells not present?

Answer 6

Epidermal cells, CNS and gastric mucosa

Question 7

What do histamines and prostaglandins cause?

Answer 7

Tickling, itchiness, nose rubbing and the allergic salute

Question 8

What do histamines and leukotrienes cause?

Answer 8

Sneezing, runny nose, post nasal drip, throat clearing

Question 9

What do histamine, leukotrienes, bradykinin and platelet activating factor cause?

Answer 9

Nasal congestion, mouth breathing, stuffy nose (mucosal edema) and snoring

Question 10

Where are eosinophils and basophils found?

Answer 10

In the blood
Basophils also have IgE
Also release leukotrienes, proteins, platelet activating factor

Question 11

What is histamine?

Answer 11

An autocoid used for self relief using NO, prostaglandins, serotonin, bradykinin that is stored in tissue mast cells and blood basophils

Question 12

What is histamine released by?

Answer 12

Anitgens, allergic responses (immediate hypersensitivity), drugs, morphine, succinylcholine, radio contrast media, insect venoms, phsyical factors (scratching, cold)

Question 13

What does the H1 receptor cause?

Answer 13

The target of classic antihistamines. Causes increased nasal and bronchial secretion, bronchoconstriction, constriction of GI smooth muscle (cramping, diarrhea), itching and pain

Question 14

What does the H2 receptor cause?

Answer 14

Gastric acid secretion

Question 15

What do the H1 and H2 receptors cause?

Answer 15

Reduced blood pressure and triple responses on the skin (red, wheal, flare)

Question 16

What do the H3 receptors cause?

Answer 16

Negative feedback to inhibit neurotransmitters

Question 17

What do the H4 receptors cause?

Answer 17

Chemotaxis of mast cells, esoinophils and neutrophils

Question 18

What is the triple response of histamine on the skin?

Answer 18

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

Question 19

What occurs in allergic rhinitis?

Answer 19

Rhinorrhea, plugged nasal passages, itching, tearing, fatigue, headache
Can be seasonal or perennial
Occurs more in those with asthma

Question 20

How do antihistamines work?

Answer 20

Block the H1 receptor to decrease itching, vascular permeability, bronchial secretions, relax bronchial smooth muscle and decrease the cough receptor stimulation

Question 21

What is the pharmacotherapy for allergic rhinitis?

Answer 21

Antihistamines, intranasal glucocorticoids (fluticasone), leukotriene modifiers (montelukast), decongestants (phenylephrine), mast cell stabilizers (cromolyn sodium), anticholinergic (ipratropium), anti-IgE therapy (omalizumab) and systemic steroids

Question 22

What are some examples of antihistamines?

Answer 22

1st gen: chlorpheniramine, diphenhydramine,
2nd gen: certizine, loratidine
3rd gen:fexofenadine ,azelastine

Question 23

What else can be used to treat allergic rhinitis?

Answer 23

Avoidance and allergen specific immunotherapy

Question 24

What are the additional effects of 1st generation antihistamines?

Answer 24

Non-histamine blockage actions such as sedation, atropinic and antiemetic, problems with cognition, learning and memory, psychomotor

Question 25

What are the additional effects of 2nd and 3rd generation antihistamines?

Answer 25

Prevent mast cell release of mediators that cause inflammation
No sedation
Don’t get through BBB as easily

Question 26

What can be combined with an antihistamine?

Answer 26

A decongestant such as phenylephrine and pseudoephedrine

Question 27

How should antihistamines be given?

Answer 27

Best given before an anticipated allergic reaction

Question 28

What are the drug interactions with antihistamines?

Answer 28

Metabolized by CYP3A4 (grapefruit juice may block metabolism)

Question 29

Why might IV antihistamine not be helpful?

Answer 29

Because the action is immediate and by the time a patient gets to the hospital, it may not be helpful anymore

Question 30

What should be used in severe allergic rhinitis?

Answer 30

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

Question 31

What dosage forms does azelastine come as?

Answer 31

Intranasal (rapid) and eyedrops

Question 32

What are the potential effects of intranasal glucocorticoids?

Answer 32

Effect on growth, bone density, cataract formation and intraocular pressure

Question 33

How do corticosteroids work?

Answer 33

Block phospholipase A2 and protein synthesis (to make COX-1 and 2)

Question 34

What is a leukotriene receptor antagonist used with?

Answer 34

Normally used with an antihistamine or intranasal glucocorticoid

Question 35

What is phenylephrine?

Answer 35

An alpha 1 agonist that causes increased vasoconstriction and reduced nasal swelling
Replacing pseudoephedrine
Use for 3 days at most, otherwise rebound congestion

Question 36

What are the side effects of decongestants?

Answer 36

Insomnia, nervousness, headache, palpitations, hypertension and urinary retention
Intranasal application will reduce these side effects

Question 37

What is a mast cell stabilizer?

Answer 37

Inhibits mast cell degranulation and release of mediators

Less effective, must be given before exposure but almost no local/systemic toxicity

Question 38

How can an anticholinergic (ipratropium) help?

Answer 38

Reduces mucus secretion with no effect on inflammation (no relief of sneezing, itching or congestion)
Useful if primary symptom is nasal discharge

Question 39

What are the adverse effects of ipratropium?

Answer 39

Atropinic (dry mucus membranes, urinary retention)

Caution in glaucoma and prostatic hypertrophy

Question 40

How can an anti-IgE antibody (omalizumab) help?

Answer 40

Will selectively bind to IgE and prevents IgE from binding to cells and reduces free IgE in serum

Question 41

How does allergen specific immunotherapy work?

Answer 41

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)

Question 42

What are the indications for immunotherapy?

Answer 42

IgE in the serum or skin sensitivity to the allergen, poor pharmacotherapy response or side effects, patient preference

Question 43

When should immunotherapy be avoided?

Answer 43

Severe asthma, cardiovascular disease, high dose beta blocker, pregnancy (initiation)