Drugs and Allergy

Question 1

Name 6 different allergic disorders

Answer 1

allergic rhinitis (hay fever)
allergic conjunctivitis (pink eye)
atopic dermatitis (eczema)
urticaria (hives)
asthma
anaphylaxis

Question 2

what is an allergy?

Answer 2

an autoimmune disorder where there is a hyperimmune response to allergens

Question 3

what causes an allergy?

Answer 3

maladaptive immune system response creating memory to antigens

Question 4

what are 7 key players involved in an allergic reaction? which are involved in the immediate reaction?

Answer 4

Immediate: IgE, mast cells, basophils
eosinophils
dendritic cells
T-cell (Th1 and 2)
B cells
All components involved in late phase reaction

Question 5

What is the initial response to an allergen?

Answer 5

allergen binds to dendritic cells
an antigen acts on the T cells
Th2 acts on the B cells
B cells act on plasma cells
Creates IgE antibodies that will bind to mast cell upon exposure to the allergen
upon subsequent exposures, allergen binds directly with IgE bound to mast cell, causing release of IL-4 and TNFalpha, that act on Th2, which releases IL-4 that binds to plasma cell and releases IgE antibodies

Question 6

what are mast cells?

Answer 6

tissue cells of the immune system found in loose connective tissue, organs, vasculature, nerves, skin, respiratory tract, etc.
not present in epidermal cells, CNS, gastric mucosa

Question 7

what is the function of mast cells?

Answer 7

store histamine, interleukins, proteoglycans and various enzymes in their granules at cytoplasm

Question 8

what 3 things occur when the mast cell is degranulated?

Answer 8

1) increased blood flow and permeability of blood vessels (inflammation and swelling)
2) contraction of smooth muscles
3) increased mucus production and fluid secretion

Question 9

what mediators are associate with tickling, itching, nose rubbing, and allergic salute?

Answer 9

histamine and prostaglandins released by mast cells

Question 10

what mediators are associated with sneezing, runny nose, post nasal drip, and throat clearing?

Answer 10

histamine and leukotrienes released by mast cells, eosinophils and basophils

Question 11

what mediators are associated with nasal congestion, mouth breathing, stuffy nose, and snoring?

Answer 11

histamine, leukotrienes, bradykinin, and platelet activating factor released by mast cells, eosinophils, and basophils

Question 12

what is histamine?

Answer 12

an autacoid (self-relief) which function like hormones but are not actually hormones
stored in tissue mast cells and blood basophils

Question 13

what will cause antihistamine release?

Answer 13

antigens
allergic responses
drugs (morphine, succinylcholine)
insect venoms
scratching, cold

Question 14

what is the H1 receptor important for?

Answer 14

important for allergic disorders and is the target of classic antihistamines

Question 15

what effects does the H1 receptor exert when bound to histamine?

Answer 15

1) contraction; gastrick and respiratory smooth muscle
2) vasodilation
3) increased vascular permeability
4) pruritus
5) increased bronchial secretions and viscosity

Question 16

what effects does the H2 receptor exert when stimulated? inhibited?

Answer 16

stim: gastric acid secretion
inhibited: decreased gut acidity
also involved in vasodilation

Question 17

what is the H3 receptor involved with?

Answer 17

cholinergic neurotransmission

Question 18

what types of cells are H4 receptors involved with?

Answer 18

eosinophils
neutrophils
CD4 T cells

Question 19

what is the triple response of histamine when pricked into the skin?

Answer 19

1) red area at site of injection due to vasodilation
2) wheal replaces red area (edema)
3) bright red flare - indirect vasodilation

Question 20

what are some symptoms of allergic rhinitis?

Answer 20

rhinorrhea
plugged nasal passages
itching (eyes, nose, throat)
tearing
fatigue
headache

Question 21

what are the two different kinds of allergic rhinitis?

Answer 21

seasonal (airborne pollen)

perennial (animal dander, mold, dust)

Question 22

what are the various treatment options for AR? (8 points)

Answer 22

1) antihistamines
2) intranasal glucocorticoids
3) leukotriene modifiers
4) decongestants
5) mast cell stabilizers
6) anticholinergic
7) anti-IgE therapy
8) systemic steroids

Question 23

how do antihistamines work?

Answer 23

block the action of histamine by blocking the H1 receptor

Question 24

what are the effects of antihistamines?

Answer 24

decreased itching
decreased vascular permeability
decreased bronchial secretions
relaxation of bronchial smooth muscle
decreased cough receptor stimulation

Question 25

what are some additional effects of 1st gen AH?

Answer 25

non-histamine blocking actions leading to sedation, atropinic and anti-emetic effects

Question 26

what are some additional effects of 2nd and 3rd gen AH?

Answer 26

prevent mast cell release of mediators that cause inflammation

Question 27

what are some examples of AH's? indicate which is 1st, 2nd, or 3rd gen

Answer 27

``` first: chlorpheniramine diphenhydramine second: cetirizine loratadine 3rd: fexofenadine ```

Question 28

why do 2nd and 3rd gen AH have minimal sedating/anticholinergic effects?

Answer 28

they don't pass through the BBB very easily so CNS effects are minimal

Question 29

what are antihistamines usually combined with?

Answer 29

decongestants such as pseudoephedrine and phenylephrine

Question 30

describe the PK for antihistamines?

Answer 30

half lives variable (8-24h) concentration in breast milk parallels concentration in plasma most metabolized by Cyt P450 (Cyp3A4) grapefruit juice may block metabolism

Question 31

what are the routes of admin for AH?

Answer 31

``` oral intranasal intravenous (anaphylaxis) ```

Question 32

what are the indications for antihistamines?

Answer 32

drug of choice for mild-mod allergic rhinitis relieves sneezing, itching, nasal discharge, and ocular symptoms (tearing, itching, erythema) best for exudative allergies (hay fever)

Question 33

what is the drug of choice for severe AR?

Answer 33

intranasal glucocorticoid (fluticasone)

Question 34

what are some side effects of first gen AH?

Answer 34

``` atropinic effects somnolence (drowsiness) problems with cognition learning and memory impairment psychomotor effects ```

Question 35

what is the youngest age that can use first gen AH?

Answer 35

6 y.o

Question 36

what is the name of the intranasal second gen AH?

Answer 36

azelastine

Question 37

which second gen AH is best to use in children?

Answer 37

cetirizine

Question 38

what is fluticasone effective for?

Answer 38

nasal and ocular symptoms; itching, sneezing, discharge, congestion most effective for prevention and treatment

Question 39

what is the dosing for fluticasone and how long does it take to reach max effect?

Answer 39

OD dosing | may take 7 days

Question 40

what is the function of leukotrienes?

Answer 40

involved in infiltration of inflammatory cells, mucous secretion, and affect airway constriction released during allergic inflammation by mast cells, eosinophils, basophils, and inflammatory cells

Question 41

name a leukotriene receptor antagonist

Answer 41

montelukast

Question 42

what is the indication for montelukast?

Answer 42

modest relief of congestion, itching, discharge less effective than intranasal glucocorticoids normally used with AH or intranasal glucocorticoid

Question 43

what is the mechanism of phenylephrine?

Answer 43

alpha 1 receptor agonist to cause | increased vasoconstriction, reduced nasal swelling

Question 44

what is phenylephrine helpful for?

Answer 44

congestion only | not helpful for sneezing, itching, discharge

Question 45

what are the side effects of decongestants?

Answer 45

``` insomnia nervousness headache palpitations hypertension urinary retention ```

Question 46

what is an important counselling point for decongestants?

Answer 46

if you use more than 3-5 days, could cause rebound congestion

Question 47

what do mast cells do?

Answer 47

activated by response to allergens by releasing mediators such as histamine, leukotrienes, PG, PAF, etc.

Question 48

what is an example of a mast cell stabilizer? what does it do?

Answer 48

cromolyn sodium | inhibits mast cell degranulation and release of mediators

Question 49

what are some counselling tips for mast cell stabilizers?

Answer 49

less effective than intranasal corticosteroids must be given before exposure almost no local/systemic toxicity

Question 50

what is an example of an anticholinergic?

Answer 50

ipratropium

Question 51

how does ipratropium help with allergic rhinitis

Answer 51

reduces mucus secretion no effect on inflammation no relief of sneezing, itching, congestion useful if primary symptom is nasal discharge

Question 52

what are some side effects to ipratropium?

Answer 52

atropinic like: dry mucous membranes urinary retention

Question 53

who should use caution when using ipratropium?

Answer 53

glaucoma | prostatic hypertrophy

Question 54

what is another drug used to treat allergic rhinitis?

Answer 54

Omalizumab

Question 55

how does omalizumab work?

Answer 55

anti-IgE antibody - given SC that selectively bind human immunoglobulin E (IgE) prevents IgE bindings to cells and reduces free IgE in serum

Question 56

why are oral glucocorticoids not preferred for allergic rhinitis?

Answer 56

major side effects

Question 57

how does allergen specific immunotherapy work treat allergic rhinitis?

Answer 57

subcutaneous allergen immunotherapy administer increasing doses of a solution of allergens sc to which a patient is shown to be sensitive (skin test) weekly then monthly injections for years - dose increased until fewer symptoms with natural exposure once desired dose established, monthly maintenance

Question 58

how long does allergen specific immunotherapy last?

Answer 58

3-5 years | benefit may continue when discontinued

Question 59

who should avoid allergen specific immunotherapy?

Answer 59

severe asthma patients CV disease pts those using a high dose of beta blockers pregnant patients

Question 60

what are the indications for immunotherapy?

Answer 60

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