Drugs For Allergic Reactions

Question 0

H1 receptor antagonists (Antihistamines)

Answer 0

First generation:
Chlorpheniramine
Diphenhydramine

Second generation:
Cetirizine
Fexofenadine
Loratadine

Question 1

Autacoids

Answer 1

Histamine
Prostaglandins
Thromboxane
Leukotrienes

Question 2

Modulators of histamine release

Answer 2

Mast cell stabilizers:
Cromolyn
Omalizumab

Question 3

Leukotriene receptor antagonist

Answer 3

Montelukast

Question 4

Histamine

Answer 4

Increases capillary permeability to leukocytes & some proteins
Synthesized from histidine by histidine-decarboxylase
Stored in mast cells located predominantly in skin, gastric mucosa, lung, tissues surrounding blood vessels & nerves
Stored in basophils
High amount found in cerebral spinal fluid & in neurons
(See notes for all effects)

Question 5

Causes of histamine release

Answer 5

Anaphylaxis/allergy
Venoms
Drugs (morphine, vancomycin)
Inflammatory mediators (cytokines)

Question 6

Histamine receptor subtypes

Answer 6

H1 & H2
Located on effector cells
Physiological effect depends on cell & ratio of H1:H2 receptors
Both are g-protein coupled; H1 coupled to Gq (IP3, DAG) & H2 coupled to Ga (adenylyl cyclase)
H3 & H4
Found in CNS & on inflammatory cells respectively
No clinically useful purpose found yet

Question 7

H1 antagonists pharmacological properties

Answer 7

Cardiovascular- partially inhibit vasodilation; incomplete since H2 receptors also involved//block capillary permeability//flare & itch inhibited
Airway smooth muscle- antagonize histamine-induced bronchoconstriction in asthmatics//not effective in inhibiting allergic bronchoconstriction since autocoids other than histamine are involved (leukotrienes)
Neural tissue- inhibit pruritus

Question 8

H1 antagonists therapeutic uses

Answer 8

Acute exudative types of allergy (hay fever, pollinosis) that present w/ rhinitis, urticaria, & conjunctivitis
First generation are also used for their effects on CNS (prevention of motion sickness, sedation)
Not effective for treating anaphylaxis or asthma

Question 9

H1 antagonists drug interactions

Answer 9

CNS effects of first gen are potentiated by concurrent ingestion of alcohol or other CNS depressants

Question 10

Cromolyn MOA

Answer 10

Block release of inflammatory mediators from mast cells & basophils
Decrease number of infiltrating inflammatory cells
Decrease bronchial hyperresponsiveness

Question 11

Cromolyn therapeutic uses

Answer 11

Inhalation for asthma
Nasal insufflation for allergic rhinitis
Eye drops for conjuctivitis

Question 12

H1 antagonists administration & elimination

Answer 12

First generation- oral, topical, parenteral
Second generation- oral only//exhibit very long duration of action (days)- metabolites are active & bind with very high affinity to the H1 receptors

Metabolized by P450 enzymes in the liver

Question 12

H1 antagonists adverse reactions

Answer 12

CNS depression- diminished alertness, slow reaction, somnolence
CNS stimulation- certain individuals (especially children)- a feature of poisoning
GI- anorexia, nausea, vomiting, diarrhea or constipation
Antimuscarinic side effects- dry mouth, urinary retention
Second generation are generally devoid of sedative effects, anti muscarinic effects & GI effects (except Cetirizine)

Question 12

Cromolyn administration

Answer 12

Powder & solution for inhalation; nasal & ocular
Not effective orally
Used prophylactically- May not be effective for 2-6 weeks

Question 13

Cromolyn adverse reactions

Answer 13

Minimal- cough, wheezing on inhalation; irritation to nasal mucosa & eye

Question 14

Omalizumab MOA

Answer 14

Recombinant humanized (chimeric) monoclonal IgG antibody directed against circulating IgE
Recognizes specific Fc portion of IgE that binds to the high affinity IgE receptors (Fc-epsilon RI) blocking binding of IgE to mast cells & basophils
Decreases circulating free IgE

Question 15

Omalizumab administration

Answer 15

IV or subcutaneous administration every 2-4 weeks

Question 16

Omalizumab adverse reactions

Answer 16

Can cause injection site reactions & headache

Question 17

Omalizumab therapeutic uses

Answer 17

Asthma; although effective, it is not approved for treatment of allergic rhinitis

Question 18

Montelukast MOA

Answer 18

Competitive antagonists at the cysLT1

Block the effects of LTC4, LTD4, & LTE4

Question 19

Montelukast adverse effects

Answer 19

GI upset

Question 20

Montelukast drug interactions

Answer 20

Inducers & inhibitors of P450 have corresponding effects on its metabolism

Question 21

Montelukast therapeutic uses

Answer 21

Allergic rhinitis- decrease nasal congestion, itching, sneezing
Asthma- prevent bronchoconstriction