Anti-histamines and Allergy Pharmacology

Question 1

What stores histamine in blood? In peripheral tissues?

Answer 1

Blood - basophils, Peripheral tissues - Mast cells

Question 2

For which Histamine receptors do we have drugs targeting them?

Answer 2

H1 and H2 (no drugs for H3 and H4)

Question 3

How many histamine receptor subtypes are there, and name the primary physiologic role for each

Answer 3

H1 - Allergic inflammation, H2 - Gastric acid secretion, H3 - neurotransmitter modulation, H4 - propagation of inflammatory cells

Question 4

These 5 things cause histamine release without IgE binding

Answer 4

Venoms, morphine, tubocurarine, succinylcholine, cold or tissue injury

Question 5

Anaphylactoid reactions

Answer 5

Clinically identical to anaphylaxis, but caused by a non-immune mediated mechanism (eg venoms, succinylcholine, etc)

Question 6

Triple response of Lewis

Answer 6

Red spot (capillary dilation), Wheal (capillary permeability) and Flare (arteriole dilation 1 cm away), follows IM injection of histamine

Question 7

Antihistamines can antagonize other receptors besides histamine receptors. What other receptors?

Answer 7

Muscarinic, alpha-adrenergic, serotenergic, cardiac ion and calcium channels

Question 8

Inverse agonist

Answer 8

Something that binds a constitutively active receptor and keeps it in its INACTIVE state

Question 9

What is the improvement from first to second generation antihistamines?

Answer 9

Second gen have less penetrance into CNS and therefore less sedation

Question 10

Nasal and ophthalmalogic antihistamines

Answer 10

Nasal - azelastine (astelin), Ophthalmologic - Olopatadine (patanol)

Question 11

In addition to poorer penetration of the BBB, why do second generation antihistamines not end up in the CNS?

Answer 11

They are pumped out by P-glycoprotein

Question 12

What is added in combination products such as Clairitin-D and Allegra-D and why?

Answer 12

A decongestant, because the antihistamine isnt as effective as a decongestant (congestion mediated mainly by leukotrienes, not histamine)

Question 13

What often causes chronic urticaria?

Answer 13

Autoantibody IgG to IgE or IgE receptor

Question 14

Histamine can affect the vestibular system. What use of histamine arises from this?

Answer 14

Antiemetic to prevent nausea and vomiting associated with motion sickness

Question 15

Why might antihistamines be administered to a patient receiving antipsychotics?

Answer 15

Some antipsychotics cause Parkinson like symptoms, and antihistamines (eg diphenhydramine) can reduce these symptoms

Question 16

How do steroids achieve downregulation of inflammatory mediators?

Answer 16

They bind glucocorticoid response elements which lead to inhibition of Histone Acetyl Transferases (HAT) by recruitment of histone deacetylases, altering the acetylation of certain histones

Question 17

What is the first line therapy for allergic rhinitis?

Answer 17

Topical steroids (nasal sprays)

Question 18

What drug has leukotriene effects and how?

Answer 18

Montelukast, a high affinity competitive antagonist at leukotriene receptor (cys-LT1)

Question 19

Omalizumab

Answer 19

Approved for asthma, also used for allergic rhinitis, is an anti-IgE drug

Question 20

Which H2 antagonist has the most side effects and what are they?

Answer 20

Cimetidine - antiandrogen effects, cypotenias (especially thrombocytopenia), and drug-drug interactions (inhibits several CYP enzymes)

Question 21

What antimuscarinic is used as a second line therapy for allergic rhinitis?

Answer 21

Ipratropium

Question 22

List 4 commonly used H2 blockers

Answer 22

Cimetidine (tagamet), Ranitidine (Zantac), Famotidine (Pepcid), Nizatidine (Axid)

Question 23

List 5 second generation antihistamines

Answer 23

Fexofenadine (allegra), Loratadine (claritin), desloratadine (clarinex), cetirizine (zyrtec), levocetirizine (xyzal)

Question 24

What class of drug is diphenhydramine?

Answer 24

A first generation antihistamine (H1 functional antagonist)

Question 25

Treatments for anaphylactic shock

Answer 25

Epi (top priority), as needed any of the following: volume expansion, corticosteroids, beta-2 agonists, antihistamine, H2 blockers