Histamine and Antihistaminic Drugs

Question 1

What are the two enzymes that can convert histidine to histamine?

Answer 1

1. Histidine decarboxylase

2. Aromatic L-amino acid decarboxylase

Question 2

What is the H1 receptor responsible for?

Answer 2

1. Mucous secretion
2. Vascular relaxation
3. Bronchoconstriction
4. Itching
   All mediated by phospholipase C

Question 3

What is the agonist for H1/H2 receptors

Answer 3

2-methylhistamine/ 4-methylhistamine

Question 4

What is the H2 receptor responsible for

Answer 4

gastric acid secretions and some vascular effects mediateded by adenyly cyclase

Question 5

Which two tissues have the highest histamine content?

Answer 5

Lung and skin of the face

Question 6

How is histamine stored?

Answer 6

In secretory granules bound to heparin

Question 7

What are the three mechanism of histamine release from mast cells

Answer 7

1. Antigen binding to bound antibody (second exposure)
2. Via Drugs
3. By physical stimulation (heat, cold, light, touch)

Question 8

Which receptors on the mast cell directly inhibits histamine release from mast cells?

Answer 8

H2 receptors and Beta adrenergic receptor agonists (formation of cAMP in both cases)

Question 9

What are the affects of histamine on the smooth muscle of the lung and which receptor mediates it?

Answer 9

Bronchospasm, H1

Question 10

What are effects does H1 have on the smooth muscle of the vasculature?

Answer 10

1. Smooth muscle relaxation
2. Increased vascular permeability
3. Endothelial cell contraction
4. Capillary dilation

Question 11

What are the effects of H2 have on the smooth muscle of the vasculature?

Answer 11

1. Smooth muscle relaxation

2. Arteriolar dilation

Question 12

What effect does histamine have on gastric parietal cells?

Answer 12

H2 receptor stimulation leads to the release of HCl into the stomach

Question 13

What is the histamine triple response?

Answer 13

1. histamine induced vasodilatory effect
2. histamine induced axon reflex causing “flare”
3. Wheal formation from increased vascular permeability and edema

Question 14

What are the medical uses of histamine?

Answer 14

1. To determine bronchial hypereactivity of asthmatic patients
2. Used as a positive control for allergen skin test
3. Used neurologically to test the axon flare response

Question 15

List the classical H1 blockers and the mechanism of action for this group

Answer 15

1. diphenyhydramine, chlorpheniramin, fexofenadine, Loratidine/desloratidine/cetirizine (second generation H1 blockers, less hydrophobic)
2. Competitive blockade of H1 receptor

Question 16

List the therapeutic uses of H1 blockers

Answer 16

1. Blocks symptoms of allergies
2. Sedation (except fexofenadine)
3. Used as local anesthetic (diphenyhydramine)
4. Anticholinergic
5. Anti motion sickness (part of the anticholinergic effect)

Question 17

Describe the effects of H1 blocker toxicity on children and adults

Answer 17

1. In children it causes fever, flush, and CNS excitement

2. In adults it causes less fever and CNS excitement, more CNS depression

Question 18

This drug is used to stabilize mast cells from releasing histamine and can be used in asthmatic patients before the release of histamine

Answer 18

cromolyn sodium

Question 19

This drug is used to bind to the Fc portion of IgE thus preventing the binding and eventual activation of the mast cell

Answer 19

Omalizumab

Question 20

List the H2 blockers in order of drug that most blocks P450 enzymes in the liver to the least, also what is the effect of these drugs

Answer 20

1. Cimetidine> ranitidine> nizatidine> famotidine
2. They competitively block H2 and thus prevent the release of acid in the stomach, used to treat peptic ulcers (all OTC)

Question 21

Besides blocking P450, what other effect does cimetidine have?

Answer 21

Blocks testosterone receptor, can cause gynecomastia when using large doses for Zollinger-Ellison syndrome