Histamine/antihistamines

Question 1

Where is histamine stored?

3

Answer 1

(1) Vesicles
(2) Mast cells
(3) Basophils

Question 2

Where is histamine synthesized on demand?

4

Answer 2

(1) Skin
(2) Gastric mucosa
(3) Intestinal mucosa
(4) CNS

Question 3

When is histamine released?

3

Answer 3

(1) Antigen binding to IgE antibodies on mast cells
(2) Cell damage
(3) Selected drug action such as morphine and curare

Question 4

Where are H1 receptors found?

3

Answer 4

(1) Smooth muscle
(2) Endothelium
(3) Brain

Question 5

Where are H2 receptors found?

3

Answer 5

(1) Gastric mucosa
(2) Cardiac muscle
(3) Brain

Question 6

Where are H3 receptors found?

Answer 6

Presynaptic membranes of the brain

Question 7

Where are H4 receptors found?

Answer 7

Eosinophils and neutrophils

Question 8

What are the H1 receptor-mediated effects?

6

Answer 8

(1) Vasodilation of arterioles and precapillary sphincters via NO release
(2) Increased permeability of postcapillary venule (edema)
(3) Bronchoconstriction
(4) Pain and itch
(5) Increased GI contractions
(6) Wakefulness

Question 9

What are the H2 receptor-mediated effects?

Answer 9

(1) Vasodilation of arterioles and precapillary sphincters
(2) Positive inotropic effect (increased heart contractility)
(3) Positive chronotropic effect (increased heart rate)
(4) Increased gastric acid secretion
(5) Increased pepsin secretion

Question 10

What is the most important use of therapeutic H2 receptor blockers?

Answer 10

Block gastric acid secretion

Question 11

What is the histamine triple response?

Answer 11

(1) Vasodilation - localized red spot
(2) Wheal - increased permeability and local edema
(3) Flare or flush - axon reflex vasodilation

Question 12

What are the major pharmacological actions of first generation antihistamines?
(5)

Answer 12

Desired:
(1) H1-receptor blockade

Undesired (due to nonselectivity):

(2) Muscarinic receptor blockade
(3) Alpha adrenoreceptor blockade (leading to orthostatic hypotension)
(4) Serotonin receptor blockade
(5) Local anesthesia

Question 13

How is histamine synthesized?

Answer 13

Histidine is converted to histamine by histidine decarboxylase, requiring pyridoxal

Question 13

What are the first generation antihistamines?

4

Answer 13

(1) Diphenhydramine
(2) Pyrilamine
(3) Hydroxyzine
(4) Promethazine

Question 15

What is diphenhydramine*?

4

Answer 15

(1) First generation antihistamine
(2) Ethanolamine class
(3) Causes marked sedation
(4) Used to combat motion sickness
* one of two important 1st gen antihistamines

Question 16

What is pyrilamine?

4

Answer 16

(1) First generation antihistamine
(2) Ethylenediamine class
(3) Causes moderate sedation
(4) Used as OTC sleep aid

Question 17

What is hydroxyzine*?

3

Answer 17

(1) First generation antihistamine
(2) Piperazine class
(3) Causes marked sedation
* one of two important 1st gen antihistamines

Question 18

What is promethazine?

3

Answer 18

(1) First generation antihistamine
(2) Phenothiazine class
(3) Causes marked sedation
(4) Used as an anti-emetic

Question 19

What are the major adverse effects of 1st gen antihistamines?
(7)

Answer 19

(1) Sedation (H1 blockage)
(2) Blurred vision (muscarinic blockage)
(3) Dry mouth (muscarinic blockage)
(4) Excitation and convulsions in children
(5) Constipation
(6) Postural hypotension (α1 blockage)
(7) Drug allergy

Question 20

What are the second generation antihistamines?

3

Answer 20

(1) Fexofenadine
(2) Loratadine
(3) Cetirizine

Question 21

What histamine receptors do 2nd gen antihistamines target?

Answer 21

H1 receptors, little effect at other receptors

Question 22

What is a major pharmacological difference between 1st and 2nd generation antihistamines?

Answer 22

2nd gen antihistamines cause minimal sedation because they do not enter the CNS

Question 23

What are adverse effects of 2nd gen antihistamines?

2

Answer 23

Very few because of specificity

(1) Risk of QT prolongation
(2) Cardiac arrhythmias

Question 24

What is terfenadine and why was it removed from the pharm market?
(2)

Answer 24

(1) 2nd gen antihistamine

2) Caused cardiac arrhythmias, so replaced with fexofenadine (metabolite of terfenadine with low risk of arrhythmia

Question 25

What are therapeutic uses of H1 blockers?

5

Answer 25

(1) Treat allergic reactions (rhinitis and urticaria/hives)
(2) Treat motion sickness with diphenhydramine
(3) Antitussive - diphenhydramine
(4) OTC sleep aids - diphenhydramine and doxylamine
(5) Non-rational treatment of common cold

Question 26

What are four H2 antagonists?

4

Answer 26

(1) Cimetidine
(2) Ranitidine
(3) Famotidine
(4) Nizatidine

Question 27

What is the mechanism of action of H2 blockers?

4

Answer 27

Blockage of acid secretion due to (1) histamine, (2) gastrin, (3) vagal stimulation, and (4) cholinomimetics

Question 28

What are adverse effects of H2 blockers?

6

Answer 28

(1) Diarrhea
(2) Dizziness
(3) Somnolence
(4) Headache
(5) Rash
(6) Liver toxicity with elevated liver enzymes

Question 29

What are adverse effects of cimetidine?

3

Answer 29

(1) CNS delirium and confusion, particularly in the elderly
(2) Antiandrogenic effects - gynecomastia and galactorrhea, reduction in sperm count and reversible impotence
(3) Blood dyscrasias

Question 30

What are potential drug interactions of antihistamines?

2

Answer 30

(1) Cimetidine inhibits CYP450-catalyzed drug metabolism pathway, leading to interaction with warfarin and other drugs
(2) Ethanol bioavailability also increased due to inhibition of gastric first-pass metabolism

Question 31

Wat are H2 blockers used to treat?

4

Answer 31

(1) Peptic duodenal ulcers
(2) Gastric ulcers
(3) Erosive esophagitis (due to GERD)
(4) Hypersecretory conditions (Zollinger-Ellison syndrome - pancreatic tumor secretes excess gastrin, leading to acid production and ulceration)