Antihistamines

Question 1

Distribution of mast cells

Answer 1

high numbers in the skin, nose, mouth, lungs, and intestinal mucosa

Question 2

Histamine is complexed with

Answer 2

sulfated-polysaccharides, heparin sulfate, chondroitin sulfate, and proteases

Question 3

Where is the non-mast cell histamine located?

Answer 3

nerve terminals in some areas of the brain (NT) and in the fundus of the stomach (specialized cells store histamine for stimulation of acid secretion)

Question 4

Causes of histamine release from mast cells and basophils

Answer 4

1. Antigen mediated binding of antigen to antibodies bound to IgE on the cell surface
2. Non-antigen mediated thermal or mechanical stress, cytotoxic agents (venoms/drugs)

Question 5

What kind of receptors are histamine receptors?

Answer 5

G-protein coupled

Question 6

Where are H1 receptors distributed?

Answer 6

distributed throughout CV, respiratory system, and G.I. smooth muscle

Question 7

The H1 receptor is linked to what pathway?

Answer 7

linked to the phosphoinositol pathway, activation causes contraction of smooth muscle

Question 8

What is the H1 receptor also linked to?

Answer 8

also linked to vasodilation and stimulation of sensory nerves

Question 9

Where is the H2 receptor distributed?

Answer 9

distributed in the CV system, GI smooth muscle and stomach

Question 10

What is the H2 receptor linked to?

Answer 10

linked to relaxation of vascular smooth muscle and gastric secretion

Question 11

Where are H1 and H2 receptors colocalized?

Answer 11

vascular smooth muscle and endothelium

Question 12

Where are H3 receptors located?

Answer 12

mainly in the CNS; autoreceptor in neurons that use histamine as a neurotransmitter

Question 13

What are H3 receptors linked to?

Answer 13

linked to inhibition of neurotransmitter releases

Question 14

Where are H4 receptors located?

Answer 14

located on mast cells, basophils and eosinophils

Question 15

What are H4 receptors linked to?

Answer 15

linked to histamine-induced chemotaxis; promising target for future antiinflammatory drugs

Question 16

What does histamine do to the cardiovascular system?

Answer 16

Causes a moderate increase in rate and force of contraction of the heart; H2 receptors causes an increased in SA conduction; reflex tachycardia

Question 17

What does histamine do to the respiratory system?

Answer 17

H1 mediated constriction of bronchial smooth muscle

Question 18

What does histamine do to acid release in the stomach?

Answer 18

H2 mediated release from parietal cells in the stomach

Question 19

What happens with histamine and anaphylaxis?

Answer 19

hypotension and loss of fluid to the interstitial space; lowers effective blood volume; swelling

Question 20

Triple response that occurs when you inject histamine into the skin

Answer 20

1. red spot at the point of injection (immediate)
2. red flare radiating ~ 1 cm from injection site (~10s)
3. wheal (raised welt) at site of injection (1-2 min)

Question 21

Skin pathologies caused by histamine

Answer 21

1. Urticaria (hives, rash, edematous welts
2. Dermatographia (redness or welt with mechanical stimulation
3. Flushing (erythema, redness in skin due to vasodilation)

Question 22

H1 receptor antagonists are referred to as

Answer 22

antihistamines

Question 23

H2 receptor antagonists are referred to as

Answer 23

acid blockers

Question 24

First generation antihistamines

Answer 24

Brompheniramine, cyproheptadine, diphenhydramine, promethazine, hydroxyzine, pyrilamine

Question 25

What can happen when children take H1 receptor antagonists?

Answer 25

paradoxical excitation in children at normal doses

Question 26

What happens with antihistamines at high doses?

Answer 26

CNS stimulation at high doses

Question 27

The most sedative antihistamines

Answer 27

ethanolamines and phenothiazies

ex. diphenhydramine and promethazine

Question 28

OTC sleep aids

Answer 28

diphenhydramine: Sominex and Nytol

Question 29

Second generation H1 antagonists

Answer 29

Loratadine, desloratadine, fexofenadine, citirizine, levocetirizine

Question 30

How are second generation H1 antagonists different from first generation H1 antagonists?

Answer 30

decreased lipid solubility, little or no sedation, no anti-muscarinic activity, no anti-emetic activity, no anti-motion sickness activity

Question 31

Topical H1 receptor antagonists (eye drops and nasal sprays)

Answer 31

Olopatadine, azelastine, ketotifen

Question 32

What are topical H1 receptor antagonists indicated for?

Answer 32

indicated for treatment of seasonal allergic rhinitis and/or conjunctivitis; approved for prevention of asthma symptoms in Europe

Question 33

Clinical use of H1 antagonists

Answer 33

1. Seasonal and perennial allergic rhinoconjuctivitis
2. Chronic urticaria
3. Motion sickness
4. Adjunct with epinephrine to treat anaphylaxis

Question 34

H1 antagonists for motion sickness

Answer 34

demenhydrinate, meclizine, promethazine

Question 35

Adverse effects and drug interactions for H1 receptor antagonists

Answer 35

sedation; 1st gen drugs tend to enhance CNS depression; antimuscarinic effects

Question 36

What are 1st generation antihistamines contraindicated in

Answer 36

urinary retention and narrow angle glaucoma

Question 37

Specific effects of phenothiazine

Answer 37

extrapyramidal effects: dystonia, akathisia, and Parkinsonian rigidity

Question 38

Mechanism of CNS depression by H1 antagonists

Answer 38

1. Drug must gain entry to the CNS
2. H1 receptors in the thalamic relay cells maintain a relatively depolarized membrane potential, low frequency action potentials and wakefullness
3. H1 antagonists block these receptors, leading to hyperpolarization, bursts of action potentials and sleep