Anti-Histamines

Question 1

2 Broad mechanisms of histamine release from mast cells

Answer 1

cytolytic - membrane damage, high levels of drugs, mechanical damage

non-cytolytic - immune response, non-immunological response, substances can displace it from granules

Question 2

H1 receptor

Answer 2

Smooth muscle cells (vascular, respiratory, GI)
Vascular endothelial cells
CNS neurons
Peripheral sensory nerves

Gq protein

Question 3

H2 receptor

Answer 3

Gastric parietal cells
Cardiac muscle
CNS neurons

Gs protein

Question 4

H3 receptor

Answer 4

CNS neurons
Peripheral sensory nerves

Gi/o protein

Question 5

H4 receptor

Answer 5

Neutrophils
Eosinophils
Monocytes
Other immune cells

Gi/o protein

Question 6

Both peripheral and CNS histamine receptors mediate _____

Answer 6

itch

Question 7

Histamine in the CNS released in _____

Answer 7

circadian pattern

controls release of pituitary hormones, wakefullness, appetite, satiety

Question 8

Histamine physiologic effects

Answer 8

vasodilation - decreased TPR

increased vascular permeability - edema

epidermis - itch
dermis - pain

lungs - increased fluid and electrolyte secretion, bronchoconstriction

Cardiac (H2) - increase calcium (increase contracitility), increase SA node

Question 9

Diseases that increase histamine levels

Answer 9

myelogenous leukemia

gastric carcinoid tumors

systemic mast cell diseases - mast cell leukemia

Question 10

Classes of Anti-histamines

Answer 10

Physiological antagonists
Release inhibitors
Receptor Antagonists

Question 11

Important characteristic of 2nd generation H1-anti-histamines

Answer 11

Non-sedating - don’t penetrate BBB

Question 12

H1-antihistamines MOA

Answer 12

reversibly bind receptor and stabilize INACTIVE FORM

Question 13

Potential adverse effects of 1st generation H1-antihistamines

Answer 13

CNS H1 receptors - sedation, decreased alertness

Muscarinic receptors - dry mouth, urinary retention, sinus tachycardia

Serotonin receptors - increase appetite and wt gain

Alpha- receptors - dizziness and postural hypotension

Question 14

1st generation H1-antihistamines

Answer 14

Chlorpheniramine
Diphenhydramine
Pyrilamine
Hydroxyzine
Meclizine
Promethazine
Cyproheptadine

Question 15

Chlorpheniramine primary uses

Answer 15

allergic rhinitis and other allergic conditions

Question 16

Diphenhydramine characteristics

Answer 16

sedative
anti-muscarinic
anti-motion sickness

Question 17

Pyrilamine characteristics

Answer 17

low to moderate sedative actions

Question 18

Hydroxyzine important characteristics

Answer 18

marked sedation and anti-muscarinic

Question 19

Meclizine important characteristics

Answer 19

less sedating than hydroxyzine
minimal anti-muscarinic

primarily for motion sickness and vertigo

Question 20

Promethazine important characteristics

Answer 20

strong anti-motion sickness and anti-emetic activities

local anesthetic

alpha-1 and muscarinic inhibition

Question 21

Phenothiazines (promethazine and chlorpromazine) can also

Answer 21

BLOCK D2 RECEPTORS

anti-psychotic

Question 22

Cyproheptadine important characteristics

Answer 22

Low to moderate sedative and antimuscarinic actions

Anti-serotonin activity

Question 23

H1 Antihistamines with strongest anti-emetic effects (4)

Answer 23

Diphenhydramine
Promethazine
Hydroxyzine
Meclazine

Question 24

H1 Antihistamines with strongest sedative effects (3)

Answer 24

Diphenhydramine
Hydroxyzine
Promethazine

Question 25

Strongest cholinergic anti-histamines

Answer 25

diphenhydramine | promethazine

Question 26

Strongest alpha-1 antagonist anti-histamine

Answer 26

promethazine

Question 27

strongest serotonin antagonist anti-histamine

Answer 27

cyproheptadine

Question 28

Drug-interactions with 1st generation H1 antihistamines

Answer 28

MAOI's Opioids, alcohol, sedatives Anti-cholinergics

Question 29

2nd Generation H1 Anti-histamines characteristics

Answer 29

bind non-competitively to H1 reduced lipophilicity higher selectivity toward H1

Question 30

2nd Generation H1 Anti-histamines

Answer 30

``` Fexofenadine Loratadine Desloratadine Levocetirizine Cetirizine Azelastine ```

Question 31

Azelastine characteristics

Answer 31

ALSO INHIBITS MAST CELL HISTAMINE RELEASE INTRANASAL AND OPTHALMIC

Question 32

Cromolyn and Nedocromil MOA

Answer 32

stabilize mast cells inhibition of chloride channels in cell membranes nasal spray, eye drops, aerosols

Question 33

Omalizumab MOA clinical

Answer 33

recombinant humanized IgE ANTIBODY - binds and sequesters IgE urticaria, asthma

Question 34

Other drugs with anti-histaminic activity

Answer 34

Doxepin - TCA Ketotifen - H1 antihistamine with mast cell and basophil stabilizing properties