Antihistamines

Question 1

what are the general mechanisms for histamine release from mast cells?

Answer 1

cytolytic

noncytolytic

Question 2

what leads to cytolytic mechanism of histamine release?

Answer 2

1. membrane damage
2. high levels of drugs (opioids)
3. mechanical damage

Question 3

what leads to noncytolytic mechanism of histamine release?

Answer 3

1. immune response
2. non-immunological response from basic polypeptides
3. displacement of histamine from granules by drugs (morphine, codeine, radiocontrast)

Question 4

where are H1 receptors expressed? what is the result of activation?

Answer 4

1. smooth muscle cells (vascular, respiratory, GI)
2. vascular endothelial
3. CNS neurons
4. peripheral sensory nerves

Gq (PLC - IP3 - Ca)

Question 5

where are H2 receptors expressed? what is the result of activation?

Answer 5

gastric parietal cells
cardiac muscle
CNS neurons

increased adnenylyl cyclase, cAMP / PKA

Question 6

1. smooth muscle cells (vascular, respiratory, GI)
2. vascular endothelial
3. CNS neurons
4. peripheral sensory nerves

contain what type of histamine receptor? what is the result of activation?

Answer 6

H1

Gq (PLC - IP3 - Ca)

Question 7

gastric parietal cells
cardiac muscle
CNS neurons

contain what type of histamine receptor? what is the result of activation?

Answer 7

H2

increased adnenylyl cyclase, cAMP / PKA

Question 8

what are some of the physiological functions of histamine in the nervous system?

Answer 8

pituitary hormone release
wakefulness
appetite / satiety

Question 9

what leads to the vasodilation effect of H1 activation?

Answer 9

PLC - calcium - increased eNOS - increased NO - vasodilation

Question 10

what leads to the vasodilation effect of H2 activation?

Answer 10

AC - PKA - vasodilation

Question 11

what leads to the increased vascular permeability / edema of histamine? is it mediated by H1 or H2?

Answer 11

PLC - calcium - increased contraction of endothelial cells - disruption of endothelial junctions - increased plasma proteins and fluid leak into tissue

H1

Question 12

what is the result of H1 activation in the epidermis?

Answer 12

itch

Question 13

what is the result of H1 activation in the dermis?

Answer 13

pain

Question 14

what does H1 activation in the lungs cause?

Answer 14

elevated secretion of airway fluid and electrolytes - bronchoconstriction

Question 15

activation of what histamine receptor type leads to elevated secretion of airway fluid and electrolytes - bronchoconstriction?

Answer 15

H1

Question 16

what are the results of histamine receptor activation in heart muscle? is this mediated by H1 or H2?

Answer 16

1. increased calcium - positive inotropic
2. speeds up SA node - positive chronotropic

H2

Question 17

antihistamines refer to agents that specifically target what receptor?

Answer 17

H1

Question 18

what drug is a physiological antagonist of the histamine response itself?

Answer 18

EPI

Question 19

what are the release inhibitor antihistamines?

Answer 19

cromolyn, nedocromil

omalizumab

Question 20

what type of drug is omalizumab?

Answer 20

monoclonal IgE Ab

Question 21

how do 2nd generation antihistamines differ from 1st generation?

Answer 21

2nd gen - more strongly target H1
2nd gen - do not enter brain (reduced lipophilicity)
less sedation

Question 22

how do H1 antihistamines exert their effect?

Answer 22

reversibly bind to receptor and stabilize inactive form

Question 23

what are the main adverse effects of first generation H1 antihistamines?

Answer 23

CNS - cognitive
muscarinic - anticholinergic (dry)
5-HT - increased appetite and weight gain
alpha - increased dizziness

excitation and seizures

Question 24

chlorpheniramine is used to treat what conditions?

Answer 24

allergic rhinitis and allergies

Question 25

diphenhydramine (benadryl) has what effects, physiologically?

Answer 25

sedative antimuscarinic antimotion

Question 26

what are the therapeutic uses for benadryl?

Answer 26

allergic rhinitis cough suppressant motion sickness

Question 27

what is the unique feature of pyrilamine?

Answer 27

low sedative effects very little antimuscarinic action no antimotion activity

Question 28

what is the primary use of hydroxyzine?

Answer 28

antiemetic

Question 29

what are the primary uses of meclizine? what makes it different from hydroxyzine?

Answer 29

motion sickness, vertigo less sedating than hydroxyzine

Question 30

what is the primary MOA of promethazine?

Answer 30

significant inhibition of alpha adrenergic receptors

Question 31

what are the primary uses of promethazine?

Answer 31

antiemetic | anti motion sickness

Question 32

promethazine can also block what receptor type, in addition to H1?

Answer 32

D2

Question 33

cyproheptadine can also block what receptor type, in addition to H1?

Answer 33

5-HT

Question 34

which drugs have the strongest antiemetic effects?

Answer 34

diphenhydramine promethazine hydroxyzine meclazine

Question 35

which H1 antihistamines have the highest sedative effects?

Answer 35

diphenhydramines hydroxyzine promethazine

Question 36

which antihistamine is the significant alpha adrenergic receptor antagonist? what is the result?

Answer 36

promethazine postural hypotension dizziness reflex tach

Question 37

which antihistamine is the significant serotonin receptor antagonist? what are its adverse effects? what can it be used for therapeutically?

Answer 37

cyproheptadine antimuscarinic increased weight gain serotonin syndrome

Question 38

what are the drug interactions with antihistamines?

Answer 38

MAOIs opioids, ethanol anticholinergics

Question 39

azelastine is an antagonist of what receptor?

Answer 39

H1

Question 40

which antihistamines have lower sedation profiles and are more useful for people working in jobs that require increased wakefulness?

Answer 40

loratidine | fexofenadine

Question 41

why are loratidine and fexofenadine beneficial?

Answer 41

less sedation

Question 42

fexofenadine should be avoided with coadministration of what agents?

Answer 42

antacids | citrus juices

Question 43

what are the MOAs of cromolyn and nedocromil?

Answer 43

1. stabilize mast cell | 2. inhibition of chloride channels in cell membranes

Question 44

what are the therapeutic uses of omalizumab?

Answer 44

(chronic) urticaria | asthma

Question 45

what drugs are used for chronic urticaria?

Answer 45

doxepin | omalizumab

Question 46

what drug is useful for treating allergic conjunctivitis? what is the MOA?

Answer 46

ketotifen H1 antihistamine with additional mast cell and basophil stabilization

Question 47

ketotifen is used to treat what condition?

Answer 47

allergic conjunctivitis?