LLecture 25: Antihistamines

Question 1

Histamine synthesis

Answer 1

-in mast cells and basophils
-histidine to histamine
-catalyzed by L-histidine decarboxylase

Question 2

Histamine is stored in

Answer 2

granules

Question 3

histamine is released from granules in response to

Answer 3

-antigens
-cell lysis

Question 4

Metabolism of Histamine

Answer 4

-N-methylation
-Oxidation
-or imidazoleacetic acid 5’phosphoribosyl transferase

Question 5

Slide 6

Answer 5

Slide 6

Question 6

Distribution of mast cells

Answer 6

-skin
-mouth
-nose
-lungs
-intestinal mucosa

Question 7

Stored histamine

Answer 7

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

Question 8

Non-mast cell histamine

Answer 8

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

Question 9

Release of histamine from mast cells

Answer 9

-antigen mediated
-non-antigen mediated

Question 10

antigen mediated release of histamine from mast cell

Answer 10

-binding of antige/allergen to antibodies on surface (IgE)
-other inflammatory agents are also released

Question 11

non-antigen mediated release of histamine from mast cells

Answer 11

-thermal or mechanical stress
-cytotoxic agents (venoms)
-various drugs (high dose morphine)

Question 12

Mast cell degranulation requires:

Answer 12

-binding of IgE to FcER
-binding of antigen to IGE
-clustering of FCER receptors
-influx of Ca2+ via CRAC

Question 13

CRAC

Answer 13

ca release activated channels

Question 14

Binding of antigen to antibody molecules causes cytoplasmic Ca2+ concentration:

Answer 14

to increase

Question 15

Drugs that prevent histamine release

Answer 15

-cromolyn sodium
-nedocromil
-B agonists

Question 16

Cromolyn sodium

Answer 16

-Rx- mastocytosis (oral)
-OTC: allergic rhinitis (nasal spray)

Question 17

Nedocromil

Answer 17

-Rx- allergic conjunctivitis (eye drops)

Question 18

acetylcholine effect on histamine

Answer 18

-stimulate

Question 19

B-agonist effect on histmaine

Answer 19

-inhibit release

Question 20

Histamine receptors

Answer 20

-4 subtypes
-all GPCRs

Question 21

H1 receptor location

Answer 21

-distributed throughout CV, respiratory systems, GI, smooth muscle

Question 22

H1 linked to

Answer 22

-smooth muscle contraction
-vasodilation
-stimulation of sensory nerves

Question 23

H1 activation that causes smooth muscle contraction

Answer 23

-Gq –> PLC –> IP3 –> DAG
-inc Ca2+ –> phospho MLC

Question 24

H1 vasodilation mech

Answer 24

-inc NO release
-NO diffuses to vasc smooth muscle
=inc cGMP and dec Ca2+

Question 25

H1 sensory nerve stimulation mech

Answer 25

-Hist + H1 binding in cutaneous or nasal nerve ending -causes itching and sneezing

Question 26

H2 receptor distribution

Answer 26

-CV system -GI smooth muscle -stomach

Question 27

H2 receptor linked to:

Answer 27

-relaxation of vasc smooth muscle -gastric secretion

Question 28

H1 and H2 colocalization

Answer 28

? slide 14

Question 29

H3 receptor location

Answer 29

CNS

Question 30

H3 linked to

Answer 30

-inhibition of neurotransmitter release -inhibition of adenylyl cyclase

Question 31

H3 mech

Answer 31

-Gi/Go -dec Ca2+

Question 32

H4 location

Answer 32

-mast cells -basophils -eosinophils -coupled to Gi/Go

Question 33

H4 linked to

Answer 33

-histamine-induced chemotaxis -promising target for new anti-inflammatory drugs

Question 34

Histamine effect on heart

Answer 34

-tiny inc in rate and force of contraction -H2 inc SA conduction, reflex tachycardia

Question 35

Histamine effect on vasodilation

Answer 35

-H1 in endothelium -H2 in smooth muscle

Question 36

bronchial constriction

Answer 36

H1

Question 37

acid release in stomach

Answer 37

H2

Question 38

Anaphylaxis

Answer 38

-hypotension -loss of fluid to intersitial space -dec in effective blood volume; swelling

Question 39

Histamine positive chronotropy + inotropy mech

Answer 39

-inc diastolic depolarization current -inc HR -inc cAMP -inc Ca -inc force

Question 40

Vasodilation of endothelium

Answer 40

-high affinity H1 receptors -signal via NO pathway

Question 41

vasodilation of smooth muscle

Answer 41

-H2 -PKA pathway

Question 42

histamine causes vasoconstriction of

Answer 42

veins

Question 43

Histamine inc capillary permeability mech

Answer 43

-H1 endothelial contraction -tight-junction disruption -releases plasma proteins, fluid -occurs in small vessels -results in edema -enhances immune cell ability to respond to antigen

Question 44

Histamine cardiovasc effects

Answer 44

-positive intropy -positive chronotropy -vasodilation (constrict veins tho) -inc capillary permeability

Question 45

Histamine effects in skin

Answer 45

-triple response -uticaria -dermatographia -flushing (erythema)

Question 46

triple response

Answer 46

1. red spot at point of injection 2. Red flare radiating ~1 cm from injection site 3. wheal (welt) at injection site

Question 47

insect bites

Answer 47

-flare and edma

Question 48

uticaria

Answer 48

-hives -rash -welts

Question 49

dermatographia

Answer 49

-redness/welt with mechanical stimulation

Question 50

flushing (erythema)

Answer 50

-redness in skin due to vasodilation

Question 51

Histamine effect in the lungs

Answer 51

-H1 -Smooth muscle contraction -bronchoCONSTRICTION -Ca2+ mobilization

Question 52

Systemic anaphylaxis

Answer 52

-hypersensitivity/allergic rxn -severe -histamine and autocoids released -skin, respiratory, GI, CV, etc

Question 53

anaphylaxis treatment

Answer 53

-epinephrine injection -use of antihistamines is often not effective

Question 54

H1 antagonists referred to as

Answer 54

antihistamines

Question 55

H2 antagonists referred to as

Answer 55

acid blockers