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Therapeutics > LLecture 25: Antihistamines > Flashcards

LLecture 25: Antihistamines Flashcards

1
Q

Histamine synthesis

A

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

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2
Q

Histamine is stored in

A

granules

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3
Q

histamine is released from granules in response to

A

-antigens
-cell lysis

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4
Q

Metabolism of Histamine

A

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

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5
Q

Slide 6

A

Slide 6

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6
Q

Distribution of mast cells

A

-skin
-mouth
-nose
-lungs
-intestinal mucosa

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7
Q

Stored histamine

A

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

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8
Q

Non-mast cell histamine

A

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

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9
Q

Release of histamine from mast cells

A

-antigen mediated
-non-antigen mediated

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10
Q

antigen mediated release of histamine from mast cell

A

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

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11
Q

non-antigen mediated release of histamine from mast cells

A

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

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12
Q

Mast cell degranulation requires:

A

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

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13
Q

CRAC

A

ca release activated channels

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14
Q

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

A

to increase

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15
Q

Drugs that prevent histamine release

A

-cromolyn sodium
-nedocromil
-B agonists

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16
Q

Cromolyn sodium

A

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

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17
Q

Nedocromil

A

-Rx- allergic conjunctivitis (eye drops)

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18
Q

acetylcholine effect on histamine

A

-stimulate

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19
Q

B-agonist effect on histmaine

A

-inhibit release

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20
Q

Histamine receptors

A

-4 subtypes
-all GPCRs

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21
Q

H1 receptor location

A

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

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22
Q

H1 linked to

A

-smooth muscle contraction
-vasodilation
-stimulation of sensory nerves

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23
Q

H1 activation that causes smooth muscle contraction

A

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

24
Q

H1 vasodilation mech

A

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

25
Q

H1 sensory nerve stimulation mech

A

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

26
Q

H2 receptor distribution

A

-CV system
-GI smooth muscle
-stomach

27
Q

H2 receptor linked to:

A

-relaxation of vasc smooth muscle
-gastric secretion

28
Q

H1 and H2 colocalization

A

? slide 14

29
Q

H3 receptor location

A

CNS

30
Q

H3 linked to

A

-inhibition of neurotransmitter release
-inhibition of adenylyl cyclase

31
Q

H3 mech

A

-Gi/Go
-dec Ca2+

32
Q

H4 location

A

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

33
Q

H4 linked to

A

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

34
Q

Histamine effect on heart

A

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

35
Q

Histamine effect on vasodilation

A

-H1 in endothelium
-H2 in smooth muscle

36
Q

bronchial constriction

A

H1

37
Q

acid release in stomach

A

H2

38
Q

Anaphylaxis

A

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

39
Q

Histamine positive chronotropy + inotropy mech

A

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

40
Q

Vasodilation of endothelium

A

-high affinity H1 receptors
-signal via NO pathway

41
Q

vasodilation of smooth muscle

A

-H2
-PKA pathway

42
Q

histamine causes vasoconstriction of

A

veins

43
Q

Histamine inc capillary permeability mech

A

-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

44
Q

Histamine cardiovasc effects

A

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

45
Q

Histamine effects in skin

A

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

46
Q

triple response

A
  1. red spot at point of injection
  2. Red flare radiating ~1 cm from injection site
  3. wheal (welt) at injection site
47
Q

insect bites

A

-flare and edma

48
Q

uticaria

A

-hives
-rash
-welts

49
Q

dermatographia

A

-redness/welt with mechanical stimulation

50
Q

flushing (erythema)

A

-redness in skin due to vasodilation

51
Q

Histamine effect in the lungs

A

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

52
Q

Systemic anaphylaxis

A

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

53
Q

anaphylaxis treatment

A

-epinephrine injection
-use of antihistamines is often not effective

54
Q

H1 antagonists referred to as

A

antihistamines

55
Q

H2 antagonists referred to as

A

acid blockers

Therapeutics (78 decks)

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