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Biomed > Histamine > Flashcards

Histamine Flashcards

1
Q

features of histamine and 5-HT

A

biogenic amines
act as hormones or autacoids
act as neurotransmitters and local hormones in vascular and smooth muscle

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2
Q

histamine associated diseases

A

allergy
peptic ulcer - break in the stomach lining

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3
Q

what is the N-terminus of histamine

A

imidazole ring
pKa = 5.74
normally uncharged

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4
Q

outline the synthesis of histamine

A

histidine decarboxylase converts histidine into histamine
removes the COOH at the C-terminal

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5
Q

what happens when histamine is exposed to diamine oxidase and what happens when that product is exposed to ribose

A

gets converted into imidazoleacetic acid
converted into imidazoleacetic acid riboside

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6
Q

what converts N-methylhistamine into N-methylimidazole acetic acid

A

MAO-B

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7
Q

storage of histamine in the lung, skin, gut and stomach

A

lung - 15μg/g of tissue
skin - 6-8μg/g
gut - 60-80μg/g
stomach - 10μg/g

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8
Q

what do mast cell granules contain

A

histamine bound to a proteoglycan core - usually heparin
also contains proteolytic enzymes:
- tryptase
- chymase

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9
Q

what happens when activation of mast cells occur

A

granules fuse with the membrane, releasing histamine

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10
Q

what is IgE

A

a receptor on the surface of mast cells

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11
Q

what causes allergic reactions

A

IgE exposed to allergen
causes release of granules and histamine
IgE dependent release of histamine

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12
Q

what can mast cells also be activated by

A

bacterial products - lipopolysaccharide
complement peptides - C3a and C5a

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13
Q

name 2 drugs that release histamine by non-receptor action and another non-specific reason histamine is released

A

morphine
tubocurarine
trauma to tissues

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14
Q

features of H1

A

wide distribution in cardiovascular system, smooth muscle and nerves

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15
Q

features of H2

A

regulates gastric acid secretion in the stomach
increases HR and CO

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16
Q

actions of H1

A

vasodilation
increased vascular permeability
stimulation of peripheral nerves
smooth muscle contractions

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17
Q

what is the action of histamine on cardiovascular system

A

constricts arteries and veins
dilates arterioles and capillaries

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18
Q

what can a large dose of histamine cause

A

a large drop in blood pressure and fluid loss in the capillaries
leads to circulatory collapse - anaphylactic shock
(severe allergic reaction)

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19
Q

what are H1 antagonists and the difference

A

mepyramine
cetirizine - causes less problems with drowsiness, impermeable to BBB

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20
Q

actions of H1

A

stimulate gastric acid secretion
regulates cardiac output and rate
modulates actions of immune cells

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21
Q

how is gastric acid synthesis blocked

A

histamine binding to H2R receptor of parietal cell

22
Q

what is a classical H2 antagonist

A

cimetidine

23
Q

function of cimetidine

A

inhibits cytochrome P450

24
Q

actions of H3

A

can act as a neurotransmitter

25
Q

actions of H4

A

appear on inflammatory cells
appear to regulate cytokine network in the inflammatory response

26
Q

what is 5-hydroxytryptamine known as

A

seretonin

27
Q

where is 5-HT found

A

CNS
GI tract
in platelets

28
Q

outline the synthesis of 5-HT

A

tryptophan hydroxylase converts tryptophan into 5-hydroxytryptophan
L-aromatic acid decarboxylase converts it into 5-HT

29
Q

why does dietary intake of 5-HT not contribute to the body’s pool of 5-HT

A

it is rapidly metabolised and excreted in the urine

30
Q

outline the metabolism of 5-HT

A

monoamine oxidase (MAO) converts 5-HT into an intermediary with an aldehyde
aldehyde dehydrogenase converts it into 5-hydroxyindole acetic acid (5-HIAA)

31
Q

where is 5-HT synthesised

A

in the CNS and enterochromaffin cells in the gut

32
Q

where is 90% of 5-HT stored

A

in the gut

33
Q

what type of receptor is 5-HT3

A

internal cationic channel

34
Q

what are the transducers instead of cAMP of 5-HT2a/b/c

A

IP3/DAG

35
Q

where are 5-HT1 receptors located

A

mainly in the CNS

36
Q

role of 5-HT1 recptors

A

mood/behaviour
thermoregulation
feeding
sleep

37
Q

what can activation of 5-HT1 cause

A

neural inhibition
vasoconstriction

38
Q

what is the most effective 5-HT1 agonist

A

sumatriptan
5-HT1D agonist

39
Q

what 5-HT1 antagonist works on all 5-HT1 receptor subtypes

A

methiothepin

40
Q

where are 5-HT2 receptors located

A

in the CNS
widely distributed in the periphery

41
Q

how does LSD effect 5-HT2 receptors

A

agonist at central receptors - causing hallucination
antagonist of receptors in the periphery

42
Q

what are the antagonists for 5-HT2

A

methysergide
ketotifen

43
Q

function of 5-HT3 found in the brain and the periphery

A

periphery - evokes pain
brain - involved in vomiting reflex

44
Q

what is a 5-HT3 antagonist and its use

A

ondansetron - anti-emetics
controls severe vomiting and nausea after chemotherapy

45
Q

where is 5-HT4 located and its function

A

found in the CNS
regulates gut motility

46
Q

5-HT4 antagonist and its use

A

tegaserod
used to treat abdominal discomfort, bloating constipation and chronic idiopathic constipation

47
Q

5-HT in relation to migraines and what is found in the urine of those with migraines

A

5-HT causes vasoconstriction in the cerebral arteries
5-HIAA

47
Q

5-HT in relation to migraines and what is found in the urine of those with migraines

A

5-HT causes vasoconstriction in the cerebral arteries
5-HIAA

48
Q

how is GI motility stimulated

A

directly - 5-HT2 receptors on smooth muscle cell
indirectly - 5-HT3/4 receptors on enteric neurons

49
Q

what happens when 5-HT receptors are stimulated in the stomach

A

fluid secretion
nausea
vomiting

Biomed (9 decks)

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