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Pharm > Lecture 9- Histamine > Flashcards

Lecture 9- Histamine Flashcards

1
Q

What cell type is histamine mostly found in?

A

Mast Cells

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2
Q

Where are the highest amounts of histamine found?

A

Lung, skin, nasal and Gi mucosa

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3
Q

Mast cells have high affinity _______ binding sites on their plasma membranes.

A

IgE

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4
Q

Histamine is formed by decarboxylation of what amino acid?

A

Histidine

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5
Q

Histamine is stored in _______.

A

Granules

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6
Q

What are some instances where histamine is released?

A 
Trauma
Allergies
Anaphylaxis
Cold
Bacterial toxins
Bee strings
Venom
Drugs
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7
Q

What are the 2 types of histamine release from mast cells?

A

Cytolytic release

Noncytolytic release

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8
Q

What causes cytolytic release of histamine?

A

Damage to plasma membrane then there is leakage of cytoplasmic contents

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9
Q

What 2 things induce cytolytic release of histamine?

A

Phenothiazines

Narcotic analgesics

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10
Q

What type of histamine release requires ATP and calcium?

A

Noncytolytic release

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11
Q

What causes histamine release in noncytolytic release?

A

IgE antibodies binding to antigen

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12
Q

These 6 drugs (d-tubocurare, succinylcholine, morphine, codeine, doxorubicin, protamine) can cause what with histamine?

A

Stimulate histamine release from mast cells without prior sensitization

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13
Q

What drug causes red man syndrome- flushing, pruritus, chest pain, muscle spasms and hypotension?

A

Vancomycin

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14
Q

What can help reduce the symptoms of red man syndrome?

A

Pretreatment with IV antihistamines

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15
Q

What are 2 inhalation powders that block the release of histamine from mast cells?

A

Cromolyn

Nedocromil

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16
Q

What are Cromolyn and Nedocromil used for?

A

Decrease symptoms of allergic rhinitis

Used to block asthmatic rxns

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17
Q

Are Cromolyn and Nedocromil effective during an actual asthma attack?

A

No, only preventative

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18
Q

Which histamine receptor uses adenylyl cyclas mechanism and parietal cell acid secretion?

A

H2

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19
Q

Which histamine receptor is proinflammatory activity?

A

H4

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20
Q

What histamine receptor is on neurons and inhibits the release of histamine (feedback inhibition)?

A

H3

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21
Q

Which histamine receptor uses phospholipase C mechanism (respiratory and allergic reactions)?

A

H1

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22
Q

Which histamine receptor increases mucus in nasal cavity and bronchi resulting in respiratory symptoms

A

H1

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23
Q

What histamine receptor stimulates gastric secretions?

A

H2

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24
Q

Which histamine receptor constricts bonrchi and intestines (cramps, diarrhea)?

A

H1

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25
Q

The activation of which histamine receptor leads to the stimulation of sensory nerve endings (itching/ pain)?

A

H1

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26
Q

How does histamine directly increase HR and contractility?

A

Increasing influx of calcium

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27
Q

How does histamine indirectly increase HR and contractility?

A

Baro-receptor mediated increase in sympathetic tone in response to histamine induced vasodilation

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28
Q

What are the 2 ways H1 leads to vasodilation?

A

Decrease in blood pressure

increase in nitric oxide

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29
Q

Is there a release of catecholamines from the adrenal medulla in allergy and anaphylaxis?

A

Yes

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30
Q

What are the three parts of the triple response of lewis?

A

Red line/ spot
Flare (large area of red around)
Wheal (edema)

31
Q

In hypersensitivity rxns what are the 2 principle targets?

A

Mast cells and Basophils

32
Q

What happens in an allergic response?

A

An antigen produces the formation of IgE antibodies which bind to high affinity receptors specific for these IgE antibodies and activates tyrosine kinase

33
Q

The activation of phospholipase A2 produces _________ and __________.

A

Leukotrienes

Prostaglandins

34
Q

____________ contract smooth muscle of the bronchi. Are involved in hypersensitivty rxns?

A

Leukotrienes

35
Q

What happens if histamine is released rapidly and diffuses via the blood then the response may be full-blown .

A

Anaphylactic reaction

36
Q

What do you treat true anaphylaxis with?

A

Epinephrine

37
Q

What is histamine phosphate used for?

A

to assess nasal and bronchial reactivity

for allergy skin testing

38
Q

What should individuals discontinue before allergy skin testing with histamine phosphate?

A

antihistamines, tricyclic antidepressants, corticosteroids, benzodiazepines.

39
Q

1st generation antihistamines block which histamine receptor?

A

H1

40
Q

What are the 5 hisatmine H1 receptor blockers, first generation?

A 
triprolidine
diphenhydramine
promethazine
hydroxyzine
chlorpheniramine
41
Q

What is the benefit of 2nd generation H1 receptor blockers?

A

Less CNS toxicity or side effects since they don’t cross the BBB and are excluded by p-glycoprotein

42
Q

What are the 4 second generation H1 receptor blockers?

A

loratadine (Claritin, OTC),
desloratadine (Clarinex),
azelastine (Astelin) ,
cetirizine (Zyrtec,OTC)

43
Q

What effects are lesser in reversible, competitive blockers of H1 receptors?

A

Less effect on bronchoconstrction and vasodilation which are caused predominatly by prostaglandins and leukotrienes

44
Q

For H1 blockers is there a tolerance to the suppressive effect on skin test reactivity to allergens?

A

No

45
Q

Tolerance to what effect of H1 blockers may occur?

A

Sedative effects

46
Q

What is the active metabolite of loratadine (Claritin)?

A

Desloratadine (Clarinex)

47
Q

What is the metabolite of terfenadine (Seldane)?

A

Fexofenadine (Allegra)

48
Q

What is terfenadine metabolized by?

A

CYP3A4 family

49
Q

Is terfenadine currently on the market?

A

No- it was withdrawn due to risk of life threatening cardiac arrhytmias, torsades de pointes

50
Q

What do all FDA approve antihistamines no prolong?

A

QT interval

51
Q

What is the main difference b/w 1st and 2nd generation H1 blockers?

A

2nd generation have no anticholinergic affect, no CNS sedation and are longer acting

52
Q

What allergic conditions do antihistamines (H1) treat?

A

Allergic rhinitis
Urticaria
Allergic drug rxns (prophylactic)
Allergic conjunctivitis

53
Q

What is the most effective antihistamine used for prevention of symptoms of motion sickness?

A

Promethazine

54
Q

What are 3 other antihistamines (besides promethazine) used for prevention of motion sickness?

A

diphenhydramine, cyclizine, meclizine

55
Q

When should you administer promethazine?

A

1 hour before anticipated motion

56
Q

What is the most effect drug (not an antihistamine) used to prevent motion sickness?

A

Scopolamine

57
Q

WHat drug class is used to prevent nausea and vomiting?

A

Phenothiazine class

58
Q

What are 2 drugs in the phenothiazine class that are used to prevent N/V?

A

Promethazine

Timeprazine

59
Q

How does the phenothiazine class work?

A

Blocks dopamine D2 receptors

60
Q

What drug is used for OTC treatment of hyposomnia?

A

Diphenhydramine

61
Q

How many consecutive nights should antihistamines used for sleep medications be limited to?

A

10 consecutive nights

62
Q

What antihistamine drug is used for antiparkinsonism effect, especially antimuscarinic actions.

A

Diphenhydramine

63
Q

What antihistamine is found in sunburn preparations for local anesthetic actions?

A

Promethazine

64
Q

How do antihistamines work as local anesthetics- specifically what channels do they block?

A

Block sodium channels

65
Q

What is an antihistamine used to treat oral ulcers, infections, inflammation and pain?

A

Magic Mouthwash

66
Q

What are the 2 main adverse effects of antihistamines?

A

Antimuscarinic and sedative actions (usually lower with second generation)

67
Q

What does CNS sedation correlate with for antihistamines?

A

H1 receptor binding in brain

68
Q

What are some of the anticholinergic effects associated with antihistamines?

A

Dry mouth and nasal passages
Constipation
Blurred vision
Urinary retention

69
Q

What can occur in children who are given antihistamines?

A

Paradoxical excitation

70
Q

Combing CNS H! antagonists with what other medications can be dangerous?

A

Other sedating medications

71
Q

H1 antagonists potentiate _________________

A

all other CNS depressants

72
Q

What population is acute poisoning with H1 antagonists relatively common?

A

Young children

73
Q

What are the acute effects of poisoning with H1 antagonists?

A

initial excitement
ataxia and convulsions
coma and cardiorespiratory collapse

Pharm (29 decks)

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