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Musculoskeletal > Autocoids/Histamine > Flashcards

Autocoids/Histamine Flashcards

1
Q

Autacoids

A

Self remedy
Substances brief lifetime act near sites of synthesis
Local hormones conduct affairs closeted from circulation
Reach sites via bloodstream

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2
Q

Lipid Derived Eicosanoids

A

Prostaglandins
Thromboxanes
Leukotrienes

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3
Q

Endogenous Peptides

A

Histamine, 5HT, Ergot Alkaloids

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4
Q

Cytokines

A

Interleukins, TNF

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5
Q

Vasoactive peptides

A 
Angiotensin
Kinins
Vasopressin
Natriuretic peptides
Endothelins
Substance P
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6
Q

Histamine Synthesis

A

Synthesized from one step histidine decarboxylase (CO2 removed from histidine to form histamine)

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7
Q

Histamine Storage

A

Bound in granules in mast cells and basophils

Histamine content

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8
Q

Histamine Tissue Locations

A
  1. Mast cells-nose, mouth, feet, internal body surfaces, blood vessels, pressure pts/bifurcation
  2. Non-Mast Cell Histamine-brain, like neurotransmitter
  3. Non-neuronal site histamine- ECL cells of stomach
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9
Q

Immunologic Histamine Release Initial Exposure

A 
Major type
Ca2+ and energy dependent
Immune response-->activate B cells
B-cells secrete IgE abs
Bind Mast cell Fc receptors (sensitization)
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10
Q

Histamine Subsequent Exposure

A

Allergen cross-links 2 IgE/Fc receptor complexes on mast cell surface
Degranulation occurs

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11
Q

Histamine Mechanical Release

A

Na+ causes release of histamine from granules when mast cells injured

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12
Q

H1

A

Gq/11-increased IP3, DAG and intracellular Ca2+, activated NFkB
Smooth muscle, vascular endothelium, brain

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13
Q

H2

A

Gs-Increased cAMP
Gastric parietal cells, cardiac muscle, mast cells, brain
Mediates gastric acid secretion in stomach

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14
Q

H3

A

Gi/o-Decreased cAMP
CNS and some peripheral nerves
Autoreceptors limit synthesis and release of histamines and other neurotransmitters

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15
Q

H4

A

Gi/o-Decreased cAMP, increased intracellular Ca2+
Hematopoietic cells, gastric mucosa
Mediates histamine-induced LTB4 production
Adhesion molecule up-regulation
Chemotaxis of mast cells, eosinophil and dendritic cells

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16
Q

NFkB

A

Promotes expression of adhesion molecules and pro-inflammatory cytokines

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17
Q

Describe and Demonstrate the Triple Response of Histamine

A
  1. Histamine-induced post-capillary venule dilation engorges local microvasculature with blood, initiates repair processes in damaged area, causes erythema (red spot)
  2. Histamine induces endothelial cell contraction and separation, release of plasma proteins and fluids from PCV, edema (wheal)
  3. Histamine depolarizes afferent nerve terminal, itching/pain (flare)
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18
Q

Clinical use Histamine

A
  1. Positive control for allergenic (immediate hypersensitivity)
  2. Off-label use for diagnosis of asthma and gastric histamine test
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19
Q

Histamine Antagonism

A
  1. Anti-histamine
  2. Prevent mast cell degranulation
  3. Functional antagonists
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20
Q

Anti-Histamines

A

Inverse agonist
H1 or H2
Competitive antagonists selective for histamine receptors

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21
Q

Preventing Mast Cell Degranulation

A

Induced by binding of an antigen to the IgE/Fc receptor complex on mast cells

22
Q

Functional Histamine Antagonists

A

Act on different pathway to counteract effects of histamine

23
Q

H1 Anti-histamines

A

H1 receptor antagonists
Inverse agonists
Bind to inactive state and shifts the equilibrium towards inactive

24
Q

H1 Receptors 2 States

A
  1. Active
  2. Inactive
    Basal State: receptor tends toward constitutive activation
25
Q

1st Generation Histamines

A

Neutral at physiologic pH
Cross BBB to block H1 receptors in the CNS
CNS depression (drowsiness)
May additionally bind cholinergic, a-adrenergic, and 5HT receptors at standard doses (dry mouth)

26
Q

2nd Generation Histamines

A

Ionized at physiologic pH
Does not readily cross the BBB
Less CNS depression (drowsiness)
H1-selective, less anticholinergic effects (dry mouth)

27
Q

1st Generation Ethanolamines

A

Diphenhydramine

Dimenhydrinate

28
Q

Diphenhydramine

A

Given parentally to improve anti-psychotic-induced Parkinsonism movement disorder
Indicated for atopic dermatitis mostly for sedative side effects that reduce awareness of itch
Biggest sedative effect
Decrease itch
1st generation Ethanolamines

29
Q

Dimenhydrinate

A

Similar to dephenhydramine
Used recreationally as OTC hallucinogens due to narrow therapeutic index
Treats motion sickness
1st generation ethanolamines

30
Q

1st Generation Alkylamines

A

Chropheniramine

31
Q

Chlorpheniramine

A 
least sedating 1st generation for this characteristic
US class is mostly widely used along with 2nd generation antihistamines for allergic reactions
More expensive
32
Q

1st Generation Phenothiazines

A

Promethazine

33
Q

Promethazine

A

1st generation phenothiazines
Alpha receptor blockade effect
Orthostatic hypotension in some susceptible individuals

34
Q

1st Generation Piperidines

A

Cyproheptadine

35
Q

Cyproheptadine

A

Strong 5HT receptor antagonist and is promoted as antiserotonin agent
Anti-5Ht agent

36
Q

2nd Generation Antihistamines

A
  1. Loratadine
  2. Fexofenadine
  3. Cetirizine
37
Q

Loratadine

A

2nd Generation Anti-histamines
Metabolized by liver-3A4, 2D6
Like other antihistamines to form other metabolites (Desloratadine)

38
Q

Fexofenadine

A

2nd Generation Antihistamines
Not metabolized by CYP
Mostly eleminated in feces! Yay!

39
Q

Cetirizine

A

2nd Generation Antihistamines
Derived from hydroxyzine
Not metabolized by CYP
Mostly eliminated in the urine

40
Q

Glucocorticoids

A

1st line for allergic reactions

41
Q

Urticaria

A

Drug of choice for hives

Histamine primary mediator

42
Q

Allergic Rhinitis

A

2nd generation anti-histamines primarily indicated

43
Q

Treatment for motion sickness and vestibular distrubances

A

Only indication of dimenhydrinate

44
Q

Treatment for insomnia

A

Diphenhydramine

45
Q

Antimuscarinic effects 1st generation anti-histamines

A

Pupillary dilation, dry eyes, dry mouth, urinary retention and hesitancy

46
Q

Anti-histamines Adverse Effects Children/Elderly

A 
Cause hallucinations
Irritability
Convulsions
Relapses into respiratory failure and cardiovascular collapse
Postural hypotension
47
Q

1st Generation Anti-histamine Side Effects

A
  1. Sedation
  2. Dry Mouth
    Ex. diphenhydramine
48
Q

What metabolizes most antihistamines?

A

CYP3A4
CYP2D6
Compete with other agents that are metabolized by the same enzyme and increase adverse effects

49
Q

H2 Antagonists

A

Cimetidine
Ranitidine
Famotidine
Nizatidine

50
Q

Cromolyn

A

Mast cell degranulation
Shape and volume changes mediated by opening of chloride channels followed by opening of Ca2+ channels
Inhibits Cl- channels
Indicated for allergic rhinitis, systematic mast cell disease

51
Q

Epinephrine

A

Functional antagonist
Adrenergic agonist induces bronchodilation (B2) and vasoconstriction
Counters bronchoconstriction, vasodilation and hypotension caused by histamine during anaphylactic shock

52
Q

Histamine bronchoconstriction

A

H1 receptors

Musculoskeletal (7 decks)

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