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Asthma, COPD, Rhinitis > Histamine > Flashcards

Histamine Flashcards

1
Q

What are functions of histamine?

A

Mediates allergic responses

Gastric acid secretion

CNS neurotransmitter

Promotes bronchoconstriction, mucus secretion

Increases permeability

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2
Q

Where is histamine stored?

A

Mast cells (CT around blood vessels, skin, lung mucosa gut, mouth, nose, eyes) - secretory granules

Histamine generation and storage occur in the epidermis, gastric mucosa, neurons, cells in regenerating tissues

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3
Q

What stimulates degranulation (release of histamine)?

A

Immunoglobulin (IgE)

Chemicals

Toxins

Basic drugs (D-tubocurarine, morphine)

Trauma

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4
Q

Where are H1 receptors found?

A

Smooth muscle

Endothelial cells

CNS

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5
Q

What is the G protein associated with H1 receptors? What effect results from stimulation?

A

Gq

Gq => inc. PLC => more intracellular calcium

Effects:
CONTRACTION
NO release
Neurotransmitter release

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6
Q

Where are H2 receptors found?

A

Parietal cells in gut/stomach

Mast cells

Vascular SM

Myocardium

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7
Q

What G protein is associated with H2 receptors? What effects does the signal transduction have?

A

Gs

Gs => inc. cAMP => PKA activity

Effects:
Inc. gastric secretion
SM relaxation

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8
Q

Where are H3 receptors found?

A

CNS

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9
Q

What does the signal transduction pathway of H3 receptors look like?

A

Gi/o => dec. cAMP

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10
Q

Where are H4 receptors distributed?

A

Eosinophils

Neutrophils

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11
Q

Signal transduction pathway of H4 receptors?

A

Gi/o => dec. cAMP

Inc. intracellular calcium

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12
Q

Which histamine receptors mediate vasodilation in the cardiovascular system?

A

H1 and H2

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13
Q

Compare vasodilation effects among H1 and H2 receptors

A 
H1 = endothelium
H2 = smooth muscle
H1 = NO-dependent
H2 = cAMP-dependent
H1 = rapid dilation, short lived
H2 = slow dilation, sustained
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14
Q

How do H1 receptors affect capillaries?

A

Increased post-capillary venule permeability

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15
Q

How do H1 receptor stimulation lead to increased permeability?

A

Endothelial cell contraction results in disruption of cell-cell junctions, exposing the basement membrane.

This makes vessel more permeable to plasma proteins and fluids, as well as inflammatory cell infiltration.

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16
Q

What is the local CV response induced by histamine?

A

Erythema

Flare

Wheal

17
Q

What is the mechanism behind erythema?

A

H1 and H2 receptors lead to capillary dilation

18
Q

What is the mechanism behind erythema + flare?

A

H1 receptors lead to indirect dilation mediated by sensory nerves

19
Q

What is the mechanism behind the wheal?

A

H1 receptor leads to receptor-mediated capillary permeability

20
Q

What are peripheral nerve ending responses from histamine?

A

Itch, pain, flare in the triple response = H1 receptors

21
Q

What are respiratory system responses to histamine?

A

Bronchial SM contraction + increased secretions (H1, DOMINANT) and relaxation via H2

22
Q

How do histamine and gastric acid secretion relate?

A

Histamine released from ECL cells in stomach will stimulate parietal cells in the stomach to release gastric acid

23
Q

Describe histamine release under hormonal and neural control.

A

Hormonal
Gastrin binds to gastrin/CCK receptors on ECL cells
=> inc. histamine release

Neural
ACh stimulates mAChRs on ECL cells => inc. histamine release

24
Q

What are the effects of H1 antihistamines?

A

Block:

Histamine-induced contraction of GI + bronchial SM

Flare + itch response

Histamine-elicited upper respiratory secretions and increases in capillary permeability

25
Q

Why do H1 antihistamines only partially block histamine-elicited vasodilation?

A

There are two receptors! H1 and H2

26
Q

Why do H1 antihistamines have a partial effect on anaphylaxis?

A

Other mediators are also secreted from mast cells that can also promote anaphylaxis response

27
Q

What are H1 antihistamine side effects?

A

Anti-muscarinic side effects:

dry mouth
Dec. nasal/ upper respiratory secretions
Urinary retention
Sedation

Motion sickness, anti-emitic effects (some)

28
Q

What are therapeutic uses for H1 antihistamines?

A

Upper respiratory tract allergic symptoms, hay fever, and pollinosis, common cold

Urticaria (allergic CD) - systemically!

Anaphylactic shock - prophylactically!

delayed hypersensitivity reactions

Sedation in OTC sleep medications

Anti-motion sickness

29
Q

What are therapeutic uses of H2 antihistamines?

A

Acid-peptic ulcer disease

Zollinger-Ellison syndrome (gastrin-secreting tumor)

Prevention of damage from pulmonary aspiration

Potential anti-inflammatory

Asthma, COPD, Rhinitis (2 decks)

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