Pb&t Histamine Pharmacology

Front 1

A molecule secreted locally to increase or decrease the activity of nearby cells.

Back 1

Autacoid

Front 2

Synthesized from L-histidine

Back 2

Histamine

Front 3

Catalyzes the decarboxlation of histidine to histamine.

Back 3

Histidine decarboxylase

Front 4

Where is histamine synthesized

Back 4

Mast cells, basophils, ECL cells in gastric mucosa, and certain neurons in CNS.

Front 5

What can be measured in the urine to assess the amt of histimine released systematically?

Back 5

Imidazole

Front 6

Where is the slow turning over pool of histimine? Why is it named such?

Back 6

Mast cells and basophils, stored in granules. Several weeks are required to replenish the stores of histamine after degranulation.

Front 7

Where is the fast turning over pool of histimine? Why is it named such?

Back 7

Gastric ECL cells and histaminergic CNS neurons (for gastric secretions and neurotransmission) This histimine is made when it is used.

Front 8

Effects smooth muscle, vascular endothelium, afferent nerve terminals, heart, GI tract and CNS.

Back 8

Histamine

Front 9

What does histamine do to bronchial smooth muscle?
People with asthma?

Back 9

Causes it to contract
Can be 1000X more sensitive.

Front 10

Effect of histamine on terminal arteriols and postcapillary venules? On Veins?

Back 10

Dialates
Constricts

Front 11

Though not clinically significant, smooth muscle in the bowel, bladder, iris and uterus ________ due to histamine.

Back 11

contract

Front 12

Vascular endothelial cells _________ due to histamine, causing edema.

Back 12

Contract

Front 13

Histamine on vascular smooth muscle, vascular endothelial cells, and nerve terminals are responsible for the:

Back 13

wheal and flare noted following histamine release in the skin.

Front 14

Inotropy

Back 14

an agent that alters the force or energy of muscular contractions. Negatively inotropic agents weaken the force of muscular contractions. Positively inotropic agents increase the strength of muscular contraction.

Front 15

Cardiac effects of histamine:

Back 15

Minor increases in force and rate of contraction.
Enhancement of Ca++ influx into cardiac myocytes (inotropy)
(Increase in phase 4 depolarization in SA nodal cells)

Front 16

Three molecules that regulate acid secretion in the stomach:

Back 16

Histamine
Gastrin
Acetylcholine

Front 17

What does histamine cause in the stomach?

Back 17

Activation of histamine receptors --> increase in intracellular Ca++ in parietal cells --> increase in HCL secretion by gastric mucosa.

Front 18

(CNS) Histidine decarboxylase and histamine receptors are expressed in the:

Back 18

Hypothalamus

Front 19

Believed to be important in the maintenance of wakefulness and to act as an appetite suppressant.

Back 19

histamine

Front 20

Histamine receptor subtypes are ___ ___ ___ ___ and all four are ________________

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H1 H2 H3 H4
seven transmembrane G protein coupled receptors

Front 21

Where are H1 receptors found and what cascade do they start?

Back 21

Vascular sm muscle, vascular endothelium, Lungs, peripheral nerves.
Hydrolysis of phosphitidylinositol, leading to increased IP3 & DAG.
IP3 --> increased Ca++.
DAG--> PKC phosphorylates cytosolic target proteins.

Front 22

Does activation of H1 receptor effect transcription factor NFkB?

Back 22

Yes, which promotes the expression of adhesion molecules and proinflammatory cytokines such as IL1 & TNF

Front 23

3 tissue specific responses to H1 receptor stimulation:

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Edema
Bronchoconstriction
Sensitization of primaryafferent nerve terminals

Front 24

What do H1 receptors do in the hypothalamus?

Back 24

function as autoreceptors to inhibit further histamine release

Front 25

Major fx of H2 receptor?
Cascade effect?

Back 25

mediate gastric acid secretion, therefore expressed in parietal cells in gastric mucosa.
cAMP cascade

Front 26

Where are H2 receptors found?

Back 26

Parietal cells
Cardiac muscle cells
Some immune cells
Certain presynaptic neurons

Front 27

H? receptors suppress neuronal firing and histamine release. Downstream effects of H? receptor activation are mediated via decrease in Ca++

Back 27

H3

Front 28

H? receptors have been localized to presynaptic histaminergic neurons (supressing neuronal firing and histamine release) in the CNS and ECL cells in stomach.

Back 28

H3

Front 29

H? are localized to cells of hematopoietic, primarily mast cells, basophils and eosinophils.

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H4

Front 30

H? leads to decreased cAMP, activation of phospholipase CB, and eventual increased intracellular Ca++.

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H4

Front 31

histamine plays a major role in what type of hypersensitivity reactions?

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Type I, also known as IgE mediated hypersensitivity reactions

Front 32

Sensitization:
Allergen stimulates B lymphocytes via T helper cells, and B cells produce IgE ab that are specific for the allergen. That IgE then bindsto Fc receptors on:

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Mast cells and basophils. After sensitization the allergen thus triggers degranulation.

Front 33

Mast cells or basophils?
Degranulation can also occur as a response to local tissue damage, in the absence of a humoral immune response.

Back 33

Mast cells

Front 34

Responsible for initiation of certain inflammatory disorders, including allergic rhinitis and acute urticaria.

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IgE mediated hypersensitivity reaction.

Front 35

In anaphylaxis, the histamine release causes:
What should you treat it with?

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Systemic vasodilation resulting in hypotension
Bronchoconstriction
Epiglottal swelling
Epinephrine

Front 36

Antihistamines are typically

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inverse agonists or competative antagonists selective for H1-H4

Front 37

What are cromolyn and nedocromil used for? How do they work?

Back 37

To prevent asthma attacks by preventing mast cell degranulation inducedby binding ofan antigen to the IgE/Fc receptor complex on mast cells, and then disrupting the Cl transport across mast cells (a key step in the degranulation process).

Front 38

Why is epinephrine used to treat anaphylaxis?

Back 38

Bc it is an adrenergic agonist, and so induces bronchodilation and vasoconstriction.

Front 39

H1 antihistamines are

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inverse agonists, shifting equilibrium towards the inactive state.

Front 40

First generation H1 antihistamines consist of 6 main subgroups:

They are typically:

Back 40

Ethanolamines, ethylenediamines, alkylamiines, piperazines, phenothiazines and piperidines.
Neutral compounds that can cross the BBB

Front 41

4 most frequently used First generation H1 antihistamines

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Diphenhydramine
Hydroxyzine
Chlorpheniramine
Promethazine

Front 42

Widely used second generation H1 antihistamines (3)
What is the advantage of the second generation H1 antihistamines?

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Loratadine
Cetirizine
Fexofenadine
They do not cause CNS depression (drowsiness), because they do not cross the BBB.

Front 43

Hydroxyzine and doxepin are

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potent ANTIPURITIC agents.

Front 44

Can H1 antihistamines be used as the sole therapy for asthma?

Back 44

Nope

Front 45

H1 antihistamines (dimenhydrinate, diphenhydramine, meclizine, and promethazine) can be usefula as

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antiemetics

Front 46

H1 antihistamines such as diphenhydramine, doxylamine and pyrilamine can be used to treat

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insomnia (cns effects)

Front 47

Oral antihistamines are absorbed readily from the GI tract and most are metabolized in the liver. Therefore,

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Dose adjustments should be ocnsidered in pts with severe liver disease.

Front 48

H1 antihistamines are inducers of

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hepatic cytochrome P450 enzymes.

Front 49

Second generation H1 antihistamines are less likely to cross the BBB. Why?

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They are less lipophillic than 1st gen.
The are ionized at pH 7.4 and so do not diffuse readily.
They exhibit high binding to albumin and are therefore less free to diffuse.

Front 50

Former 2nd gen H1 antihistamines were pulled from the market bc

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they caused prolonged QT intervalsthat sometimes led to ventricular arrhythmias.

Front 51

General adverse effects of H1 antihistamines

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Pupillary dilation, dry eyese, dry mouth, and urinary retention and hesitancy.

Front 52

Cimetidine and ranitidine are two of the most commonly used

Significant side effect of cimetidine:

Back 52

H2 receptor antagonists for acid reflux and peptic ulcer disease.

Inhibition of cytochrome P450 mediated drug metabolism

Front 53

H? receptors are thought to provide feedback inhibition

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H3

Front 54

Second generation H1 antihistamines are less likely to cross the BBB. Why?

Back 54

They are less lipophillic than 1st gen.
The are ionized at pH 7.4 and so do not diffuse readily.
They exhibit high binding to albumin and are therefore less free to diffuse.

Front 55

Former 2nd gen H1 antihistamines were pulled from the market bc

Back 55

they caused prolonged QT intervalsthat sometimes led to ventricular arrhythmias.

Front 56

General adverse effects of H1 antihistamines

Back 56

Pupillary dilation, dry eyese, dry mouth, and urinary retention and hesitancy.

Front 57

Cimetidine and ranitidine are two of the most commonly used

Significant side effect of cimetidine:

Back 57

H2 receptor antagonists for acid reflux and peptic ulcer disease.

Inhibition of cytochrome P450 mediated drug metabolism

Front 58

H? receptors are thought to provide feedback inhibition

Back 58

H3