Autocoids/Histamine

Question 1

Autacoids

Answer 1

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

Question 2

Lipid Derived Eicosanoids

Answer 2

Prostaglandins
Thromboxanes
Leukotrienes

Question 3

Endogenous Peptides

Answer 3

Histamine, 5HT, Ergot Alkaloids

Question 4

Cytokines

Answer 4

Interleukins, TNF

Question 5

Vasoactive peptides

Answer 5

Angiotensin
Kinins
Vasopressin
Natriuretic peptides
Endothelins
Substance P

Question 6

Histamine Synthesis

Answer 6

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

Question 7

Histamine Storage

Answer 7

Bound in granules in mast cells and basophils

Histamine content

Question 8

Histamine Tissue Locations

Answer 8

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

Question 9

Immunologic Histamine Release Initial Exposure

Answer 9

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

Question 10

Histamine Subsequent Exposure

Answer 10

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

Question 11

Histamine Mechanical Release

Answer 11

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

Question 12

H1

Answer 12

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

Question 13

H2

Answer 13

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

Question 14

H3

Answer 14

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

Question 15

H4

Answer 15

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

Question 16

NFkB

Answer 16

Promotes expression of adhesion molecules and pro-inflammatory cytokines

Question 17

Describe and Demonstrate the Triple Response of Histamine

Answer 17

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)

Question 18

Clinical use Histamine

Answer 18

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

Question 19

Histamine Antagonism

Answer 19

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

Question 20

Anti-Histamines

Answer 20

Inverse agonist
H1 or H2
Competitive antagonists selective for histamine receptors

Question 21

Preventing Mast Cell Degranulation

Answer 21

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

Question 22

Functional Histamine Antagonists

Answer 22

Act on different pathway to counteract effects of histamine

Question 23

H1 Anti-histamines

Answer 23

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

Question 24

H1 Receptors 2 States

Answer 24

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

Question 25

1st Generation Histamines

Answer 25

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)

Question 26

2nd Generation Histamines

Answer 26

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

Question 27

1st Generation Ethanolamines

Answer 27

Diphenhydramine | Dimenhydrinate

Question 28

Diphenhydramine

Answer 28

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

Question 29

Dimenhydrinate

Answer 29

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

Question 30

1st Generation Alkylamines

Answer 30

Chropheniramine

Question 31

Chlorpheniramine

Answer 31

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

Question 32

1st Generation Phenothiazines

Answer 32

Promethazine

Question 33

Promethazine

Answer 33

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

Question 34

1st Generation Piperidines

Answer 34

Cyproheptadine

Question 35

Cyproheptadine

Answer 35

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

Question 36

2nd Generation Antihistamines

Answer 36

1. Loratadine 2. Fexofenadine 3. Cetirizine

Question 37

Loratadine

Answer 37

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

Question 38

Fexofenadine

Answer 38

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

Question 39

Cetirizine

Answer 39

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

Question 40

Glucocorticoids

Answer 40

1st line for allergic reactions

Question 41

Urticaria

Answer 41

Drug of choice for hives | Histamine primary mediator

Question 42

Allergic Rhinitis

Answer 42

2nd generation anti-histamines primarily indicated

Question 43

Treatment for motion sickness and vestibular distrubances

Answer 43

Only indication of dimenhydrinate

Question 44

Treatment for insomnia

Answer 44

Diphenhydramine

Question 45

Antimuscarinic effects 1st generation anti-histamines

Answer 45

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

Question 46

Anti-histamines Adverse Effects Children/Elderly

Answer 46

``` Cause hallucinations Irritability Convulsions Relapses into respiratory failure and cardiovascular collapse Postural hypotension ```

Question 47

1st Generation Anti-histamine Side Effects

Answer 47

1. Sedation 2. Dry Mouth Ex. diphenhydramine

Question 48

What metabolizes most antihistamines?

Answer 48

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

Question 49

H2 Antagonists

Answer 49

Cimetidine Ranitidine Famotidine Nizatidine

Question 50

Cromolyn

Answer 50

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

Question 51

Epinephrine

Answer 51

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

Question 52

Histamine bronchoconstriction

Answer 52

H1 receptors