Lecture 9- Histamine Flashcards
What cell type is histamine mostly found in?
Mast Cells
Where are the highest amounts of histamine found?
Lung, skin, nasal and Gi mucosa
Mast cells have high affinity _______ binding sites on their plasma membranes.
IgE
Histamine is formed by decarboxylation of what amino acid?
Histidine
Histamine is stored in _______.
Granules
What are some instances where histamine is released?
Trauma Allergies Anaphylaxis Cold Bacterial toxins Bee strings Venom Drugs
What are the 2 types of histamine release from mast cells?
Cytolytic release
Noncytolytic release
What causes cytolytic release of histamine?
Damage to plasma membrane then there is leakage of cytoplasmic contents
What 2 things induce cytolytic release of histamine?
Phenothiazines
Narcotic analgesics
What type of histamine release requires ATP and calcium?
Noncytolytic release
What causes histamine release in noncytolytic release?
IgE antibodies binding to antigen
These 6 drugs (d-tubocurare, succinylcholine, morphine, codeine, doxorubicin, protamine) can cause what with histamine?
Stimulate histamine release from mast cells without prior sensitization
What drug causes red man syndrome- flushing, pruritus, chest pain, muscle spasms and hypotension?
Vancomycin
What can help reduce the symptoms of red man syndrome?
Pretreatment with IV antihistamines
What are 2 inhalation powders that block the release of histamine from mast cells?
Cromolyn
Nedocromil
What are Cromolyn and Nedocromil used for?
Decrease symptoms of allergic rhinitis
Used to block asthmatic rxns
Are Cromolyn and Nedocromil effective during an actual asthma attack?
No, only preventative
Which histamine receptor uses adenylyl cyclas mechanism and parietal cell acid secretion?
H2
Which histamine receptor is proinflammatory activity?
H4
What histamine receptor is on neurons and inhibits the release of histamine (feedback inhibition)?
H3
Which histamine receptor uses phospholipase C mechanism (respiratory and allergic reactions)?
H1
Which histamine receptor increases mucus in nasal cavity and bronchi resulting in respiratory symptoms
H1
What histamine receptor stimulates gastric secretions?
H2
Which histamine receptor constricts bonrchi and intestines (cramps, diarrhea)?
H1
The activation of which histamine receptor leads to the stimulation of sensory nerve endings (itching/ pain)?
H1
How does histamine directly increase HR and contractility?
Increasing influx of calcium
How does histamine indirectly increase HR and contractility?
Baro-receptor mediated increase in sympathetic tone in response to histamine induced vasodilation
What are the 2 ways H1 leads to vasodilation?
Decrease in blood pressure
increase in nitric oxide
Is there a release of catecholamines from the adrenal medulla in allergy and anaphylaxis?
Yes
What are the three parts of the triple response of lewis?
Red line/ spot
Flare (large area of red around)
Wheal (edema)
In hypersensitivity rxns what are the 2 principle targets?
Mast cells and Basophils
What happens in an allergic response?
An antigen produces the formation of IgE antibodies which bind to high affinity receptors specific for these IgE antibodies and activates tyrosine kinase
The activation of phospholipase A2 produces _________ and __________.
Leukotrienes
Prostaglandins
____________ contract smooth muscle of the bronchi. Are involved in hypersensitivty rxns?
Leukotrienes
What happens if histamine is released rapidly and diffuses via the blood then the response may be full-blown .
Anaphylactic reaction
What do you treat true anaphylaxis with?
Epinephrine
What is histamine phosphate used for?
to assess nasal and bronchial reactivity
for allergy skin testing
What should individuals discontinue before allergy skin testing with histamine phosphate?
antihistamines, tricyclic antidepressants, corticosteroids, benzodiazepines.
1st generation antihistamines block which histamine receptor?
H1
What are the 5 hisatmine H1 receptor blockers, first generation?
triprolidine diphenhydramine promethazine hydroxyzine chlorpheniramine
What is the benefit of 2nd generation H1 receptor blockers?
Less CNS toxicity or side effects since they don’t cross the BBB and are excluded by p-glycoprotein
What are the 4 second generation H1 receptor blockers?
loratadine (Claritin, OTC),
desloratadine (Clarinex),
azelastine (Astelin) ,
cetirizine (Zyrtec,OTC)
What effects are lesser in reversible, competitive blockers of H1 receptors?
Less effect on bronchoconstrction and vasodilation which are caused predominatly by prostaglandins and leukotrienes
For H1 blockers is there a tolerance to the suppressive effect on skin test reactivity to allergens?
No
Tolerance to what effect of H1 blockers may occur?
Sedative effects
What is the active metabolite of loratadine (Claritin)?
Desloratadine (Clarinex)
What is the metabolite of terfenadine (Seldane)?
Fexofenadine (Allegra)
What is terfenadine metabolized by?
CYP3A4 family
Is terfenadine currently on the market?
No- it was withdrawn due to risk of life threatening cardiac arrhytmias, torsades de pointes
What do all FDA approve antihistamines no prolong?
QT interval
What is the main difference b/w 1st and 2nd generation H1 blockers?
2nd generation have no anticholinergic affect, no CNS sedation and are longer acting
What allergic conditions do antihistamines (H1) treat?
Allergic rhinitis
Urticaria
Allergic drug rxns (prophylactic)
Allergic conjunctivitis
What is the most effective antihistamine used for prevention of symptoms of motion sickness?
Promethazine
What are 3 other antihistamines (besides promethazine) used for prevention of motion sickness?
diphenhydramine, cyclizine, meclizine
When should you administer promethazine?
1 hour before anticipated motion
What is the most effect drug (not an antihistamine) used to prevent motion sickness?
Scopolamine
WHat drug class is used to prevent nausea and vomiting?
Phenothiazine class
What are 2 drugs in the phenothiazine class that are used to prevent N/V?
Promethazine
Timeprazine
How does the phenothiazine class work?
Blocks dopamine D2 receptors
What drug is used for OTC treatment of hyposomnia?
Diphenhydramine
How many consecutive nights should antihistamines used for sleep medications be limited to?
10 consecutive nights
What antihistamine drug is used for antiparkinsonism effect, especially antimuscarinic actions.
Diphenhydramine
What antihistamine is found in sunburn preparations for local anesthetic actions?
Promethazine
How do antihistamines work as local anesthetics- specifically what channels do they block?
Block sodium channels
What is an antihistamine used to treat oral ulcers, infections, inflammation and pain?
Magic Mouthwash
What are the 2 main adverse effects of antihistamines?
Antimuscarinic and sedative actions (usually lower with second generation)
What does CNS sedation correlate with for antihistamines?
H1 receptor binding in brain
What are some of the anticholinergic effects associated with antihistamines?
Dry mouth and nasal passages
Constipation
Blurred vision
Urinary retention
What can occur in children who are given antihistamines?
Paradoxical excitation
Combing CNS H! antagonists with what other medications can be dangerous?
Other sedating medications
H1 antagonists potentiate _________________
all other CNS depressants
What population is acute poisoning with H1 antagonists relatively common?
Young children
What are the acute effects of poisoning with H1 antagonists?
initial excitement
ataxia and convulsions
coma and cardiorespiratory collapse
