Anti-Histamines Flashcards
What are some common 1st generation anti-histamines?
- Diphenhydramine (Bendryl)
- Dimenhydrinate (Dramamine)
all short acting (4-6 hrs)
What are some 2nd generation anti-histamines?
- Fexofenadine (Allegra)
- Loratadine (Claritin)
- Cetirizine (Zyrtec)
How is histmaine synthesized?
via L-histadine by giving off water
What cells make histamine?
- mast cells (less likely to circulate)
- basophils
- CNS neurons (its a neurotransmitter)
- epidermal cells and intestinal mucosa
Functions of histamine?
- stimulate production of hydrochloric acid in stomach
- vasodilation in allergies/etc.
- neurotransmitter: regulates sleep, brain arousal, memory
Histamine is mediated by 4 receptors and is only active when bound to an appropriate receptor
Histamine is mediated by 4 receptors and is only active when bound to an appropriate receptor
What are the effects of H1 binding?
-increased vascular permeability
-enhancement of histamine and arachidonic acid
derivatives release,
-NO formation,
-increased wakefulness
Clinical effects of H1 binding?
Sneezing, itching, rhinorrhea
and perhaps some degree of nasal congestion via increase vascular permeability with leakage of fluid into the tissues and vasodilation
What are the effects of H2 binding?
stimulate mucous glands
in airways, increases vascular permeability;
stimulate release of gastric acid (most important)
Clinical effects of H2 binding?
Potentially increase nasal
airway swelling, producing
nasal congestion and perhaps increased rhinorrhea
What are the effects of H3 binding?
stimulate nasal sub-mucosal gland secretion
Clinical effects of H3 binding?
can produce a runny nose
What are the effects of H4 binding?
Chemotaxis and chemokinesis of mast cells and eosinophils, enhancement of the activity of other chemoattractants (e.g. chemokines) on eosinophils, upregulation of adhesion molecules
Clinical effects of H4 binding?
Could enhance the
inflammatory response to nasal allergen exposure
What causes histamine release?
IgE binding and crosslinking to mast cells (takes several days to restore the reserves of histamine)
How does H1 binding affect arteries? arterioles?
capillaries?
venules? veins?
arteries- smooth muscle constriction and endothelium dilation
arterioles- rapid onset, short term dilation
capillaries-none
venules- rapid onset, short term dilation, capillary permeability
veins- smooth muscle constriction and endothelium dilation
How does H2 binding affect arteries? arterioles?
capillaries?
venules? veins?
H2 all dilation (slower onset, but more persistent)
capillaries still not effect (same as H1)
What is the net effect of histamine in the vasculature?
vasodilation via H1 receptors everywhere (H2 is minor everywhere outside the stomach)
What does H1 binding in the lungs cause?
broncho-constriction
Roles of H1 antagonists?
- attenuation of allergy and hay fever symptoms
- treatment of symptoms of insect bites, stings, and contact flora poisoning
What additional effect do 1st gen H1 antihistamines have?
attenuation of motion sickness and vertigo
Which generation of anti-histamines have anti-cholinergic effects?
1st generation only
Which generation of anti-histamines has a shorter duration of action?
1st-multiple doses required
Why do the 1st generation anti-histamines cause sedation?
H1 receptors in the hypothalamus binding to histamine promotes alertness (these can pass the BBB because they are mostly uncharged)
