Antihistamines Flashcards
Histamine is synthisized from histidine, and is found as granules in what two cell types?
Mast Cells
Basophils
What two body systems typically have histamine receptors?
brain, GI
Normally, histamine is complexed with proteases, heparin, or proteoglycans which ensure it is (active/inactive)
inactive storage
In the allergic reaction, T-Helper cells bind to a naive B-cell, which secretes _______ to plasma. ______ can then bind which receptors on mast cells/basophils to release histamine in the effector phase?
IgE
6 major effects of histamine
SM contraction Vasodilation vascular permeability platelet aggregation complement activation mucus secretion
IgE binds which receptors on mast cells/basophils?
Fc
An allergen forms what on which mast cell structures that results in activation?
allergen bridges IgE
The activated mast cells utilizes PK to increase concentrations of what two substances?
IP3 and Calcium
increased intracellular concentration of IP3 and Calcium activates ______, which has what 4 effects?
IP3 and Calcium activate PLA2
PLA2 increases platelet activating factor, leukotrienes, kinins, histamine release
The below have what effect on mast cells?
Contrast dyes Organic bases Morphine d-TC, Succinylcholine Many venoms Scratching, cold, sun
Cause histamine release without sensitization (IgE)
Is the itching after morphine administration an allergic response? why or why not?
no… no IgE Abs to morphine.
Morphine causes direct histamine release
What effect does the H1 receptor have on endothelium?
activates NO
H1 receptor mediates the allergic response present on what 2 tissue types?
smooth muscle
endothelium
H1 receptor has what 2 effects on the brain?
wakefullness
appetite control
What three tissue types have the H1 receptor?
smooth muscle
endothelium
brain
What three cell types have the H2 receptor?
heart, brain, mast cells
The main function of the H2 receptor…
gastric acid secretion (via cAMP)
Which histamine receptor types cause vasodilation?
H1 and H2
Which histamine receptor types cause bronchospasm?
H1
In order for H2 receptors to exert vasodilatory effects, what concentration of histamine must be present?
high concentration
What are 3 major effects of histamine mediated vasodilation?
- decreased BP + reflex tachycardia
- capillary permeability
- edema, swelling
What effect does histamine have on the skin?
causes pruritis
what is described below?
red spot via vasodilation
flare due to out axon-reflexes
wheal in 2-3 minutes due to capillary permeability
triple response
What is the first sign of histamine release?
burning/itching (esp. ears)
Antihistamines are technically which type of drug?
inverse agonist (decrease transmitter activity)
Why are antihistamines good for motion sickness and insomnia?
Blocks muscarinic receptors/anticholinergic properties
Increased _______ blockade means more sedation
muscarinic
Histamine has a ________ relationship with antihistamines, meaning __________ can overcome the blockade
competitive relationship
high concentration
Why are 1st gen H1 antagonists more sedating than 2nd gen?
lipophilic, so enters brain to have anticholinergic effect
The below have what effect?
diphenhydramine
doxylamine
hydroxyzine
Sedation
The below have what effect?
Diphenhydramine
Dimenhydrinate
anti-motion sickness (M blocker)
The below have what effect?
promethazine
anti-emetic/motion sickness
What additional receptor does promethazine block that gives it an anti-emetic property?
D2 receptor blocker
Diphenhydramine and histamine are structurally related to…
ACh
Do 2nd gen H1 antagonists have anticholinergic effects? What does this mean for motion sickness?
no, not good for motion sickness
Antihistamines are metabolized by _______ which may be _____ in chronic use
metabolism by CYP450
induced metabolism in chronic use
Which three 2nd gen H1 blockers are excreted directly by the kidney?
cetirizine
levocetirizine
acrivastine
cetirizine
levocetirizine
acrivastine
these drugs would be a good choice for which patients?
liver disease, multiple drugs
cetirizine
levocetirizine
acrivastine
These drugs would be a bad choice for which patients?
impaired kidney function
Antihistamines for allergic rhinitis and motion sickness have best effect when used…
prophylacticly
1st gen antihistamines for sedation should be used _______ due to ________ development
occasionally, tolerance
Which generation of H1 blocker will dry up secretions? why?
1st gen, anticholinergic
what is an important S/E of 1st gen H1 blockers in the CNS?
decreased seizure threshold
Beacuse of anticholinergic properties, 1st gen H1 receptors have what side effect?
dry mouth & and other anticholinergic SEs
1st gen H1 blockers interact with…
CNS depressants
2nd gen H1 blockers interact with…(4)
erythromycin
ketoconazole
cimetidine
grapefruit juice
Children under _____ shouldn’t use any OTC cold or cough product…
under 4 yo
OD of 1st gen H1 blockers is similar to…
atropine poisoning (blind as a bat, hot as a hare, red as a beet, mad as a hatter, etc)
OD of newer 2nd gen H1 blockers …
sinus tachy
OD of older 2nd gen H1 blockers …
cardiac arrhythmia
this drug directly inhibits histamine release by stabilizing mast cells…
Cromolyn
This drug inhibits histamine release directly and also blocks receptors
azelastine
This 2nd gen H1 blocker may also inhibit histamine release
cetirizine
