Antihistamines Flashcards
what are the general mechanisms for histamine release from mast cells?
cytolytic
noncytolytic
what leads to cytolytic mechanism of histamine release?
- membrane damage
- high levels of drugs (opioids)
- mechanical damage
what leads to noncytolytic mechanism of histamine release?
- immune response
- non-immunological response from basic polypeptides
- displacement of histamine from granules by drugs (morphine, codeine, radiocontrast)
where are H1 receptors expressed? what is the result of activation?
- smooth muscle cells (vascular, respiratory, GI)
- vascular endothelial
- CNS neurons
- peripheral sensory nerves
Gq (PLC - IP3 - Ca)
where are H2 receptors expressed? what is the result of activation?
gastric parietal cells
cardiac muscle
CNS neurons
increased adnenylyl cyclase, cAMP / PKA
- smooth muscle cells (vascular, respiratory, GI)
- vascular endothelial
- CNS neurons
- peripheral sensory nerves
contain what type of histamine receptor? what is the result of activation?
H1
Gq (PLC - IP3 - Ca)
gastric parietal cells
cardiac muscle
CNS neurons
contain what type of histamine receptor? what is the result of activation?
H2
increased adnenylyl cyclase, cAMP / PKA
what are some of the physiological functions of histamine in the nervous system?
pituitary hormone release
wakefulness
appetite / satiety
what leads to the vasodilation effect of H1 activation?
PLC - calcium - increased eNOS - increased NO - vasodilation
what leads to the vasodilation effect of H2 activation?
AC - PKA - vasodilation
what leads to the increased vascular permeability / edema of histamine? is it mediated by H1 or H2?
PLC - calcium - increased contraction of endothelial cells - disruption of endothelial junctions - increased plasma proteins and fluid leak into tissue
H1
what is the result of H1 activation in the epidermis?
itch
what is the result of H1 activation in the dermis?
pain
what does H1 activation in the lungs cause?
elevated secretion of airway fluid and electrolytes - bronchoconstriction
activation of what histamine receptor type leads to elevated secretion of airway fluid and electrolytes - bronchoconstriction?
H1
what are the results of histamine receptor activation in heart muscle? is this mediated by H1 or H2?
- increased calcium - positive inotropic
- speeds up SA node - positive chronotropic
H2
antihistamines refer to agents that specifically target what receptor?
H1
what drug is a physiological antagonist of the histamine response itself?
EPI
what are the release inhibitor antihistamines?
cromolyn, nedocromil
omalizumab
what type of drug is omalizumab?
monoclonal IgE Ab
how do 2nd generation antihistamines differ from 1st generation?
2nd gen - more strongly target H1
2nd gen - do not enter brain (reduced lipophilicity)
less sedation
how do H1 antihistamines exert their effect?
reversibly bind to receptor and stabilize inactive form
what are the main adverse effects of first generation H1 antihistamines?
CNS - cognitive
muscarinic - anticholinergic (dry)
5-HT - increased appetite and weight gain
alpha - increased dizziness
excitation and seizures
chlorpheniramine is used to treat what conditions?
allergic rhinitis and allergies
diphenhydramine (benadryl) has what effects, physiologically?
sedative
antimuscarinic
antimotion
what are the therapeutic uses for benadryl?
allergic rhinitis
cough suppressant
motion sickness
what is the unique feature of pyrilamine?
low sedative effects
very little antimuscarinic action
no antimotion activity
what is the primary use of hydroxyzine?
antiemetic
what are the primary uses of meclizine? what makes it different from hydroxyzine?
motion sickness, vertigo
less sedating than hydroxyzine
what is the primary MOA of promethazine?
significant inhibition of alpha adrenergic receptors
what are the primary uses of promethazine?
antiemetic
anti motion sickness
promethazine can also block what receptor type, in addition to H1?
D2
cyproheptadine can also block what receptor type, in addition to H1?
5-HT
which drugs have the strongest antiemetic effects?
diphenhydramine
promethazine
hydroxyzine
meclazine
which H1 antihistamines have the highest sedative effects?
diphenhydramines
hydroxyzine
promethazine
which antihistamine is the significant alpha adrenergic receptor antagonist? what is the result?
promethazine
postural hypotension
dizziness
reflex tach
which antihistamine is the significant serotonin receptor antagonist? what are its adverse effects? what can it be used for therapeutically?
cyproheptadine
antimuscarinic
increased weight gain
serotonin syndrome
what are the drug interactions with antihistamines?
MAOIs
opioids, ethanol
anticholinergics
azelastine is an antagonist of what receptor?
H1
which antihistamines have lower sedation profiles and are more useful for people working in jobs that require increased wakefulness?
loratidine
fexofenadine
why are loratidine and fexofenadine beneficial?
less sedation
fexofenadine should be avoided with coadministration of what agents?
antacids
citrus juices
what are the MOAs of cromolyn and nedocromil?
- stabilize mast cell
2. inhibition of chloride channels in cell membranes
what are the therapeutic uses of omalizumab?
(chronic) urticaria
asthma
what drugs are used for chronic urticaria?
doxepin
omalizumab
what drug is useful for treating allergic conjunctivitis? what is the MOA?
ketotifen
H1 antihistamine with additional mast cell and basophil stabilization
ketotifen is used to treat what condition?
allergic conjunctivitis?
