61: Antihistamines Flashcards
triple response of Lewis
- red spot
- flare
- wheal
Mast cells are found in greater numbers where?
bronchial mucosa
intestinal mucosa
skin
they secrete just about everything
Mechanisms for histamine release form mast cells
- Cytolytic
- Membrane damage
- High levels of certain drugs
- Mechanical damage
- NON-cytolytic
- immune response that requires prior sensitization
- non-immunologic response to polypeptide (substance P, wasp venom)
- displacement from granules by substances such as opiods and antibiotics
where are H1 receptors primarily expressed?
- smooth muscle cells
- vascular endothelial cells
- CNS neurons
- peripheral sensory nerves
what type of signaling do H1 receptors use?
Gq with PLc-Ip3-Ca2+ pathway
where are H2 receptors primarily expressed?
- gastric parietal cells
- cardiac muscle
- CNS neurons
what type of signaling do H2 receptors use?
Gs
increases adenylyl cyclase and cyclic AMP –> PKa
organ system effects of histamine =
vasodilation
decreased total peripheral resistance and fall in systemic blood pressure can cause reflex tachycardia and edema
H1 in lung smooth m. cells causes…
elevated secretion of airway fluid and electrolytes and bronchoconstriction
H1 in peripheral neurons…
activation in epidermis causes itch
- activation in dermis causes pain
histamine ______ the following things
- vascular permeability
- immune cell adhesion molecules (p-selectin)
- chemotaxis of eosinophils and neutrophils
- release of inflammatory cytokines
- antigen presentation from APC cells
increases
name 3 diseases that increase histamine levels
myelogenous leukemia
gastric carcinoid tumros
mast cell leukemia
physiological antagonists of histamine
epinephrine
3 histamine release inhibitors
cromolyn
nedocromil
omalizumab
can be used as prophylactic treatment of allergy
why are 2nd gen antihistamines non-sedating?
they do not penetrate BBB
3 common conditions treated by 1st gen antihistamines
allergic rhinitis
allergic conjunctivitis
urticaria
H1 antihistamines are inverse agonists?
reversibly bind to receptor and stabilize the inactive form
what do you need to watch out for when giving first gen antihistamine to neonates and young children?
paradoxical excitation and seizures
why are mydriasis, constipation, and dry mouth/throat adverse effects of first gen antihistamines?
binding to muscarininc receptors as well
chlorpheniramine
1st gen antihistamine
diphenydramine
1st gen antihistamine
pyrilamine
1st gen antihistamine
hydroxyzine
1st gen antihistamine
meclizine
1st gen antihistamine
promethazine
1st gen antihistamine
can also block dopamine receptors
cyproheptadine
1st gen antihistamine
can be used to treat serotonin syndrome
4 antihistamines with strongest antiemetic effects
diphenydramine
promethazine
hydroxyzine
Meclazine
3 antihistamines with highest sedative effects
diphenydramine
hydroxyzine
promethazine
which drugs are known for being anticholinergic?
diphenhydramine
promethazine
observe dry mouth, urinary retention, sinus tachycardia
which drugs are known for being anti adrenergic?
promethazine
observe hypotension, izziness, reflex tachycardia
which drug is know for being anti- serotonergic?
cyproheptadine
antihistamine drugs ___ appetite
increase
2nd generation antihistamines have a ____ selectivity towards H1 receptor than 1st gen
higher
- they bind noncompetitively to H1 receptor
- have a reduced lipophilicity
Azelastine
2nd gen antihistamine
Cetirizine
2nd gen antihistamine
Levocetirizine
2nd gen antihistamine
Desloratadine
2nd gen antihistamine
Loratadine
2nd gen antihistamine
Fexofenadine
2nd gen antihistamine
MOA cromolyn and nedocromil
inhibit degranulation of mast cells by inhibition of chloride channels in cell membrane s
treat chronic urticaria with
omalizumab
monoclonal antibody that bind IgE
also used in tx asthma
MOA doxepin
TCA
useful in treatment chronic urticaria b/c inhibits both H1 and h2 receptors
what would you use ketotifen for?
only an opthalmic preparation
treat allergic conjunctivitis
