Part 13: Allergies Flashcards
type 1 hypersensitivity reactions are more commonly known as ___
allergic reaction
type 1 hypersensitivity rxns involve ___ antibodies recognizing an antigen, causing the release of _____ from mast cells
igE; inflammatory mediators
what are the 2 phases of igE mediated rxns?
- sensitization phase and
2. the effector phase
does the first exposure to an allergen typically generate an allergi response? why or why not
no, bc the immune system has never seen the antigen before, so it doesnt know what to do other tahn get rid of it
if a new allergen arrives and there are other cytokines and activated helper T cells, ___ cells may be suspicious of the antigen and make igE antibodies against it. what is this process called?
B ; sensitization
IgE antibodies are found at the surface of ___ cell
mast
resting mast cells are typically found around the membrane barriers of the body such as the ___, ___, ____ and ___
skin, mucous membranes, respiratory tract and GI tract
mast cells participate in ___ immune response, where they recruit other immune cells to the site of injury or infection
early
what happens during a second exposure to an allergen that the body has already been sensitized to ?
IgE antibodies in the mast cells bind to the antigen and cause amst cell degranulation, releasing tons of histamines and other infalmmatory mediators and chemotactic cytokines
the proinflammatory and cytokines produce immediate localized effects such as increased ____ and ___
vasodilation and vascular permeability
what is the purpose of increasing vascular permeability and vasodilation in an allergic rxn?
recruit immune cells
during an allergic rxn , there are increased secretions from the ___ and ___
GI tract, eyes etc
during an allergic rxn, smooth muscle contraction can also occur in response to ___
mast cell degranulation
contraction of smooth muscle in response to allergens results in allergic ____
asthma
when mast cells release ___, ___, and ___ these mediators cause smooth muscle contraction and promote blood vessel permeability allowing immune cells in and the inflammation of the airwyas
histamine, prostaglandins, leukotrienes
t/f immune responses are predictable and repeatable in a patient once the first reaction to allergen occurs
t
allergic rhinitis
upper airways respond to exposure of an inhaled allergen
when an allergic reaction is systemic it can be life-threatening and this is called ___
anaphylaxis
in anaphylactic reaction, exposure to an allergen causes systemic ____, airway ____ and peripheral ___ which can result in respiratory arrest
inflammation; obstruction; edema
what is desensitization therapy?
repeated microdosing of allergen to deplete IgE antibodies and decrease mast cell response over time
what can an allergic rxn look like in the skin?
itchy rash, urticaria
how can an allergic reaction present in the eyes?
redness, watering, itching
how can an allergic reaction present in the lungs?
increased mucous secretions, bronchoconstriction
how can an allergic reaction present in the GI tract?
cramping, bloating, diarrhea, nausea
what happens to BP during anaphylaxis?
hypotensive
how is an allergy test performed?
skin pricks to break skin barrier, then add a drop of a specific antigen as well as a positive control (histamine) and a negative control, then wait for mast cells to act (10-15min)
why can antigens cause a greater allergic reaction than histamine alone?
amplification process of IgE on mast cells and recruiting more immune cells
t/f a limitation of allergy testing is that there is not always every possible allergen available for testing
t
what are the 2 pharm approaches to managing allergies
- target the immune response to the allergen
2. target the physiologic symptoms associated with that response
what 3 classes of drugs are most often used in the setting of mild to moderate seasonal or environmental allergies
antileukotrienes, antihistamines, mast cell stabilizers
drugs like antileukotrienes, antihistamines, and mast cell stabilizers reduce the ____ response to allergen but are insufficient in managing severe events like ____
inflammatory; anaphylaxis
what are some of the physiologic symptoms of allergic rhinitis? what drugs can be used to manage them?
nasal congestion, runny nose; decongestants
what drug is needed for anaphylaxis
epinephrine
how does epinephrine help with anaphylaxis?
restores airway and increases cardiac output
stimulation of alpha 1 adrenergic receptors causes
smooth muscle and blood vessel constriction
stimulation of a1a receptors activates a ____ coupled signalling pathway
Gq
what happens in cells when a1a receptor actiavtion in smooth muscle signals Gq activation?
DAG and IP3 increases, causing increase in intracellualr Ca 2, causing contraction
what is the benefit of targeting A1A receptors in the sinuses?
constriction of the blood vessels, reducing leakiness and infiltration of immune cells, helping resolve congestion and runny nose
phenylephrine is a ____ A1A receptor agonist
selective
pseudophedrine is a ____receptor agonist
mixed alpha and beta adrenergic
should phenylephrine and pseudophedrine be used long term?
no
is there an issue with patients with hypertension taking phenylephrine or pseudophedrine?
not really recommended becease they are adrenergic agonists and may cause an increase in BP
is the increase in BP caused by phenylephrine and pseudophedrine as noticeable in normotensive patients?
no, but some patients may experience palpations or tachycardia with pseudophedrine
___ is the 1st key step in the initiation of allergic responses
mast cell degranulation
if we can reduce the release of ___, we can dampen the allergic response
inflammatory mediators
what is cromolyn?
mast cell stabilizer commonly available as an eye drop
how do mast cell stabilizers like cromolyn work?
preventative by decreasing degranulation, thus reducing the initiation of the allergic response
t/f mast cell stabilizers like cromolyn are not effective once the allergic response has started
t
what is histamine?
one of many mediators released from mast cells upon IgE binding; it is an important allergic mediator
t/f histamine on its own can elicit cellular responses
t
blocking the cellular effects of histamine can significantly reduce the strength of many allergic responses, especially in the ___
respiratory tract
antihistamines are ___ agonists of H1 receptors
inverse
what does it mean that antihistamines are inverse agonists?
reduce the response below th enormal baseline
why are antihistamines (inverse agonists) able to reduce response below the baseline?
preferentially bind to the inactive confirmation of the receptor, shifting the equilibrium towards the inactive form
what are the effects of histamine?
vascular permeability, redness, itching and other pro-inflammatory effecst
what is the most common first generation antihistamine?
diphenhydramine (Benadryl)
what is a popular 2nd generation antihistamine?
loratadine (Claritin)
Loratadine is a prodrug that transforms into ____ , which is also available as an antihistamine
desloratadine
which genration antihistamines have a longer duration of action? what is the benefit?
second ; only need to be dosed Q 24 h
what is the duration of action of 1st gen antihistamines?
6-8 hours
which generation of antihistamine is able to cross the BBB?
first
what is a CNS effect of 1st gen antihistamines?
bind to H1 in the CNS, causing drowsiness
an off target of 1st gen antihistamines are ___ receptors
muscarinic
why does diphenhydramine interact with muscarinic receptors?
shape resemble Ach
what are the effects of 1st gen antihistamines when it blocks muscarinic receptors?
anticholinergic effects (antiemetic, motion sickness, vertigo)
give an example of an LTRA
montelukast
