Lecture 14 - OTC Allergy and Insomnia Flashcards
conditions caused by hypersensitivity of the immune system to typically harmless substances in the environment
allergies
what are some of the most common allergy symptoms?
- red eyes
- itchy rash
- sneezing
- shortness of breath
- swelling
the mechanism of allergies involves:
immunoglobin E antibodies (IgE)
B-cells react inappropriately to an allergen to produce:
immunoglobin E (IgE) antibodies against the allergen
IgE antibodies bind to:
a receptor on mast cells or basophils
subsequent exposure to the allergen triggers release of:
inflammatory chemicals such as histamine
the release of substances within these cells releases inflammatory molecules like histamine
degranulation
histamine receptors are:
GPCRs
how many classes of histamine receptors are there?
four
Gq coupled receptors which play a predominant role in allergic response
H1 receptors
where are H1 receptors located?
smooth muscles, vascular endothelial cells, the heart, and the central nervous system
activation of the H1 receptors in the periphery causes:
- increased vascular permeability
- vasodilation
- stimulation of sensory neurons producing cough
- smooth muscle contraction of the bronchi
- eosinophilic chemotaxis
H1 receptors occur throughout the brain, with particularly high density in:
regions involved in arousal and waking (thalamus, cortex, and noradrenergic, serotonergic, and dopaminergic nuclei)
histamine is an important neurotransmitter in the:
wake-promoting system
diphenhydramine is an inverse agonist at the:
H1 receptor
how does diphenhydramine reduce allergic reaction symptoms?
it blocks the effects of histamine in blood vessels and smooth muscle cells
diphenhydramine readily crosses the ______ and inversely agonizes the ______, resulting in ______
blood brain barrier (BBB), H1 CNS receptors, drowsiness
diphenhydramine is marketed as:
- an OTC allergy drug (Benadryl)
- an OTC sleep aid (Nytol)
- included in many cough and cold formulations
diphenydramine competes with _____ for binding at the H1 receptor
histamine
how does the affinity of diphenhydramine for the H1 receptor compare to the affinity of histamine for the H1 receptor?
similar affinities, so you need relatively high doses of diphenydramine to block histamine effects
in addition to their activity at the H1 receptor, first generation antihistamines also bind to other receptors with lower affinity. this can contribute to:
off-target effects
how well an antagonist (or inverse agonist) binds to a receptor can be described by the:
inhibitory constant (Ki)
the Ki is determined using:
competition assays with a known labeled ligand and the antagonist of interest
the concetration of drug that displaces 50% of the labelled ligand
Ki
low Ki = ____
high affinity
first generation antihistamines bind with relatively high affinity to:
muscarinic acetylcholine receptors (where they act as antagonists and have anticholinergic effects)
where are muscarinic receptors located?
the autonomic nervous system, sweat glands, and brain
first generation antihistamine binding to muscarinic receptors has what side effects?
dry mouth, constipation, confusion
what are three negative side effects to using diphenhydramine?
- tolerance develops rapidly
- decreases the quality of sleep
- long term use may be associated with dementia and Alzheimers
what three factors distinguish second generation antihistamines from first generation antihistamines?
- second (and third) generation antihistamines have higher selectivity for the H1 receptors
- have poor blood brain barrier permeability
- have longer duration of action
cetirizine is an:
H1 receptor antagonist and a second generation antihistamine
cetirizine has poor blood brain barrier permeability, so it produces:
minimal sedation compared to first generation antihistamines
what is the duration of action of cetirizine?
~24 hours
loratidine is an:
inverse agonist at the H1 receptor and a second generation antihistamine
loratidine is almost entirely bound to:
plasma proteins (bound proteins are not active)
when given orally, rapid first pass metabolism converts loratidine into:
desloratidine
which carries most of the antihistamine effect: loratidine or desloratidine?
desloratidine
could loratidine be considered a prodrug?
yes
what is the half life of desloratidine?
27 hours
what are the effects of desloratidine?
poor penetration of blood brain barrier, weakly sedating
