Lecture 14 - OTC Allergy and Insomnia

Question 1

conditions caused by hypersensitivity of the immune system to typically harmless substances in the environment

Answer 1

allergies

Question 2

what are some of the most common allergy symptoms?

Answer 2

• red eyes
• itchy rash
• sneezing
• shortness of breath
• swelling

Question 3

the mechanism of allergies involves:

Answer 3

immunoglobin E antibodies (IgE)

Question 4

B-cells react inappropriately to an allergen to produce:

Answer 4

immunoglobin E (IgE) antibodies against the allergen

Question 5

IgE antibodies bind to:

Answer 5

a receptor on mast cells or basophils

Question 6

subsequent exposure to the allergen triggers release of:

Answer 6

inflammatory chemicals such as histamine

Question 7

the release of substances within these cells releases inflammatory molecules like histamine

Answer 7

degranulation

Question 8

histamine receptors are:

Answer 8

GPCRs

Question 9

how many classes of histamine receptors are there?

Answer 9

four

Question 10

Gq coupled receptors which play a predominant role in allergic response

Answer 10

H1 receptors

Question 11

where are H1 receptors located?

Answer 11

smooth muscles, vascular endothelial cells, the heart, and the central nervous system

Question 12

activation of the H1 receptors in the periphery causes:

Answer 12

• increased vascular permeability
• vasodilation
• stimulation of sensory neurons producing cough
• smooth muscle contraction of the bronchi
• eosinophilic chemotaxis

Question 13

H1 receptors occur throughout the brain, with particularly high density in:

Answer 13

regions involved in arousal and waking (thalamus, cortex, and noradrenergic, serotonergic, and dopaminergic nuclei)

Question 14

histamine is an important neurotransmitter in the:

Answer 14

wake-promoting system

Question 15

diphenhydramine is an inverse agonist at the:

Answer 15

H1 receptor

Question 16

how does diphenhydramine reduce allergic reaction symptoms?

Answer 16

it blocks the effects of histamine in blood vessels and smooth muscle cells

Question 17

diphenhydramine readily crosses the ______ and inversely agonizes the ______, resulting in ______

Answer 17

blood brain barrier (BBB), H1 CNS receptors, drowsiness

Question 18

diphenhydramine is marketed as:

Answer 18

• an OTC allergy drug (Benadryl)
• an OTC sleep aid (Nytol)
• included in many cough and cold formulations

Question 19

diphenydramine competes with _____ for binding at the H1 receptor

Answer 19

histamine

Question 20

how does the affinity of diphenhydramine for the H1 receptor compare to the affinity of histamine for the H1 receptor?

Answer 20

similar affinities, so you need relatively high doses of diphenydramine to block histamine effects

Question 21

in addition to their activity at the H1 receptor, first generation antihistamines also bind to other receptors with lower affinity. this can contribute to:

Answer 21

off-target effects

Question 22

how well an antagonist (or inverse agonist) binds to a receptor can be described by the:

Answer 22

inhibitory constant (Ki)

Question 23

the Ki is determined using:

Answer 23

competition assays with a known labeled ligand and the antagonist of interest

Question 24

the concetration of drug that displaces 50% of the labelled ligand

Answer 24

Ki

Question 25

low Ki = ____

Answer 25

high affinity

Question 26

first generation antihistamines bind with relatively high affinity to:

Answer 26

muscarinic acetylcholine receptors (where they act as antagonists and have anticholinergic effects)

Question 27

where are muscarinic receptors located?

Answer 27

the autonomic nervous system, sweat glands, and brain

Question 28

first generation antihistamine binding to muscarinic receptors has what side effects?

Answer 28

dry mouth, constipation, confusion

Question 29

what are three negative side effects to using diphenhydramine?

Answer 29

- tolerance develops rapidly - decreases the quality of sleep - long term use may be associated with dementia and Alzheimers

Question 30

what three factors distinguish second generation antihistamines from first generation antihistamines?

Answer 30

- second (and third) generation antihistamines have higher selectivity for the H1 receptors - have poor blood brain barrier permeability - have longer duration of action

Question 31

cetirizine is an:

Answer 31

H1 receptor antagonist and a second generation antihistamine

Question 32

cetirizine has poor blood brain barrier permeability, so it produces:

Answer 32

minimal sedation compared to first generation antihistamines

Question 33

what is the duration of action of cetirizine?

Answer 33

~24 hours

Question 34

loratidine is an:

Answer 34

inverse agonist at the H1 receptor and a second generation antihistamine

Question 35

loratidine is almost entirely bound to:

Answer 35

plasma proteins (bound proteins are not active)

Question 36

when given orally, rapid first pass metabolism converts loratidine into:

Answer 36

desloratidine

Question 37

which carries most of the antihistamine effect: loratidine or desloratidine?

Answer 37

desloratidine

Question 38

could loratidine be considered a prodrug?

Answer 38

yes

Question 39

what is the half life of desloratidine?

Answer 39

27 hours

Question 40

what are the effects of desloratidine?

Answer 40

poor penetration of blood brain barrier, weakly sedating