Pharmacology - Allergic Rhinitis

Question 1

define rhinitis

Answer 1

inflammation of the mucus membranes of the nose

causes sneezing, itching, watering, and nasal congestiona

Question 2

explain what causes rhinitis

Answer 2

inhalation of an allergen. this allergen interacts with mast cells coated with IGE antibody (type 1 allergic response)

the mast cell then releases mediators of inflammation like histamine, leukotrienes, etc which cause mucosal thickening from edema and cell infiltration

Question 3

5 types of drugs that can be used for allergic rhinitis

Answer 3

antihistamines
intranasal glucocorticoids
intranasal cromolyn
montelukast
decongestants (sympathomimetics)

Question 4

explain how histamine is formed (chemically)

include the amino acid precursor

Answer 4

from histidine in a decarboxylation rxn (enzyme = histidine decarboxylase)

Question 5

histamine is mainly released from what 2 types of cells

Answer 5

mast cells and basophils

Question 6

explain how histamine causes inflammation

Answer 6

vasodilation, increased capillary permeability - causes contraction, mucus secretion

Question 7

2 methyl vs 4 methyl histamin

Answer 7

2 methyl = h1 agonist
4 methyl = h2 agonist

Question 8

explain what happens when H1 receptors are activated

Answer 8

vasodilation, hypotension, flushing, etc

Question 9

*explain how H1 antihistamine works

Answer 9

histamine has affinity for the ACTIVE STATE of the H1 receptor. histamine stabilizes the receptor in its active conformation

H1 ANTIHISTAMINE has preferential affinity for the INACTIVE STATE and stablizes the inactive receptor

INVERSE AGONSIT

Question 10

name the type of receptor:

H1
H2
H3
H4

Answer 10

H1 - Gq
H2 - Gs
H3 - Gi
H4 - unknown

Question 11

name what each receptor does:

H1
H2
H3
H4

Answer 11

H1 - increase vascular permeabllity at sites of inflammation induced by histamine

H2 - increase release of gastric acid

H3 - neural presynaptic receptor - may release histamine

H4 - immunomodulation - immune cell chemotaxis, immune response, inflammation

Question 12

the newly discovered H4 receptor may help with the treatment of…

Answer 12

autoimmune diseases

Question 13

true or false

Histamine causes the STIMULATION of secretions

Answer 13

true

Question 14

differentiate between when a local allergic reaction occurs vs a full blown anaphylactic reaction

Answer 14

if histamine release is slow and ablle to be inactivated before it reaches the bloodstream - will be local

if release of histamine is too fast to be inactivated - anaphylactiv

Question 15

can antihistamines be used for motion sickness and parkinsons

Answer 15

yes

Question 16

differentiate between 1st and 2nd gen H1 antihistamines

Answer 16

1st gen - penetrate the CNS and cause sedation. also interact with other receptors meaning they have a lot of AE

2nd gen - SPECIFIC to peripheral H1 receptors (dont cross BBB - less CNS depression)

Question 17

which 2nd gen H1 antihistamines are partially sedating

Answer 17

ceterizine and levocetirizine

loratidine/fexofenadine are least sedating

Question 18

name the 6 2nd gen H1 antihistamines (all others are 1st gen)

Answer 18

cetirizine, levocetirizine
loratidine, desloratidine
fexofenadine
acrivastine

Question 19

what is meclizine

Answer 19

1st gen H1 antihistamine

Question 20

what is promethazine

Answer 20

1st gen H1 antihistamine

Question 21

what is brompheniramine

Answer 21

1st gen H1 antihistamine

Question 22

H1 antihistamines downregulate allergic inflammation how?

Answer 22

indirectly through NFKB and calcium ion channels

Question 23

what are the drugs of choice in controlling the symptoms of allergic rhinitis and urticaria

why?

Answer 23

oral antihistamines - bc histamine is the principle mediator that’s released by mast cells

Question 24

when are OPHTHALMIC antihistamines useful?

Answer 24

for treating allergic conjunctivitis

Question 25

true or false antihistamines are not implicated in asthma

Answer 25

true

Question 26

diphenhydramine blocks _____ reuptake

Answer 26

SEROTONIN

Question 27

cyproheptadine is used to treat....

Answer 27

serotonin syndrome bc its a 5HT2 antagonist (also H1)

Question 28

true or false cyproheptadine is also a CCB

Answer 28

true

Question 29

true or false 2nd gen antihistamines have a fast dissociation from the H1 receptor

Answer 29

FALSE - slow

Question 30

metabolite of hydroxyzine

Answer 30

cetirizine

Question 31

cetirizine is an H1.....

Answer 31

inverse agonist

Question 32

which 2nd gen antihistamine is absorbed through OATP1A2 and thus its absorption is inhibited by fruit juices

Answer 32

fexofenadine (allegra)

Question 33

true or false cetirizine has minimal anticholinergic activity

Answer 33

TRUE - much less than the 1st gens

Question 34

the max serum levels of H1 antihistamines occurs around how long after administration?

Answer 34

1-2 hrs

Question 35

___ and ___ are excreted largely unchanged in the urine ___ is excreted largely unchanged in the feces

Answer 35

cetirizine/leco = urine fexofenadine - feces the 1st gen are metabolized by CYPS

Question 36

most common AE of the SECOND GEN antihistamines

Answer 36

headache

Question 37

acute poisoning of H1 antihistamines is fairly common, esp in young kids name some effects

Answer 37

hallucinations, excitement, ataxia, coma, collapse of cardio/resp system

Question 38

*1st gen H1 antihistamins alleviate allergy symptoms primarily by....

Answer 38

inverse agonism at H1 receptors -- stabilzing the INACTIVE state

Question 39

*what is the immunological trigger for mast cell degranulation in allergic rhinitis

Answer 39

cross-linking of IGE with an allergen

Question 40

true or false hydroxyzine is a 2nd gen antihistamine

Answer 40

false - 1st gen

Question 41

true or false promethazine is a 1st gen antihistamine

Answer 41

true

Question 42

true or false loratidine is a 2nd gen antihistamine

Answer 42

true