Histamine 1st generation

Question 1

net effect of histamine in the CNS

Answer 1

increased wakefulness, alertness and reaction time

Question 2

histamine antagonist in the CNS

Answer 2

histamine that distributes to the CNS leads to drowsiness and functional impairment

Question 3

first generation vs second generation histamine and the CNS

Answer 3

first generation- extensive distribution to the CNS

second generation-much less distribution to the CNS

Question 4

histamine vascular effects

Answer 4

histamine is a direct vasodilator
can lead to edema due to increased vascular permeability
can also manifest urticaria to certain patients

Question 5

histamine and cardiac effects

Answer 5

minimal but H1- slows AV node conduction in large amounts can lead to dysrhythmias
H2 increase heart rate and cardiac output

Question 6

histamine and anaphylaxis

Answer 6

histamine contributes to large blood pressure falls-called histamine shock

Question 7

steps of histamine shock

Answer 7

1) small blood vessels dilate
2) large amount of blood trapped
3) plasma leaks into circulation
4) blood volume diminished
5) reduction in venous return
6) reduced cardiac output and reduced tissue perfusion

Question 8

anithistamines and anaphylaxis

Answer 8

considered a useful but optional adjunct and not a life saving therapy
even with urticaria these are used for symptom relief

Question 9

histamine and respiratory

Answer 9

histamine relseased from mast cells act on H1R

• smooth musk constriction
• bronchospasm
• mucosal edema/secretion

Question 10

histamine and HEENT

Answer 10

promotes many symptoms of allergic conjunctivitis, allergic rhinitis

• increased nasal mucus production
• increased neutrophil and eosinophil chemotaxis

Question 11

histamine and GI

Answer 11

in the GI histamine stimulation of the H2 receptors increases secretion of gastric acids from parietal cells
- in large amounts histamine may stimulate smooth msk contractions and cause diarrhea

Question 12

1st generation H1R antagonists

Answer 12

diphenhydramine, dimenhydrinate, meclizine, doxylamine, chlorpheniramine.

Question 13

2nd generationH1R antagonists

Answer 13

loratadine, cetirizine, fexofenadine

Question 14

Important 1st gen H1RAs with additional unique pharmacology or roles

Answer 14

cyproheptadine, hydroxyzine, doxepin, promethazine.

Question 15

therapeutic uses of H1R antagonists

Answer 15

allergic rhinitis- can manage symptoms but much more effective at preventing taken before exposure

Question 16

MOA of H1R antagonists

Answer 16

H1R are not actually antagonists they are inverse agonists
because of their ability to down-regulate the H1 receptor activity
-they shift the equilibrium from an active form of the H1 receptor to an inactive form

Question 17

ADVERSE effects and risks of H1R antagonists 1st generation

Answer 17

• more lipophilic so tend to cross the blood brain barrier
• sedating (but can be activating in kids)
• functional impairment w or w/o drowsiness
• weight gain
• hypersensitive reactions
• prolonged QT interval and ventricular arrhythmias
• some are highly anticholinergic (dry mouth and eyes, urinary hesitancy, confusion/falls, glaucoma increase IOP)

Question 18

usefulness of H1R antagonists

Answer 18

• highly effective when applied locally for a single symptoms
• rapid onset but best results when taken continuously

Question 19

ADVERSE effects and risks of H1R antagonists 2nd generation

Answer 19

relatively non-sedating at appropriate doses
less lipophilic (less BBB permeation)
-generally better tolerated and longer duration of action 
-some are anticholinergic but more peripherally (bladder/vision)

Question 20

first generation to use during pregnnacy category A

Answer 20

doxylamine - Rx is usually combined with B6 for nausea and vomiting but can be taking by itself and is OTC-nyquil

Question 21

antihistamines with anit-muscarinic effects list

Answer 21

cyproheptadine>promethazine>desloratdine>diphenhydramine>loratadine>chlorpheniramine
* do not give to elderly

Question 22

antihistamines with zero anti-muscarinic effects list

Answer 22

fexofenadine and certirizine

Question 23

1st generation antihistamines add more CNS effects and antimuscarinic effects

Answer 23

Disorientation, reduced cognition, fall risk…
Risky in older adults, comorbid diseases (bladder, glaucoma, etc.)
Watch for “Tylenol PM” and related, in the older adult

Question 24

diphenhydramine

Answer 24

aka benadryl
1st genration H1RA with strong anti-muscarinic properties
-is metabolized by the liver and an inhibitor of CYP2D6

Question 25

diphenhydramine dosing and 1/2 life

Answer 25

oral: 25-50 mg every 4-8 hrs, max dose 300 mg/day | but T1/2 life in elderly can be 9-18 hrs of groggy sedation, even after therapeutic effect has stopped

Question 26

indications for diphenhydramine

Answer 26

``` allergic rhinitis anaphylaxis (adjunct) common cold insomnia (short term) motion sickness parkinsonism pruritus ```

Question 27

cough and diphenhydramine

Answer 27

dries up post nasal drip | but not an antitussive persay but can reduce rhinitis associated cough

Question 28

antihistamines used for motion sickness and vertigo

Answer 28

dimenhydinate | meclizine

Question 29

dimenhydrinate

Answer 29

highly sedating most effective OCT for motion sickness 30 min onset contraindicated for under 2 years

Question 30

meclizine

Answer 30

``` bonine-motion sickness antivert-rx only -less sedating but less effective usually for motion sickness and vertigo 1 hr onset 12 an older ```

Question 31

doxepin

Answer 31

a tricyclic antidepressant and 1st generation -MOST SEDATING MOST POTENT use only after other antihistamines used with no response

Question 32

insomnia and depression/anxiety

Answer 32

doxepin insomnia 3-6 mg HS | anxiety/depression 25-50 mg HS

Question 33

hydroxyzine

Answer 33

rx only sedative hypnotic considered the preferred antihistamine for acute anxiety

Question 34

hydroxyzine pamoate uses

Answer 34

anxiety pruitus off label seasonal allergic rhinitis

Question 35

hydroxyzine hydrochloride

Answer 35

``` alcohol withdrawal anxiety (associated with EtOH withdrawal) nausea vomiting pruritus ```

Question 36

hydroxyzine mmajor active metabolite

Answer 36

cetirizine second generation (zertac) commonly added to opiods for pain for nausea also adds a dose sparing analgestic effect for opiods *but is high CNS depression

Question 37

promethazine

Answer 37

``` phenergan for nausea and vomiting contraindications under 2 under 12 arterial and subcutaneous administration cautions: hypersensitivtiy, treatment of lower respiratory tract, temperature dysregulation**, h/o neuroleptic malignant syndrome, cardiac conduction issures ```

Question 38

fever and promethazine

Answer 38

discontinue&** and monitor

Question 39

cyproheptadine

Answer 39

broad spectrum allergic condition | -blocks histamine and serotonin so long term use associated with depression

Question 40

Chlorpheniramine and brompheniramine

Answer 40

OTC antihistamine alone (Chlortrimeton®) and in combination (bromphenirmaine with pseudoephedrine) in original “Children’s” Dimetapp® [now only 12 and older…] Rx in combination with hydrocodone in Tussionex® extended release cough syrup. (C-II)