Histamine 1st generation Flashcards
net effect of histamine in the CNS
increased wakefulness, alertness and reaction time
histamine antagonist in the CNS
histamine that distributes to the CNS leads to drowsiness and functional impairment
first generation vs second generation histamine and the CNS
first generation- extensive distribution to the CNS
second generation-much less distribution to the CNS
histamine vascular effects
histamine is a direct vasodilator
can lead to edema due to increased vascular permeability
can also manifest urticaria to certain patients
histamine and cardiac effects
minimal but H1- slows AV node conduction in large amounts can lead to dysrhythmias
H2 increase heart rate and cardiac output
histamine and anaphylaxis
histamine contributes to large blood pressure falls-called histamine shock
steps of histamine shock
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
anithistamines and anaphylaxis
considered a useful but optional adjunct and not a life saving therapy
even with urticaria these are used for symptom relief
histamine and respiratory
histamine relseased from mast cells act on H1R
- smooth musk constriction
- bronchospasm
- mucosal edema/secretion
histamine and HEENT
promotes many symptoms of allergic conjunctivitis, allergic rhinitis
- increased nasal mucus production
- increased neutrophil and eosinophil chemotaxis
histamine and GI
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
1st generation H1R antagonists
diphenhydramine, dimenhydrinate, meclizine, doxylamine, chlorpheniramine.
2nd generationH1R antagonists
loratadine, cetirizine, fexofenadine
Important 1st gen H1RAs with additional unique pharmacology or roles
cyproheptadine, hydroxyzine, doxepin, promethazine.
therapeutic uses of H1R antagonists
allergic rhinitis- can manage symptoms but much more effective at preventing taken before exposure
MOA of H1R antagonists
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
ADVERSE effects and risks of H1R antagonists 1st generation
- 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)
usefulness of H1R antagonists
- highly effective when applied locally for a single symptoms
- rapid onset but best results when taken continuously
ADVERSE effects and risks of H1R antagonists 2nd generation
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)
first generation to use during pregnnacy category A
doxylamine - Rx is usually combined with B6 for nausea and vomiting but can be taking by itself and is OTC-nyquil
antihistamines with anit-muscarinic effects list
cyproheptadine>promethazine>desloratdine>diphenhydramine>loratadine>chlorpheniramine
* do not give to elderly
antihistamines with zero anti-muscarinic effects list
fexofenadine and certirizine
1st generation antihistamines add more CNS effects and antimuscarinic effects
Disorientation, reduced cognition, fall risk…
Risky in older adults, comorbid diseases (bladder, glaucoma, etc.)
Watch for “Tylenol PM” and related, in the older adult
diphenhydramine
aka benadryl
1st genration H1RA with strong anti-muscarinic properties
-is metabolized by the liver and an inhibitor of CYP2D6
diphenhydramine dosing and 1/2 life
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
indications for diphenhydramine
allergic rhinitis anaphylaxis (adjunct) common cold insomnia (short term) motion sickness parkinsonism pruritus
cough and diphenhydramine
dries up post nasal drip
but not an antitussive persay but can reduce rhinitis associated cough
antihistamines used for motion sickness and vertigo
dimenhydinate
meclizine
dimenhydrinate
highly sedating
most effective OCT for motion sickness
30 min onset
contraindicated for under 2 years
meclizine
bonine-motion sickness antivert-rx only -less sedating but less effective usually for motion sickness and vertigo 1 hr onset 12 an older
doxepin
a tricyclic antidepressant and 1st generation
-MOST SEDATING MOST POTENT
use only after other antihistamines used with no response
insomnia and depression/anxiety
doxepin insomnia 3-6 mg HS
anxiety/depression 25-50 mg HS
hydroxyzine
rx only
sedative hypnotic
considered the preferred antihistamine for acute anxiety
hydroxyzine pamoate uses
anxiety
pruitus
off label seasonal allergic rhinitis
hydroxyzine hydrochloride
alcohol withdrawal anxiety (associated with EtOH withdrawal) nausea vomiting pruritus
hydroxyzine mmajor active metabolite
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
promethazine
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
fever and promethazine
discontinue&** and monitor
cyproheptadine
broad spectrum allergic condition
-blocks histamine and serotonin so long term use associated with depression
Chlorpheniramine and brompheniramine
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)
