Antihistamines & Allergic Rhinitis Flashcards
Describe Synthesis of Histamine
Histidine –> CO2 + Histamine
Done in Mast cells and basophils
Histamine containing cells can be found in what parts of the body?
- Mast cells in mucosa places (skin; nose; mouth; lungs; intestinal)
- Non-Mast Cells Histamine (in nerve terminals and fundus of stomach)
How is Histamine Metabolized
2 main enzymes are N-methyl transferase and Diamine Oxidase
another enzyme is a phosphoribosyl transferase
what are the 2 main ways that histamine can be released
- Antigen mediated (antigen binds to IgE)
- Non antigen mediated (thermal or mechanical stress)
What are the steps for Histamine Release
- IgE binds to FcER
- Antigen binds to IgE
- Cluster of FcERs
- influx of Ca2+ via CRAC
(NEED CALCIUM FOR HISTAMINE RELEASE)
what drugs prevent histamine release
cromolyn sodium
Nedocromolin
Beta -Adrenergic or Ach?
can inhibit antigen induced histamine release from mast cells
beta adrenergic
Beta -Adrenergic or Ach?
can stimulate histamine release from mast cells
Ach
where are H1 receptors found
distributed through CV
Respiratory systems
GI
smooth muscle
what GPCR does H1 use
Gq (PLC, IP3, DAG, increase Ca2+ –> MLCK will phosphorylate MLC)
H1 receptors can cause smooth muscle ______ AND vaso______
muscle contraction; vasoDILATION
how do H1 receptors lead to vasodilation
in VASC Endothelial Cells - NO released
H2 Receptor linked to vascular smooth muscle ______ and _____ secretion
relaxation; gastric
what GPCR does H2 use
Gs (increase adenylate cyclase = increase cAMP)
where is H3 located
in CNS
what GPCR does H3 use
Gi/Go
what GPCR does H4 use
Gi/Go
where is H4 located
located on mast cells/basophils/eosinophils
H3 is linked to inhibition of ________
H4 is linked to ___________
H3: inhibition of neurotransmitter release
H4: linked to histamine induced chemotaxis
what are the 4 main pharmacological effects of histamine
- cardiovascular
- Respiratory
- Acid release in stomach
- Anaphylaxis
Histamine Regulation of the Heart
Positive Chronotropy (increased heart rate; increased diastolic depoarlization current) Positive Inotropy (enhance force of contraction)
Histamine Regulation of the Vasculature:
Vasodilation
increased capillary permeability
Histamine effects in lungs
Bronchoconstriction; Smooth muscle contraction
H1 antagonists are predominantly _______
Full, partial, inverse agonist or neutral antagonist
Inverse agonist
what are the first gen. antihistamines
- Diphenhydramine
- Hydroxyzine
- Promethazine
- Brompheniramine
- cyproheptadine
- pyrilamine
2 main side effects of first gen antihistamines
- sedation (CNS efffect)
- Anti-cholinergic
what are anticholinergic side effects
decrease urination
dry mouth
Anticholinergics = Antimuscarinic = ______-like
Atropine
what are some other first gen H1 antagonist side effects
- local anesthetic
- Anti-serotonin (HA)
- alpha adrenergic antagonism (hypotension)
- extrapyramidal (dystonia, akathisia)
what are the 2nd gen antihistamines
loratadine
desloratadine
fexofenadine
cetirizine
2nd gen antihistamines:
have decreased ______ solubility
Efflux from ______ by _______
decrease lipid;
from CNS; P-glycoprotein transporter
what are the topical H1 receptor antagonists
Olopatadine
Azelastine
Ketotifen
clinical uses for H1 antagonists
- Seasonal/Perennial allergic rhinoconjunctivitis
- Chronic urticaria
- Motion sickness
- Adjunct w/ epinephrine to treat anaphylaxis
Antihistamines are contraindicated for what things?
urinary retention
narrow angle glaucoma
what are the therapeutic uses for H2 antagonists
- reduce gastric acid secretion
- treat peptic ulcers and GERD
Severe side effects of H2 antagonists
CNS dysfunction Antiandgrogen (gynecomastia, galactorrhea) impotence blood dyscrasias hepatotoxicity
First line therapy for mild allergic rhinitis symptoms
SGAs (second generation antihistamines)
first line therapy moderate to severe symptoms
nasal corticosteroids
how to add on therapy to monotherapy of Intra-nasal steroid
- add intranasal antihistamine or Oxymetazoline (3 days or less)
(do NOT add oral antihistamine or leukotriene receptor antagonist)
how to add on therapy to monotherapy of oral antihistamine
- add oral decongestant
- leukotriene receptor antagonist
- do not add intra-nasal steroid (switching to ok but do not add…)
how to avoid mold allergen
use dehumidifier
vent bathroom/kitchen
how to avoid dust mite allergen
use damp washcloth to dust use dehumidifier encase pillow/mattress/box spring wash bedding w/ hot water weekly remove stuffed animals from bedroom replace carpet w/ hard surface flooring
what are the temporal patterns of allergic rhinitis
perennial
Seasonal
what are mild allergic rhinitis symptoms
normal sleep
no impairment of daily activities
normal work/school functioning
no troublesome symptoms
what are moderate to severe allergic rhinitis symptoms
one or more of the following:
- abnormal sleep
- impairment of daily activities
- abnormal work/school functioning
- troublesome symptoms
3 phases of pathophysiology of Allergic Rhinitis
1) Sensitization (longest phase)
2) early phase response
3) late phase response
Pharmacologic options for allergic rhinitis
antihistamines corticosteroids decongestants anticholinergics mast cell stabilizers leukotriene modifiers
dosing for diphenhydramine
2 -6 yo
under drs supervision
dosing for diphenhydramine
6 - 11 yo
12.5 - 25 mg Q46H
dosing for diphenhydramine
12+ yo
25 - 50 mg Q46H
dosing for cetirizine
6 - 12 mos
2.5 mg QD
dosing for cetirizine
1 - 5 yo
2.5 mg QD or BID
dosing for cetirizine
6+ yo
5 or 10 mg QD
dosing for fexofenadine
2 - 11 yo
30 mg BID
dosing for fexofenadine
12+ yo
60 mg BID or 180 mg QD
dosing for loratadine
2 - 6 yo
5 mg QD
dosing for loratadine
7+ yo
10 mg QD
Antihistamine Interaction
First generations and ________
MAO inhibitors
Antihistamine Interaction
Chlorpheniramine and ________
phenytoin
Antihistamine Interaction
Loratadine and ___________
Ketoconazole/Erythromycin
Antihistamine Interaction
Fexofenadine and ________
grapefruit juice
Antihistamine Interaction
First generations and MAO inhibitors:
what is the response?
increase in anticholinergic effects
Antihistamine Interaction
Chlorpheniramine and Phenytoin: what is the response?
increase in phenytoin concentrations
Antihistamine Interaction
Loratadine and Ketoconazole/Erythromycin: what is the response
increase in loratadine concentrations
Antihistamine Interaction
Fexofenadine and grapefruit juice: what is the response
increase in fexofenadine concentrations
which intranasal corticosteroids are OTC
triamcinolone; Fluticasone; budesonide
Intranasal Corticosteroids:
Improvement seen in _______
and then max benefit is seen in ______
improvement: 3 days
max: 1 -2 weeks
pseudoephedrine dosing:
4 - 5 yo
15 mg Q46H
pseudoephedrine dosing:
6 - 11 yo
30 mg Q46H
pseudoephedrine dosing:
12+ yo
60 mg Q46H
MOA of Leukotriene modifiers
decrease mucous secretion and increase bronchodilation
which antihistamines are alkylamines
Brompheniramine; Chlorphenarmine
which antihistamines are ethanolamines
diphenhydramin; Dimenhydrinate
which first gen antihistamine is a phenothiazine
promethazine
which second gen antihistamine is a piperadine
fexofenadine (and 1st gen: cyproheptadine?)
which first gen antihistamine is a piperazine
hydroxyzine, meclizine, cyclozine
which first gen antihisatmine is an ethylenediamine
pyrilamine
which classes of first gen antihistamines are known to cause sedation
ethanolamines and phenothiazines (aka diphenhydramine and promethazine)
