Anti-histamines and Allergy Pharmacology Flashcards
What stores histamine in blood? In peripheral tissues?
Blood - basophils, Peripheral tissues - Mast cells
For which Histamine receptors do we have drugs targeting them?
H1 and H2 (no drugs for H3 and H4)
How many histamine receptor subtypes are there, and name the primary physiologic role for each
H1 - Allergic inflammation, H2 - Gastric acid secretion, H3 - neurotransmitter modulation, H4 - propagation of inflammatory cells
These 5 things cause histamine release without IgE binding
Venoms, morphine, tubocurarine, succinylcholine, cold or tissue injury
Anaphylactoid reactions
Clinically identical to anaphylaxis, but caused by a non-immune mediated mechanism (eg venoms, succinylcholine, etc)
Triple response of Lewis
Red spot (capillary dilation), Wheal (capillary permeability) and Flare (arteriole dilation 1 cm away), follows IM injection of histamine
Antihistamines can antagonize other receptors besides histamine receptors. What other receptors?
Muscarinic, alpha-adrenergic, serotenergic, cardiac ion and calcium channels
Inverse agonist
Something that binds a constitutively active receptor and keeps it in its INACTIVE state
What is the improvement from first to second generation antihistamines?
Second gen have less penetrance into CNS and therefore less sedation
Nasal and ophthalmalogic antihistamines
Nasal - azelastine (astelin), Ophthalmologic - Olopatadine (patanol)
In addition to poorer penetration of the BBB, why do second generation antihistamines not end up in the CNS?
They are pumped out by P-glycoprotein
What is added in combination products such as Clairitin-D and Allegra-D and why?
A decongestant, because the antihistamine isnt as effective as a decongestant (congestion mediated mainly by leukotrienes, not histamine)
What often causes chronic urticaria?
Autoantibody IgG to IgE or IgE receptor
Histamine can affect the vestibular system. What use of histamine arises from this?
Antiemetic to prevent nausea and vomiting associated with motion sickness
Why might antihistamines be administered to a patient receiving antipsychotics?
Some antipsychotics cause Parkinson like symptoms, and antihistamines (eg diphenhydramine) can reduce these symptoms
How do steroids achieve downregulation of inflammatory mediators?
They bind glucocorticoid response elements which lead to inhibition of Histone Acetyl Transferases (HAT) by recruitment of histone deacetylases, altering the acetylation of certain histones
What is the first line therapy for allergic rhinitis?
Topical steroids (nasal sprays)
What drug has leukotriene effects and how?
Montelukast, a high affinity competitive antagonist at leukotriene receptor (cys-LT1)
Omalizumab
Approved for asthma, also used for allergic rhinitis, is an anti-IgE drug
Which H2 antagonist has the most side effects and what are they?
Cimetidine - antiandrogen effects, cypotenias (especially thrombocytopenia), and drug-drug interactions (inhibits several CYP enzymes)
What antimuscarinic is used as a second line therapy for allergic rhinitis?
Ipratropium
List 4 commonly used H2 blockers
Cimetidine (tagamet), Ranitidine (Zantac), Famotidine (Pepcid), Nizatidine (Axid)
List 5 second generation antihistamines
Fexofenadine (allegra), Loratadine (claritin), desloratadine (clarinex), cetirizine (zyrtec), levocetirizine (xyzal)
What class of drug is diphenhydramine?
A first generation antihistamine (H1 functional antagonist)
Treatments for anaphylactic shock
Epi (top priority), as needed any of the following: volume expansion, corticosteroids, beta-2 agonists, antihistamine, H2 blockers
