Histamines Flashcards
What is histamine?
endogenous biogenic amine which is synthesized, stored, and released from mast cells, basophils, and neurons
Histamine synthesis occurs from?
synthesis of histidine by l-histidine decarboxylase
How is histamine metabolized?
metabolized by hepatic P450 systems via 2 distinct pathways:
Methylation to N-methyl histamin and N-methyl imiadazole acetic acid (MAO) prior to urinary excretion
Oxidative deamination to imidazole acetic acid (DAO) and imidazole acetic acid ribodide prior to urinary excretion
Histamine recpetors are all members of what family?
G-protein coupled receptors
H1 receptors
in bronchial and intestinal smooth muscle, vascular endothelium, cardiac tissue, and CNS
H2 receptors
vascular smooth muscle, cardiac tissue, basophils, and parietal cells
H3 receptors
distributed throughout CNS
H4
within bone marrow and WBCs
Mild to moderate pathological effects of histamine include?
skin reactions (erythema, urticaria, itching), tachycardia, dysrhythmias, hypotension, mild resp distress
Anaphylactic pathological effects of histamine include?
hypotension, VF, cardiac arrest, bronchospasm, resp arrest
Histamine vascular effects
dilation of small blood vessels (H1 and H2) and increased permeability of post capillary venules
What is triple respone of Lewis in response to intradermal histamine injection?
- localized red spot
- flare develops more slowly extending beyond red spot
- wheal is disccemable 1-2 min at intial site
Histamine cardiac effects
increased inotropy (H1 and H2) increased chronotropy (H2) decreased AV conduction (H1)
Histamine pulmonary effects
bronchoconstriction and increased mucous visccity (H1)
slight bronchodilation and increased mucous secretion (H2)
cough (H1)
Histamine GI effects (TQ)
increased acid production (H2)
Histamine neuronal effects
cutaneous itching (H1 and H2) presynaptic inhibition of histamine synthesis and release regulation of dopamine, GABA, ACh, 5-HT, and NE
1st generation H1 receptor antagonist MOA and use
reversible, competitive antagonism of H1 receptor
mildly anticholinergic–> ANTI-SLUDE
used as adjuvant to epi in anaphylaxis, allergies, sedation, prevetion N/V, motion sickness, vertigo, local anesthetic, antitussive
Will cross BBB
1st generation H1 antagonist drugs
for allergy- diphenhydramine, hydroxyzine, chlorpheniramine
for motion sickness- cyclizine, dimenhydrenate (dramamine), meclizine (antivert)
for nausea- promethazine
1st generation H1 antagonist adverse effects
avoid with MOIs (chlorpheniramine)
sedation, dizziness, fatigue, tachycardia, allergic reactions, anti-muscarinic effects
additive with anti-muscarinics and CNS depressants
2nd generation H1 receptor antagonist uses
anti-allergy therapeutic d/t non-sedating properties
Cetirizine adverse effect (TQ)
more CNS actions that other 2nd gen antihistamines and therefore NOT recommended for use by pilots
2nd generation H1 drugs examples
acrivistine, fexofenadine (allegra), loratadine (claritin), cetirizine (zyrtec), desloratadine
H2 receptor antagonist used for?
to decrease gastric acid production
treatment of GERD
H2 receptor antagoinst drugs examples
cimetidine, famotadine (pepsid), nizatidine, ranitidine (zantac)
