Flashcards in Regal- Histamines and Anti-Histamines Deck (32)
Where is histamine synthesized?
nearly every tissue w/ highest concentration in the lungs and stomach
in mast cells or basophils
(any cells that contain L-his decarboxylase)
What does L-histadine decarboxylase do?
Converts histadine to histamine
Found in mast cells and basophils
What are the two pools of histamine?
Mast cell histmaine (mast cells and basophils)
Non-mast cell histamine (CNS nerve endings)
How is histamine degraded?
Inactivated by metabolic enzymes
Where are the enzymes that degrade histamine located?
Widely distributed (small intestine mucosa, skin, kidney, liver thymus, WBC)
Intestinal bacteria convert it to N-actylhistamine
What are the three ways that histamine contributes to inflammation?
1. vasodilation--> redness/heat
2. increased vascular permeability--> swelling
What happens to orally administered histamine?
Absorbed and inactivated by enzymes of intestinal wall/liver
What happens to intracutaneously administered histamine?
vasodilation-->Localized redness (s/m)
nerves dilating neighboring arterioles--> diffuse redness (slower)
Increased capillary permeability--> localized edema
What are nasal sxs associated w/ intranasal histamine?
Intravenous administration of histamine leads to....
wheal and flare
stimulation of mucous secretion
stimulation of gastric secretion
What type of agonists are histamines?
Inverse agonists--reduce receptor activity below basal levels observed in absence of ligand (looks like a competitive antagonist)
What leads to the endogenous release of histamine?
Antigen interaction w/ IgE Ab on mast cells and basophils
Activation of H1 leads to:
rapid and short lived VASODILATION
contraction of GI smooth muscle
increased capillary permeability (wheal)
pruritits and pain
release of catecholamines from adrenal medulla
Activation of H2 leads to:
Gastric acid secretion
SLOWER and SUSTAINED VASODILATON
Activation of H3 leads to:
Present on histaminergic nerve terminals
Activation of H4 leads to:
Present on immune cells
What is the triple response caused by histamine and what receptors does it effect?
flare-H1 (some 2)
wheal- H1, some 2
pain and itching- H1
What triggered histamine receptors lead to cardiac effects?
H1 and H2
Increased HR, force, arrythmias
Decreased AV conduction
What are the two first generation antihistamines?
What is the MOA of first generations antihistamines?
5-HT receptors (cholinergic properties)
Where are antihistamines distributed?
D: widely includes CNS
How are antihistamines eliminated?
A: liver inactives enzymes
What are the major toxicities associated w/ antihistamines?
Drying of secretions
What receptor does Diphenhydramine act on?
H1 receptor antagonist
What is a antihistamine toxicity that is minized by using diphenhydramine?
Lowers incidence of GI SE
What is a unique property of diphenhydramine?
It's good if you want a sedative effect (children)
When is chlorepheniramine commonly used?
What are the second generation antihistamines?
What is the MOA of SG antihistamines?
Block H1 recetpors
MINIMAL anticholinergic propgerites