PHARM: Antihistamines Flashcards
What are the three roles of antihistamines?
1) Endogenous mediator of vascular and smooth muscle tone
2) Principle regulator of gastric acid secretion
3) Neurotransmitter
How many histamine receptors are there?
4 (H1-H4)
Which histamine receptors have drugs directed against them?
H1 and H2 only
What are the pathophysiological effects of histamine?
Edema
Itching
Rhinitis
Through which receptors is the edema, itching, and rhinitis caused by histamine mediated?
H1 receptors
Where are H2 receptors located?
primarily in the GI tract
Explain the biosynthesis of histaine?
L-histidine and water are converted into histamine and CO2 by L-Histidine decarboxylase
Where is histamine synthesized (mainly)?
Mast cells
Basophils
List some activators of histamine release.
GM-CSF IL-3 Endotoxin (bacterial infection) PGs IgE-immune/allergic response kinins
What are some inhibitors of histamine release?
histidine analogs
Beta-antagonists
cromolyn Na+
What is involved with Th-1 inflammatory response?
Allergen–>IL-12 stimulates Th1 cells–> IFN-gamma is released –> stimulates cytotoxic T cells and also stimulates B cell to make IgG
What is involved with a Th-2 inflammatory response?
Allergen==> Th-2 cell releases IL-3, IL-5, GM-CSF–> stimulates eosinophils
Th-2 also releases IL-4 which tells B cells to make Ig-E to interact with mast cells
HOw is IgE involved with histamine release?
IgE binds to Fc receptors of mast cells and multivalent antigen cross-links adjacent IgE molecules (leading to histamine release by exocytosis)
What are the primary roles of H1 receptors?
smooth muscle contraction
stimulation of NO formation
endothelial cell contraction
increased vascular permeability
What is the primary role of H2 receptors?
stimulation of gastric acid secretion
What is the primary role of H3 eceptors?
inhibition of neurotransmitter release
H1 receptors act via which molecules?
guanylate cyclase increasing cGMP (leading to increased PG)
H2 receptors act via which molecules?
adenylate cyclase increasing cAMP (leading to increased PG)
What ae the major vasculature effects of histamine (and what receptors)?
Microvasodilation (H1 and H2) Capillary permeability (H1) Vasoconstriction (H1)
What are the major pulmonary effects of histamine (and what receptors)?
Bronchoconstriction (H1)
Bronchodilation (H2)
What are the major neural effects of histamine (and what receptors)?
Nerve ending stimulation (H1, H3)
Wakefulness and sedation (H1 and H3)
How do first generation antihistamines differ from second generation?
first generation are short-acting, can cross the BBB (have associated sedation), and have anti-cholinergic effect (bind to muscarinic receptors impairing ciliary movement and mucus clearing).
Second generation are longer acting, do NOT cross the BBB, and are safer for asthmatics (because they do not have anti-cholinergic effects)
How do the structures of first and second generation antihistamines differ?
first generation is based on the structure of histamine and second generation is not
List the 1st generation antihistamines.
ETHER DERIVATIVE
Diphenhydramine
Dimenhydrinate
ALKYLAMINE DERIVATIVE
Chlorpheniramine
PHENOTHIAZINE DERIVATIVE
Promethazine
What are therapeutic applications for H1 antagonists?
allergy/hayfever symptoms
Bug bites/stings
motion sickness/vertigo
List some side effects of first generation H1 antagonists?
Sedation, decreased alertness, dizziness, dystonia, etc.
True or false: H1-receptor antagonists are selective but not specific.
TRUE!
Diphenhydramine and promethazine can also inhibit muscarinic recptors and promethazine can inhibit alpha-adrenergic receptors!
List the second generation H1 antagonists.
Fexofenadine
PIPERDINE DERIVATIVES
Loratadine
PIPERAZINE DERIVATIVES
Cetirizine
What are some side effects of 2nd generation H1-antagonists?
Mild cognitive disturbances
appetite stimulation
