Histamine and Antihistaminic Drugs Flashcards
What are the two enzymes that can convert histidine to histamine?
- Histidine decarboxylase
2. Aromatic L-amino acid decarboxylase
What is the H1 receptor responsible for?
- Mucous secretion
- Vascular relaxation
- Bronchoconstriction
- Itching
All mediated by phospholipase C
What is the agonist for H1/H2 receptors
2-methylhistamine/ 4-methylhistamine
What is the H2 receptor responsible for
gastric acid secretions and some vascular effects mediateded by adenyly cyclase
Which two tissues have the highest histamine content?
Lung and skin of the face
How is histamine stored?
In secretory granules bound to heparin
What are the three mechanism of histamine release from mast cells
- Antigen binding to bound antibody (second exposure)
- Via Drugs
- By physical stimulation (heat, cold, light, touch)
Which receptors on the mast cell directly inhibits histamine release from mast cells?
H2 receptors and Beta adrenergic receptor agonists (formation of cAMP in both cases)
What are the affects of histamine on the smooth muscle of the lung and which receptor mediates it?
Bronchospasm, H1
What are effects does H1 have on the smooth muscle of the vasculature?
- Smooth muscle relaxation
- Increased vascular permeability
- Endothelial cell contraction
- Capillary dilation
What are the effects of H2 have on the smooth muscle of the vasculature?
- Smooth muscle relaxation
2. Arteriolar dilation
What effect does histamine have on gastric parietal cells?
H2 receptor stimulation leads to the release of HCl into the stomach
What is the histamine triple response?
- histamine induced vasodilatory effect
- histamine induced axon reflex causing “flare”
- Wheal formation from increased vascular permeability and edema
What are the medical uses of histamine?
- To determine bronchial hypereactivity of asthmatic patients
- Used as a positive control for allergen skin test
- Used neurologically to test the axon flare response
List the classical H1 blockers and the mechanism of action for this group
- diphenyhydramine, chlorpheniramin, fexofenadine, Loratidine/desloratidine/cetirizine (second generation H1 blockers, less hydrophobic)
- Competitive blockade of H1 receptor
List the therapeutic uses of H1 blockers
- Blocks symptoms of allergies
- Sedation (except fexofenadine)
- Used as local anesthetic (diphenyhydramine)
- Anticholinergic
- Anti motion sickness (part of the anticholinergic effect)
Describe the effects of H1 blocker toxicity on children and adults
- In children it causes fever, flush, and CNS excitement
2. In adults it causes less fever and CNS excitement, more CNS depression
This drug is used to stabilize mast cells from releasing histamine and can be used in asthmatic patients before the release of histamine
cromolyn sodium
This drug is used to bind to the Fc portion of IgE thus preventing the binding and eventual activation of the mast cell
Omalizumab
List the H2 blockers in order of drug that most blocks P450 enzymes in the liver to the least, also what is the effect of these drugs
- Cimetidine> ranitidine> nizatidine> famotidine
- They competitively block H2 and thus prevent the release of acid in the stomach, used to treat peptic ulcers (all OTC)
Besides blocking P450, what other effect does cimetidine have?
Blocks testosterone receptor, can cause gynecomastia when using large doses for Zollinger-Ellison syndrome
