Histamine Antagonists Flashcards
What is the physiological effect of histamine?
Contributes to the regulation of vascular smooth muscle tone, neural transmission, gastric acid secretion and the transfer of plasma into surrounding tissues as a means of directing immune factors to the site where they are needed
- Mediated through H1 - H4 receptors
What is the pathophysiological role of histamine?
Produces edema, itching, rhinitis
- mediated primarily through H1 receptors
What are the sites of histamine biosynthesis?
- Mast cells
- Basophils
- Epidermal cells
- Intestinal mucosa
- CNS neurons
- Rapidly dividing cells
What are the activators of histamine synthesis and release?
- GM-CSF
- IL-3
- Endotoxin-bacterial infection
- Prostaglandins
- IgE-immune/allergic response
- Peptides (kinins)
What are the inhibitors of histamine synthesis and release?
- Histidine analogs
- Transcription and translation inhibitors
- Histamine
- B-antagonists
- Cromolyn Na+
- Certain H1 Antagonists
What are the activating factors for histmaine synthesis and release?
- Gastrin and Ach-gastric acid regulation
- Ca2+ mobilizers
- Vancomycin
- Venoms
H1 receptor location and operational characteristics
Location: smooth muscles, endothelial cells, adrenal medulla, heart, CNS
Characteristics: smooth muscle contraction, stimulation of NO formation, endothelial cell contraction, increased vascular permeability.
H2 receptor location and operational characteristics
Location: gastric parietal cells, vascular smooth muscle, suppressor T cells, neutrophils, CNS, heart
Characteristics: stimulation of gastric acid secretion, smooth muscle relaxation
H3 receptor location and operational characteristics
Location: CNS, peripheral nerves (heart, lung, GI tract), enodthelium, enterochromaffin cells
Characteristics: inhibition of NT release
Described the physiological effects of histamine in the
- vasculature
- lungs
- neural
NEURAL
- Microvasodilation (H1, H2)
- Capillary permeability and vasoconstriction (H1)
Lungs
- Bronchoconstriction (H1)
- Bronchodilation (H2)
Neural
- Nerve ending stimulation (H1, H3)
- Wakefulness and sedation (H1, H3)
First vs. Second Generation H1 Antagonists
First Generation
- Based on the structure of histamine
- Often short-lived
- Multiple dosing
- **Highly sedative **
- Anticholinergic side-effects
Second Generation
- Divergent structures, different from histamine
- Longer therapeutic actions
- Single or multiple dosing
- Limited or nonsedating
- Limited or no anticholinergic side effects
- Demonstrated cardiac effects
Second Generation (Metabolites) H1 Antagonist
- Potential for equal or superior potency
- Potential for enhanced safety proflies (e.g. cardiac arrythmias and drug-drug interactions)
- Lilkely to have comparable bioavailability
- Potential for equal or enhanced onset of action
- Potential for equal or extended duration of activity
Which of the H1 antagonists can cross the BBB and why is this important?
First generation H1 antagonists cross BBB d/t to thier lipophilic structure and bind to H1 receptors in brain; histamine binding to H1 receptors in hypothalamus produces wakefullness, so blockade of these receptors causes the characteristic sedation associated with these agents.
Also have anticholinergic effect d/t the ability of these to bind to muscarinic receptors. Confers antiemetic effects to several of these first generation agents and alos limits the utility of these agents in asthmatics b/c despite H1 blockade, the anticholinergic effects can** impede ciliary movement and mucus clearence** from the bronchus passage
Name the 1st Generation H1 Blockers
Names contain “-en/-ine” or “-en/-ate”
Ether or Ethanolamine derivatives: Diphenhydramine, Dimenhydrinate
Promethazine
Alkylamine derivatives: Chlorpheniramine
What are the therapeutic applications of H1 antagonists?
- Allergy and hayfever Sx (rhinitis and urticaria)
- Treatment of Sx of insect bites and stings and contact flora poisonings
- Motion sickness and vertigo
- Sleep aid
