Histamine and Antihistamine Flashcards
Major Effects of Histamine
- Mediates hypersensitivity “allergic” reactions, acute inflammatory responses, and asthma attacks
- Stimulates gastric acid secretion
- Inhibitory CNS neurotransmitter
Histamine Receptor Subtypes
H1, H2, H3, H4
H1
SM: GI, Vasc, uterus, bronchi, CNS
SM contraction (except vasc.) ↑ nausea, ↓ sleep
H2
Parietal cells, heart, Mast Cells, CNS
Acid release in stomach
↑ heart rate, allergy
H3
CNS
Inhibitory auto R
H4
Mast cells, lymphocytes, CNS
Inflammation, pruritis
Hypersensitivity/Inflammatory Response
- ↑ heart rate and cardiac contractile force
- ↑ blood flow
- Bronchoconstriction (bronchospasm /coughing)
- Stimulation of cutaneous nerve endings = itching / pain
- Loss of fluid from cardiovascular system /associated tissue swelling - “runny nose”
Cytolytic Histamine Release
- Involves membrane rupture
- Promoted by high concentrations of
-phenothiazines
-H1 receptor antagonists
-opioid analgesics
(not involving IS)
Non-Cytolytic Histamine Release
- ATP and calcium-dependent
- Occurs through exocytosis of granules
- Triggered by binding of IgE-allergin
- complement factors C3a and C5a,
- opioids
- non-depolarizing muscle relaxants - Concentration-independent
(G-protein mechanism = vesicle fusion with membrane)
Anaphylaxis/Anaphylactic Shock
- Induced by binding of IgE-allergin to Fc receptor on
basophil/mast cell - Symptoms: hypotension, vasodilation, irregular heartbeat, urticaria (hives), angioedema (movement of fluid from circulatory system to tissues), bronchoconstriction/bronchospasm
- Non-cytolytic release of histamine = independent of drug dose
Anaphylaxis/Anaphylactic Shock Treatment
Epinephrine is used to treat hypotension, irregular
heartbeat, and bronchoconstriction associated with
anaphylactic shock
(stimulate B2 R - relaxation// propanolol worsens - B blocker)
Anaphylactoid
reaction has symptoms of anaphylaxis but is induced by factors other than IgE (e.g. drugs);
Cytolytic release = drug dose-dependent
Antihistamine Drugs
- Histamine release inhibitors
- H1 receptor antagonists
- H2 receptor antagonists
What do Histamine Release Inhibitors do
Used primarily for the treatment of asthma
Mechanism: Inhibits Non-Cytolytic release of histamine from mast cells Exact mechanism unknown but appears to involve the phosphorylation of a moesin-like protein.
Phosphorylation causes this protein to cluster
around histamine-filled secretory granules
Histamine Release Inhibitors
Examples: CROMOLYN SODIUM, nedocromil
Side effects: bronchial irritation, revolting taste,headache
What do H1 Antagonists do
Uses: Treatment of allergies, insomnia, and taken to avoid motion sickness
Mechanism: competitive inhibition of the binding of histamine to H1 receptors
Inhibit histamine release from mast cells
H1 Antagonists
DIPHENHYDRAMINE + LORATADINE
Side effects of diphenhydramine: Antimuscarinic effects (result of binding to ACh receptors) including desiccation of mucous membranes; drowsiness (CNS effect) can be an undesired effect when taken for allergy
What do H2 Antagonists do
Uses: peptic ulcer and acid reflux disease
Mechanism: Competitive inhibitor of H2 receptors, decreases H+ ion secretion from gastric parietal cells
H2 Antagonists
CIMETIDINE, ranitidine
Side effects: May interfere with metabolism of numerous other drugs
not recommended for long-term use = decrease H+ secretion chronically - problems with digestion / broken down by P450 enzymes (drug interactions)
Non-Histamine Blocking Ulcer Treatment:
Proton Pump Inhibitors
• Uses: Peptic ulcer and acid reflux disease
• Mechanism: Irreversible inhibition of parietal cell H+K+ ATPase
Proton Pump Inhibitor
OMEPRAZOLE
• Side effects: diarrhea and headache (rare/severe)
• Recent report indicates proton pump inhibitors
may reverse cisplatin and 5FU drug resistance
what are 2 types of WBC that contain histamine
basophils (circulating form) and neutrophils
histamine synthesis and metabolism
product of metabolism of amino acid L-histidine by histidine decarboxylase => histamine
histamine can be degraded by enzymes but is not a potential drug target why / alternative
enzyme inhibitor
target: histidine decarboxylase = synthesis of histamine
2 types of histamine release
cytolytic and non-cytolytic
secretion of H+ into stomach
H/K ATPase - K IN from lumen/ H OUT to stomach
activated by ACh M3, Histamine H2, Gastrin G
Histamine antagonist = block H2 pathway
how do gastrin and ACh act to promote acid secretion
directly by acting on mast cells
why does loratadine not have side effects of diphenhydramine
the selectivity of different H1 receptors peripherally as opposed to effects of CNS
specifically targets receptors peripherally = release of fluids from sinuses - runny nose
(without drowsiness/nausea)
