Histamine Flashcards
What is the precursor to histamine?
Histidine
What enzyme synthesizes histamine and which break it down?
Histidine Decarboxylase
Metabolized by: Deaminase Oxide (DAO) and HNMT (Histamine N-methyl transferase)
What are the uses of histamine?
Inflammation mediator, gastric acid secretion, and neurotransmitter/modulator
What areas have the most histamine?
Lungs, Skin, GI
Difference between mast cell and non-mast cell pools of histamine?
Turnover Rate. Mast Cells are slow and have to repackage and MUST HAVE PRIOR EXPOSURE to release, while nonmast cells constantly produce.
What are major effects of histamine?
Immediate itching, skin redness, increased HR, decreased BP, then shortly afterwards urticaria with normalized CV
What is redman syndrome?
After rapid infusion of Vancomycin there is a mass mast cell degranulation causing redness on the face, neck, and trunk with hypotension.
What is the use and mechanism of Cromolyn Sodium?
Used for management of chronic asthma by stabilizing mast cell membranes preventing degranulation. (Not a rescue medicine)
What is the antibody that treats persistent asthma and how does it work?
Omalizumab. It’s an anti-antibody, binding the FcE portions on IgE to prevent binding on mast cells that cause histamine release.
Where are H1 receptors located?
Endothelial Cells, Smooth Muscle, and CNS
What is an antagonist of H1 receptor?
Chlorpheniramine, Diphenhydramine, Dimenhydrinate, Phenergan
Location of H2 receptors?
Gastric Parietal Cells, Mast Cells, Cardiac Cells
What are the secondary messengers of H1 and H2?
H1 - Gq, increases Ca+2
H2 - Gs, increases cAMP
Functionality of H1 and H2 in CV system?
H1 - located on endothelium, which induce NO -> vasodilation
H2 - located on smooth muscle, which causes decreased Ca+2, thus smooth muscle relaxation
What would happen if an H1 receptor was on smooth muscle cell in the cardiovascular system?
That would cause CONSTRICTION of the vessel, due to causing INCREASED Ca+2
How do H1 receptors cause increased vascular permeability?
The H1 receptors are located on Post-Capillary venules-endothelial cells, causing them to contract due to the increased Ca+2, increasing gaps between the cells.
What are the overall effects of histamine on the cardiovascular system?
Vasodilation, Decreased BP, Increased vascular permeability, and increased cardiac contractility.
What receptors are located on the cardiac myocytes?
H2 Receptors
What does histamine illicit in the bronchioles and GI system?
Bronchioles - H1 - contraction / H2 - relaxation (minimal)
GI - H1 - contraction/motility / H2 - gastric acid secretion
What are central nervous system effects of histamine?
Pain/itching, mediates AROUSAL, decreases appetite, thermoregulation, CV regulation
Major effect of H1 Receptor Blockers?
Treat Allergic Response, suppress itching, inhibit permeability changes.
Different between 1st and 2nd generation H1 Receptor Blockers?
1st Gen can enter the CNS and 2nd Gen cannot.
Usually 1st Gen are used for acute allergic reactions and 2nd generation are used for seasonal type reactions.
Two reasons why Loratadine is less likely to cause sedation than Diphenhydramine?
Diphenhydramine blocks central H1 receptors and has an anticholinergic effect.
Toxicity of H1 Blockers in 1st generation?
Primarily sedation (paradoxical in children) and anticholinergic effects of dry mouth, dry airway, and urine retention. Loss of appetite with n/v. Most sedating 2nd Gen drug is Cetirizine
What is a distinctive toxicity of 2nd generation drugs?
CV Toxicity when taking antibiotics due to P450 metabolism.
What are the two drugs use for acute allergic reactions?
Diphenhydramine and Chlorpheniramine, both competitive antagonists.
What is the most common use of 2nd Generation antihistamines and how are they better than 1st generation?
Seasonal Allergies. They do not penetrate the CNS, so they do not induce sedation.
What are the 4 most common 2nd generation antihistamines?
Fexofenadine - Allegra
Loratadine - Claritin
Desloratadine - Clarinex
Cetirizine - Zyrtec (Most sedating)
How are antihistamines used for motion sickness?
The 1st generation drugs and their anticholinergic effects can prevent motion sickness.
- Dimenhydrinate
- Promethazine
- Diphenhydramine
What is used for vestibular disturbances?
Dimenhydrinate
What is used for nausea and vomiting?
Promethazine
What drug has another clinical use in Parkinson’s Disease?
Diphenhydramine
What are the secondary messengers of H2 Receptors and what do they do?
G-coupled - Gs, which cause a rise in cAMP, decrease in Ca+2 and releases H+ into the lumen as gastric secretions. Parietal Cells.
What are the uses of H2 Receptor Antagonists?
GERD and Gastric Ulcers. Promote Healing, Prevention, and Relieve Symptoms.
What are adverse effects of H2 Antagonists?
Typically very few side effects, but ALTERS BIOAVAILABILITY of other drugs due to changes in H+.
Less common side effects, Diarrhea, HA, drowiness, confusion/slurred speech (CNS side effects in elderly)
What are use side effects regarding Cimetidine?
Inhibits P450 CYP2C9 - prolongs half-life of Warfarin. Long term use can decrease testosterone and reduce sperm count.
What are the 3 most commonly used H2 Receptor Antagonists?
From most potent descending: Famotidine, Ranitidine, Cimetidine.
