Block 2: Autocoids: Histamine
Terms
undefined, object
copy deck
- How is histamine made?
- histidine -> (histidine decarboxylase) -> histamine
- Where in the body is histamine in highest concentrations?
-
lung
skin
stomach
gut - Name three places where histamine is stored?
-
mast cells (tissue phagocytes) and basophils (blood phagocytes)
CNS
mucosal layer of GI tract - The histamine content of most tissues is related to their ... content?
- mast cell content
- Why is histamine inert in mast cells?
- its stored in secretory granules and linked to proteoglycans
- How does histamine negatively modulate its own release?
- through H2 receptors on mast cells
- When the histamine content of mast cells is depreciated, how long does it take for the concentration to return to normal
- it can take weeks
- Are allergic reactions causing histamine release cytolytic?
- no
- Name 5 chemicals that cause chemical histamine release
-
morphine
tubocurarine
succinylcholine
vancomycin (red man syndrome)
radiocontrast - are chemicals causing histamine release cytolytic?
- no
- is energy required for histamine release mediated cellular injury
- no
- Give 5 states in which symptoms from histamine toxicity (headache, flushing, hypotension, and nausea) are also seen
-
1. mastocytosis
2. myelogenous leukemia
3. gastric carcinoid tumors
4. food poisoning from spoiled scombroid fish
5. red wine consumption when people have reduced ability to degrade histamine - What superfamily of receptors do histamine receptors belong to
-
7 transmembrane G protein-linked receptors
[like rhodopsin ;)] -
receptor in sm mm, endothelium and brain
signals PLC --> IP3, DAG, NO, and PLA - H1
-
receptor in gastric mucosa, brain, cardiac muscle, mast cells
signals cAMP, inhibition of arachidonic acid release, Ca - H2
-
receptor in presynaptic, brain, myenteric plexus, peripheral neurons
signals Ca, inhibits cAMP - H3
-
receptor in bone marrow, peripheral hematopoietic cells
signals Ca, inhibits cAMP - H4
- through what histamine receptors is vasodilation mediated?
-
H1: endothelial cells
H2: vascular sm mm - through what histamine receptors is increased cardiac contractility and increased pacemaker rate mediated?
- H2
- Through what histamine receptor is contraction of intestinal sm mm and increased GI motility mediated?
- H1
- Histamine receptor involved with bronchoconstriction
- H1
- What may happen in anaphylactic pregnant women?
- may abort due to uterine contraction
- Histamine receptor involved in stimulant of sensory nerve endings- pain and itching
- H1
- Histamine receptor involved in stimulant of gastric acid secretion from parietal cells?
- H2
- Histamine receptor involved in triple wheal and flare response to intradermal histamine injection
- H1
- Name a physiologic antagonist that acts through a different receptor and opposes action of histamine?
- epinephrine
- Name two drugs that can inhibit histamine release from mast cells?
-
cromolyn
nedocromil - histamine receptor antagonists act at which receptors?>
- H1 and H2, they are competitive
- Describe first generation antihistamines
-
small --> cross BBB
cross react w/ other receptors
available OTC
sedation as side effect - Describe second generation antihistamines
-
larger and lipophobic
more specific for H1
prescription only (except Claritin)
non-sedating - chlorpheniramine (chlortrimeton)
- 1st generation antihistamine
- clemastine
- 1st generation antihistamine
-
dimenhydrinate
(dramamine) - 1st generation antihistamine
- diphenhydramine
-
1st generation antihistamine
(benadryl) - doxylamine
- 1st generation antihistamine
- hydroxine
- 1st generation antihistamine
- meclizine
-
1st generation antihistamine
(antivert) -
promethazine
(phenergan) - 1st generation antihistamine
- fexofenadine
-
2nd generation antihistamine
(allegra) - cetirizine
- 2nd generation antihistamine
- loratadine
-
2nd generation antihistamine
(claritin) - Name two antihistamines used for sleep induction
-
diphenhydramine
doxylamine - only antihistamine approved antitussive
- diphenhydramine
- antihistamine most widely used for Parkinson's disease
- diphenhydramine
- three antihistamines to treat vertigo/motion sickness
-
meclizine (Antivert)
promethazine (Phenergan)
dimenhydrinate (Dramamine) -
When do antihistamines reach peak plasma concentration
When do antihistamines reach peak effectiveness -
2 hrs after oral administration
5-7 hrs after oral administration - All 1st generation and most 2nd generation antihistamines are metabolized by which hepatic cytochrome?
- P450
- Who eliminates antihistamines faster- adults or kids?
- kids
- Name two 2nd generation antihistamines taken off the market
-
astemizole (hismanal)
terfenadine (seldane) - Name two antihistamines thought to be of lower risk to take during pregnancy
-
dimenhydrinate
loratadine - Name four H2 receptor antagonists
-
cimetidine (tagamet)
famotidine (pepcid)
nizatidine (axid)
ranitidine (zantac)