Anti_Histamines Flashcards
Autacoids
endogenous molecules that do not fall into traditional autonomic groups. They do not act on cholinoceptors
or adrenoceptors but have powerful pharmacologic effects on
smooth muscle and other tissues.
Most important amine autacoids
Histamine and Serotonin (5-hydroxytryptamine, 5-HT)
Acid-peptic disease
The disease of the upper digestive tract caused by acid and pepsin; includes gastroesophageal reflux,
erosions, and ulcers
Carcinoid
A neoplasm of the gastrointestinal tract or bronchi that may secrete serotonin and a variety of peptides
Ergotism (“St. Anthony’s
fire”)
Disease caused by excess ingestion of ergot alkaloids; classically an epidemic caused by consumption of grain (eg, in bread) that is contaminated by the ergot fungus
Gastrinoma
A tumor that produces large amounts of gastrin; associated with hypersecretion of gastric acid and pepsin leading to ulceration
IgE-mediated immediate
reaction
An allergic response, for example, hay fever or angioedema, caused by interaction of an antigen
with IgE antibodies on mast cells; results in the release of histamine and other mediators of allergy
Oxytocic
A drug that causes contraction of the uterus
Zollinger-Ellison syndrome
Syndrome of hypersecretion of gastric acid and pepsin, often caused by gastrinoma; is associated
with severe acid-peptic ulceration and diarrhea
Histamine is synthesized by
Histidine
Where is histamine stored?
stored in high concentrations in vesicles in mast cells, enterochromaffin cells in the gut, some neurons, and a few other cell types
Histamine is metabolized by the enzymes
monoamine oxidase
and diamine oxidase.
Excess production of histamine in the body
systemic mastocytosis
How is systemic mastocytosis measured?
detected by measurement of its major metabolite, imidazole acetic acid, in the urine. Because
it is released from mast cells in response to IgE-mediated (immediate) allergic reactions,
the pathophysiologic role of Histamine
plays a pathophysiologic role in seasonal rhinitis (hay fever), urticaria, and angioneurotic edema. (The peptide bradykinin also plays an important role in
angioneurotic edema
scombroid poisoning
Fish that has been stored improperly
generates high concentrations of histamine; consumption of
such fish may produce severe histamine toxicity
receptors that have most Histamine actions
H1 and H2
triple response
histamine effect on the skin is mediated mainly by H1 and H2
receptors. This response involves a small red spot at the center of an intradermal injection of histamine surrounded by an edematous wheal, which is surrounded by a red flare.
H1
Smooth muscle, endothelium, brain Gq; ↑ IP3, DAG
Typical responses include pain and
itching in the skin, bronchoconstriction, and vasodilation, the latter caused by the histamine-evoked release of nitric oxide. Capillary endothelial cells, in addition to releasing nitric oxide (NO) and other vasodilating substances, also contract, opening gaps in the permeability barrier and leading to the formation of local edema.
These effects occur in allergic reactions and in mastocytosis
Diphenhydramine, loratidine
H2
Stomach, heart, mast cells, brain Gs; ↑ cAMP Cimetidine
This Gs-coupled receptor mediates gastric acid secretion by parietal cells in the stomach. It also has a cardiac stimulant effect. A third action is to reduce histamine release from mast cells—a negative feedback effect.
H3
Nerve endings, CNS Gi; ↓ cAMP
Clobenpropit
presynaptic modulation of histaminergic neurotransmission in the central nervous system (CNS). Food intake and body weight increase in H3-receptor knockout animals; therefore,
selective H3 agonists are under investigation as appetite suppressants. In the periphery, it appears to be a presynaptic heteroreceptor with modulatory effects on the release of another transmitter
H4
Leukocytes, CD4-T cells Gi; ↓ cAMP
Thioperamide
is located on leukocytes (especially eosinophils) and mast cells and is involved in chemotactic responses by these cells
5-HT1D/1B
Brain
Gi; ↓ cAMP
5-HT2
Smooth muscle, platelets, brain Gq; ↑ IP3, DAG Ketanserin
5-HT3
Area postrema (CNS), sensory and enteric nerves Ligand-gated Na+/K+channel
Ondansetron
5-HT4
Presynaptic nerve terminals in the
enteric nervous system
Gs; ↑ cAMP
Tegaserod (partial agonist)
H1 blockers, first-generation
Diphenhydramine, dimenhydrinate Competitive pharmacologic block of peripheral and CNS H1 receptors plus α- and M-receptor block. Anti-motion sickness effect
Hay fever, angioedema, motion sickness • used orally as OTC sleep aid; used parenterally for dystonias
Oral, parenteral
Duration: 6–8 h
Sedation, autonomic block Rare CNS excitation
Promethazine:
H1 blocker with less anti-motion sickness action and more sedative and autonomic effects
Cyclizine, meclizine
H1 blockers with more anti-motion sickness action and less sedative and autonomic effect
Chlorpheniramine
H1 blocker with negligible anti-motion sickness, sedative, and autonomic effects
H1 blockers, second generation
Cetirizine
Competitive pharmacologic block of peripheral H1 receptors.
No autonomic or anti-motion sickness effects
Hay fever, angioedema Oral
Duration: 12–24 h
Minimal toxicities
Fexofenadine, loratadine, desloratadine
similar to cetirizine
H2 blockers
Cimetidine, famotidine, ranitidine, nizatidine
Competitive pharmacologic block. No H1, autonomic, or anti-motion effects
Gastroesophageal reflux disease, stress ulcers
Oral, parenteral Duration (large doses):
12–24 h
Cimetidine: drug interactions;
other H2 blockers much less
5-HT1 agonists
Sumatriptan
5-HT1D/1B agonist • causes vasoconstriction • modulates neurotransmitter release
Migraine and cluster headache
Oral, inhaled,
parenteral
Duration: 2–4 h
Paresthesias, dizziness, chest
pain • possible coronary
vasospasm
Almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, zolmitriptan
very similar to sumatriptan; oral preparations only; durations: 2–27 h
