Antihistamine

AUTACOIDS PHARMACOLOGY
Histamine • Adm. of Histamine can provoke all the

• Histamine is endogenous to many mammalian symptoms of allergy, including asthma and
cell types, most notably mast cells in the skin & anaphylactic shock.
lungs, parietal cells of the gastric mucosa, & • Persons who have allergies are esp. responsive
basophils. to histamine.
• Histamine is also found in the CNS, where it • Additional AE are HA, dizziness, hypotension,
appear to be a NT. exacerbation of peptic ulcer symptoms.
• Secretion of gastric acid is markedly influenced • Betazole causes fewer and less intense SE.
by histamine.
• The conventional or “classic” antihistamines
• Ag-Ab interactions, as well as several drugs are H1-receptor antagonists.
(ex. Morphine, Trimethaphan) stimulate release
of histamine from mast cells.
• Allergy symptoms such as Urticaria, nasal Antihistamines
congestion, asthma, & anaphylactic shock ● H1-Receptor Antagonists :
are attributable at least in part to this amine. ● GN : Azatadine (Optimine)
• Histamine exert its effect by interacting with 2 ● Brompheniramine (Dimetane)
distinct types of binding sites, designated H1 ● Chlorpheniramine (Chlor-Trimeton)
and H2 histamine receptors. ● Clemastine (Tavist)
● Cyproheptadine (Periactin)
• H1 receptors are most responsible for allergy
● Diphenhydramine (Benadryl)
responses, while H2 receptors mediate gastric
● Terfenadine (Seldane)
secretion.
● Tripelennamine (Pyribenzamine)
• Both types of receptors are found in the brain, ● Triprolidine (Actidil)
& both receptor types probably mediate CV H2-Receptor Antagonists :
actions of histamine.
• Histamine was adm. in the past as a test for ● Cimetidine (Tagamet)
gastric secretion when pernicious anemia was ● Famotidine (Pepcid)
suspected. ● Ranitidine (Zantac)
● Nizatidine (Axid)
• Betazole, a relatively H1-receptor-specific
analogue of histamine, was used in a similar
• They are used extensively in the prevention &
manner. However, SE that can be
control of allergic reactions.
life-threatening have made this use obsolete.
• The most prominent SE is Sedation, although
• Prostaglandin has now replaced histamine as
recently developed agents such as Terfenadine
a test for gastric-acid secretory responses.
(Seldane) are reported not to cross the BBB.
• Histamine use as provocative test in the dx of • H2-antihistamines are also anticholinergic and
Pheochromocytoma is also obsolete. will produce dry mouth, urinary retention,
thickening of bronchial secretions, &
• Histamine stim. of the cells of the adrenal exacerbation of glaucoma.
medulla, coupled with an exaggerated reflex
response to histamine-induced hypotension, • OTC sleeping aids & motion sickness
results in massive release of catecholamines preventatives often contain antihistamines.
in these individuals. • H2 –receptor antagonists are used clinically
for their ability to suppress both daytime and
• Chemical assay of catecholamines are now nocturnal gastric acid secretion in response to a
used. variety of stimuli (ex. Pentagastrin, insulin,
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histamine & food ingestion). basolaterally which leads to inc. serotonin
uptake by circulating platelets & activation after
• Tx & prevention of PUD , including those that
stimulation, which give inc. stimulation of
can occur with stress or with Zollinger-Ellison
myenteric neurons and GI motility.
Syndrome, are the major indications.
• The remainder is synthesized in serotonergic
• During clinical development, Cimetidine
neurons of the CNS, where it has various
(Tagamet) appeared remarkably free of adverse
function including regulation of mood, appetite,
effects.
and sleep.
• However, post market surveillance revealed an
inhibition of hepatic metabolism that can result • Serotonin has cognitive functions including
in elevated serum levels of such drugs as memory and learning.
Diazepam, Warfarin, Theophylline, and • Serotonin can serve as vasoconstrictor or
Propranolol. vasodilator while regulating hemostasis and
blood clotting.
• Although, H2-receptor antagonists do not
readily cross the BBB, Cimetidine can cause • Vasoconstrictive property is mostly seen in
mental confusion particularly in patients who pathologic state affecting endothelium
are elderly or have impaired renal function. (atherosclerosis and chronic HPN)
• Agranulocytosis and thrombocytopenia can • In physiologic states, vasodilation occurs
occur. through the serotonin mediated release of nitric
• Ranitidine and Famotidine have fewer oxide from endothelial cells.
adverse CNS effects because they cross the • It inhibits the release of NE from adrenergic
BBB poorly. nerves.
• Is also a growth factor for some types of cells,
which may give it a role in wound healing.
Serotonin
• Or 5-hydroxytryptamine (5-HT) is a • Is converted to melatonin in the pineal gland.
monoamine neurotransmitter, popularly thought • Is metabolized mainly to 5-HIAA, chiefly by the
to be a contributor to feelings of well-being and liver.
happiness.
• Metabolism involves first oxidation by
• Biochemically, the indoleamine molecule is monoamine oxidase to the corresponding
derived from the AA tryptophan. aldehyde. This is followed by oxidation by
• This AA enter the body through diet found in aldehyde dehydrogenase to 5-HIAA , the indole
food such as nuts, cheese and red meat. acetic acid derivative. The latter is then
excreted by the kidney.
• Tryptophan deficiency can lead to lower
• Smooth muscle :
serotonin levels resulting to mood DO such as
anxiety & depression. • Increases motility of SI, stomach and LI may
also enhanced, but usual response is inhibition.
• However, it is also produced in CNS specifically
in the Raphe nuclei located in the brainstem. • Inhibitory responses are mediated by 5-HT
receptors located both in neural and muscle
• Serotonin is also stored in blood platelets and
cells
is released during agitation and
vasoconstriction, where it acts as an agonist to • 5-HT can directly stimulate the smooth muscle
other platelets. of the uterus and bronchi to contract.
• Approximately 90% of the human body’s total • Afferent nerves to the bronchi may also be
serotonin is located in the enterochromaffin stimulated by 5-HT causing inc. in RR.
cells in the GIT, used to regulate intestinal
movements.
Eicosanoids
• Serotonin is secreted luminally and
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AUTACOIDS PHARMACOLOGY

Histamine • Adm. of Histamine can provoke all the

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