Antihistamine

Anggelia Puspasari
Pharmacology and Theraupetic
Departement
Medical and Health Sciences Faculty
University Jambi

Introducing
1927 Best and colleagues isolated histamine
from fresh tissue of the lung and liver

Histamine__Histos, Greek word for tissue

Distributed through the animal kingdom

present in many venom, bacteria, plants etc

Histamine in Human Body

Formed by decarboxylation of the amino

acid l-histidine
Forming and storage histamine mainly in
mast cell and basophil cell___non mast cell
storage:epidermis, gastric mucosa, neuron
CNS, cell that regenrtaed and growth
rapdly
Low [ ] in plasma or body fluid except LCS
Tissue contain large number of mast cell
are skin, bronchial tree, mucosa of
respiratory system dan intestinal
Histamine receptor : H1, H2, H3, H4

Tissue and Organ System Effect of

the Histamine
Nervous system
a. Powerful stimulant of sensory nerve ending_pain
and itching
b. Increased weakfulness
Cardiovascular system
c. Decreased BP, Increased HR, Vasodilatation of the
blood vessel_flushing, sense of warmth, headache
d. Increased capilary permeability, permit
transudation molecul outward_hives
Bronchial smooth muscle
e. Bronchocontriction

Tissue and Organ System Effect of

the Histamine
GIT smooth muscle
a. Contraction of intestinal smooth muscle in large
dose_diarrhea
Other smooth muscle organ
b. Insignificant effect on genitourinary tract and eye.
c. Pregnant women can induced uterus contraction in large
dose
Secretory tissue
d. Powerful stimulant of gastric acid secretion, gastric pepsin
e. Enhanced salivary and lacrimal gland secretion in large dose
f. Stimulated chromaffin cells to secrete cathecolamine
Triple response of lewis
g. Intradermal injection of histamine causes red spot, edema
and flare

Histamine in Allergic
Response

Antagonist Histamine Action

Histamine Antagonist
Physiologic antagonists, especially

epinephrine, have smooth muscle actions

opposite to those of histamine, but they act
at different receptors
Release inhibitors reduce the
degranulation of mast cells that results
from immunologic triggering by antigen-IgE
interaction__Cromolyn and nedocromil .
Histamine receptor antagonists
represent a third approach to the reduction
of histamine-mediated responses

Antihistamine
H1 receptor
antagonist

Mechanismof action
Compounds that competitively block

histamine at H1 receptors also block

autonomic receptors.
The H1 antagonists are conveniently
divided into first-generation and secondgeneration agents.
Distinguished by the relatively strong
sedative effects , 2nd generation have less
sedative effect.

Classes of The Drug (AH-1, 1st generation)

Classes of the Drug (AH1_2nd Generation)

Pharmakokinetic
Absorption

Rapidly absorbed following oral administration

Peak plasma [ ] 1-3 h
DOA usually 4-6 h, some of the drug longer (meclizine and 2 nd
gen)
Distribution
Widely distributed through the body, 1 st generation enter CNS
Metabolism
Extensively metabolized, primarily by microsomal systems in
the liver
Excretion
Renal Excretion in metabolite form 1 st generation.
Cetirizine and loratadine excreted in urine in ummetabolized
form, fezofenadine excreted in feces.

Pharmacodynamic
Histamine receptor Blocker
a. AH1 inhibit most effect of histamin on smooth

muscle (inhibit bronchocontriction, inhibit

vasodilatation)
b. AH1 strongly block the increased capillary
permeability and formation of oedema and
wheal
c. AH1 inhibit flare and itch
d. AH1 dont suppress gastric secretion

Pharmacodynamic
Non Histamine receptor Blocker Effect
a. AH1 can both stimulated and depress the CNS
b.

c.
d.
e.

(older generetion)__sedation effect.

Have antimuscarinic effect__lessened secretion in
cholinergically innervated gland and reduce
ongoing secretion, potent prevented motion
sickness but can cause urinary retention and
blurred vission
Local anesthetic effect__promethazine
Adrenoreceptor blocking action caused orthostatic
hypotension__phenotiazine group
Serotonin blocking action__cyproheptadine

Indication/Clinical uses
Allergic Response
Motion Sickness and vestibular

disturbances__diphenhydramine,
promethazine, cyclizine and meclizine
Sedation
Antinausea and antiemetic
agent__Doxylamine_now withdraw from the
market
Antiparkinsonism effect__diphenhydramine

Adverse Effect
The most frequent side effect in the first-generation H 1

antagonists is sedation.
The next most frequent side effects involve the digestive
tract.
Dryness of the mouth and respiratory passages
(sometimes inducing cough), urinary retention or
frequency, and dysuria.
Untoward central actions include dizziness, tinnitus,
lassitude, incoordination, fatigue, blurred vision, diplopia,
euphoria, nervousness, insomnia, and tremors.
azelastine, hydroxyzine, and fexofenadine showed
teratogenic effects in animal studies whereas others
(e.g.,chlorpheniramine, diphenhydramine, cetirizine, and
loratadine) did not.

Toxicity
In acute poisoning with H1 antagonists,

their central excitatory effects constitute

the greatest danger.
Lend the syndrome a remarkable similarity
to that of atropine poisoning.
Deepening coma with cardiorespiratory
collapse and death usually within 2 to 18
hours.
Treatment is along general symptomatic
and supportive lines.

Drug Interaction
a. Drug interaction with inhibitor CYP450

enzyme (macrolide, azole antifungal or

calcium antagonist)__increased plasma[ ]
__induced arrythmia, especially for
terfenadine
b. Drug Interaction with inducer CYP450
enzym benzodiazepin exe__decreased
plasma [ ]
c. CYP inhibitor enzym__Alcohol or other
CNS depressants produces an additive
effect that impairs motor skills

TERIMAKASIH