DRUGS USED IN

HYPERSENSITIVITY
REACTIONS
Dewi Selvina Rosdiana

Modul infeksi & imunologi, 21-3-2013

Drugs used in Hypersensitivity reactions:

- Antihistamine
- Adrenaline
- Glucocorticoid
- Sodium cromoglicate & nedocromil

Histamine
Histamine biogenic amine
Important mediator in :
- Immediate hypersensitivity & allergic
responses
- Inflamation
- Gastric acid secretion
- Modulates neurotransmitter release
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Storage & release of histamin

Storage : (inactive bound form of histamine)
Granulle of Mast cell & Basophils
Non-mast cell histamine
- Brain, as neurotransmitter
- Gaster, enterochromaffin-like (ECL) cell
Release :

immunological reaction
chemical and mechanical
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Pharmacodynamics
Type
Location
H1 smooth muscle,
endothelium, CNS

H2
H3
H4

gastric parietal cell,

cardiac muscle, CNS
CNS:presynaptic,
myenteric plexus
eosinophils, neutrophils,
CD4 T cell

Function
Vasodilation,bronchoconstriction
smooth muscle activation,
vascular permeability,
pain, itching, allergic rhinitis
symptoms & motion sickness
Gastric acid secretion
neurotransmitter release
chemotactic effect
(alergic & inflamation responses)
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Histamine effects on :
Nervous system
- sensory nerve endings pain & itching (H1)
- modulates neurotransmitter release (H3)
CVS
- Vasodilation (H1&H2): BP, flushing, headache
High dose: hypotension
shock
- Vascular permeability : edema, urticaria (H1)
Triple response: red spot, flare, edema
- Heart : contraction , heart rate , automaticity
(H2 stimulation & a reflex tachycardia)
High dose: arrhythmias

Bronchial smooth muscle:

H1 : bronchoconstriction, H2 : bronchodilation.
Patient with bronchial asthma : bronchoconstriction
GIT smooth muscle:
High dose : contraction
diarrhea (H1)
Other smooth muscle organs :
Iris, genitourinary tract: less affected
Uterus : no oxitoxic effect
Exocrine glands :
Gastric acid secretion (H2)
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H1 - Receptor Antagonists
Two types :
First generation / sedating
Second generation / nonsedating
Mechanism of action: reversibly compete with
histamine at H1 receptor sites
Pharmacokinetic:
Peroral absorption: rapidly absorbed
OOA: 15-30, Tmax 1-2 hours
DOA: 4-6 hours, 2nd generation : 12-24 hours
Metabolized by CYP3A4
Excretion: via urine after 24 hours

Some H1 antagonist drugs in clinical use:

Class
1st generation AH1
1. Ethanolamines
2. Ethylaminediamine
3. Piperazine derivatives
4. Alkylamines
5. Phenothiazine deriv.
6. Miscellaneous
2nd generation AH1
1. Piperidine
2. Miscellaneous

Drugs
dimenhydrinate, diphenhydramine,
carbinoxamine
tripelennamine
hydroxyzine, cyclizine, meclizine
brompheniramine, chlorpheniramine
promethazine
cyproheptadine
fexofenadine
loratadine, cetirizine, desloratadine,
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levocetirizine

Indications:
1. Allergic reactions
to prevent or treat the symptoms of allergic
reactions
- Allergic rhinitis, urticaria
- Atopic dermatitis (sedative effect)
- Not effective for bronchial asthma

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2. Motion sickness
- diphenhydramine, promethazine, cyclizine
meclizine
3. Vestibular disturbances & vertigo:
- dimenhydrinate, meclizine
4. Hypnotics : (sedation side effect)
- esp. Etanolamin class : diphenhydramine
5. Common cold :
- weak anticholinergic effect of 1st gen H1
antagonist may tend to lessen rhinorrhea.
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Side effects:
drowsiness/sedation (1st generation)
dry mouth
dizziness
nausea, vomiting
Cetirizine, loratadine, desloratadine, fexofenadine,
terfenadine: less likely to cross the blood brain
barriere relatively free of drowsiness effect
Topical antihistamine preparation can be allergenic
Pregnancy:
Teratogenic (hydroxyzine, fexofenadine, azelastine)
Non teratogenic (chlorpheniramine,diphenhiyramine,
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cetirizine, loratadine)

Side Effects of H1 Antagonist

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Drug interactions:
- Combination with inhibitor CYP3A4 :
antifungal (Ketokonazol,itrakonazol) or macrolide
antibiotics (erythromycin)
Terfenadine/astemizole blood concentration
potentially fatal abnormality in cardiac rhythm
Terfenadine and astemizole have been withdrawn
from the market
- Alcohol, sedatives, hypnotics and anxiolytic :
CNS deppresant effects
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H2 - Receptor Antagonists
H2 receptor antagonists reversibly compete
with histamine at H2 receptor sites
Effect: to reduce the secretion of gastric acid
Cimetidine, ranitidine, famotidine
(H2 antagonists were discussed in GIT module)

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H3 & H4 Receptor Antagonists

Still in trials
None has yet been approved for clinical
use.

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Other drugs
Adrenalin
Anaphylaxis: Medical emergency
Due to the systemic release of
histamine
other mediators ie.
5-hydroxytryptamine (5-HT, serotonine)
Leukotrienes (SRS-A) asthma
Massive vasodilation shock death.
Bronchoconstriction asphyxia
Management of anaphylaxis:
Adrenaline 0,3-0,5 mg s.c give immediately!!
(Antihistamine alone is not enough)
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Corticosteroids
- Hypersensitivity reactions that do not
respond to H1-antagonists
- Prednisone, dexametasone, etc
(corticosteroids will be discussed in the next lecture)

Sodium cromoglicate, nedocromil

- Prophylaxis for bronchial asthma
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Serotonin
Serotonin effects:
1. Nervous system
- present in a variety of sites in the brain.
- sensory nerve endings : a potent stimulant of
pain & itch
- activation of serotonin receptors on vagal nerve
endings chemoreceptor reflex bradycardia
& hypotensi
- serotonin receptor in GIT & in vomiting center
of the medulla vomiting reflex
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2. Respiratory System :
-A weak bronchoconstriction effect, hyperventilation
3. CVS:
- Vasoconstriction (through 5-HT2 receptors), except
in skeletal muscle and heart (vasodilation)
- Triphasic blood pressure response :
1st phase : HR, CO, BP (caused by
chemoreceptor response)
2nd phase : BP (as a result of vasoconstriction)
3rd phase : BP (vasodilation in vessels supplying
skeletal muscle)
- Platelets aggregation (5-HT2)
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4. GIT System :
- powerfull stimulant of GIT smooth muscle
tone & peristalsis (5-HT2)
- activation 5-HT4 receptors in enteric nervous
system prokinetic effect
5. Skeletal muscle :
- 5-HT2 receptors are present on skeletal
muscle membranes, but their physiologic role
is not understood.

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Serotonin agonists :
-Buspirone (5-HT1A agonist) : anxiolytic
-Tegaserod (5-HT4 agonist): irritable bowel syndrome
-Sumatriptan (5-HT1D/1B agonist) : migraine
Serotonin antagonists:
- Ondansetron (5-HT3 antagonist) :
prevention & treatment of nausea & vomiting
associated with surgery and cancer chemotherapy
- Cyproheptadine (5-HT2 blocker & AH1) :
treatment of cold-induced urticaria
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