UNIT 29:

ANTIHISTAMINES

Prof. Mª Dolores Guerrero Masiá PhD.

Dept. of Pharmacy
Faculty of Health Sciences. University CEU Cardenal Herrera
Histamine….

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INDEX

1. Introduction
2. Histamine receptors
3. Actions of Histamine
4. Agonists and Antagonists
5. Clinical uses.
6. Adverse effects.

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 1. INTRODUCTION

Histamine is a basic amine.

• It is found in most tissues but is present in high
concentrations in tissues exposed to the outside world
(lungs, skin and gastrointestinal tract).

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 1. INTRODUCTION HISTAMINE RELEASE
• Histamine is released from mast cells by exocytosis
during inflammatory or allergic reactions.

• Histamine is metabolised by histaminase and/or by a

methylating enzyme.

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INDEX

1. Introduction
2. Histamine receptors
3. Agonists and Antagonists
4. Actions of Histamine
5. Clinical uses.
6. Adverse effects.

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 2. HISTAMINE RECEPTORS

• Four types of histamine receptor have been identified, H 1-4

• All four are implicated in the inflammatory response
in some capacity.

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INDEX

1. Introduction
2. Histamine receptors
3. Actions of Histamine
4. Agonists and Antagonists
5. Clinical uses.
6. Adverse effects.

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 3. ACTIONS OF HISTAMINE

SMOOTH MUSCLE EFFECTS. (H1)

– Contracts the smooth muscle of the ileum, bronchi,
bronchioles and uterus.

CARDIOVASCULAR EFFECTS.
– H1:
• Histamine dilates human blood vessels and increases
permeability .
– H2:
• Increases the rate and the output of the heart.

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3. ACTIONS OF HISTAMINE
GASTRIC SECRETION.

– H2: Histamine stimulates

the secretion of
gastric acid
• Implicated in the
pathogenesis of
peptic ulcer.

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 3. ACTIONS OF HISTAMINE

EFFECTS ON SKIN.
H1:
Intradermally, hista- mine causes a reddening of the skin. Flare.
Histamine causes intense itch.
H1 antagonists are used to control itch caused by allergic reactions,
insect bites, etc.

• Histamine is, however, important in type I hypersensitivity

reactions such as allergic rhinitis and urticaria.

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 INDEX

1. Introduction
2. Histamine receptors
3. Actions of Histamine
4. Agonists and Antagonists
5. Clinical uses.
6. Adverse effects.

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 4. AGONISTS AND ANTAGONISTS
• ‘ANTIHISTAMINE’ conventionally refers only to the H 1 -receptor
antagonists that are used for treating various inflammatory
and allergic conditions.

– ANTAZOLINE
– AZELASTINE
– EPINASTINE
– OLAPATADINE
– EMADASTINE.

USED TOPICALLY (in nasal sprays or eye drops)

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H1 SYSTEMIC ANTAGONISTS

Most orally active antagonists are

well absorbed

The duration of the action of many

antihistamines is 24 hours facilitating once
daily dosing.

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INDEX

1. Introduction
2. Histamine receptors
3. Agonists and Antagonists
4. Actions of Histamine
5. Clinical uses.
6. Adverse effects.

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 5. CLINICAL USES

H 1 -RECEPTOR ANTAGONISTS

ALLERGIC REACTIONS
– Non-sedating drugs are used for allergic rhinitis
(hay fever) and urticaria. Ex: Fexofenadine, Cetirizine
– Topical preparations may be used for insect bites,nasal
sprays or eye drops.
– Injectable formulations are useful as an adjunct to
adrenaline (epinephrine) for severe drug hypersensitivity
reactions and emergency treatment of anaphylaxis.
ANTIEMETICS
Motion sickness
Nausea, especially labyrinthine disorders.
FOR SEDATION. Ex: Prometazine 18
INDEX

1. Introduction
2. Histamine receptors
3. Agonists and Antagonists
4. Actions of Histamine
5. Clinical uses.
6. Adverse effects.

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 6. ADVERSE EFFECTS

• They are mainly metabolised in the liver and excreted in

the urine.
• To treat allergies, the sedative CNS effects are
generally unwanted.
• Gastrointestinal disturbances are fairly common.

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 6. ADVERSE EFFECTS
• ‘FIRST-GENERATION’ DRUGS, which cross the BBB
and often have sedating actions.
• ‘SECOND-GENERATION’ DRUGS (superseed)
– some cardiac toxicity
• The risk was increased when the drug was taken
with grapefruit juice or with agents that inhibit
cytochrome P450 in the liver (withdrawn and
replaced by)
• ‘THIRD-GENERATION’ ‘cardio-safe’ drugs (often active
metabolites of the original drugs: second generation
drugs)
– Levocetirizine
– Desloratadine
– Fexofenadine
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