Saturday, April 16, 2011


A depressor amine (as it causes lowering of the blood pressure). It is derived from histidine (as shown below) and is also present in ergot and animal tissues.

It is stored in most tissues in
(1) mast cells and in blood, in
(2) basophil. Histamine is stored in their secretary granules.
It is also present in
(3) cells of the epidermis,
(4) cells in the gastric mucosa,
(5) neurons in the central nervous system and
(6) cells in regenerating or rapidly growing tissues.

Release of Histamine:
Histamine is released by the process of exocytosis. This is stimulated
1. Either by the interaction of complement components C3a and C5a with specific receptors on the cell surface or
2. Interaction of antigen with cell fixed IgE antibodies.

This secretion of histamine is initiated by Ca2+.

Some drugs like morphine and tubocurarine, release histamine by some non-receptor action.

Metabolized by
1. Histaminase
2. Methylating enzyme “Imidazole N. Methyltransferase” which converts this into methylhistamine.
Histamine receptors:
Following are the histamine receptors and the table shown below is giving an overview histamine receptors:
Clinical Uses of Histamine agonists:
1. As a provocative test of bronchial asthma hyperactivity.
2. As a diagnostic agent in testing for gastric acid secreting ability.

Histamine antagonists:

Mechanism of action of Histamine antagonists:
They block the action of histamine receptors at all level.

Generations of H1 receptor blocking agents:
There are two generations of H1 receptor blocking agents:

1st generation:

Key Members

• Diphenhydramine
• Chlorpheniramine
• Doxylamine
• Hydroxyzine

• High lipophilicity, easily enters CNS
• Highly sedative (Triprolidine, Promethazine, Hydroxyzine)
• Anti-muscarinic, anti-α-adrenergic, anti-5HT
• Some have anti-motion sickness effect (Dimenhydrinate)
• Some have local anaesthetic effect.
• May cause increase appetite and weight gain. (Cyproheptadine)

2nd generation:

Key Members
• Desloratadine (loratadine)
• Fexofenadine (terfenadine)
• Cetirizine
• Azelastine
• Astemazole

• No CNS entry (Low lipophilicity, most ionized; also protein binding)
• Non-sedating
• No significant autonomic receptor blocking effect
• Generally long-acting
• Some are cardiotoxic
• May cause anorexia. (Loratidine)

1. Orally they are well absorbed with maximum serum levels occur after 1-2 hours.
2. Average plasma T1/2 is 4-6 hours.
3. H1 receptor blockers distribute to all the tissues.
4. Biotransformation is mainly in the liver.
5. Excreted in the urine.

Clinical uses of H1 receptor antagonists:
1. Allergic conditions.
2. Motion sickness and nausea.
3. Somnifacients. Diphenhydramine can be used for the treatment of insomnia.

Clinical uses of H2 receptor antagonists:
1. In the treatment of ulcers.
2. Treatment of Zollinger-Ellison syndrome (severe hypersecretion and ulceration).
3. Gastro-esophageal reflux disease (GERD).

Adverse effects:
Sedation, Headache, Flushing, tachycardia, Diarrhea, Cause itching and pain.
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