Histamine & Antihistamine

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Histamine

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Substance found to be involved in inflammatory & anaphylactic rxns

- local application causes swelling, redness, and edema, mimicking a mild inflammatory rxn

- large doses systemically administered lead to profound vascular changes similar to those seen after shock or anaphylactic origin

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Converts histidine to histamine

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Histidine decarboxylase

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Conditions that release histamine

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- Tissue injury

- Allergic rxn (requires prior exposure)

- Drugs and other foreign compounds

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Where is histamine released from?

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Mast cells degranulation

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Pharmacological effects of histamine on the cardiovascular system

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Triple effect (most common association) :
- reddening at injection site (vasodilation)
- wheal or disk of edema
- large crimson flare surrounding wheal

- ↓ BP, cutaneous flushing, ↑ temp, intense headache

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Pharmacological effects of histamine on smooth muscle of bronchioles

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Causes contraction of nonvascular smooth muscle

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Pharmacological effects of histamine on exocrine glands

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- potent stimulator of gastric secretion (HCL & pepsin)
- enhances salivary and lacrimal gland secretion
- stimulates chromaffin cell (adrenal medulla) to secrete catecholamines

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Pharmacological effects of histamine on the peripheral nervous system

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causes itching and pain

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Diagnostic uses of histamine

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- Gastric secretion: stimulate secretion for sampling of stomach content

- pulmonary fxn: assess bronchiole resistance (asthmatics)

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H1 Receptor

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Mediates effects on sm. muscle leading to:
- vasodilation
- ↑ vascular permeability
- contraction of nonvascular smooth muscle

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H2 Receptor

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Mediates histamine stimulation of gastric secretion

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H3 & H4 receptors

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- feedback inhibitors in CNS, GI, lung, and HRT

- within mast cells: mediates immune and inflammatory responses

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General mechanism of action of antihistamines

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Generally H1 receptor antagonist

- block action of histamine at receptor
- competes w/histamine binding
- displaces histamine from receptor

*Note: most beneficial when given early

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H1 Antagonist: Mechanism of Action

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- Displaces histamine from H1 receptor: Gq

- H1 receptor blockade → ↓ Ca inside cell

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Non-selective effects of H1 blockers

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- anti-nausea and anti-emetic effects (antimuscarinic)

- antiparkinsonsim (antimuscarinic)

- local anesthesia, blockade of Na channels

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First generation H1 blockers

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Nonselective

Many of the pharmacological effects result from actions at muscarinc, α-adrenoceptor, serotonin, local anesthetic sites

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Second generation H1 blockers

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Newer drugs that are much more selective for peripheral H1 receptors in preference to the CNS. This selectivity significantly reduces the occurrence of adverse drug reactions, such as sedation, while still providing effective relief of allergic conditions.

The reason for their peripheral selectivity is that most of these compounds are polar, meaning that they do not cross the blood brain barrier and act mainly outside the central nervous system.

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Diphenhydramine (Benadryl)

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First generation H1 antagonist

- H1 receptor antagonist
- anticholinergic → ↓CNS*

*will enhance effects of other CNS depressants

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Promethazine (Phenergan)

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First generation H1 antagonist

SE: marked sedation, antiemetic

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Cromolyn sodium

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Inhibits histamine release from mast cells

Use: mild to moderate asthma to prevent attacks

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Fexofenadine

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Allegra

Second generation H1 blockers