Histamine and Anti-Histaminic Drugs- Part III : Role Played by Histamine

In part III of this sequel, we would deal with the pharmacological actions shown by histamine and the pathophysiological phenomena occuring with a disturb in its homeostasis and regulatory upset.

3.1) Pharmacological actions of Histamine—

3.1.1) Blood Vessels-

• Histamine gives vasodilatory effect thereby increasing vascular permeability, by stimulating H1 receptors.
• It enhances constriction of larger arteries, probably due to stimulation of receptors on smooth muscles of blood vessel.
• It gives a triple response (red spot, flare and wheal) following its intravenous injection at the site of administration.
- Red spot: It’s due to the increased blood flow at the site of injection, since histamine has vasodilatatory effect.
- Flare: It’s characterized by redness at area surrounding the point of injection due to enhanced vasodialatation.
- Wheal: It’s characterized by a swelling around the site of administration due to increased vascular permeability.

3.1.2) Sensory Endings- Histamine has a stimulatory effect at the sensory ending of nerves giving rise to pruritic (itching) effect and irritation.

3.1.3) Central Nervous System- Histamine, when injected intracerebroventricularly (since it can't penetrate blood-brain-barrier), causes

• Wakefulness and alertness
• Cardiac stimulation and a rise in blood pressure
• Vomiting etc.

3.1.4) Glands- Histamine stimulates gastric acid secretion by stimulating H2 receptors. This may even lead to gastric and peptic ulcers in due course.

3.1.5) Smooth Muscles- Histamine, by stimulating H1 receptors, causes contraction of smooth muscles thereby causing effects like bronchoconstriction (and hence dyspnoea, meaning difficulty in breathing), uterine relaxation in rats and uterine contraction in guinea pigs, abdominal cramps in large doses etc.

3.1.6) Effect on adrenal medulla- Histamine causes release of adrenaline from adrenal medulla stimulating the H1 receptors and may give sympatomimetic effects like transient rise in blood pressure, dryness in mouth etc.

3.2) Patho-physiological Roles:

3.2.1) Gastric secretions- Since, H2 receptors are present largely in gastric mucosa, histamine can stimulate these receptors to enhance gastric secretion. Prolonged stimulation gives rise to ulcerative conditions which is even more marked, if the patient has a drug regimen consisting of NSAID (Non-steroidal anti-inflammatory drugs) that inhibit COX-1 (cyclo-oxygenase) enzyme as it inhibits mucosal secretion.

3.2.2) Allergic Conditions- Histamine, being a potent vasodilator has a dilatory effect and worsens respiratory involvements. It participates mainly in early phase of allergic reactions involved in asthma, hay fever etc. and plays a leading role in immediate-type hypersensitivity. It causes bronchoconstriction and produces respiratory difficulties in the patient and even dyspnoea.

3.2.3) Inflammation- Histamine is one among the various mediators taking part in the phenomenon of inflammation. It causes vasodilatory effects and produces oedema and swelling.

3.2.4) Itching- Histamine produces an itching and pruritis, as already described. This explains the phenomenon of itching, accompanied by swelling as occuring in mild mosquito bites.