VPT 321: Veterinary Neuropharmacology (2+1) copy 1

PHARMACOLOGICAL ACTION

• On blood vessels
  • On the blood vessels the actions of histamine are mediated by both H₁ and H₂ receptors.
  • Dilatation of small blood vessels including arterioles, capillaries and venules occurs.
  • On subcutaneous administration flushing, heat, increased heart rate and cardiac output with little or no fall of blood pressure is observed.
  • After rapid intravenous administration, a fall of blood pressure is noticed which is mediated by both H₁ and H₂ receptors.
  • H₁ receptors are responsible for an early short acting effect and H₂ receptors are responsible for a slow but more persistent effect on blood pressure.
  • However, with small doses, only the H₁ receptors are stimulated.
  • The effects of histamine on blood pressure can only be completely reversed, by giving both H₁ and H₂ blockers.
  • Dilatation of cranial blood vessels cause pulsatile headcahe.
  • Vasodilatation caused by histamine is partly due to EDRF.
  • Larger arteries and veins are constricted.
  • Histamine also causes increased capillary permeability due to separation of endothelial cells and exudation of plasma.
  • On intra dermal injection histamine causes a triple response of Lewis, which consists of flush, flare and wheal.
  • Red spot or flush is due to intense capillary dilatation
  • Flare - Redness in the surrounding area is due to arteriolar dilatation mediated by axon reflex.
  • Wheal is an elevated area due to exudation of fluid from the capillaries and venules.
• On heart
  • Direct effects of histamine on the heart are not prominent. But, the isolated heart is stimulated.
• On visceral smooth muscle
  • Histamine causes bronchoconstriction.
  • Asthmatic individuals are highly sensitive to histamine.
  • Gastrointestinal motility is increased.
  • In larger doses it causes abdominal cramps and colic by increasing intestinal contractions.
  • Effect on uterine smooth muscle differs from species to species.
• On glands
  • Histamine causes a marked increase in gastric secretion – primarily of acid and also of pepsin. 
  • This action is exerted on the parietal cells through H₂ receptors.
  • The response to histamine with gastric, salivary, pancreatic, bronchial and lacrimal is variable. 
• On sensory nerve endings
  • Itching occurs when histamine is injected and higher concentrations injected deeply cause pain.
  • Histamine stimulates the nerve endings to produce these effects.
• On autonomic ganglia and adrenal medulla
  • Histamine causes a stimulation of autonomic ganglia and adrenal medulla.
  • This in turn induces release of adrenaline and rise of blood pressure.
• On central nervous system
  • Histamine does not cross the blood brain barrier and hence no central effects are seen normally.
  • However, it appears to be a neurotransmitter where it may regulate wakefulness and appetite.