Pharmacology

Autacoid – Histamine & Anti-histamine

Definition

  • Autacoid is derived from two word Autos means “Self” and Akos means “healing substance”.
  • Autacoids are the biological substance that release from the cell is response to variety of stimuli to produce physiological and pathological responses locally.
  • A hormone called local hormone that are produced by specific cells, and transported through circulation to act on target tissue.

Classification of Autacoid

  1. Amine Autacoids
    • Histamine, 5HT (Serotonin)
  2. Lipid derivatives autacoids
    • Prostaglandin, leukotriene, platelet activating factor
  3. Peptide autacoids
    • Plasmakinins (Bradykinin), angiotensin

Histamine

  • Histamine is an organic nitrate compound (Formed from amino acid histidine), which is involved in:
  • Immune response (allergic and immune response)
  • Resulting physiological function
  • Acting as a neurotransmitter
  • It is a naturally occurring imidazole derivatives.
  • It is produced by endogenously by decarboxylation of amino acid histidine in the presence of enzyme histidine decarboxylase.
  • Histidine is stored in the granules of mast cells, basophils and histaminergic neuron of CNS.
  • The highest concentration of histamine is present in lungs, skin, mucosal layer of GIT and intestine, liver and placenta. Histamine is also present in blood, most body secretions, venoms and pathological fluids.

Synthesis of Histamine

  • It is synthesized locally from the amino acid histidine by the enzyme histidine decarboxylase. It is degraded by oxidation and methylation.

Release of histamine

  • Allergies and anaphylaxis trigger significant release of histamine
  • When allergies enter into the body that results trigger immune cells to produce large IgE.
  • Some IgE attaches to the surface of mast cell (sensitized). On any subsequent exposer to the same allergen, the allergen interact with the specific IgE on the surface of the mast cells.
  • In response, the activated mast cell rapidly release histamine.

Receptors of histamine

ReceptorsLocation
H1 receptorCNS, Smooth muscle, Cell of airway, GIT, Cardio vascular system, Endothelial cell, Lymphocyte.
H2 receptorParietal cell, Vascular smooth muscle cells.
H3 receptorCNS, PNS.
H4 receptorBone marrow, Immune cells.

Pharmacological or physiological effect of histamine

  1. Blood vessel
    • Histamine causes marked dilatation of smaller blood vessel including arterioles, capillaries and venules.
    • Large arteries and veins are constricted by histamine mediated by H1 receptor on vascular smooth muscles.
  2. Activation of H1 receptor
    • Decrease vital capacity
    • Bronchoconstriction
    • Spasmodic contraction of ileum
    • Contraction of uterus
  3. CVS
    • H1 and H2 receptor dilate the arterioles and post capillary venules, so BP decrease.
  4. Gastric HCL
    • Increase stimulation of gastric acid secretion by H2 receptor.
    • In large dose release of pepsin.
  5. Nervous system
    • Parenteral administration of histamine produce itching and pain.
  6. Mucous
    • Histamine increases the nasal secretion and respiratory tract mucous secretion.
  7. Skin
    • Histamine causes triple response (redness wheal flore).
  8. Autonomic ganglia and adrenal medulla
    • Stimulate and release of Adr, which can cause rise in BP.
  9. CNS
    • Intracerebroventricular administration produce rise in BP, cardiac stimulation, behavioral arousal, hypothermia, vomiting and anti-diuretic hormone (ADH) release.
    • There is no effect on administration i.v.
    • Histamine does not penetrate BBB.

Pathophysiological roles

  1. Gastric secretion
    • Histamine stimulate HCL secretion in the stomach.
    • Histamine is released locally under the influence of all stimuli that evoke gastric secretion and activate the proton pump (H+K+ ATPase). (Stimuli: Cholinergic drugs, Gastrin, vagal secretion, prostaglandin).
    • H2 blocker diminish the acid secretion and also suppress the action of Ach and gastrin.
  2. Allergic condition
    • Release of histamine from mast cell causes AG-AB reaction on their surface and immediate types of hypersensitivity reaction like urticarial, angioedema, bronchoconstriction and anaphylactic shock produce.
    • H1 receptor inhibit the action of hypersensitivity.
  3. As transmitter
    • Histamine is the afferent transmitter which initiate the secretion of itch and pain at sensory nerve ending.
  4. Inflammation
    • Histamine produce vasodilatation effect during inflammation.
  5. Tissue growth and repair
    • Histamine is present in high concentration at growing and regenerating tissue, hence it play an important role of growth and repair.
  6. Headache
    • Vascular headache but no convulsion occur.

Uses of histamine:

the uses of histamine is not used recently, but some oldest techniques are used as below:

  • Test for acid secrete at stomach.
  • Bronchialhyperreactivity.
  • Pheochromocytoma.

Antihistamine

  • Histamine has less or no clinical effect, but agents that inhibit the action of action of histamine or blocks the histamine receptor called anti-histamine.

Classification H1 – anti-histamine

Highly sedativeModerately sedativeMild sedative2nd generation
Diphenhydramine Dimenhydrinate Promethazine Hydroxyzine Pheneramine Cyproheptadine  Meclizine (Meclizine) CinnarizineChlorpheniramine Dexchlorpheneramine Triprolidine Clemastine Fexofenadine Loratadine Desloratadine Cetirizine    Levocetirizine Azelastine Mizolastine Ebastine Rupatadine   

Action of anti-histamine

  • Antagonism effect
    • Antihistamine blocks histamine, that induce;
      • Bronchoconstriction
      • Contraction of smooth muscle and intestinal muscle.
      • Triple response (a red line on the skin – swelling, itch, wheal, flare).
      • Blood pressure decrease (low dose)
    • Construction of large arteries by histamine is blocked.
  • Anti-allergic action
    • It suppress;
    • urticaria
    • Itching
    • Angioedema
    • Asthma (partially)
  • CNS
  • Anticholinergic
    • Antagonize the muscarinic action of Ach.
  • Local anesthetics
    • H1 – antihistamine is not clinically used as local anesthetic, due to irritation effect.
  • BP
    • Most antihistaminic with i.v. injection cause fall blood pressure, but there is no evidence on oral administration.

Effect of H1 – antihistamine

Pharmacokinetics

  • H1 receptor blockers are well absorbed orally.
    • Onset of action 1-3 hours.
    • Most of the drugs average plasm half-life i.e. about 4-6 hours, except Meclizine and second generation anti-histamine, which shows 12-24 hours plasma half-life.
    • Duration of action almost 24 hours (basically 2nd generation).

Uses

  • Allergic
    • An allergic is an immune disease, in which the foreign substances (allergens) are invade into the body from food, pollen, water, etc. and produce harmful effects.
  • Common cold
    • Common cold is a viral disease caused by various types of virus for example rhinovirus. It is a communicable disease which is spread by direct contact, droplets, used clothes, utensil, etc.
    • 2nd generation, but less effective.
  • Motion sickness
    • When brain receive disturbed or conflict information from visual and vestibular receptor.
    • Promethazine, diphenhydramine, Dimenhydrinate, Cyproheptadine, meclizine.
  • Pruritides
    • Unpleasant sensation of the skin that provokes the urge to scratch.
    • Diphenhydramine, Chlorpheniramine, Cyproheptadine.
  • Vertigo  
    • Sensation of spinning dizziness.
    • Cinnarizine, Dimenhydrinate.
  • Cough
    • Diphenhydramine, promethazine.
  • Sedative, hypnotic, anxiolytic
    • Promethazine produce serious respiratory depression.
  • Pre-anesthetic medication
    • Promethazine
  • Parkinsonism
    • It is a slow progressive neurological disorder characterized tremor, rigidity, bradykinesia, and postural instability.
    • Promethazine.
  • Acute muscle dystonia
    • It is a movement disorder in which muscle contract involuntarily, causing repetitive or twisting movement.
    • Parenteral administration of promethazine, hydroxyzine, diphenhydramine.

Hello! My name is Smrutiranjan Dash, a pharmacy professional. belonging from, Bargarh, Odisha. I have acquired Master degree in Pharmacy (Pharmacology) form B.P.U.T, Rourkela, Odisha. Currently I am working as an Assistant Professor at The pharmaceutical college, Barpali.

Leave a Reply

Your email address will not be published. Required fields are marked *

', 'auto'); ga('send', 'pageview');