At the end of this lecture, student will be able to

• Explain autacoids

• Describe the pharmacology of histamine

• Discuss the pharmacology of antihistamine







                                Histamine receptors

                                Pharmacological action

                                Pathophysiological role



Autacoid: derived from Greek: autos-self, akos-healing substance or remedy

These are diverse substances produced by a wide variety of cells in the body, having intense biological activity, but generally act locally at the site of synthesis and release

Also known as local hormones

Autacoids are involved in a number of physiological and pathological processes

Even serve as transmitters or modulators in the nervous system

Classification of autacoids:

1. Amine autacoids Histamine, 5-Hydroxytryptamine (Serotonin)

2. Lipid derived autacoids: Prostaglandins, Leukotrienes, Platelet activating factor

3. Peptide autacoids: Plasma kinins (Bradykinin), Cytokines (interleukins, INFo., GM-CSF etc)


Synthesized in 1907 & later isolated from mammalian tissue

Tissue amine

Present in animal tissues, certain plants, venoms

Manifestations of certain allergic reactions

Mediator of hypersensitivity, phenomena and tissue injury reactions

Play important physiological roles

Present mostly within storage granules of mast cells (Tissues rich in histamine are skin, gastric and intestinal mucosa, lungs and placenta)

Non mast cell histamine occurs in brain, epidermis, gastric mucosa and growing regions

Synthesis, storage and destruction

Histamine is imidazolylethylamine

Synthesized from amino acid histidine

Degraded rapidly by oxidation and methylation

IgE antibody is produce and get bound to receptor-1 on the surface of mast cell

An binds to Ab and forms An-Ab complexs

ca2+ induce Exocytosis for release of histamine

Histamine receptor

Pharmacological action of Histamine

Blood vessels:

Dilatation of smaller blood vessels (arterioles, capillaries and venules)

• Vasodilatation is partly indirect mediated through EDRF

• Large arteries and veins are constricted mediated by H1 receptor

• ↑se capillary permeability due to separation of endothelial cells which leads to exudation of plasme (H1 receptor)

       Intra dermal inj: Elicits triple response

                Red spot: due to intense capillary dilatation

                Wheal: due to exudation of plasma

Flare: redness in surrounding area due to arteriolar dilation

Heart (H1 receptor):

↑se  HR, FOC, +ve chronotropy and +ve inotropy

Smooth muscle (H1 receptor): Bronchoconstriction, uterus and intestinal smooth muscle (abdominal cramps) constriction

• Glands (H2 receptor): ↑se gastric secretions

• Sensory nerve ending (H1 receptor): stimulated cause itching, pain etc

• Adrenal medulla (H2 receptor): increase the release of AD produce secondary hypertension

• CNS(H1 & H2 receptor): does not penetrate BBB & no central effects are seen

Pathophysiological role of Histamine

Gastric secretions: ↑se HCl secretion in stomach and cause ulcers (H2 receptor)

Allergicphenomena: Mediate by hypersensitivity reactions leads to urticaria, angioedema, bronchoconstriction and anaphylactic shock

As transmitter: initiates the sensation of itch and pain at sensory nerve ending,  act as a transmitter in regulating body temperature, CVS function, Thirst, Hormone release from anterior pituitary

Inflammation: mediator of vasodilatation and other changes that occur during inflammation and promotes adhesion of leukocytes to vascular endothelium

Uses of Histamine 

       Histamine has no therapeutic use. Only for experimental use

       Contraindications: in asthmatic and ulcer patients

Antihistamines or H1 antagonists 

       These drugs competitively antagonize actions of histamine at the H1 receptors

       Classification of antihistamines

                All antihistamines have similar action, but differs in sedative property

  1. Highly sedative: Diphehydramine, Promethazine, Hydroxyzine
  2. Moderately sedative: Pheniramine, Cyproheptadine, Cinnarizine
  3. Mild Sedative: chlorpheniramine, Cyclizine, Dexchlorpheniramine
  4. Non sedative (Second generation antihistamines): Cetirizine, Loratadine, Levocetirizine 

Pharmacological action of H1 antagonists 

       Histamine antagonism:

Blocks:  histamine induced bronch, intestinal and uterus contraction

                                Triple response-especially wheal, flare and itch

                                Fall in BP

                                Release of Adr from adrenal medulla

                                Constriction of larger blood vessel

       Anti allergic action: Immediate hypersensitivity (type I reactions) are suppressed

                Urticaria, itching and angioedema are well controlled

                Anaphylactic fall in BP is only partially prevented

       CNS: Older antihistamines produce variable degree of CNS depression

                Sedative antihistamine causes CNS depression

                Stimulant effects like restlessness and insomnia

                Excitement and convulsions are frequently seen at toxic doses

                Effective in preventing motion sickness

                Controls vomiting of pregnancy

                Reduce tremor, rigidity of parkinsonism

       Anticholinergic action: antagonize muscarinic actions of Ach

       Local anaesthetics: it has membrane stabilizing property

       BP: cause a fall in BP on i.v. injection

       H1 antihistaminics are well absorbed from oral and parenteral routes

       Metabolized in the liver

       Excreted in urine

       Widely distributed in the body and enter brain

       Newer compounds penetrate brain poorly

       Duration of action of most agents is 4 to 6 hours, except meclizine, loratadine, cetirizine and fexofenadine which act for 12-24 hours or more

Side effects and toxicity of H1 antagonists 

       Sedation, diminished alertness and concentration, light headedness, motor incoordination, fatigue and tendency to fall asleep are the most common

       Impairment of psychomotor performance

       Few individuals become restless, nervous and are unable to sleep (Second generation compounds are largely free of CNS effects)

       Dryness of mouth, alteration of bowel movement, urinary hesitancy and blurring of vision due to anticholinergic property

       Epigastric distress and headache are also common

       Local application can cause contact dermatitis

       Acute overdose produces central excitation, tremors, hallucinations, muscular incordination, convulsions, flushing, hypotension, fever and some other features of belladonna poisoning

       Death is due to respiratory and cardiovascular failure

Advantages of second generation H1 antagonists 

       Higher H1 selectivity

       No anticholinergic side effects

       Absence of CNS depressant property

       Additional antiallergic mechanisms apart from histamine blockade

       Inhibit late phase allergic reaction by acting on leukotrienes or by anti platelet activating factor effect

       Advantage of not impairing psychomotor performance

       No sleepiness, Do not potentiate alcohol or benzodiazepines

Uses of H1 antagonists 

       Allergic disorders: Antihistaminics do not suppress AG:AB reaction, but block the effects of released histamine-are only palliative (allergies, e.g. itching, urticaria, seasonal hay fever, allergic conjunctivitis and angioedema of lips, eyelids, etc)


       Common cold, Cough

       Motion sickness, Vertigo

       Preanaesthetic medication


       Acute muscle dystonia

       As sedative, hypnotic, anxiolytic


       Histamine is an amine autacoid

       Mediator of hypersensitivity , phenomena and tissue injury reactions

       Betahistine is histamine receptor analogue

       Antihistamines competitively antagonize actions of histamine at the H1 receptors

       Antihistamines are commonly used in Allergic disorders

Post a Comment