Histamine

It is a potent tissue amine widely distributed in plant and animal tissues and in the venoms of
bees. In man, it is formed by decarboxylation of histidine and major portion is stored in mast
cells and basophils.
Mechanisms of Action: It acts on 2 major types of receptors
a. Stimulation of H1 receptors results in smooth muscle contraction, increased vascular
permeability, and mucus production. These effects are blocked competitively by H1
antagonists.
b. Activation of H2 receptors increases gastric acid production, and this effect is blocked by H2
blockers such as cimetidine.
Both types of receptors are involved in vascular dilatation and edema formation.
Pharmacological Actions:

1. Cardiovascular system
   Histamine produces dilatation of capillaries and venules accompanied by a fall in blood
   pressure. The mechanism is direct relaxation of the smooth muscles of blood vessels. This
   effect cannot be adequately reversed by antihistaminic agents but by adrenaline.
   
   It also has positive inotropic and chronotropic actions on the heart, impairs AV conduction, and
   increases coronary blood flow.
2. Smooth Muscles:
   Histamine directly stimulates the smooth muscles of various tissues including the bronchi and
   uterus. Histamine-induced bronchospasm is effectively antagonized by adrenaline.
3. Exocrine Glands:
   It is a powerful stimulant of HCl secretion by the gastric mucosa.
4. CNS: Histamine is formed locally in the brain and is believed to be a “waking amine”, acting
   by “increasing the sensitivity of large cerebral areas to excitation inputs”
5. Miscellaneous actions include induction of itching and pain.
   Histamine has no valid therapeutic use currently. But it plays very important role in anaphylaxis
   and other forms of allergic reactions. Its release may be induced by various agents including
   certain venoms, drugs, trauma (thermal, chemical, radiation), and antigen-antibody reactions.
   Treatment of Anaphylaxis
6. Exposure to the offending agent should be terminated.
7. Adrenaline has actions opposite to those of histamine and thus acts as a physiological
   antagonist. It may be given by SC or IM route.
8. Hypotension should be corrected with the infusion of intravenous fluids.
9. Corticosteroids are occasionally used.
10. Other supportive measures include administration of oxygen and artificial respiration if
    necessary.
    N.B. Antihistaminic drugs are not able to counteract the hypotension and brochospasm
    characteristic of anaphylactic shock.
    Antihistaminc Drugs
    These drugs competitively block histamine receptors and are of two types:
11. H1 receptor antagonists
12. H2 receptor antagonists (used in the treatment of acid-peptic disease)
    H1 Receptor Antagonists
    Classification of H1 recepror antagonists:
13. Potent and sedative: such as diphenhydramine and promethazine.
14. Potent but less sedative: such as cyclizine and chlorpheniramine
    
15. Less potent and less sedative: such as pheniramine
16. Non-sedative: such as terfenadine, loratadine, and cetrizine.
    The newer generation agents are relatively free of central depressant effects.
    These agents may also possess anti-emetic effects.
    Pharmacological Actions:
17. Antihistaminic Actions:-they block histamine effects at various sites.
18. Other Effects: are independent of the antihistaminic effects and vary widely according to
    the drug used.
    Most of them produce CNS depression resulting in sedation, drowsiness, inability to
    concentrate, and disturbances of coordination. But very few agents such as phenindamine may
    produce stimulation.Anti-motion sickness effects are exhibited by promethazine,
    diphenhydramine, and dimenhydinate.Promethazine and mepyramine have significant local
    anesthetic effect.Majority possess atropine-like effects.Some have central antimuscarinic
    actions which is useful in the treatment of Parkinsonism.
    Pharmacokinetics:
    They are well-absorbed following oral and parenteral administration. And are mainly
    metabolized by the liver; degradation products are removed in the urine.
    Therapeutic Uses:
19. Allergic Disorders:-Including urticaria, seasonal hay fever, atopic and contact dermatitis,
    mild blood transfusion reactions.
    N.B. Their topical use is not recommended because of the risk of sensitization and a high
    tendency to cause eczematous reactions.
    They are not effective in bronchial asthma and common cold.
20. Other uses:
    Diphehydramine and promethazine are used as hypnotics. Diphenhydramine and orphenadrine
    are effective in the treatment of Parkinsonism .Dimehydrinate and promethazine are employed
    in the prevention and treatment of motion sickness, other vomiting disorders associated with
    labyrinthine dysfunction as well as nausea and vomiting associated with pregnancy.
    Diphenhydramine is frequently used in the treatment of cough as combination preparation with
    other agents.
    
    Adverse Effects:

• Are usually mild. Most common is sedation. The most common anticholinergic adverse effect
  is dryness of the mouth. They may themselves occasionally cause allergic reactions.

1. -Hydroxytreptamine (Serotonin)
   It is widely distributed in plants and animals. Highest concentration in mammals is found in the
   pineal gland, acting as a precursor for melatonin. It is synthesized from the amino acid
   tryptophan and acts on several types of receptors.