Histamine and Anti Histamine – Uses Targets

Histamine definition

A chemical found in some of the body cells – causes many of the symptoms of allergies, such as a runny nose or sneezing.

• When a person is allergic to a particular substance, such as a food or dust, the immune system mistakenly believes that this usually harmless substance is actually harmful to the body.

Anti histamine definition

An anti histamine is any drug that neutralizes the effect of histamine, or inhibits its production in the body.

• Anti histamines are used in the treatment of allergies and works by blocking the effects of histamine, a protein released during an allergic reaction.

Histamine is inactive orally because liver degrades all histamine that is absorbed from intestine.

Receptors of Histamines

Histamine receptors are four in numbers i.e.

H1R to H4R are characterized by their function, structure, distribution, and their affinity to histamine.

1. The H1-receptor drives cellular migration, vasodilatation, and bronchoconstriction.
2. The H2-receptor modifies gastric acid secretion, airway mucus production, and vascular permeability.
3. The H3-receptor plays an important role in neuro-inflammatory diseases.
4. The H4-receptor has also been shown to be involved in allergy and inflammation.

Pharmacological actions of histamines on

• Blood vessels– dilation occurs in small artery and veins.
• Heart– high contraction force seen
• Visceral smooth muscle– histamine cause bronchio constrictor, and large dose causes abdominal cramps.
• Glands– increase in gastric secretion primarily of acid.
• Itching occurs when histamine is injected.

Use of histamine

No therapeutic use, used for test acid secretion capacity of stomach.

Beta histamine– is orally active,used to control vertigo in patient of Meniere’ disease (inner ear disorder that cause vertigo) by causing vasodilation in internal ear contraindicated in disease asthmatics and ulcer patient.

Targets of histamine

H1 antagonist

Also called convential antihistamines.

H1 antagonists, also called H1 blockers, are a class of medications that block the action of histamine at the H, receptor, helping to relieve allergic reactions.

More commonly employed now are less sedating or non sedating secondary generation H1 antihistamine.

Pharmacological actions– H1 Anti histamine have similar actions but there are quantitative difference, especially in sedative property (act of sleep)

Antagonism of histamine– effectively block histamine induced. Brocho constrictor , contraction of intestinal and other smooth muscle .

Action of histamine on gastric secretion is not affected by these drugs.

Cyproheptadine had aadtional 5-HT2 receptor blocking activity.

Antiallergic Action

• immediate hypersensitivity are supressed.
• Urticaria, itching and angioedema are well controlled
• Fall in bp partially prevented
• Asthma remains unaffected.

It is now well established that leukotriene( group of biologically active compounds, originally isolated from leucocytes ) and PAF ( Platelet-activating factor)are more important mediators for human asthma.

CNS

• older antihistamine produce variable degree of CNS depression
• Some individual also experienced stimulant effect like insomnia, restlessness, excitement and convulsions are seen at toxic doses.
• Second generation antihistamine are non sedative
• H1 antihistamine are effective in preventing motion sickness.

Promethazine reduce tremor , rigidity etc. Also control vomiting in pregnancy.

Cyproheptadine have appetite stimulating effect.

Anticholinergic Action

If H1 blockers used concurrently with atropine or its substitutes, phenothiazines, tricyclic antidepressant or disopyramide, the anticholinergic Actions adds up, greaded as- high low and minimum.

High– Promethazine, Diphenhydramine, Dimenhydramine,pheniramines

Low– chlorpheniramine,hydroxyzine, triprolidine, Cyproheptadine

Minimal – fexofenadine,astemiazole,loratadine, cetrizine

Local anesthesia

Drugs like pheniramine, promethazine, Diphenhydramine,have strong membrane stabilising property, but cause irritation when injected.

BP

Most Anti histamine cause a fall in BP on I.V injection, direct smooth muscle relaxation or alpha adregenic blockade as in promethazine.

dosage of H1 antihistamine

Highly sedative

• Diphenhydramine – 25-50mg oral

• Dimenhydrinate – 25-50 mg oral
• Promethazine – 25-50 mg oral
• Hydroxyzine – 25-50mg oral

Moderately sedative

• pheniramine – 20-50mg oral
• Cyproheptadine – 4 mg oral
• Meclozine – 25-50 mg oral
• Cinnarizine – 25 -50 mg oral

Mild sedative

• Chlorpheniramine – 2-4 mg oral
• Dexchlorpheniramine– 2 mg oral
• Triprolidine – 2.5 -5 mg
• Clemastine – 1-2 mg oral

Second generation antihistamine (newer compounds)

• fexofenadine – 120-180 mg orally
• Loratadine – 10 mg orally
• Desloratadine– 5 mg orally
• Cetrizine – 10 mg orally
• Levocetrizine – 5-10 mg orally

pharamacokinetics

H1 antihistamine well absorbed from oral and parenteral route, metabolised in liver and excreted in urine. The newer compounds penetrate brain poorly accounting for their absent of sedating Action .

Duration of action – 4-6 hours except meclozine, chlorpheniramine ,mesolastine,loratadine, cetrizine and fexofenadine which act for 12-24 hours or more.

side effects and toxicity

Ist generation of H1 antihistamine side effects are sedation, diminished alertness and concentration, motor incordintaion, fatigue and tendency to fall asleep are common, also affect CNS

2nd generation compounds are free from CNS effect, dryness of mouth, alteration of bowel movement,urinary hesitancy and blurring of vision can be ascribed to anti cholinergic property.

CAUTION– nevertheless to be exercised in prescribing antihistamine during pregnancy.

Second generation antihistamine

Have following properties-

• absence of CNS depressant property
• Higher H1 selectivity, no anticholinergic side effects.
• Additional Antiallergic mechanism apart from histamine blockade, some also inhibit late phase allergic reaction by acting on leukotriens or by antiplatelet activating factor effect.

drugs under second generation have following properties

1. fexofenadine– first second generation drug withdraw because of several death due to polymorphic ventricular tachycardia.
2. Astemiazole – also banned for same reason as of fexofenadine
3. Loratadine – long acting selective peripheral H1 antagonist with lack of CNS depressant effect and is fast acting. Not to produce cardiac arrhythmia in over dose.
4. Desloratadine – effective at half dose only.
5. Cetrizine – metabolite of hydroxyzine with marked affinity for peripheral H1 receptors, penetrates brain poorly,mild sedation ,produce arrythmias when given with erythromycin ,it has high and longer lasting concentration in skin.
6. Levocetrizine– effective at half dose.
7. Azelastine– it inhibit histamine release and given by nasal spray for seasonal and perennial allergic rhinitis.
8. Mizolastine– non sedating Anti histamine effective in allergic rhinitis and urticia.
9. Ebastine – non sedating and active in nasal and skin allergies.
10. Rupatadine– relief allergic rhinitis.

uses–

Uses of H1 antihistamine are based on their ability to block certain effect of histamine released endogenously as well as sedative and anti cholinergic effect.

• allergic disorders – antihistamine control allergy immediately.
• Combination with H2 antagonist succeds in some case of chronic urticaria.
• Do not effect the course of illness but afford symptomatic relief by anticholinergic and sedative actions.
• Pre anaesthesia- promethazine for its sedative and anticholinergic property
• Cough- chlorpheniramine, Diphenhydramine and promethazine are the best
• Hydroxyzine– has been used in anxiety.