5-HT & Histamine & Anti-histaminic Drugs

1. Histamine – Derived from-histidine -stored in mast cell with Heparin.
2. Type of Histamine Receptor – 4 types
   • H₁
   • H₂
   • H₃
   • H₄– Allergic & inflammation
3. Histamine  Non-selective agonist at H₁+ H₂+ H₃ Receptor
4. Selective H_1­-Agonist-2-methyl histamine, 2-pyridyl-ethyl amine, 2-Thiazolyl ethylamine
5. Selective H₂ –Receptor agonist – 4-methyl histamine, Dimaprit, Impramidine

Action/Role of Histamine:

1. Blood Vessel :- Dilation of Small Blood vessel  Flushing & hypotension
2. Increase capillary permeability  Edema through H₁ Receptor
3. Intradermal Inj. :- Triple Response due to Primarily H₁ – Receptor mediated
   1. Red Rxn. = due to Vasodilation
   2. Wheal = Exudation of fluid due to increased permeability
   3. Flare = Spreading redness due to Axon reflex
4. Visceral smooth muscle:- Powerful contractor of visceral S.M via H₂ Receptor  Bronchoconstriction & abdominal cramps via H₁ receptor
5. Gastric :- Increase Acid secretion gastric secretion by stimulation of H₂-Histaminic Rec.
6. Neuron – Stimulates nerve ending – may result in pruritis & pain
7. Brain – Maintain wakefulness through H₁-Receptor – Block LCZ
8. Histamine (H₁) – serve as a mediator of inflammation & immediate type of hypersensitivity reaction.

Note:-

Betahistine:- Histamine analogue – used to control vertigo in Meniere’s disease

H₁ Anti – Histaminic:- These drugs act as competitive antagonist at H₁-Receptor.

Classification of Anti-histaminic Drugs

On the basis of CNS penetration & Anticholinergic properties, Anti-histaminic drug are classified into 1^st generation & 2^nd generation.

1^st Generation – Anti-histaminic (H₁):-

• Can penetrate BBB  Sedation & psychomotor impairment so 1^st generation Anti-histaminic contradicted in person requiring constant attention (like driving, machinery operators, swimmers etc)
• 1^st Anti-histaminic also posses Anti-Cholinergic activity
• Major Adverse effect of 1^st Generation = Sedation, Psychomotor impairment & Anti-cholinergic effects (dryness of mouth, blurred vision, urinary retention, constipation etc)

2^nd Generation Anti-histaminic (H₁)

• Little CNS penetration (No sedation)
• No Anti-Cholinergic activity
• Additionally has Anti-allergic [Cetrizine & Axelastine]

Use of Antihistaminic drugs

Based on H1-Blocking action	Based on Anti-cholinergic properties	Other uses
Allergic condition – itching, urticaria, hay fever etc.Insect bite, prevention of adverse effect due to histamine release	Common cold to control rhinorrhoeaMotion sickness (Prophylactic)Parkinsonism (promethazine)Acute muscular dystonia	Idiopathic pruritis Anti-vertigo (cinnarizine)

Note:

• Cetrizine – It is active metabolite of 1^st generation drug hydroxyzine.
• Levocetirizine – ‘l’ isomer of cetrizine
• All second generation Anti-histaminic are metabolized to active product except cetrizine & mizolastine.