Dr.Rakshitha

Pharma PG

HIMS,Hassan

Histamine and antihistamine drugs

Histamine and antihistamine drugsContents:

• Introduction

• Synthesis, storage, distribution of Histamine

• Role of Histamine

• Anti histamine

• Its therapeutic uses

• Adverse effects

• Summary

Introduction

Autacoids

• Biological agents

• act locally (e.g.within inflammatory pockets) at

the site of synthesis and release.

• k/a “local hormones”

Autacoids

• Amine : Histamine

Serotonin

• Lipid derived: Prostaglandins

Leukotrienes

• Peptide : Plasma kinins,

Angiotensin

Histamine

• Histos: Tissue

N N

NH2

H

1

2

3

45

Histamine

Histamine

• Biogenic amine present in

-animal and plant tissues

-venoms and stinging secretions

• One of the mediators involved in inflammatory

& hypersensitivity reactions.

Synthesis, storage & metabolism of histamine

• Synthesized by decarboxylation of amino acid histidine

• Histamine is present in storage granules of mast cells & also found in skin, lungs, liver, gastric mucosa etc.

Histamine

Distribution:

• Histamine - storage granules of mast cells.

Tissues rich in histamine-skin,

gastric and intestinal mucosa,

lungs, liver and placenta.

• Nonmast cell histamine occurs in

brain, epidermis, gastric mucosa.

Histamine: Storage and Release

Immunologic Release:

immunological stimulus.

↓

• In mast cells, if sensitized by surface IgE antibodies, degranulate when exposed specific antigen.

• Degranulation is involved in the immediate (type I) allergic reaction.

Histamine: Storage and Release

MoA of Histamine Receptors

Histamine

H1 Receptors H2 Receptors H3 Receptors (presynaptic auto

receptors)

↑ Ca2+

Smooth muscle contractionIncreased capillary permeability Vasodilation Sensory nerve endings pain & itching

↑ cAMP

↑ Gastric acid secretion Blood vessels: vasodilation Increased capillary permeability

↓ histamine release↓secretion

Vasodilation

↓ cAMP

Histamine

PATHOPHYSIOLOGICAL ROLES

1. Gastric secretion

Histamine - ↑ secretion of HCl in the stomach

• It is released – feeding,

vagal stimulation,

cholinergic drugs and

gastrin

Histamine

Histamine

PATHOPHYSIOLOGICAL ROLES

2. Allergic phenomenon

3. As transmitter -initiates the sensation of itch

and pain at sensory nerve endings.

Histamine

PATHOPHYSIOLOGICAL ROLES

4. Inflammation -Histamine is a mediator of

vasodilatation

5. Tissue growth and repair.

Histamine

PHARMACOLOGICAL EFFECTS

Exocrine Glands

• Gastric glands

• Salivary glands

• Sweat glands

• Pancreas ↑ Secretion

• Bronchial glands

• Lacrimal glands

Histamine

PHARMACOLOGICAL EFFECTS

Arterioles, Capillaries & Venules

• Vasodilation

• Increased permeability, (edema)

• Systemic hypotension

Histamine

PHARMACOLOGICAL EFFECTS

Vascular Smooth Muscles

• Bronchial tree

• Gastrointestinal tract ↑ Contraction

• Uterus

Anti-HistaminesGeneral Mechanism of Action of Antihistamines

• Blocks action of histamine at receptor

• Competes with histamine for binding

• Displaces histamine from receptor

• Most beneficial when given early

Anti-Histamines

H1 ANTAGONISTS

PHARMACOLOGICAL ACTIONS

1. Antagonism of histamine

block - bronchoconstriction,

-contraction of intestinal & smooth muscle

and triple response—wheal,

flare and

Redness.

Anti-HistamineH1 ANTAGONISTS

PHARMACOLOGICAL ACTIONS

2. Antiallergic action -immediate hypersensitivity

(type I reactions)are suppressed

3. CNS- variable degree of CNS depression.

4. Anticholinergic action- antagonize muscarinic

actions of Ach

5. Local anaesthetic - pheniramine,

promethazine,

diphenhydramine

Classification of Anti -HistamineDrug DOSE ROUTE

I. HIGHLY SEDATIVE

Diphenhydramine 25–50 mg Capsule , Syrup

Promethazine 25–50 mg oral,,

i.m. (1 mg/kg)

tab., elixer

II. MODERATELY SEDATIVE

Pheniramine 20–50 mg oral, Tab, syr, Injection

Cyproheptadine 4 mg oral Tab , syrup

Cinnarizine 25–50 mg Tab,

III. MILD SEDATIVE

Chlorpheniramine 2-4 mg Oral,I.M

Clemastine 1-2 mg Oral, syrup

Classification of Anti -HistamineDRUG DOSAGE PREPARATIONS

Fexofenadine 120–180 mg oral TAB

Loratadine 10 mg oral Tab,Suspension

Cetirizine 10 mg oral Tab,syrup

Levocetirizine 5-10 mg oral Tab,syrup

Azelastine 4 mg oral Nasal spray

Mizolastine 10 mg oral Tab

Ebastine 10 mg oral Tab

Anti-Histamines

SECOND GENERATION ANTIHISTAMINICS

• Absence of CNS depressant property.

• Higher H1 selectivitiy: no anticholinergic side

effects.

• Also inhibit late phase allergic reaction by

acting on leukotrienes or by antiplatelet

activating factor effect

Anti-Histamines2nd GENERATION ANTIHISTAMINICS

Fexofenadine:

active metabolite of Terfenadine.

Terfenadine withdrawn

↓

PVT(Torsades de pointes)

+

CYP3A4 inhibitors(Erythromycin,

Clarithromycin,

Ketoconazole,

Itraconazole, etc.).

Uses: Allergic rhinitis ; Urticaria and other skin allergies

• Free of arrhythmogenic potential,

Anti-Histamines2nd GENERATION ANTIHISTAMINICS

Loratadine:

• Another long-acting selective peripheral H1

antagonist

• lacks CNS depressant effects and is fast acting.

• Uses- urticaria and atopic dermatitis

Desloratadine - active metabolite of loratadine

effective at half the dose.

Anti-Histamines• 2nd GENERATION ANTIHISTAMINICS

Cetirizine - metabolite of Hydroxyzine

• Affinity for peripheral H1 receptors;

• Penetrates brain poorly, but mild sedation

• Inhibits release of histamine and of cytotoxicmediators from platelets as well as eosinophilchemotaxis during the secondary phase of the allergic response

Levocetirizine - active R(–) enantiomer

of cetirizine.

Anti-Histamines

USES

1. Allergic disorders.

2. Other conditions- insect bite and ivy poisoning.

-Abnormal dermographism is suppressed.

-blood/saline infusion induced rigor

3. Pruritides -antipruritic action

4. Common cold

Anti-HistaminesUSES

5. VERTIGO

1. Labyrinthine suppressants

(a) Antihistaminics (with anticholinergic action)—Cinnarizine,

Dimenhydrinate, Diphenhydramine, Promethazine.

(b) Anticholinergics— Atropine, Hyoscine.

(c) Antiemetic phenothiazines— Prochlorperazine.

2. Vasodilators —Betahistine , Nicotinic acid.

3. Diuretics

—Acetazolamide, Thiazides, Furosemide.

4. Anxiolytics, antidepressants—Diazepam, Amitriptyline.

5. Corticosteroids.

Parenteral Prochlorperazine is the most effective drug for

controlling violent vertigo and vomiting

Anti-Histamines

USES

7. Preanaesthetic medication- Promethazine

8. Cough - Chlorpheniramine,

Diphenhydramine and Promethazine

9. Parkinsonism- Promethazine

10. Acute muscle dystonia- Promethazine,

Diphenhydramine

or

Hydroxyzine.

Anti-HistaminesAdverse effect

• Sedation,

• Diminished alertness and concentration,

• Light headedness,

• Motor incoordination,

• Fatigue and tendency to fall asleep

• Dryness of mouth,

• Alteration of bowel movement,

• Urinary hesitancy and blurring of vision

Anti-Histamines

H2 receptor antagonists

1. Cimetidine (tagamet) associated with most

side effects

2. Rantidine (zantac)

3. Famotidine (pepcid)

4. Nizatidine (axid)

Summary

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