This document discusses histamine and antihistamine drugs. It begins by introducing histamine as a biogenic amine involved in inflammatory and hypersensitivity reactions. Histamine is synthesized from the amino acid histidine and stored in mast cells. It is involved in processes like gastric acid secretion and allergic responses. Antihistamines work by blocking the action of histamine at receptors. First generation antihistamines are more sedating while second generation ones have less side effects. Common antihistamines and their uses in conditions like allergies and vertigo are described. The document provides an overview of histamine function and the mechanisms of antihistamine drugs.

1. Dr.Rakshitha
Pharma PG
HIMS,Hassan
Histamine and antihistamine drugs

2. Histamine and antihistamine drugs
Contents:
• Introduction
• Synthesis, storage, distribution of Histamine
• Role of Histamine
• Anti histamine
• Its therapeutic uses
• Adverse effects
• Summary

3. Introduction
Autacoids
• Biological agents
• act locally (e.g.within inflammatory pockets) at
the site of synthesis and release.
• k/a “local hormones”

4. Autacoids
• Amine : Histamine
Serotonin
• Lipid derived: Prostaglandins
Leukotrienes
• Peptide : Plasma kinins,
Angiotensin

5. Histamine
• Histos: Tissue
N N
NH2
H
1
2
3
45
Histamine

6. Histamine
• Biogenic amine present in
-animal and plant tissues
-venoms and stinging secretions
• One of the mediators involved in inflammatory
& hypersensitivity reactions.

7. 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.

9. 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.

10. 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.

11. Histamine: Storage and Release

12. MoA of Histamine Receptors
Histamine
H1 Receptors H2 Receptors H3 Receptors
(presynaptic auto
receptors)
↑ Ca2+
Smooth muscle contraction
Increased capillary
permeability
Vasodilation
Sensory nerve endings pain
& itching
↑ cAMP
↑ Gastric acid secretion
Blood vessels:
vasodilation
Increased capillary
permeability
↓ histamine release
↓secretion
Vasodilation
↓ cAMP

13. Histamine
PATHOPHYSIOLOGICAL ROLES
1. Gastric secretion
Histamine - ↑ secretion of HCl in the stomach
• It is released – feeding,
vagal stimulation,
cholinergic drugs and
gastrin

14. Histamine

15. Histamine
PATHOPHYSIOLOGICAL ROLES
2. Allergic phenomenon
3. As transmitter -initiates the sensation of itch
and pain at sensory nerve endings.

16. Histamine
PATHOPHYSIOLOGICAL ROLES
4. Inflammation -Histamine is a mediator of
vasodilatation
5. Tissue growth and repair.

17. Histamine
PHARMACOLOGICAL EFFECTS
Exocrine Glands
• Gastric glands
• Salivary glands
• Sweat glands
• Pancreas ↑ Secretion
• Bronchial glands
• Lacrimal glands

18. Histamine
PHARMACOLOGICAL EFFECTS
Arterioles, Capillaries & Venules
• Vasodilation
• Increased permeability, (edema)
• Systemic hypotension

19. Histamine
PHARMACOLOGICAL EFFECTS
Vascular Smooth Muscles
• Bronchial tree
• Gastrointestinal tract ↑ Contraction
• Uterus

20. Anti-Histamines
General 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

21. Anti-Histamines
H1 ANTAGONISTS
PHARMACOLOGICAL ACTIONS
1. Antagonism of histamine
block - bronchoconstriction,
-contraction of intestinal & smooth
muscle
and triple response—wheal,
flare and
Redness.

22. Anti-Histamine
H1 ANTAGONISTS
PHARMACOLOGICALACTIONS
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

23. Classification of Anti -Histamine
Drug 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

24. Classification of Anti -Histamine
DRUG 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

25. 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

26. Anti-Histamines
2nd 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,

27. Anti-Histamines
2nd 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.

28. 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 cytotoxic
mediators from platelets as well as eosinophil
chemotaxis during the secondary phase of the
allergic response
Levocetirizine - active R(–) enantiomer
of cetirizine.

29. 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

30. 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

31. Anti-Histamines
USES
7. Preanaesthetic medication- Promethazine
8. Cough - Chlorpheniramine,
Diphenhydramine and Promethazine
9. Parkinsonism- Promethazine
10. Acute muscle dystonia- Promethazine,
Diphenhydramine
or
Hydroxyzine.

32. Anti-Histamines
Adverse 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

33. Anti-Histamines
H2 receptor antagonists
1. Cimetidine (tagamet) associated with most
side effects
2. Rantidine (zantac)
3. Famotidine (pepcid)
4. Nizatidine (axid)

34. Summary

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