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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
THANK YOU