This document discusses histamine, antihistamines, and their mechanisms of action. It provides details on histamine biosynthesis, storage, release, receptors, and pharmacological actions. It describes the classification and effects of first and second generation antihistamines. The therapeutic uses of H1 and H2 receptor antagonists for allergic disorders, pruritus, cough, and more are outlined. Pharmacokinetics including absorption, distribution, metabolism, and excretion of antihistamines are covered. Finally, the document reviews the adverse effects of antihistamines such as sedation, dry mouth, and fatigue.

1. INTEGRAL UNIVERSITY LUCKNOW
Presented to:
Dr. Tarique Mahmood Ansari
(Associate Prof. & Head),
Mrs. Arshiya Shamim
(Assistant Prof.)
Pharmacology of
Autocoids-HISTAMINES,
and Mechanism of action,
Pharmacokinetics, Clinical
Uses, and Adverse effects
of ANTIHISTAMINICS drugs.
Presented by:
Mudassir Sada,
Asiya Mustapha
Pharm.D 2nd year.

2. Autacoids
These are diverse substances produced by wide variety of cells,
having intense biological activity, but act locally at the site of
synthesis and release
Classification of Autocoids
Amine autacoids
- Histamine, 5-HT (Serotonin)
Peptide autacoids
- Plasma kinins (Bradykinin, Kallidin),Angiotensinogen
Lipidautacoids
- Prostaglandins, Leucotrienes, PAF

3. HISTAMINE, BIOSYNTHESIS AND
METABOLISM
 Histamine: means Tissue Amine
It is a compound which is released
by cells in response to injury and in
allergic and inflammatory reactions.
It is widely distributed in animal
tissue and in certain plants.
It is formed by decarboxylation of
HISTIDINE
It is inactivated by
1.METHYLATION and 2.OXIDATION

4. Storage And Release
• Storage
- Mast cellsand Basophils
- Non– mastcell histamine
* Stomach(ELC)
* Brain
• Release
- Immunological
- Nonimmunologicale.g.
Chemical& mechanical

5. HISTAMINE RECEPTORS AND LOCATION

6. MECHANISM OF ACTION

7. M.O.A

8. Pharmacological actions of Histamine
• CNS
- No BBBpenetration
- OnIntracerebrovascular injection:
* Vomiting,ADHrelease
• Heart
- Insitu heart – No prominent action
- Isolated heart - ↑ in rate & FOC

9. Pharmacological actions of HistamineContd.
• BloodVessels
- Dilation of smaller Bl.Vessels
- S.C.injection- heat, flushing, ↑ in HR& CO
- Rapid IVinjection- ↓ BP
- Intradermal Injection: (TripleResponse)
* Red Spot – Capillary dilatation
* Wheal – Exudation of fluid from capillaries andvenules
* Flare–Arteriolar dilation

10. • ViceralSmooth Muscles
- Bronchoconstriction
- ++ dose Abd.Cramps&colic
• Glands
- ↑ in GITsecretion
• Sensorynerve endings
- IV,IC – itching, Pain
• Autonomic ganglia& Adrenal medulla
- Releaseof Adrenaline →secondary↑ in BP
Pharmacological actions (contd.)

11. ROLES OF HISTAMINE
PATHOPHYSIOLOGICAL
GastricSecretion
Allergicphenomena
AsTransmitter
Inflammation
Tissuegrowthandrepair
• THERAPEUTIC
No therapeutic Role
DiagnosticUses:
* Secreting (Acid) capacity
of stomach
* Pheocromocytoma
* Bronchial hyper-
reactivity in Asthmatics
$ COPD

12. SYNTHETIC ANALOGUES
H1: Betahistine (control vertigo_minierse disease)
H2: Betazole, Impromidine (gastric stimulant)
H3: α-Methyl histamine (lowers Bp, decrease H.R)
H4: Imitit, Clozapine (chemotaxis of mast cells,
shape $ size of eusinophils)

13. Antagonistsof Histamine
 Physiologicalantagonists :
Adrenaline – effects are opposite to effectsof
histamine
 Histamine releaseInhibitors →
Mast cell stabilizers : Cromoglycate
 Histamine receptor blockers:
H1blockers and H2 blockers

14. Antihistaminics (H1- Antagonists)
• Classification:
1st Gen. Lipophilic,poorselectivity,sedation
• HighlySedative:
- Hydroxyzine
- Promethazine
• Moderately sedative:
- Cyproheptadine
- Buclizine
• Mild Sedative:
- Cyclizine
- Chlorophenaramine
• NonSedative:2nd Gen. Non-lipophilic, H1selectivity,non-
sedative
- Cetrizine,levocetrizine
- Loratidine
ANTIEMETIC
-cyclizine
-meclizine

15. • CNS:Variable degree of CNSdepression
• Antagonismof Histamine
Effectivelyblocks:
-Bronchoconstriction,Contractionofsm.,Tripleresponse
-Anti-allergic action:
type-1reactionsaresuppressed
-Anticholinergic Action:
antagonise muscarinic actions of Ach.
-Local Anesthetics:
membrane stabilizing activity
Pharmacological actions

16. H2-RECEPTORS ANTAGONIST
•Histamine H2 receptor antagonists act competitively with
histamine at receptors on gastric parietal cells.
They reduce basal acid secretion
and pepsin production and
prevent the increase secretion
that occurs in response to
several secretory stimuli.
-Cimetidine, Famotidine
-Nizatidine
-Ranitidine

17. Therapeutic Usesof H1-Antagonists
AllergicDisorders
Pruritus
CommonCold
Motion sickness
Vertigo
Preanesthetic medication
Cough
•
•
•
•
•
•
•
• Assedative, hypnotic

18. PK& SE
• PK
- A– Well absorbed
- D- Wide distribution
- M- Metabolized in liver
- E - Excreted through urine
D.O.A :4-6 hrs 2ndGen:12-24 hrs
• AE
- Sedation, Diminished alertnes & concentration,
dry mouth & fatigue,
- Dryness of mouth, Alteration ofbowl movements,
Urinary hesitancy.

19. ThankYou
Histamine