antihistaminic drugs

1. Autacoids
Dr Mukesh Gupta
Asso. prof
TIDSHRC

2. AUTACOIDS

3. Substances present or formed in the body and act near their sites of synthesis 
Local Hormones
autos = self
Autacoids
akos = ‘medicinal agent’ or ‘remedy’

4. CLASSIFICATION
Amine autacoids
Histamine
5-hydroxytryptamine
Lipid derived autacoids
Prostaglandins
Platelet activating factor
Peptide autacoids
Plasma kinins
Angiotensin

5. Histamine

6. Histamine & ACh  first detected as uterine stimulants in extracts of ergot
Later proved to be contaminants
1927Isolated histamine from liver & lungs. Later from other tissues
HISTAMINE Greek word histos = tissue
Histamine receptors  H1, H2 & H3

7. From HISTIDINE by action of L-histidine decarboxylase
Stored:
Mast cells  Skin, mucosa of bronchial tree & intestine
Non mast cell  Epidermis, gastric mucosa, neurons &
cell in rapidly growing tissue.
Synthesis & storage

8. Increased proliferation of mast cells and basophils
Urticaria pigmentosa (cutaneous mastocytosis) Systemic
mastocytosis Myelogenous leukemia
Gastric carcinoid tumors
Drugs that cause histamine release
Tubocurarine
Succinylcholine Morphine
Vancomycin
Polymixin B

9. 1. Role in allergic response:
Principal target cells of immediate hypersensitivity reactions
are mast cells and basophils.
IgE mediated release of histamine from storage granules 
features of hypersensitivity reaction/allergic response.
Functions of endogenous histamine

10. Immunologic release of histamine

11. 2. Gastric acid secretion:
Histamine is a powerful gastric secretagogue  acid secretion by parietal
cells (H2 receptor)
3. Central nervous system
Functions as neurotransmitter in CNS
Histamine  H1 receptor  inhibits appetite

12. 1. Cardiovascular system:
A. Vasodilation (small blood vessels)
- Characteristic action of histamine on vessels
- H1 (endothelial cells) rapid onset and short lived.
- H2 (vascular smooth muscles)  slowly and sustained
B. Increased capillary permeability
- action on postcapillary venules
- mediated through H1
Pharmacological effects: H1 and H2 receptors
C Heart
- H2 receptor ↑ force of contraction
↑ heart rate
- H1 receptor  slowed AV conduction

13. 2. Extravascular smooth muscle
- Bronchial smooth muscle
- Uterus
- Intestine
3. Exocrine gland
- Physiological regulation of gastric acid secretion
4. Nerve endings: Pain and itch
5. Triple response
- Red spot
- Flush or flare
- Wheal

14. Diagnostic
1. Asthmatics  assess non-specific bronchial hyperreactivity
2. Allergic skin testing  positive control
Therapeutic
BETAHISTINE
-Histamine agonist drug
- orally active, H1 selective, histamine analog
- control vertigo  MENIERE’S disease
USES

15. H1-Receptor antagonists

16. Drugs/ chemicals that liberate histamine
• Morphine, d-tubocurarine, pentamidine,
succinyl choline, dextran, PVP, bile salts, radio
contrast media
• Heat, cold exposure to sunlight & X-rays
• Proteolytic enzymes
• venoms

17. Drugs that inhibit histamine release
• Adrenaline
• Ephedrine
• Isoproterenol
• Mast cell stabilizers

18. Histamine-related Drugs
• Mast Cell Stabilizers (Cromolyn Na, Nedocromil )
• H1 Receptor Antagonists (1st and 2nd generation)
• H2 Receptor Antagonists (Ranitidine, Cimetidine)
• H3 Receptor Agonist and Antagonists (potential new
drugs being developed)

19. Histamine H1- Antagonists
• First Generation:
• Second Generation:

20. First Generation Agents
Examples
Ethanolamines: DIPHENHYDRAMINE (Benadryl
CLEMASTINE (Tavist)
Ethylenediamine: TRIPELENNAMINE
Alkylamine: CHLORPHENIRAMINE
Phenothiazine: PROMETHAZINE (Phenergan)
Piperazines: HYDROXYZINE (Vistaril)
CYCLIZINE (Antivert)

21. First Generation Agents
Pharmacokinetics:
• Well absorbed from the GI-tract
• Widely distributed
–Cross BBB (except 2nd generation agents)
–Placental transfer (meclizine is teratogenic in
laboratory animals)
• Hepatic transformation, renal elimination of the
metabolites (induce hepatic microsomal enzymes)

22. Uses:
• Adjunctive in anaphylaxis and other cases
where histamine release can occur (H2
antagonist, and epinephrine also used)
• Antiallergy (allergic rhinitis, allergic
dermatoses, contact dermatitis)
• Sedative/sleep aid
• To prevent motion sickness (meclizine,
cyclizine)
First Generation Agents

23. Drug interactions:
• Additive with classical antimuscarinics
• Potentiate CNS depressants
• opioids
• sedatives
• general and narcotic analgesics
• alcohol
First Generation Agents

24. Second Generation Agents
Pharmacokinetics:
Cetirizine (C), loratadine (L), fexofenadine (F)
• well absorbed and are excreted mainly
unmetabolized form.
• C and L are primarily excreted in the urine
• F is primarily excreted in the feces
• They induce Cyt P450 liver enzymes

25. Uses
• Antiallergy
Examples
• Cetrizine (Zyrtec)
• Fexofenadine (Allegra)
• Loratadine (Claritin)
• Desloratadine
• Loratadine
• Azelastin (Intranasal Spray)
• Levocetrizine
Second Generation Agents

26. Adverse effects:
• In general, these agents have a much lower incidence
of adverse effects than the first generation agents.
• terfenadine and astemizole were removed from the
market due to effects on cardiac K+ channels - prolong
QT interval (potentially fatal arrhythmia “torsades de
pointes”)
• fexofenadine is active metabolite of terfenadine
Second Generation Agents

27. 1st gen. antihistamines
• Short to intermediate
acting
• Sedation
• Anti muscarinic actions
2nd gen. antihistamines
• Long acting
• Least / No sedation
• No autonomic effects