2. Submitted to:
Dr. Sufia Islam,
Associate Professor.
East West University
Course Code: PHRM 301
Course Title: Pharmacology I
Submitted By:
Name ID NO:
Shahanaj Ferdous , 2014-3-70-003
Fahmida Maliha, 2014-3-70-011
Jannatun Nur Mishu, 2014-3-70-030
Sabayet Jahan, 2014-3-70-037
Nusrat Jahan, 2014-3-70-039
Nadia Yeasmine, 2014-3-70-050
Md.Asaduzzaman, 2014-3-70-045

3. AUTACOIDS
 The term autacoid is used for a group of hormone like
substances, which
-originate from tissues
- produce effects at the site of release.
 Biological actions of autacoids are :
-modulation of the activity of
- smooth muscles,
- glands,
- nerves,
- platelets and
-other tissue

4. Classification of Autacoids:
# Biogenic Amine autacoids: Histamine, serotonin
# Phospholipids autacoids: Prostaglandins
# Polypeptides autacoids: Angiotensin
# Others: Gastrin, Cytokines etc.

5. HISTAMINE RECEPTORS:
 H1 Histamine Receptor:
-Distributed to the peripheral nervous system, smooth muscle
and blood vessels and eosinophiles
 H2 Histamine Receptor:
 - Distributed in Parietal cells, stomach, heart, immune cells and
vascular smooth muscles.
 H3 Histamine Receptor:
- Distributed in nerve cells
 H4 Histamine Receptor:
-Distributed highly in bone marrow and white blood cells.
- It’s also expressed in colon, liver, lung, small intestine,
spleen, testes, thymus, tonsils, and trachea.

6. HISTAMINE RECEPTORS
MECHANISMS

7. HISTAMINE SYNTHESIS:
 Histamine is formed by decarboxylation of the amino acid.
 Histidine decarboxylase generates histidine by catalyzing the
removal of the carboxyl group from the amino acid L-histidine

8. HISTAMINE RELEASE
MECHANISM:
 Histamine is released from storage granules as a result of the
interaction of antigen with immunoglobulin E (IgE) antibodies on
the mast cell surface.
Fig: Histamine release mechanism

9. ANTIHISTAMINES AND TYPES:
• An antihistamine is a type of pharmaceutical drug that
- opposes the activity of histamine receptor in the
body.
• Antihistamine includes four types of drugs:
1.H1-receptor antagonists
2.H2-receptor antagonists
3.H3 -receptor antagonists &
4.H4 - receptor antagonists

10. H1 RECEPTOR ANTAGONISTS
Location:
Specifically in
- smooth muscles
- vascular endothelial cells
- heart
-CNS
Action:
- Mediates an increase in vascular permeability at sites of
inflammation induced by histamine.
-It is used in allergies, nausea, sleep disorders.
Example:
Dimetindene,bastine,Doxylamine,Hydroxyzine,Meclozine etc.

11. Mechanism of Action of H1 Antagonists:
 The H1 receptor couples to G protein stimulating phospholipase C.
 phospholipase C cleaves off IP3.
 Only diacylglycerol (DAG) situates on the membrane and IP3 cross
the ER and then bind with ligand gated ca++ ion channel.
 When IP3 binds, channel is opened and calcium can go into the
membrane to give different cellular activity.
Fig: Mechanism of action of H1 antagonists

12. Therapeutic Uses of H1 Antagonists:
 Allergic rhinitis & common cold
 Mild blood transfusion reactions
 Motion sickness: dimenhydrinate,
promethazine
 Morning sickness: promethazine
 Chronic urticaria
 Appetite stimulant: cyprohepatidine
 Drug induced parkinsonism

13. Toxic Reaction and Side Effects of H1
Antagonists:
 Anticholinergic properties
-dryness of mouth
- alteration of bowel movement,
-urinary hesitancy and
-blurring of vision.
 Epigastric distress and headache.
 Acute overdose causes
-excitation,
-tremors,
-hallucinations,
- convulsions,
- hypotension etc.

14. HISTAMINE H2 RECEPTOR
ANTAGONIST
Location:
- mainly in gastric parietal cells, a low level can be found in
vascular smooth muscle, neutrophils, CNS, heart, uterus.
Action:
- increases the release of gastric acid which is the treatment of
stomach ulcers.
Example: Cimetidine, Ranitidine, Famotidine, Nizatidine etc.

15. HISTAMINE H3 RECEPTOR
ANTAGONIST
Location:
-primarily found in the brain and are inhibitory autoreceptors
Action:
- H3 receptor antagonist is a classification of drugs used to block
the action of histamine at the H3 receptor.
Example: Ciproxifan, pitolisant, clobenpropit, conessine etc.

16. HISTAMINE H4 RECEPTOR
ANTAGONIST
 Location:
-highly in bone marrow and white blood cells
-lung, small intestine , spleen etc
 Action:
- allergic, inflammatory and neuropathic pain
 Examples:
Thioperamide

17. FIRST GENERATION ANTIHISTAMINE
Action;
 Effective in the relief of
- allergic symptoms, but
- moderately to highly potent muscarinic
acetylcholine receptor antagonists as well.
Common Adverse Effects
- dizziness, -anxiety
- tinnitus, -urinary retention
- blurred vision, - palpitations
- euphoria - tremor, dry mouth

18. FIRST GENERATION ANTIHISTAMINE
Common Adverse Effect
-hypotension
- nausea and vomiting,
-constipation, diarrhea,
- headache, hallucination etc
Some commonly used antihistamines are:
Chlorpheniramine, Cyclizine, Doxepin, Benadryl, Dramamine,
Hydroxyzine, Karbinal ER, Sominex etc.

19. SECOND GENERATION
ANTIHISTAMNIE:
Action: more selective for peripheral H1 receptors as opposed to
the central nervous system H1 receptors and cholinergic
receptors.
 - reduces the occurrence of adverse drug reactions, such as
sedation
 very polar, that’s why do not cross the blood brain barrier
Some commonly used second generation antihistamines are:
Cetirizine, Allerga, Claritin, Clarinex, fexofenadine,
Loratadine, Levocetirizine etc.

20. THIRD GENERATION
ANTIHISTAMINE:
Action:
Third generation antihistamines formally labelled because the
active enantiomer (Levocetirizine) or metabolite
(Desloratadine) derivatives of second generation drugs
intended to have increased efficacy with fewer adverse drug
reactions.
Examples:
1) Norastemizole ( Metabolite of astemizole)
2) Descarboethoxy loratadine ( Metabolite of loratadine)
3) Levocetirizine (Active enantiomer of cetirizine)

21. SECOND GENERATION
ANTIHISTAMINES OVER FIRST
GENERATION ANTIHISTAMINES:
Second Generation First Generation
 larger molecules and
less lipophilic, and thus
less likely to cross the
blood-brain barrier
 mainly block histaminic
receptors
 It produces less side
effect as they are
selective
 highly lipid soluble,
crossing the blood-brain
barrier easily
 block both histaminic
and muscarinic receptors
 More side effect as it’s
non selective

22. HISTAMINE VS ANTIHISTAMINE
EFFECTS
Cardiovascular (Smooth muscle effect)
 Histamine Effects:
-dilation and increased permeability
(allowing substance to leak into tissues)
 Antihistamine Effects:
- prevent dilation of blood vessels
- prevent increased permeability

23. HISTAMINE VS ANTIHISTAMINE
EFFECTS
Smooth Muscle Effects (Exocrine glands)
 Histamine Effects:
-stimulate salivary, gastric, lacrimal and bronchial secretion
 Antihistamine Effects:
-prevent salivary, gastric, lacrimal and bronchial secretion

24. HISTAMINE VS ANTIHISTAMINE
EFFECTS
 Immune Effects
 Histamine Effects:
-mast cell release histamine and other substances,
resulting in allergic reaction
 Antihistamine Effects:
-binds to histamine receptors, thus preventing
histamine from causing a response

25. THANK YOU