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Autacoids
Autacoids are biologically active substances
of different chemical nature formed, stored
& released within the normal tissues & act
very close to the site where they are
generated & protect the body from some
adverse situations.
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Autacoids
Eg. Histamin, Serotonin, Prostaglandin,
Leukotriens, VIP etc.
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Autacoids
Q. Why they are called so?
Q. How does autocoids differ fromhormone?
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Classification of Autacoids
Autacoids can be divided into three catagories on the basis of
their structure-1. Decarboxylated amino acids-
a. Histamine
b. Serotonin
2. Polypeptides-a. Angiotensins
b. Bradykinin
c. VIP (Vasoactive Intestinal Polypeptide)
d. Substance Pe. Vasopressin
f. Slow reacting substance of Anaphylaxis (SRS-A)
g. Neurotensin
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Classification of Autacoids
3. Eicosanoids-
a. Prostaglandins
b. Leukotrienes
c. Thromboxanesd. Interleukins
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Properties of Autocoids-1. Produced within the body.
2. Protect the body from different adversesituations.
3. They act as neurotransmitter.
4. They act as local hormone.
5. They are vasodilator.
6. They are bronchoconstrictor.
7. Increase GIT motility.
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Important role of Autocoids/ Histamine
1. Influence the process of inflammation. Role in disease
2. Allergic reactions & anaphylactic shock.
3. Regulation of microcirculation.
4.Responsible for gastric acid & pepsinsecretion & thus helps in digestion. Role in Health
5. Tissue repair & growth.
6. Neurotransmission.
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Histamine
Histamine is a biologically active amine that is foundmany tissues.
Synthesis of Histamine-
Histamine is formed by decarboxylation of the amino-acid L-histidine by the enzyme histidine decarboxylase.
Histidine decarboxylase
L-Histidine Histamine
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Histamine
Storage & release-
Storage- Histamine stores as granules in the
A. Mast cells mainly.
Mast cells are specially rich at the sites of potential tissue
injury. eg.- Nose
- Mouth
- Feet
-Internal body surface-Blood vessels at pressure point & bifurcation.
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Histamine
B. Non-mast cell histamine-
-Basophils
-Platelets
-Gastric parietal cells
-Neurones of the CNS
-Peripheral nerve fibres
-Blood
In human mast cells & basophils, storage granulescontain histamine with heparine or chondroitin
sulphate & an acidic protein.
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Histamine
Release of Histamine-
The bound form of histamine can be released through severalmechanism-
A. Immunologic release.
B. Chemical & mechanical release.
A. Immunologic release-1. Mast cells & basophils if sensitized by Immunoglobulin-E (Ig
E) antibodies attached to their surface membranes, degranulatewhen exposed to the appropriate antigen. This type of releaserequires energy & calcium.
Degranulation leads to the release of histamine, ATP & othermediators.
2. By a negative feed back control mechanism, histamine canmodulate its own release from sensitized mast cells in skin &
basophils.
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Histamine
B. Chemical & mechanical release-
Certain drugs such as Morphine & Tubocurarine can displacehistamine from the heparin-protein complex within cells. This typeof release does not require energy & is not associated with mastcell injury or degranulation.
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Histamine
Drugs causing histamine release-
1. Chemotherapeutic agents-
eg. - Chlortetracycline
- Polymixine B
2. Spasmolytic agent-
- Atropine
3. Vasodilators-
- Hydralazine
-Tolazoline
4. Centrally acting drugs-
- Morphine
- Pethidine
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Histamine
5. Sympathomimetic agents-
- Amphatamine6. Neuromuscular blocking agents-
-D-tubocurarine
- Gallamine
7. Others-
-Penicillin
-Dextran
-Radiocontrast media
- Codeine
Other agents responsible for histamine release-
1. Physical factors-Scrach, burn, soap, radiation
2. Chemical agents-Dextran, bile salts, polysaccharide.
3. Antigen-antibody reaction ( Ag-Ab reaction)
4. Food like-Crabs, lobster etc.
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Tissue and Organ System Effects of Histamine
Nervous System
Cardiovascular System
Bronchiolar Smooth Muscle
Gastrointestinal Tract Smooth Muscle
Secretory Tissue Metabolic Effects
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The "Triple Response
Intradermal injection of histamine causes acharacteristic red spot, edema, and flare response that
was first described many years ago. The effect
involves three separate cell types: smooth muscle in
the microcirculation, capillary or venular endothelium,and sensory nerve endings. At the site of injection, a
reddening appears owing to dilation of small vessels,
followed soon by an edematous wheal at the injection
site and a red irregular flare surrounding the wheal.
The flare is said to be caused by an axon reflex. A
sensation of itching may accompany these effects.
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Clinical Uses
In pulmonary function laboratories, histamine aerosol
has been used as a provocative test ofbronchialhyperreactivity. Histamine has no other currentclinical applications.
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Histamine Antagonists
Physiologic antagonists, especially epinephrine, have
smooth muscle actions opposite to those ofhistamine, but they act at different receptors. This isimportant clinically because injection of epinephrine
can be lifesaving in systemic anaphylaxis and in other
conditions in which massive release of histamineandother mediatorsoccurs.
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Release inhibitors reduce the degranulation of mast
cells that results from immunologic triggering by
antigen-IgE interaction. Cromolyn and nedocromilappear to have this effect (see Chapter 20) and are
used in the treatment of asthma, although the
molecular mechanism underlying their action is not
fully understood. Beta2-adrenoceptor agonists alsoappear capable of reducing histamine release.
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Histamine receptor antagonists
H1-Receptor Antagonists
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Drugs Usual Adult Dose AnticholinergicActivity
Comments
FIRST-GENERATION
ANTIHISTAMINES
Ethanolamines
Dimenhydrinate (saltof diphenhydramine)
+++ Marked sedation;anti-motion sickness
activity
Diphenhydramine 2550mg +++ Marked sedation;
anti-motion sicknessactivity
Piperazinederivatives
Cyclizine 2550mg Slight sedation; anti-
motion sicknessactivity
Meclizine 2550mg Slight sedation; anti-motion sickness
activity
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Drugs Usual Adult Dose AnticholinergicActivity
Comments
FIRST-GENERATION
ANTIHISTAMINES
Alkylamines
Chlorpheniramine 48mg + Slight sedation;common component
of OTC "cold"medication
P
henothiazinederivative
Promethazine 1025 mg +++ Marked sedation;antiemetic; block
Miscellaneous
Cyproheptadine(Periactin, etc)
4 mg + Moderate sedation;also has antiserotonin
activity
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Drugs Usual Adult Dose AnticholinergicActivity
Comments
SECOND-
GENERATION
ANTIHISTAMINESPiperidine
Fexofenadine (Allegra) 60 mg -
Miscellaneous
Loratadine (Claritin) 10 mg Longer action
Cetirizine (Zyrtec) 510mg
Desloratidine
Levocetrizine
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Pharmacological Action:
Antagonism of histamine
Antiallergic action Sedation
Antinausea and Antiemetic Actions
Antiparkinsonism Effects Anticholinoceptor Actions
Adrenoceptor-Blocking Actions
Serotonin-B
locking Action Local Anesthesia
Other Actions
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Uses:
Allergic disorder
insect bites
Prophylactic value in blood/ saline infusion induced
rigor
Pruritus
Common cold
Motion sickness
Vertigo
Preanaesthetic medication
Cough
Perkinsonism