autocoids - copy

8/6/2019 Autocoids - Copy

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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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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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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

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