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.

Autacoids

 Eg. Histamin, Serotonin, Prostaglandin,

Leukotriens, VIP etc.

Autacoids

 Q. Why they are called so?

 Q. How does autocoids differ from hormone?

Classification of Autacoids
Autacoids can be divided into three catagories on the basis of their structure1. Decarboxylated amino acidsa. Histamine b. Serotonin 2. Polypeptidesa. Angiotensins b. Bradykinin c. VIP (Vasoactive Intestinal Polypeptide) d. Substance P e. Vasopressin f. Slow reacting substance of Anaphylaxis (SRS-A) g. Neurotensin

Classification of Autacoids

3. Eicosanoidsa. Prostaglandins b. Leukotrienes c. Thromboxanes d. Interleukins

Properties of Autocoids1. Produced within the body. 2. Protect the body from different adverse situations. 3. They act as neurotransmitter. 4. They act as local hormone. 5. They are vasodilator. 6. They are bronchoconstrictor. 7. Increase GIT motility.

Important role of Autocoids/ Histamine

1. Influence the process of inflammation. 2. Allergic reactions & anaphylactic shock. 3. Regulation of microcirculation. 4.Responsible for gastric acid & pepsin secretion & thus helps in digestion. 5. Tissue repair & growth. 6. Neurotransmission. Role in disease

Role in Health

Histamine
Histamine is a biologically active amine that is found many tissues. Synthesis of HistamineHistamine is formed by decarboxylation of the aminoacid L-histidine by the enzyme histidine decarboxylase. Histidine decarboxylase L-Histidine Histamine

Histamine

Storage & releaseStorage- 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.

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 granules contain histamine with heparine or chondroitin sulphate & an acidic protein.

Histamine

Release of HistamineThe bound form of histamine can be released through several mechanismA. Immunologic release. B. Chemical & mechanical release. A. Immunologic release1. Mast cells & basophils if sensitized by Immunoglobulin-E (Ig E) antibodies attached to their surface membranes, degranulate when exposed to the appropriate antigen. This type of release requires energy & calcium. Degranulation leads to the release of histamine, ATP & other mediators. 2. By a negative feed back control mechanism, histamine can modulate its own release from sensitized mast cells in skin & basophils.

Histamine
B. Chemical & mechanical releaseCertain drugs such as Morphine & Tubocurarine can displace histamine from the heparin-protein complex within cells. This type of release does not require energy & is not associated with mast cell injury or degranulation.

Histamine
Drugs causing histamine release1. Chemotherapeutic agentseg. - Chlortetracycline - Polymixine B 2. Spasmolytic agent- Atropine 3. Vasodilators- Hydralazine - Tolazoline 4. Centrally acting drugs- Morphine - Pethidine

Histamine
5. Sympathomimetic agents- Amphatamine 6. Neuromuscular blocking agents- D-tubocurarine - Gallamine 7. Others-Penicillin -Dextran -Radiocontrast media - Codeine Other agents responsible for histamine release1. 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.

 Receptors

Receptor Subtype H1 H2 H3 H4

Distribution Smooth muscle, endothelium, brain Gastric mucosa, cardiac muscle, mast cells, brain Presynaptic: brain, myenteric plexus, other neurons Eosinophils, neutrophils, CD4 T cells

 Tissue and Organ System Effects of Histamine  Nervous System  Cardiovascular System  Bronchiolar Smooth Muscle  Gastrointestinal Tract Smooth Muscle  Secretory Tissue  Metabolic Effects

 The "Triple Response  Intradermal injection of histamine causes a

characteristic 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.

 Clinical Uses  In pulmonary function laboratories, histamine aerosol

has been used as a provocative test of bronchial hyperreactivity. Histamine has no other current clinical applications.

 Histamine Antagonists  Physiologic antagonists, especially epinephrine, have

smooth muscle actions opposite to those of histamine, but they act at different receptors. This is important clinically because injection of epinephrine can be lifesaving in systemic anaphylaxis and in other conditions in which massive release of histamine and other mediators occurs.

 Release inhibitors reduce the degranulation of mast

cells that results from immunologic triggering by antigen-IgE interaction. Cromolyn and nedocromil appear 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 also appear capable of reducing histamine release.

 Histamine receptor antagonists  H1-Receptor Antagonists

Drugs FIRST-GENERATION ANTIHISTAMINES Ethanolamines Dimenhydrinate (salt of diphenhydramine) Diphenhydramine

Usual Adult Dose

Anticholinergic Activity

Comments

+++

Marked sedation; anti-motion sickness activity Marked sedation; anti-motion sickness activity

25 50 mg

+++

Piperazine derivatives Cyclizine 25 50 mg Slight sedation; antimotion sickness activity Slight sedation; antimotion sickness activity

Meclizine

25 50 mg

Drugs FIRST-GENERATION ANTIHISTAMINES Alkylamines Chlorpheniramine

Usual Adult Dose

Anticholinergic Activity

Comments

4 8 mg

Slight sedation; common component of OTC "cold" medication

Phenothiazine derivative Promethazine Miscellaneous Cyproheptadine (Periactin, etc) 4 mg + Moderate sedation; also has antiserotonin activity 10 25 mg +++ Marked sedation; antiemetic; block

Drugs SECONDGENERATION ANTIHISTAMINES Piperidine Fexofenadine (Allegra) Miscellaneous Loratadine (Claritin) Cetirizine (Zyrtec) Desloratidine Levocetrizine

Usual Adult Dose

Anticholinergic Activity

Comments

60 mg 10 mg 5 10 mg

Longer action

 Pharmacological Action:  Antagonism of histamine  Antiallergic action  Sedation  Antinausea and Antiemetic Actions  Antiparkinsonism Effects  Anticholinoceptor Actions  Adrenoceptor-Blocking Actions  Serotonin-Blocking Action  Local Anesthesia  Other Actions

 Uses:  Allergic disorder  insect bites  Prophylactic value in blood/ saline infusion induced        

rigor Pruritus Common cold Motion sickness Vertigo Preanaesthetic medication Cough Perkinsonism As sedative, hyupnotics & anxiolytics