Autocoids
- 1. BY -: NITESH KUMAR B.PHARM 4TH YEAR JAIPUR COLLEGE OF PHARMACY. JAIPUR, RAJASTHAN
- 2. AUTOCOIDS A number of substances naturally occurring in the body are called as local hormones. They differ in their chemical structure but posses potent biological actions. These are called as tissue factor or autocoids. Autocoids mean self remedy. These are called as autocoids because of their self regulatory action. Unlike hormones these are produced in tissue and not by the endocrine glands. They play important role in allergic reactions. E.g. Histamine, 5-Hydroxytryptamine (Serotonin), Prostaglandin, Bradykinin, Angiotensin &
- 3. HISTAMINE It is synthesized from the amino acid histidine in the presence of histidine decarboxylase enzyme. It is a potent biogenic amine. It is found in the fixed tissues, in mast cells or in circulating basophiles. In the cells it is present in the inactive form. It is also synthesized by microflora in the gastrointestinal tract, however most of the histamine is destroyed during passage through the liver. Histamine is released from mast cells or basophiles by the substances which damages the store cells i.e. antigens & certain drugs. Histamine is also present in various plants and animal tissues, venom of bees & wasps.
- 4. PHYSIOLOGICAL ROLE OF HISTAMINE Physiological role of histamine is not precisely known but it is involved to play following roles as- 1. Histamine may play a part in gastric acid secretion with the hormone gastrin. 2. It also plays part as transmitter in CNS. 3. It also plays a part in tissue growth & repair. 4. It also plays a part in antigen-antibody reaction. HISTAMINE IN ALLERGIC REACTION Liberation of histamine is probably the cause of a number of toxic effects in man. Any process involving mechanical, thermal or radiant damage will cause its release. Many allergic states due to antigen-antibody reactions also release histamine in the body from mast cells. Most prominent effects of histamine are urticaria, bronchoconstriction & hypotension.
- 5. HISTAMINE RECEPTORS Histamine produces the various effects by acting on some receptors which are called as histamine receptors. These are of two types as follows 1. H1 Receptors 2. H2 Receptors
- 6. PHARMACOLOGICAL ACTIONS The effect produced by histamine release depends upon amount of histamine & site of administration.
- 7. 1. Blood vessels It causes constriction of blood vessels. It produces following effects- Dilation of pulmonary vessels Stretching of nerve endings around cranial vessels. It increases cerebrospinal fluid pressure producing throbbing headache. Dilation of venules & capillaries producing decrease in total peripheral resistance and blood pressure. In large doses Increase capillary permeability, decreasing blood volume and produce flushing (redness of skin) in neck & face region. 2. Blood pressure In moderate doses hypotensive effect is for short duration. But in large doses it produces prolonged hypotension
- 8. 3. Triple response On intradermal injection it shows three responses as follows: a) Flush - Dilation of capillaries at site of injection & area becomes red. It is called as flush. b) Bright flare - Flush formation is followed by formation of bright flare beyond flush. It is an irregular shaped reaction producing urticaria. c) Edema - After 10 min. development of localized edema due to increased permeability of the capillaries to fluids. It is also called as wheel formation . This effect is called as triple response. 4. Heart It increases heart rate and contractility of heart. In high doses it produces ventricular arrhythmia.
- 9. 5. Smooth Muscles It stimulates smooth muscles of various organs directly. Bronchial & uterine smooth muscles are highly sensitive. It shows bronchospasm. Histamine induced bronchospasm can be easily relieved by administration of adrenaline, Isoprenaline, aminophylline etc. but not by atropine & other antihistaminic drugs. 6. Exocrine glands In smaller doses it stimulates gastric acid secretion. In larger doses stimulates secretion of pepsin along with acid. Hence it serves as useful tool for studying stomach’s secretary capacity & to diagnose achlorhydria & pernicious anemia
- 10. ADVERSE EFFECTS Hypotension, Headache, Diarrhea, Flushing and Dyspnoea. CLINICAL USES Histamine has minor use in clinical medicine for the diagnosis of hypo or acholrhydria.
- 11. ANTI-HISTAMINIC DRUGS / ANTI-HISTAMINES These are the competitive blockers of histamine receptors and prevent most of the histamine effects in our body. CLASSIFICATION 1. H1- Antihistamines a) Potent H1- Antihistamines with sedative effect. E.g. Diphenhydramine b) Potent H1- Antihistamines with less sedative effect E.g. Chlorpheniramine c) Less Potent H1- Antihistamines with less sedative effect. E.g. Mepyramine d) Non sedating H1- Antihistamines E.g. Terfenadine, Cetrizine 2. H2- Antihistamines-- E.g. Cimetidine, Ranitidine,
- 12. PHARMACOLOGICAL ACTIONS 1. Anti-histamine effects - These drugs effectively antagonizes the action of injected histamine on smooth muscles. 2. Other effects a) CNS - These normally are sedative in action but in higher doses it causes excitement. b) Local Anesthetic - Many antihistamines having quiet potent local anesthetic action together with quinidine. c) Cardio-depressant action - Some antihistamines have cardio depressant action & hence useful in some arrhythmia. d) Autonomic effects - In higher doses these antagonize acetyl choline and produces atropine like actions like
- 13. e) Miscellaneous Some antihistamine may cause histamine release. Some may have anti-5HT action also. Hypersensitivity reaction can occur due to topical use of all H1- antihistamines. SIDE EFFECTS- Drowsiness is main side effect (driving is not safe). Potentiates the action of other CNS depressants like tranquilizers, MAO inhibitors etc. thus serious side effects can be produced if combined therapy is used. Anti-cholinergic effects like dry mouth, blurring of vision
- 14. PHARMACOKINETICS These are readily absorbed by oral route. Peak effect is seen in 1 hr & duration is 4 hrs. Metabolized in liver & excreted through urine. THERAPEUTIC USES 1. To prevent allergic reactions or their symptoms like allergic rhinitis (inflammation of nasal mucosal membrane), Hay fever, urticaria. 2. Prevention & treatment of motion sickness (promethazine). But its use in nausea & vomiting in pregnancy is contraindicated. 3. These are also used for the management of cardiac arrhythmia & Parkinsonism
- 15. PROSTAGLANDINS These are a family of naturally occurring unsaturated fatty acid. They were first found in seminal fluids. As semen is present in prostate gland they were named prostaglandins. These are widely distributed in the body including brain and exert effects on many organs and tissues. Prostaglandins are released in response to inflammation, pain, trauma, bacterial attack & allergic reactions. Prostaglandins are divided into six groups as A, B, C, D, E & F.
- 16. •In addition to prostaglandins, recent research has revealed the existence of other biologically active lipids biosynthesized from the same precursors as prostaglandins through interrelated enzymatic pathways. These include thromboxanes, prostacyclins, hydro peroxy eicosa tetraenoic acids (HPETE), hydroxyl ecosa tetraenoic acids (HETE) & leukotrines
- 17. SEROTONIN / 5-HYDROXY TRYPTAMINE It is another important autocoids widely distributed in body. Its major amount is found in intestinal chromaffin cells. Also present in platelets and certain neurons of brain. Pharmacological actions- It acts powerfully on smooth muscles of vessels and gastro-intestinal tract. Effect on blood vessels produces triphasic response as First transient fall in blood pressure followed by brief rise in blood pressure and then prolonged hypotension. It plays important role in blood coagulation.
- 18. It also plays an important role in pathophysiology of psychosis. Pharmacokinetic It is oxidatively deaminated by Mono Amine Oxidase enzyme and excreted through urine. Degradation of 5- HT may be blocked by MAO inhibitors which causes elevation of 5-HT level in brain. Some fruits like banana, cheese contain 5-HT. Hence patients on MAO inhibitors therapy should not eat such food. 5-HT Antagonists E.g. Lysergic acid Diethylamine (LSD) & Cryptoheptadine.