SEROTONIN KININ AND PROSTAGLANDIN AUTACOID

In serotonin anti-serotonin, kinin and prostaglandin autacoid we are learn all about Serotonin, its receptor, synthesis serotonin action on various body part, its uses, adverse effect, serotonin antagonist(anti-serotonin),all about kinin and prostaglandin

1. SEROTONIN ANTISEROTONIN, KININ AND PROSTAGLANDIN AuTaCOIDS SUBJECT NAME: ADVANCE PHARMACOLOGY
GUIDED BY : Dr. D. S. SHIRODE
PRESENTED BY : ANKITA S. HALDANKAR
(M. Pharm 1 st year Pharmacology) D. Y. Patil College Of Pharmacy Akurdi , Pune

2. INTRODUCTION Serotonin ( 5 – Hydroxytryptamine ) is a monoamine Neurotransmitter. It has a popular image as a contributor to feeding of well being and happiness. It is a important neurotransmitter widely distributed in animals and plants (banana, pineapple,Tomato ) 80-90% Found in enterochromafin cells in a gut where it is used to regulate intestine movement, rest is present in platelet and brain. Serotonin does not cross BBB necessitates the synthesis of serotonin with in the brain. Serotonin is synthesized from the amino acid tryptophan which derived from the diet.

3. RECEPTORS Seven subtype of serotonin receptors(1-7) Receptor Location 5HT1 CNS, Cranial blood vessel 5HT 2 Platelets, smooth muscles 5HT3 CTZ 5HT4 GIT, CNS 5HT 5-7 CNS All of them are G – Protein coupled receptor except 5-HT 3( ligand gated ion channel) Drug acting on 5HT1A, 5HT1 B/D and 5HT 4 – Agonist Drug acting on 5HT 2 A/C and 5HT 3 - Antagonist

4. 1.5HT 1A : anxiety Drugs : Buspirone stimulate 5HT1A Treatment :Anxiety (chronic anxiety) 2. 5HT 1B/D : Blood vessel of brain Stimulant: Vasoconstriction Treatment : Migraine Drugs :(1) Sumatriptan (2) Naratriptan 3. 5HT 2A/C : Blood vessel – Vasoconstriction Stimulant – Increase BP ( Vasoconstriction ) Drugs: Antagonist – kitaserin , Ritaserin 4. 5HT 3 : CTZ Stimulant : Vomiting ( Cisplatin – maximum incidance of vomiting ) Drug : Ondansetron , Granisetron 5. 5HT 4 : 1)Present in GIT 2) Increase forward movement of GIT Drugs : Cisapride , Mosapride

5. •CLASSIFICATION:

6. PHARMACOLOGICAL ACTION OF 5-HT 1) Heart : Bradycardia due to stimulation of coronary chemoflex through vegus nerve. 2) Blood pressure : Triphasic response on BP Early sharp fall – Due to increase vagal activity Brief rise in BP – Due to Vasoconstriction Prolong fall in BP – Due to Arteriolar dilation 3) Gastrintestinal Tract : Increase gastric motility +contraction = Diarrhoea Activation of 5HT Receptor –Ach release – Prokinetic Effect PROKINETIC EFFECT : Any drug which increse the forward movement of GIT

7. 4) Gland : 5HT Decrease gastric secretion result in decrese acid and pepsin Increse mucus production – Ulcer protective effect 5) Nerve Ending : 5HT Activate Afferent nerve ending – Tingling And Pain 6) Platelet : 5HT 2 Promote platelet aggregation 7) CNS : Poor entry to BBB Direct injection in brain : hunger, behavioral changes, sleepness

8. PATHOPHYSIOLOGICAL ROLE Neurotransmitter : Action : Sleep, Temperature Regulation, mood stabilizer, Pain, Cognitive function , Behavioural activity, Vomiting, Thoughts, Appetite 2. Precursor of Melatonin : Precursor of melatonin at Pineal gland Maintain Circadian rhythm 3. Neuroendocrine function :Regulate anterior pitutary hormone 4. Nausea and Vomiting :Cytotoxic drug and radiotherapy receptor of gut 5HT 3 5. Migraine : Vasoconstrictor phase of Migraine – Sumatriptan

9. 5HT ANTAGONIST Cyproheptadine : Block 5HT 2A receptor Utilized in Controlling Intestinal Manifestation of carcinoid & postgastrectomy syndrome. Side effect : dry mouth, drowsiness, ataxia 2) Methylsergide : Antagonise the action of 5HT on smooth muscle including that of blood vessels. Used for migraine prophylaxis. 3) Resperidone : 5HT 2A antagonist. Produce extrapyramidal effect on slightly higher dose. 4) Ondansetron : Selectively 5HT3 antagonist. Remarkable efficacy in controlling nausea and vomiting following administration of highly emetic anticancer drug & radiotherapy.

10. Kinins : Vasoactive polypeptide. Formed from plasma globulin kininogen . Enzyme involved Kallikrein . Generated by proteolytic reaction trigger by tissue injury, inflammation, allergic reaction, etc Important kinin are: Kallidin ( decapeptide ) Bradykinin ( nonapeptide ) Kinin Receptor Two types of receptor
B1 receptor
B2 receptor ( kallidin & bradykinin)

11. B1 receptor Mediate kinin action in inflamed tissue. Cause contraction of vein, large vessels,enhance prostaglandin synthesis etc. B2 receptor Mediate kinin action in non inflamed tissue. Cause visceral smooth muscle contraction. Action of kinin : Kidney : Increase renal blood flow. Facilitates watee and salt excretion. 2. Smooth muscle : Contraction of intestine Bronchoconstriction in guinepig and asthmatic patients. .

12. 3. Neuron : Strongly stimulate nociceptive Afferent and produce burning sensetion . Bradykinin produce intense, transient pain so used in analgesic testing. Increase permeability of BBB. 4. Blood vessels : Potent vasodilator (via endothelial No and PGI 2 ) release. Increase capillary permeability due to separation of endothelial cell. No direct effect on heart; reflex stimulation due to fall in BP. • PATHOPHYSIOLOGICAL ROLE OF KININS : Mediation of inflammation. Mediation of pain. Major role in development of angioedema. Hereditary angioedema

13. PROSTAGLANDIN Prostaglandin – product of long chain fatty acid. Prostaglandin are derivative of prostanoic acid. Prostaglandin are C20 prostanoic acid, 7( 2-octyl cyclopentyl ) heptanoic acid. Prostaglandin are differ in their structure due to substituent group & double bond on cyclopentane ring. PG, LT, TX are collectively called as ecosonoid , and it is synthesized from membrane phospholipid.

14. COX( Cyclooxygenase) COX–1 It is a constitutive enzyme (not inducible, always present in cell) Serve house keeping It participates in physiological functions such as secretion of mucus for protection of gastric mucosa, haemostasis and maintainance of renal function. COX–2 It is an inducible enzyme It involve in inflammatory & other pathological changes. COX–3 Involve in pain perception & fever but not in the inflammation. This isoenzyme is inhibited by paracetamol .

15. PHARMACOLOGICAL ACTION 1)Platelets: TXA2 – Potent aggregator of platelets. PGI2 – Inhibit platelet aggregation. 2) Blood vessels: PGI2 & PGE2 –Vasoconstriction TXA2 – Vasoconstriction 3) Uterus : PGE2,PGF2a – Constriction Dysmenorrhea – occur due to increase local production of PG by the endometrium. 4) Bronchi: PGE2>>PGI2 – Bronchodilation PGF2a, TXA2 – Bronchoconstriction 5) GIT Intestine – increase water, electrolyte, mucus secretion – diarrhoea. Stomach – (PGE2) – increase mucus and decrease HCL Secretion 6) EYE – (PGF2a) Decrease intraocular tension.

16. Preparation and uses of prostaglandin PGE1 ( Alprostadil )- Erectile dysfunction PGE2 ( Gemeprost ) – Cervical ripening in early pregnancy PGE2 ( Misoprostol) – Peptic ulcer, Abortion PGE2 ( Dinoprostone ) – Induction of labour PGF2a ( Dinoprostone )- Mild term abortion PGF2a ( Latanoprost ) – Glaucoma PGI2 ( Epoprostenol ) – Pulmonary hypertension