This document discusses histamines, antihistamines, and 5-hydroxytryptamine (5-HT, serotonin) and their antagonists. It describes how histamines are synthesized and stored in mast cells and basophils and released during allergic reactions. The pharmacological actions of histamines are also explained. Antihistamines are described as drugs that block the actions of histamine by competing for H1 receptors. The document also covers the synthesis, receptors, pharmacological actions and functions of 5-HT as well as some 5-HT antagonists and their clinical uses.
Seretonin (5HT) and Its Antagonists PharmacologyPranatiChavan
Serotonin is a chemical that has a wide variety of functions in the human body. It is sometimes called the happy chemical, because it contributes to wellbeing and happiness.
The scientific name for serotonin is 5-hydroxytryptamine, or 5-HT. It is mainly found in the brain, bowels, and blood platelets.
Serotonin is used to transmit messages between nerve cells, it is thought to be active in constricting smooth muscles, and it contributes to wellbeing and happiness, among other things. As the precursor for melatonin, it helps regulate the body’s sleep-wake cycles and the internal clock.
It is thought to play a role in appetite, the emotions, and motor, cognitive, and autonomic functions. However, it is not known exactly if serotonin affects these directly, or if it has an overall role in co-ordinating the nervous system.
Learn the nor adrenergic transmission in ANS. Synthesis, storage ,release, uptake,metabolism of nor-adrenaline. Types of adrenoceptors. Agonist and antagonist of adrenoceptors.
5-Hydroxytryptamine & it’s Antagonist is a Topic in Pharmacology which will defiantly Help You in pharmacy field All information is related to pharmacology drug acting and it's effect on body. it is collage project given by our department i would like to share with you.
Autacoids - pharmacological actions and drugs related to them. SIVASWAROOP YARASI
Autacoids or "autocoids" are biological factors which act like local hormones, have a brief duration, and act near the site of synthesis. The word autacoids comes from the Greek "autos" (self) and "acos" (relief, i.e. drug).
Seretonin (5HT) and Its Antagonists PharmacologyPranatiChavan
Serotonin is a chemical that has a wide variety of functions in the human body. It is sometimes called the happy chemical, because it contributes to wellbeing and happiness.
The scientific name for serotonin is 5-hydroxytryptamine, or 5-HT. It is mainly found in the brain, bowels, and blood platelets.
Serotonin is used to transmit messages between nerve cells, it is thought to be active in constricting smooth muscles, and it contributes to wellbeing and happiness, among other things. As the precursor for melatonin, it helps regulate the body’s sleep-wake cycles and the internal clock.
It is thought to play a role in appetite, the emotions, and motor, cognitive, and autonomic functions. However, it is not known exactly if serotonin affects these directly, or if it has an overall role in co-ordinating the nervous system.
Learn the nor adrenergic transmission in ANS. Synthesis, storage ,release, uptake,metabolism of nor-adrenaline. Types of adrenoceptors. Agonist and antagonist of adrenoceptors.
5-Hydroxytryptamine & it’s Antagonist is a Topic in Pharmacology which will defiantly Help You in pharmacy field All information is related to pharmacology drug acting and it's effect on body. it is collage project given by our department i would like to share with you.
Autacoids - pharmacological actions and drugs related to them. SIVASWAROOP YARASI
Autacoids or "autocoids" are biological factors which act like local hormones, have a brief duration, and act near the site of synthesis. The word autacoids comes from the Greek "autos" (self) and "acos" (relief, i.e. drug).
Histamine, meaning ‘tissue amine’ (histos—tissue) is almost ubiquitously present in animal tissues and in certain plants, e.g. stinging nettle. Its pharmacology was studied in detail by Dale in the beginning of the 20th century when close parallelism was noted between its actions and the manifestations of certain allergic reactions. It was implicated as a mediator of hypersensitivity phenomena and tissue injury reactions. It is now known to play important physiological roles.
Introduction to the endocrine system
Growth hormone: Mechanism of Action, secretion, regulation.
Prolactin
Sex hormones
Oral contraceptives
Corticosteroids
Explanation of Preclinical (Animal) Models of Seizure and Epilepsy.
General overview of Seizure and Epilepsy and its current Management. Need to develop newer drugs and Newer models. Current models for Acute Seizure. Kindling explained. PPT contains overview and Protocol.
Serotonin is major neurotransmitter and affects the physiology of our body. Serotonin antagonists are used in various pathological conditions of body. This is a small presentation showing feature of serotonin.
Neurohumoral transmission in CNS ,special emphasis on importance of various neurotransmitters like with GABA, Glutamate, Glycine, serotonin and dopamine
this will give brief about the peptic ulcer and give information about the drug used for peptic ulcer and classification of drugs including drugs and there use adverse effect.
pharmacology of Histamines , Serotonin and its antagonistibrahimussa
Histamine is an organic nitrogenous compound involved in local immune responses, as well as regulating physiological function in the gut and acting as a neurotransmitter for the brain, spinal cord, and uterus. Histamine is involved in the inflammatory response and has a central role as a mediator of itching
Histamine, meaning ‘tissue amine’ (histos—tissue) is almost ubiquitously present in animal tissues and in certain plants, e.g. stinging nettle. Its pharmacology was studied in detail by Dale in the beginning of the 20th century when close parallelism was noted between its actions and the manifestations of certain allergic reactions. It was implicated as a mediator of hypersensitivity phenomena and tissue injury reactions. It is now known to play important physiological roles.
Introduction to the endocrine system
Growth hormone: Mechanism of Action, secretion, regulation.
Prolactin
Sex hormones
Oral contraceptives
Corticosteroids
Explanation of Preclinical (Animal) Models of Seizure and Epilepsy.
General overview of Seizure and Epilepsy and its current Management. Need to develop newer drugs and Newer models. Current models for Acute Seizure. Kindling explained. PPT contains overview and Protocol.
Serotonin is major neurotransmitter and affects the physiology of our body. Serotonin antagonists are used in various pathological conditions of body. This is a small presentation showing feature of serotonin.
Neurohumoral transmission in CNS ,special emphasis on importance of various neurotransmitters like with GABA, Glutamate, Glycine, serotonin and dopamine
this will give brief about the peptic ulcer and give information about the drug used for peptic ulcer and classification of drugs including drugs and there use adverse effect.
pharmacology of Histamines , Serotonin and its antagonistibrahimussa
Histamine is an organic nitrogenous compound involved in local immune responses, as well as regulating physiological function in the gut and acting as a neurotransmitter for the brain, spinal cord, and uterus. Histamine is involved in the inflammatory response and has a central role as a mediator of itching
Autocoids are the self treating substance and local hormones . which is create changes in body Phisiology on the situation of to admine poisonous as well as foreign substance.
in this ppt gives Physiology of 5HT , Prostaglandin, and Histamine with their clinical use and adverse effect.
Also discussed about anti histamine , 5 HT antagonist with suitable examples.
Hello friends. In this PPT I am talking about Autacoids. If you like it, please do let me know in the comments section. A single word of appreciation from you will encourage me to make more of such videos. Thanks. Enjoy and welcome to the beautiful world of pharmacology where pharmacology comes to life. This video is intended for MBBS, BDS, paramedical and any person who wishes to have a basic understanding of the subject in the simplest way.
This presentation is about the neurotransmitter 5-HT (serotonin), we focused on its definition, biosynthesis, storage and destruction, with mentioning its both central and peripheral effects, and lastly the serotonin receptors in the human body, as well as their agonist and antagonists.
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
MANAGEMENT OF ATRIOVENTRICULAR CONDUCTION BLOCK.pdfJim Jacob Roy
Cardiac conduction defects can occur due to various causes.
Atrioventricular conduction blocks ( AV blocks ) are classified into 3 types.
This document describes the acute management of AV block.
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Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
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Pharmacology of autacoids
1. Pharmacology I 7.Autacoids III B.Pharm 2015-16 Dr.KPS Gowda Page 1
7. Pharmacology of autacoids and their antagonists
a) Histamines and Antihistamines
b) 5-Hydroxytryptamine and its antagonists
c) Lipid derived autacoids and platelet activating factor
a) Histamines and Antihistamines
Autacoids- Autos= self, akos= remedy/healing. Autacoids are also called local hormones.
Generally they act at the site of synthesis and release.
Classification of autocoids- 1.Amine autacoids- Histamine, 5hydroxy tryptamine (5HT or
serotonin).
2.Lipid derived autacoids- Prostaglandins, leukotrienes, platelet activating factors.(PAF).
3.Peptide autacoids- Plasma kinins (bradykinin, kallidin), angiotensin.
Histamine-It is present in the mast cells, basophils and platelets. It is present in high
concentration in skin, lungs, gastric mucosa, and in the enterochromaffin cells in the stomach. It
acts as neurotransmitter in the brain. Histamine is synthesized from the aminoacid L-histidine.
The enzyme histidine decarboxylase catalyzes the conversion of L-histidine to histamine. In mast
cells histamine (positively charged) is held by an acidic protein and heparin (-vely charged)
within intracellular granules. When present in the cells it is inert but when released it becomes
active and produces a number of biological actions. Release of histamine from mast cell occurs
as a result of a. allergic reactions, b.chemical/drug induced- morphine, dTC, penicillins, and
radio-contrast media. After release from the cells, histamine is rapidly degraded to methylation
and oxidation and excreted in urine as metabolites (N-methyl imidazole acetic acid and
imidazole acetic acid). It cannot cross BBB.
L-Histidine Histamine
2. Pharmacology I 7.Autacoids III B.Pharm 2015-16 Dr.KPS Gowda Page 2
Pharmacological actions of histamine-MOA- Histamine combines with specific receptors (H1,
H2, and H3 ) producing effects. All histaminic receptors are G-protein coupled receptors.
Histaminic receptors-
H1- Gq- effector-PLC-> second messengers- IP3 and DAG -> IP3-> Increases Ca2+
concentration
and DAG-> activation of PKC. The Ca2+
combines with calmodulin-> Ca2+-
calmodulin activates
MLCK-> phosphorylation of myosin light chain -> smooth muscle contraction.
Locations- Blood vessels, intestines, bronchi, uterus, nerve endings, and brain. Bronchial,
intestinal smooth muscles-> contraction. Vascular endothelium -> vasodilatation through NO.
H2-Gs- effector-AC-> second messenger- cAMP-> activation of PKC.
Locations- Gastric parietal cells. Heart, uterus and brain. When histamine binds with H2
receptors present on the parietal cells-> stimulation of AC-> cAMP-> activation of PKC->
stimulation of the proton pump-> more H+
ions pumped out by these pumps, these H+
ions
combines with Cl-
ions to form HCl.
H3-( Gi ) Brain ( auto receptor) These receptors are located on the central and peripheral nerves.
Actions of histamine-
1. Stimulate nerve ending- Itching and pain.(H1 receptor)
2. Smooth muscles- Contraction of smooth muscles of bronchi, intestine, uterus.(H1 receptor)
3. Exocrine secretions- Increase in salivary, lacrimal, bronchial, gastric juice secretions.
4. CVS- H1 and H2 receptors are involved.
a. Dilatation of the arterioles.
b. Increase in capillary permeability-edema.
c. Triple response- Intradermal injection of histamine (10-20µg ) in man produces a
characteristic effect called triple response. It consists of :
i) Development of a red spot within a minute at the site of injection, which is called ‘flush’. The
flush then gradually becomes a bluish discoloration. It is due to dilatation of capillaries and
venules.
ii) Development of a bright red area called ‘flare’ which is irregular in outline and extending to
5cms beyond the flush. It is due to dilatation of arterioles produced by axon reflex.
3. Pharmacology I 7.Autacoids III B.Pharm 2015-16 Dr.KPS Gowda Page 3
iii) Development of localized edema called ‘wheal’. It is due to increased capillary permeability
leading to exudation of plasma proteins and fluid from the capillaries into the extracellular
spaces. The triple response is accompanied by itching.
d. Increase in heart rate and contraction.(H2 receptors)
e.CNS- Wakefulness, hypothermia, rise in BP, arousal, vomiting, nociception. (H1 & H2).
f.Gastric glands- Increase in gastric acid secretion.(H2).
Functions of endogenous histamine-
1. Regulates gastric acid secretion.
2. Plays a central role in immediate hypersensitivity responses.
3. Functions as a neurotransmitter in the brain.
Uses- Histamine has no therapeutic use. It is used in diagnostic tests.
1. Used to test acid secreting capacity of the stomach.
2. Used to diagnose pheochromacytoma.
3. Used to test bronchial hyperactivity in asthmatics and allergic disorder.
4.To test the integrity of sensory nerves in leprosy (intradermal injection of histamine fails to
elicit the flare in the affected region due to loss of axon reflex.)
4. Betahistine- (histamine analog) is used to control vertigo in Meniere’s disease.
Antihistamines- (H1 blockers) are the drugs act by blocking the actions of histamine on H1
receptors.
Classification-
1. Highly sedative-Diphenhydramine, dimenhydrinate, promethazine, hydroxyzine.
2. Moderately sedative- Pheniramine, cyproheptadine, meclizine, buclizine, cinnarazine.
3. Mild sedatives- Chlopheniramine, mepyramine, triprolidine, cyclizine, clemastine.
4. Non sedative antihistamines-Terfinadine, astemazole, loratidine, cetirizine,
Pharmacological actions-
1. Vascular actions- Antihistamines block the histamine induced vasodilatation, increase in
capillary permeability, edema and triple response.
2. Antiallergic actions- They relieve uriticaria, itching and angioedema. Fall in BP and
bronchospasm are not relieved, but are prevented. Decrease the release of mediators from
basophils and mast cells.
4. Pharmacology I 7.Autacoids III B.Pharm 2015-16 Dr.KPS Gowda Page 4
3. CNS- Depression-sedation, larger dose-> insomnia, restlessness, convulsions.
4. Anti- motion sickness action-Diphenhydramine, cyclizine, meclizine.
5. Antiemetic action-Promethazine, hydroxyzine.
6. Anti-parkinsonism action- Diphenhydramine, promethazine.
7. Anticholinergic action- Except non sedative antihistamines.
8. Alpha blocking action- Promethazine.
9. Local anesthetic action- Promethazine. Diphenhydramine.
10. 5HT antagonism- Cyproheptadine.
ADME-The classical H1 antihistamines are well absorbed from oral and parenteral routes,
metabolized in the liver and excreted in urine. They are widely distributed in the body and enter
the brain. The non sedative antihistamines penetrate brain poorly. Duration of action of most of
the antihistamines 4-6 h, for some antihistamines-12-24 h.
ADRs- 1.Sedation, drowsiness, in coordination of movements, diplopia, blurred vision. 2. Anti-
cholinergic effects- Dryness of mouth, urinary retention. 3. CVS-Hypotension, palpitation. 4.
GIT- Anorexia, nausea, vomiting. 5. Miscellaneous- Teratogenic, contact dermatitis.
Uses- 1. Used in allergic conditions- Uriticaria, pruritus, food allergy, insect bite, hay fever
(allergic rhinitis), drug allergy, common cold. 2. Other uses- a. To treat vertigo in Meniere’s
disease. b. Parkinsonism. c. Motion sickness. d. Antiemetic. e. Cough f. As sedative in children.
Marketed preparations.1.Diphenhydramine HCl tabs, syps.
2.Promethazine HCl suppositories, tablets, syrups.
3.Hydroxyzin HCl tabs,syps.
4. Chlorpheniramine tabs, inj, syps. 5. Cyproheptadine- tablet, syps.
6. Meclizine HCl tabs, 7.Mepyramine cream.
8. Citirizine tabs, syrups.
H2 blocker –Cimetidine, ranitidine,famotidine, nizatidine, roxatidine, loxatidine.
These are the agents which block the H2 receptor mediated actions of histamine. They are mainly
used in the treatment of peptic ulcer.
They act by competitively blocking the H2 receptors located on the gastric parietal cells of the
gastric juice. This inhibits the formation of the HCl.
5. Pharmacology I 7.Autacoids III B.Pharm 2015-16 Dr.KPS Gowda Page 5
ADME-Well absorbed orally. These produces high first pass metabolism. Antacids decrease the
absorption of these drugs.
ADRs-1. Cimetidine increases prolactin secretion- gynacomastia, decreased libido and
impotence,( this is only with cimetidine), 2. Inhibition of cytochrom P-450 enzymes. This is with
cimetidine only. This decreases the metabolism of other drugs. 3. Nausea, vomiting, diarrhea. 4.
Reduces hepatic blood flow. 5. CNS- confusion, dizziness, restlessness. 6. Rarely allergic
reactions, bone marrow depression.
Uses- Duodenal ulcer, gastric ulcer, Zollinger-Ellison syndrome, gastro-esophageal reflux
disorder (GERD).
Preparations-Cimetidine 200, 400mg tabs, ranitidine 150, 300mg tab, 50mg inj.
b. 5-Hydroxy tryptamine (5HT, serotonin)
Synthesis and storage:
Tryptophan in diet is converted by tryptophan hydroxylase (rate-limiting enzyme) to 5-
hydroxytryptophan which is converted by amino acid decarboxylase to 5-hydroxytryptamine (5-
HT).
About 90% of 5-HT is stored in enterochromaffin cells of GIT. These cells contain tryptophan
hydroxylase and can synthesize 5-HT. The remaining 10% are stored mainly in platelets and
very small amount in CNS. The platelets do not contain tryptophan hydroxylase and cannot
synthesize 5-HT but obtain it by active uptake of 5-HT released from enterochromaffin cells into
the blood.
6. Pharmacology I 7.Autacoids III B.Pharm 2015-16 Dr.KPS Gowda Page 6
Biosynthesis of 5HT
Fate of 5-HT: The majority of secreted 5-HT undergoes active reuptake into the serotoninergic
neurons. The remaining part of 5-HT is metabolized by MAO to 5-hydroxyindoleacetic acid (5-
HIAA) which is excreted in urine.
Serotonin (5-HT)-receptors:
There are 7 main types of 5HT receptors. Except 5-HT3 all belongs to G protein coupled
receptors.
5HT1- Gi type, AC- decreased cAMP, inhibitory potential (IPSP).
5HT2- Gq, PLC, IP3, DAG, excitatory potential (EPSP).
5HT3- Ligand gated Na+
and K+
cation channel, Depolarization,excitatory.
5HT4- Gs - AC, increase in cAMP, excitatory.
5HT5- Gi- AC, decrease in cAMP, inhibitory.
5HT6- Gs - AC, increase in cAMP, excitatory.
5HT7- Gs - AC, increase in cAMP, excitatory.
5-HT1-receptors: Sub types are 5HT1A, 5HT1B, 5HT1D, 5HT1E (all are located in the brain).
Actions of 5HT1A – Antidepressant effect, hypothermia and hyperphagia (increased appetite).
Actions of 5HT1B – Act as autoreceptors, regulate the release of 5HT in the brain.
7. Pharmacology I 7.Autacoids III B.Pharm 2015-16 Dr.KPS Gowda Page 7
Actions of 5HT1D - Act as autoreceptors, regulate the release of 5HT in the brain.
Actions of 5HT1E – Not clear.
5-HT2-receptors: Sub types- 5HT2A, 5HT2B and 5HT2C.
5HT2A- These receptors are expressed on the vascular and visceral smooth muscle, platelets and
cerebral neurons. The actions are vasoconstriction, intestinal, uterine and bronchial contraction,
platelet aggregation and activation of cerebral neurons.
5HT2B-These receptors are expressed on the gastric fundus. 5HT causes contraction of gastric
fundus.
5HT2C- These receptors are located in the endothelium of the blood vessels. 5HT causes
vasodilatation through the formation of NO (EDRF).
5-HT3-receptors: Ligand-gated ion channel receptors which increases intracellular Ca2+
/ K+
concentration. They are present in GIT (increased peristalsis), peripheral nerve endings (pain and
itching) and vomiting center of medulla (vomiting).
5-HT4-receptors: In the brain –learning, memory, cognitive function. Also generates anxiety.
5HT5 and 5HT6 receptors: These are new receptors and actions are not clear.
Pharmacological actions of 5HT-
1.CVS- Some blood vessels get constricted (direct effect) and some blood vessels get dilated
(through the release of EDRF- NO). 5HT stimulates the heart directly and through the release of
adrenaline.
2.Smooth muscles- 5HT causes contraction of the GIT smooth muscles- increased peristalsis
and diarrhea. It also causes broncho-constriction.
3. Glands- 5HT inhibit the secretion of HCl and pepsinogen. But it increases mucous secretion.
Hence it gives protection against peptic ulcer.
4. Nerve endings - 5HT causes sensitization of afferent nerve endings. This leads to pain and
pricking sensation.
5. Respiration- Usual doses cause a brief stimulation of respiration, but larger doses leads to
transient apnoea.
6. Platelets- 5HT produce weak platelet aggregator effect. 5HT also causes the alteration of the
platelet shape.
7. CNS- 5 HT not crosses BBB and hence no central effects.
8. Pharmacology I 7.Autacoids III B.Pharm 2015-16 Dr.KPS Gowda Page 8
ADME- 5HT is inactivated on oral administration. It is absorbed on parenteral administration. It
is metabolized by MAO and the metabolite -5hydroxy indole acetic acid is eliminated through
urine.
Physiological functions of 5-HT:
1. It acts as a neurotransmitter in the CNS (decreased brain serotonin results in anxiety, psychic
depression)
2. It acts as a precursor for melatonin in the pineal gland.
3. It regulates GI motility.
4. It causes vasoconstriction and platelet aggregation in vessel injury (hemostasis).
5HT antagonists-
1. The antianxiety drug buspirone acts as a partial agonist of 5HT1A receptor.
2. Sumatriptan is an agonist on the presynsaptic 5-HT1D decreasing 5-HT release. It is used in
treatment of acute attacks of migraine.
3. Metoclopramide is 5-HT4 agonist used as prokinetic drug (stimulate tone and motility of
GIT) in treatment of delayed gastric emptying and reflux esophagitis. It is also used as antiemetic
agent.
4. Ondansetron is 5-HT3 antagonist used as antiemetic drugs for vomiting of cancer
chemotherapy and postoperative vomiting.
5.Cyproheptadine is 5-HT1 antagonist, It is used as antiallergic drug, prophylaxis of migraine.
6. Methysergide is 5-HT antagonist used in prophylaxis of migraine and treatment of carcinoid
syndrome (symptoms due to carcinoid tumors of GIT).
7.Ketanserin is a 5-HT2A antagonist used in treatment of hypertension and peripheral vascular
diseases.
Lipid derived autocoids- Eicosanoids They are a group of unsaturated fatty acids composed of
20 carbon atoms and contain double bonds. Eg Prostaglandins, Leukotrienes, thromboxanes,
Biosynthesis of eicosanoids: They are synthesized from cell membrane phospholipids. The first
step is separation of arachidonic acid from cell membrane phospholipids by the action of
phospholipase A2 which is stimulated during inflammation, allergy and cell injury.
Arachidonic acid is metabolized by one of two pathways to give different eicosanoids which are
I. Cyclooxygenase (COX) pathway- PGD2, PGE2, PGF2, PGI2, TXA2
9. Pharmacology I 7.Autacoids III B.Pharm 2015-16 Dr.KPS Gowda Page 9
II. 5-Lipooxygenase pathway (LTA4, LTB4, LTC4, LTD4, LTE4).
10. Pharmacology I 7.Autacoids III B.Pharm 2015-16 Dr.KPS Gowda Page 10
Actions of prostaglandins, prostacyclins and thromboxanes
Prostaglandin receptors- There are currently ten known prostaglandin receptors on various cell
types. These belong to G protein coupled receptors.
1. CVS- PGD2, PGE2, and PGF2 can increase the heart rate and force of heart contraction. TXA2
and PGF2 cause vasoconstriction. PGI2 causes vasodilatation.
2. Platelets- TXA2 produced locally by platelets. It produces platelet aggregation effect.
3. Uterus-PGE2 and PGF2 causes contraction of the uterus.
4. Bronchial muscle- PGD2, PGF2 and TXA2 are the potent bronchoconstrictors. PGE2 is a
powerful bronchodilator.
5. GIT- PGE2 reduces the acid secretion in the stomach, increases mucosal secretion and
mucosal blood flow.
6. CNS- PGE2 causes sedation, behavioral changes and rise in body temperature.
7. ANS- PGs may modulate the sympathetic neurotransmission.
8. Peripheral nerves- PGE2 and PGI2 increases sensitization of peripheral nerve endings.
Therapeutic uses of prostaglandins:
1. PGF2 (Dinoprost) and PGE2 (Dinoprostone) are used as vaginal suppositories for therapeutic
abortion (abortifacients) in early pregnancy and for induction of labor.
2. Misoprostol (synthetic analog of PGE2) provides cytoprotective effect on gastric mucosa and
is used in treatment of peptic ulcer and to prevent gastric ulceration during treatment with
NSAIDs.
3.PGF2 derivative (Latanoprost) decreases IOP by reducing aqueous humor synthesis and is used
as eye drops for glaucoma.
Leukotrienes: Leukotrienes are a family of eicosanoid inflammatory mediators produced in
leukocytes by the oxidation of arachidonic acid by lipoxygenase pathway. In inflammatory
responses leukotrienes are also produced along with prostaglandins and histamine. LTC4, LTD4
and LTE4 are cysteinyl leukotrienes due to the presence of amino acid cysteine in their structure.
Through autocrine and paracrinal signaling leukotrienes regulate immune responses. In asthma
leukotriens cause airflow obstruction, increased secretion of mucus, mucosal accumulation and
bronchoconstriction. Both LTB4 and the cysteinyl leukotrienes (LTC4, LTD4 and LTE4) are
partly degraded in local tissues and ultimately become inactive metabolites in the liver.
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Leukotrienes act on G-protein coupled receptors. Several leukotriene receptor antagonists such
as monteulukast and zafirlukast are used to treat asthma.
Platelet activating factor: (PAF). It is a cell membrane derived phospholipids with wide range
of biological activities. Chemically it is acetyl-glyceryl ether-phosphocholine.
Biosynthesis: It is synthesized from the precursor acylglycerophosphocholine present in the cell
membrane by the action of the enzyme phospholipase-A2. First lyso-PAF is formed and this is
converted to PAF by the action of Lyso-PAF-acetyl transferase.
Degradation of PAF- It is degraded by the action of PAF acetylhydrolases.
PAF is produced by a variety of cells, but especially those involved in host defense, such
as platelets, endothelial cells, neutrophils, monocytes, andmacrophages. It is produced in larger
quantities by inflammatory cells in response to specific stimuli.
Actions of PAF- PAF produces its effects through PAF receptors, which are expressed on the
target cells. These receptors are G-protein coupled receptors.
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CVS: It is a potent vasodilator. It causes the release of EDRF leading to fall of B.P. It increases
capillary permeability leading to edema formation.
Respiratory tract effects: It has a strong role in inflammation. It can cause broncho-
constriction and inflammation of airways. It can also produce edema of airways.
Haematological effects: It is a chemotactic (migration) factor for neutrophils, eosinophils and
monocytes. It favors platelet aggregation.
GIT effects: It is ulcerogenic to gastric mucosa. It causes contraction of smooth muscles of GIT
and increases gut motility.
Miscellaneous effects: It activates most inflammatory cells and plays important role in
inflammation. It causes renal vasoconstriction and decreases urine output.
Anti PAF drugs- Clinical trials are going on to find its efficacy in atrial fibrillation and in
allergy.
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