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Autos: self akos: reliefA chemical substance produced by one type of cell that affects the
function of different types of cells in the same region .
1. Eicosanoids: Prostaglandins (PG)Tromboxanes (TX)Leucotrienes (LT)
2. Nitric oxide (NO) and platelet activating factor (PAF)
3. Polipeptides: Angiotensine and Bradykinin.
4. Amines: Histamine and serotonin
AUTACOID
Generatedde novo
stored
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SEROTONINE5-HYDROXITRYPTAMINE
Localization: - Enterochromaffin cells (gut) (90%)
- platelets
- mast cells
- brain (1-2%)
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Synthesis of 5-HT
Diet
In enterochromaffin
cells and neurons
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Monoaminooxidase
Aldehido deshydrogenase
5-hydroxiindolacetyc acid
Serotonine
Metabolism of 5-HT
Regulation:
Diet (tryptophan,
tyrosine,phenylalanine,leucine)
O2
Daily fluctuations
Pharmacologycal
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5-HT receptor subtypes
5-HT1 (5-HT1A, 5-HT1B, 5-HT1D) CNS, blood vessels
5-HT2 (5-HT2A, 5-HT2B, 5-HT2C) CNS and PNS, smooth
muscle, platelets
5-HT3 (5-HT3A, 5-HT3B) CNS, PNS
5-HT4 CNS, PNS
5-HT5 CNS
5-HT6 CNS
5-HT7 CNS, gi tract, blood
vessels
Distribution
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Pharmacological actions of 5-HT
5-HT1A
CNS-Inhibitory (pre andpostsynaptic)
Anxyolisis, sleep, hyperfagia
5-HT1D
CNS- Inhibitory (presynaptic)
Blood vessels- Vassoconstriction
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5-HT2A receptors
Smooth muscle- contraction
Platelets-aggregation, vassodilation/Vassoconstriction
CNS- excitation- psicosis
IP3, DAG
Pharmacological actions of 5-HT
5-HT2 receptors
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Pharmacological actions of 5-HT
5-HT4
PNS- gastrointestinal motility
CNS- Neuronal excitation+
5-HT3
CNS- (area postrema) Emesis
Anxiety
PNS- nociceptive neurones-pain
+
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Pharmacological actions of 5-HT
5-HT6
CNS- increases cholinergic
transmission (memory)
5-HT7
CNSGi tract (Unknown)
+
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5-HT storage and release in the brain
Pharmacological actions of 5-HT
-Mood
-Sleep/awake cycle- Appetite
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5-HT and mood
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5-HT and weight loss
FenfluramineandPhentermine
Weigh
t(kg)
Time (weeks)
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5-HT in sleep-waking cycle
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Fluoxetine Citalopram
ParoxetineSertraline
Clinical use of 5-HT drugs (Antidepressants)
SSRI (selective serotonine reuptake inhibitors)
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Clinical use of 5-HT drugsAnxiety 5-HT1A agonist Buspirone
Migraine 5-HT1D agonist Sumatriptan,
Zolmitriptan
Migraine profilaxis 5-HT2 antagonist Dihidroergotamine
Esquizophrenia 5-HT2A antgonist Risperidone
Antiemetics 5-HT3 antagonist Ondansetron
(quimiotherapy) Granisetron
Tropisetron
Peristaltism 5-HT4 agonists Metoclopramide
(procinetics) Tegaserod
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Neurotransmitters and receptors involved in emesis control
NEUROTRANSMITTERS
DOPAMINE D2
SEROTONINE 5HT3
HISTAMINE H1
ACETYLCHOLINE MUSCARINICS
RECEPTORS
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Stimuli
Pain,images
Odour
Emotions
cinetosis
toxins
Stimuli from
the gi system
Vestibular nuclei
H1 and M1
Visceral afferents
5-HT3?
Sensory afferents
Solitary tract
nucleus
H1 and M1
Chemoreceptortrigger zone
D2 and 5-HT3
Vomitingcentre
M1
Factors involved in control of vomiting
5-HT3 antagonists
H1 antagonists
D2 antagonists
M1 antagonists
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ANTIEMETIC DRUGS
D2 ANTAGONISTS
ANTAGONISTAS 5-HT3
ANTAGONISTAS H1
Metoclopramide
Domperidone
Thietylperazine
Haloperidol
Ondansetron
Granisetron
Tropisetron
Cinarizine
Ciclizine
Dimenhidrinate
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M1 ANTAGONISTS
CORTICOSTEROIDS
CANNABINOIDS
Hioscine, escopolamine
Nabilona
Dexametasone
Metilprednisolone
ANTIEMETIC DRUGS
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CLINICAL USE OF ANTIEMETIC DRUGS
D2 ANTAGONISTS
Vomits induced by radiation, virus, pregnancy (metoclopramide)
5-HT3 antagonists
- Vomits induced by quimiotherapy (treatment of cancer)
- Vomits post surgery
- Vomits induced by radiation
H1 antagonists
- Motion sickness- Vestibular unbalance
- Early morning nausea during pregnancy (doximalmine and prometacine)
M1 antagonists
-Motion sickness (hioscine)
Cannabinoids
- Vomits induced by quimiotherapy (treatment of cancer)
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