8/14/2019 10.- Autacoides 4

1/20

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

8/14/2019 10.- Autacoides 4

2/20

SEROTONINE5-HYDROXITRYPTAMINE

Localization: - Enterochromaffin cells (gut) (90%)

- platelets

- mast cells

- brain (1-2%)

8/14/2019 10.- Autacoides 4

3/20

Synthesis of 5-HT

Diet

In enterochromaffin

cells and neurons

8/14/2019 10.- Autacoides 4

4/20

Monoaminooxidase

Aldehido deshydrogenase

5-hydroxiindolacetyc acid

Serotonine

Metabolism of 5-HT

Regulation:

Diet (tryptophan,

tyrosine,phenylalanine,leucine)

O2

Daily fluctuations

Pharmacologycal

8/14/2019 10.- Autacoides 4

5/20

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

8/14/2019 10.- Autacoides 4

6/20

Pharmacological actions of 5-HT

5-HT1A

CNS-Inhibitory (pre andpostsynaptic)

Anxyolisis, sleep, hyperfagia

5-HT1D

CNS- Inhibitory (presynaptic)

Blood vessels- Vassoconstriction

8/14/2019 10.- Autacoides 4

7/20

5-HT2A receptors

Smooth muscle- contraction

Platelets-aggregation, vassodilation/Vassoconstriction

CNS- excitation- psicosis

IP3, DAG

Pharmacological actions of 5-HT

5-HT2 receptors

8/14/2019 10.- Autacoides 4

8/20

Pharmacological actions of 5-HT

5-HT4

PNS- gastrointestinal motility

CNS- Neuronal excitation+

5-HT3

CNS- (area postrema) Emesis

Anxiety

PNS- nociceptive neurones-pain

+

8/14/2019 10.- Autacoides 4

9/20

Pharmacological actions of 5-HT

5-HT6

CNS- increases cholinergic

transmission (memory)

5-HT7

CNSGi tract (Unknown)

+

8/14/2019 10.- Autacoides 4

10/20

5-HT storage and release in the brain

Pharmacological actions of 5-HT

-Mood

-Sleep/awake cycle- Appetite

8/14/2019 10.- Autacoides 4

11/20

5-HT and mood

8/14/2019 10.- Autacoides 4

12/20

5-HT and weight loss

FenfluramineandPhentermine

Weigh

t(kg)

Time (weeks)

8/14/2019 10.- Autacoides 4

13/20

5-HT in sleep-waking cycle

8/14/2019 10.- Autacoides 4

14/20

Fluoxetine Citalopram

ParoxetineSertraline

Clinical use of 5-HT drugs (Antidepressants)

SSRI (selective serotonine reuptake inhibitors)

8/14/2019 10.- Autacoides 4

15/20

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

8/14/2019 10.- Autacoides 4

16/20

Neurotransmitters and receptors involved in emesis control

NEUROTRANSMITTERS

DOPAMINE D2

SEROTONINE 5HT3

HISTAMINE H1

ACETYLCHOLINE MUSCARINICS

RECEPTORS

8/14/2019 10.- Autacoides 4

17/20

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

8/14/2019 10.- Autacoides 4

18/20

ANTIEMETIC DRUGS

D2 ANTAGONISTS

ANTAGONISTAS 5-HT3

ANTAGONISTAS H1

Metoclopramide

Domperidone

Thietylperazine

Haloperidol

Ondansetron

Granisetron

Tropisetron

Cinarizine

Ciclizine

Dimenhidrinate

8/14/2019 10.- Autacoides 4

19/20

M1 ANTAGONISTS

CORTICOSTEROIDS

CANNABINOIDS

Hioscine, escopolamine

Nabilona

Dexametasone

Metilprednisolone

ANTIEMETIC DRUGS

8/14/2019 10.- Autacoides 4

20/20

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)