5-HT in the CNS

?
  • Created by: LBCW0502
  • Created on: 01-10-18 18:39
What is 5-HT?
5-hydroxytrypamine, serotonin. Identified in 1948. Originally found in platelets (released when blood clots). Found in GI tract and CNS. Local hormone and neurotransmitter (autacoid)
1 of 44
What is an autacoid?
Biological factors which act like local hormones, have brief duration and act near the site of synthesis
2 of 44
Which four areas is 5-HT found outside the CNS?
Intestines, high concentrations in platelets, inflammatory mediator and nociception
3 of 44
Describe features of 5-HT in the SI
90% found in wall of gut (80% of enterochromaffin cells, 10% in nerves). Released following stimulation by gut flora, toxins. Increased gut motility
4 of 44
Describe features of 5-HT found in platelets
Platelet aggregation. Released at the site of tissue damage (local hormone). Local effect on blood vessels. Local effect on smooth muscle (vasoconstriction/vasodilation)
5 of 44
In which cells is 5-HT found?
In mast cells
6 of 44
What is the function of 5-HT in nociception?
Stimulates peripheral nociceptive nerve endings
7 of 44
What percentage of 5-HT is in the brain?
1% - found in the brain
8 of 44
Actions of 5-HT involves which receptors?
G-protein coupled receptors (except 5HT3)
9 of 44
Which aspects is 5-HT important in?
Sleep, wakefulness, mood. Hallucinations and behaviour. Feeding and appetite. Sensory transmission. (Obsessive compulsive disorders, schizophrenia, depression, pain, emesis, control of food intake)
10 of 44
What are the 5-HT pathways in the NS?
Rostral raphe nuclei axons ascend to: cerebral cortex, limbic regions and basal ganglia. Serotonergic nuclei in the brain stem give rise to: descending axons which terminate in the medulla, descending axons which terminate the spinal cord
11 of 44
Outline the formation and metabolism of 5-HT
Tryptophan - (tryptophan hydroxylase) - 5- hydroxytryptophan - (aromatic amino acid decarboxylase) - 5-hydroxytryptamine - (MAOA) - 5-hydroxyindoleacetic acid
12 of 44
What can 5-hydroxytryptamine also be converted to?
Melatonin (a hormone produced in the pineal gland and regulates sleep and wakefulness)
13 of 44
Describe the molecular mechanism at 5-HT synapse (formation and storage)
Tryptophan - (tryptophan hydroxylase) - 5HTP - (aromatic amino acid decarboxylase) - 5HT in VMAT - exchange of proton and 5-HT (use of ATP)
14 of 44
Describe the molecular mechanism at 5-HT synapse (release)
Action potential in presynaptic terminal. 5-HT released from vesicles via exocytosis
15 of 44
Describe the molecular mechanism at 5-HT synapse (receptor stimulation)
Diffusion of 5-HT across synaptic cleft and binds to receptors on post-synaptic membrane. Sodium ion channels on post-synaptic membrane open. Influx of Na ions. Action potential in postsynaptic neuron
16 of 44
Describe the molecular mechanism at 5-HT synapse (removal and metabolism)
5-HT taken up by SERT. Conversion of 5-HT to 5-HIAA in presynaptic terminal using MAOA
17 of 44
Serotonin transport are specific to which type of neurotransmitters?
5-HT (selective)
18 of 44
How many sub-types of 5-HT receptors are there?
14 (7 classes)
19 of 44
State which 5-HT receptors are in each of the different classes
5HT (1A-5/F, G-protein Gi/Go), 5HT (2A-C, G-protein, Gq/G11), 5HT3 (ligand gated ion channel), 5HT 4,6,7 (G protein Gs)
20 of 44
Which drugs affect serotonin receptors (agonist)?
Buspirone, carbergoline, triptans,sumatriptan, clozapine, metaclopromide
21 of 44
Which drugs affect serotonin receptors (antagonist)?
Methysergide, Ondansetron, dolesatron, granisetron, tropisetron etc.
22 of 44
What is anxiety?
A pathological feeling of worry, nervousness, or unease about something with an uncertain outcome (linked to excessive 5-HT release)
23 of 44
What is the drug treatment for anxiety?
Buspirone (5HT1a agonist), effective in general anxiety disorder (side effects - dizziness, nausea, vomiting)
24 of 44
What is depression?
Low mood, apathy, negative thought
25 of 44
Outline features of the monoamine hypothesis
Functional deficit of monoamine 5-HT and NA. Evidence link to SERT. Decreased levels of 5-HT in brain
26 of 44
What are the treatments for depression?
Seretonin selective reuptake inhibitors (Fluoxetine/Prozac). Tricyclic antidepressants (Amitryptaline). 5-HT/NA uptake inhibitors (Venlafaxine). Receptor agonists (Mirtazapine - 5HT agonist/antagonist). MOA inhibitors (Phenelzine, Meclobemide)
27 of 44
What is schizophrenia?
Mental disorder (thinking, feeling, behaviour). Starts between ages 15 to 35. Affects 1 in 100 people during their lifetime
28 of 44
Describe features of Pimavanserin
An antipsychotic which targets 5-HT. Orally active, in vivo. FDA approved for the treatment of hallucinations and delusions associated with Parkinson's disease
29 of 44
Give examples of atypical antipsychotic
Clozapine, olanzapine, quetiapine, risperidone and asenapine (relatively potent antagonists of 5-HT2A)
30 of 44
What is a migraine?
A recurrent throbbing headache that typically affects one side of the head and is often accompanied by nausea and disturbed vision. 10-15% affected. Premonitory phase (nausea, mood, light, sensitivity). Aura. Unilateral - bilateral
31 of 44
What are the three hypotheses for the pathophysiology for migraine?
Vascular, brain, inflammation
32 of 44
Describe features of LSD
Psychomotor effects via 5H2A agonist. Inhibits firing of 5HT neurons in Raphe Nucleus
33 of 44
Describe features of Ecstasy
Party drug, euphoria, loss of inhibition, heightened energy, MDMA inhibits monoamine transporter, releases 5HT, affects DA and NA systems
34 of 44
What are the side effects of ecstasy?
Acute hyperthermia, excessive water intake and retention leading to over-hydration and hyponataemia - may lead to heart failure and coma
35 of 44
Describe features of 5-HT and pain
Serotonin in central and peripheral serotonergic neurons. Released from platelets/mast cells after tissue injury. Exerts algesic/analgesic effects depending on site of action/receptor subtype
36 of 44
What happens after nerve injury?
5HT content in lesioned nerve increases. 5HT receptors of 5HT3 and 5HT2A subtype present on C-fibres. 5HT acting in combination with inflammatory mediators, contribute to peripheral sensitisation/hyperalgesia in inflammation and nerve injury
37 of 44
Chemotherapy-induced nausea and vomiting consists of which two phases?
Conventional CINV neurotransmitter hypothesis - immediate phase (release of seretonin from enterochromaffin cells in GI tract). Delayed phase (release of substance P in brainstem)
38 of 44
Describe features of the revised hypothesis for 5HT and chemotherapy
Several emetic neurotransmitters involved in both phases of emesis (dopamine, 5HT, SP, prostaglandins, arachidonic acid derived metabolites). Occur in brainstem and in GIT enteric NS. No single antiemetic to prevent both phases in CINV
39 of 44
What is the standard antiemetic regimen?
5HT3 antagonist plus dexamethasone for prevention of acute emetic phase. 5HT3 combined with an NK1 receptor antagonist (e.g. aprepitant) for the delayed phase
40 of 44
What is serotonin syndrome?
A toxic state caused by an increase in brain serotonin activity
41 of 44
What are the symptoms of serotonin syndrome?
Neuromuscular (restlessness, myoclonus, tremor and rigidity, hyperreflexia, shivering/elevated temperature arrhythmias
42 of 44
What are the causes of serotonin syndrom
Combined or consecutive treatment of SSRIs, tricyclics, MAOIs, tryptophan etc.
43 of 44
What are the treatments for serotonin syndrome?
Stop drugs, usually resolves in no more than 24 hours. Symptomatic measures e.g. cooling, BDZs (prevention - take care when combining or switching serotonergic antidepressants)
44 of 44

Other cards in this set

Card 2

Front

What is an autacoid?

Back

Biological factors which act like local hormones, have brief duration and act near the site of synthesis

Card 3

Front

Which four areas is 5-HT found outside the CNS?

Back

Preview of the front of card 3

Card 4

Front

Describe features of 5-HT in the SI

Back

Preview of the front of card 4

Card 5

Front

Describe features of 5-HT found in platelets

Back

Preview of the front of card 5
View more cards

Comments

No comments have yet been made

Similar Pharmacy resources:

See all Pharmacy resources »See all 5-HT in the Nervous System resources »