35. Drug Action on Serotonin Flashcards
Draw the structure of serotonin.
AKA 5-hydroxytrytamine (5-HT)
Describe the physiologic distribution of serotonin.
10% CNS
90% GI tract
90% ECs
10% Neurons
Describe serotonin in the brain.
Inhibitory neurotransmitter
Acts widely across the brain, affecting the activity of nerve cells
* key role in arousal, mood, aggression, and the sleep-wake cycle
Describe serotonin in the GI tract.
Indigenous bacteria produces metabolites that singal colonic enterochromaffin cells (ECs)
* ECs increasee 5-HT biosynthesis - secreted luminally and basolaterally
* increased 5-HT uptake by circulating platelets and activation
* increased stimulation of myenteric neurons and gut motility
Explain what happens to excess serotonin in the GI tract?
Excess serotonin is soaked up by the local veins and then stored in blood platelets.
* gut serotonin stimulates nearby nerves to regulate other activities in the body.
Explain the role of serotonin in the brain.
Regulates anxiety, happiness, and mood
* low serotonin is associated with depression
Stimulates the parts of the brain that control the sleep and wake cycle
Impacts sexual function
* low levels = increased libido
* high levels = reduced libido
Explain the role of serotonin on bowel movements.
.
Helps control bowel movements and function
Explain the role of serotonin on nausea.
Production of serotonin increases to push out noxious or upsetting food faster.
* serotonin also increases in the blood, which stimulates nausea.
Explain the role of serotonin on blood clots.
Blood platelets release serotonin to help heal wounds.
* serotonin causes tiny arterties to narrow –> form blood clots
Explain the role of serotonin on bone health.
Significantly high levels of serotonin –> osteoporosis
List the potential results of abnormal low levels of serotonin?
- depression
- anxiety
- sleep disorders
- bowel movement disorders
- pains
- headache
List the potential results of abnormally high levels of serotonin.
- altered mental status: irritability, agitation, restlessness, and anxiety
- neuromuscular hyperactivity: tremors, shivering, muscle rigidity, and muscle spasms
- autonomic hyperactivity: sweating, rapid heartbeat, high blood pressure, and fever
Describe the effects of drug action on serotonin.
- altering biosynthesis in presynaptic neuron
- altering release from a presynaptic neuron to a synaptic cleft
- altering reuptake back to a presynaptic neuron
- altering degradation of serotonin
Explain the biosynthesis of serotonin: step 1
Tryptophan is hydroxylated to 5-hydroxytryptophan by tryptophan hydroxylase (TH)
Explain the biosynthesis of serotonin: step 2
5-hydroxytryptophan is decarboxylated to 5-hydroxytryptamine
(5-HT, serotonin) by aromatic amino acid decarboxylase (AADC).
Explain the biosynthesis of serotonin: step 3
Serotonin is uptaked into vesicles by vesicular monoamine transporter
Explain the uptake of serotonin: step 4
Ca2+ ions activate the vesicles to fuse with the presynaptic membrane and release serotonin into synaptic cleft.
Explain the reuptake of serotonin: step 5
Serotonin is retaken up into the presynaptic terminals by the 5-HT transporter (SERT)
* can be inhibited by SSRIs and SNRIs
Explain the degradation of serotonin: step 6
Serotonin is degraded into 5-hydroxy-3-indolacetaldehyde (5-HIAL) by monoamine oxidases (MAO)
Describe characteristics of tryptophan.
Natural amino acid found in high-protein foods and milk.
* make mood more stable and reduce extremes in behavior by restoring the balance of serotonin and melatonin in the brain.
* support mood, relaxation, and restful sleep
* sold as a dietary supplement
Describe the characteristics of 5-HTP.
A chemical by-product of L-tryptophan.
* works by increasing the production of serotonin in the brain
* important role in depression, insomnia, obesity, and other conditions
List the most commonly prescribed SSRIs.
- paroxetine
- fluoxetine
- sertraline
What do SSRIs and SNRIs treat?
depression
Explain the mechanism of monoamine oxidase inhibitors (MAOIs)
Act by inhibiting the activity of MAO –> prevents the breakdown of monoamine neurotransmitters of serotonin, dopamine, epinephrine, and norepinephrine.
* MAO-A and MAO-B
