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PHRX 3009: drug action > 35. Drug Action on Serotonin > Flashcards

35. Drug Action on Serotonin Flashcards

1
Q

Draw the structure of serotonin.

A

AKA 5-hydroxytrytamine (5-HT)

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2
Q

Describe the physiologic distribution of serotonin.

A

10% CNS
90% GI tract
90% ECs
10% Neurons

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3
Q

Describe serotonin in the brain.

A

Inhibitory neurotransmitter
Acts widely across the brain, affecting the activity of nerve cells
* key role in arousal, mood, aggression, and the sleep-wake cycle

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4
Q

Describe serotonin in the GI tract.

A

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

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5
Q

Explain what happens to excess serotonin in the GI tract?

A

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.

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6
Q

Explain the role of serotonin in the brain.

A

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

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7
Q

Explain the role of serotonin on bowel movements.

.

A

Helps control bowel movements and function

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8
Q

Explain the role of serotonin on nausea.

A

Production of serotonin increases to push out noxious or upsetting food faster.
* serotonin also increases in the blood, which stimulates nausea.

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9
Q

Explain the role of serotonin on blood clots.

A

Blood platelets release serotonin to help heal wounds.
* serotonin causes tiny arterties to narrow –> form blood clots

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10
Q

Explain the role of serotonin on bone health.

A

Significantly high levels of serotonin –> osteoporosis

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11
Q

List the potential results of abnormal low levels of serotonin?

A
  • depression
  • anxiety
  • sleep disorders
  • bowel movement disorders
  • pains
  • headache
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12
Q

List the potential results of abnormally high levels of serotonin.

A
  • 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
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13
Q

Describe the effects of drug action on serotonin.

A
  • 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
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14
Q

Explain the biosynthesis of serotonin: step 1

A

Tryptophan is hydroxylated to 5-hydroxytryptophan by tryptophan hydroxylase (TH)

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15
Q

Explain the biosynthesis of serotonin: step 2

A

5-hydroxytryptophan is decarboxylated to 5-hydroxytryptamine
(5-HT, serotonin) by aromatic amino acid decarboxylase (AADC).

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16
Q

Explain the biosynthesis of serotonin: step 3

A

Serotonin is uptaked into vesicles by vesicular monoamine transporter

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17
Q

Explain the uptake of serotonin: step 4

A

Ca2+ ions activate the vesicles to fuse with the presynaptic membrane and release serotonin into synaptic cleft.

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18
Q

Explain the reuptake of serotonin: step 5

A

Serotonin is retaken up into the presynaptic terminals by the 5-HT transporter (SERT)
* can be inhibited by SSRIs and SNRIs

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19
Q

Explain the degradation of serotonin: step 6

A

Serotonin is degraded into 5-hydroxy-3-indolacetaldehyde (5-HIAL) by monoamine oxidases (MAO)

20
Q

Describe characteristics of tryptophan.

A

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

21
Q

Describe the characteristics of 5-HTP.

A

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

22
Q

List the most commonly prescribed SSRIs.

A
  • paroxetine
  • fluoxetine
  • sertraline
23
Q

What do SSRIs and SNRIs treat?

A

depression

24
Q

Explain the mechanism of monoamine oxidase inhibitors (MAOIs)

A

Act by inhibiting the activity of MAO –> prevents the breakdown of monoamine neurotransmitters of serotonin, dopamine, epinephrine, and norepinephrine.
* MAO-A and MAO-B

25
Q

Explain the difference between MAO-A and MAO-B

A

MAO-A: deaminates serotonin, epinephrine and norepinephrine.
MAO-B: deaminates phenethylamine and certain other traces of amines
dopamine is equally deaminated in both

26
Q

Explain the difference between MAO-A and MAO-B

A

MAO-A: deaminates serotonin, epinephrine and norepinephrine.
MAO-B: deaminates phenethylamine and certain other traces of amines
dopamine is equally deaminated in both

27
Q

MAOIs are effective in the treatment of:

A
  • panic disorder
  • anxiety disorder
  • depression
  • parkinson’s
  • migraine
  • obsessive disorder
28
Q

What are the three different categories for MAOIs?

A
  • nonselective
  • MAO-A selective
  • MAO-B selective
29
Q

Abnormal high levels of serotonin is also known as…

A

Serotonin syndrome

30
Q

List the treatments of serotonin syndrome

A
  • step serotonergic agents
  • supportive care - to normalize vital signs
  • sedation with benzodiazepines
  • medical therapy with cyproheptadine (5-HT2 receptor antagonist)
31
Q

Paroxetine
Drug action:
target proteins:
therapeutic indication:

A

Drug action: SSRI
target proteins: serotonin transporter
therapeutic indication: depression

32
Q

Fluoxetine
Drug action:
target proteins:
therapeutic indication:

A

Drug action: SSRI
target proteins: serotonin transporter
therapeutic indication: depression

33
Q

Sertraline
Drug action:
target proteins:
therapeutic indication:

A

Drug action: SSRI
target proteins: serotonin transporter
therapeutic indication: depression

34
Q

Desvenlafaxine
Drug action:
target proteins:
therapeutic indication:

A

Drug action: SNRI
target proteins: serotonin or norepinephrine transporter
therapeutic indication: depression

35
Q

Venlafaxine
Drug action:
target proteins:
therapeutic indication:

A

Drug action: SNRI
target proteins: Serotonin or norepinephrine transporter
therapeutic indication: depression and anxiety

36
Q

Duloxetine
Drug action:
target proteins:
therapeutic indication:

A

Drug action: SNRI
target proteins: serotonin or norepinephrine transporter
therapeutic indication: depression and anxiety

37
Q

Levomilnacipran
Drug action:
target proteins:
therapeutic indication:

A

Drug action: SNRI
target proteins: serotonin or norepinephrine transporter
therapeutic indication: depression

38
Q

Phenelzine
Drug action:
target proteins:
therapeutic indication:

A

Drug action: MAOI
target proteins: monoamine oxidase
therapeutic indication: depression and anxiety

39
Q

Cyproheptadine
Drug action:
target proteins:
therapeutic indication:

A

Drug action: antagonist
target proteins: 5-HT2 receptor
therapeutic indication: serotonin syndrome

40
Q
A

C. enterochromaffine cells of the GI tract

41
Q
A

C. help to heal wounds

42
Q
A

E. tryptophan

43
Q
A

A. inhibiting serotonin transporter

44
Q
A

E. B and D

45
Q
A

B. phenelzine

PHRX 3009: drug action (36 decks)

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