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Pharmacology Block 2 > 07 Serotonin > Flashcards

07 Serotonin Flashcards

1
Q

What essential amino acid is serotonin synthesized from?

A

Tryptophan

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2
Q

The rate-limiting enzyme in serotonin synthesis is?

A

Tryptophan Hydroxylase

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3
Q

Is tryptophan hydroxylase rate-limiting in synthesis of serotonin in CNS?

A

Not rate-limiting because of low tryptophan levels

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4
Q

What co-factors are required for serotonin synthesis?

A

O2 and reduced pteridine cofactor

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5
Q

What enzyme is involved in synthesis of catecholamines like serotonin?

A

L-aromatic amino acid decarboxylase

Uses pyridoxine cofactor

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6
Q

What is serotonin converted into in the pineal gland?

A

Melatonin

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7
Q

How is serotonin metabolized?

A

Neuronal action terminated primarily by high affinity active reuptake mechanism (SERT) and then intraneuronal conversion by monoamine oxidase (MAO) and aldehyde dehydrogenase to 5- hydroxyindole acetic acid

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8
Q

Where is the majority of serotonin distributed?

A

90%– Enterochromaffin cells of GI mucosa

    • synthesis and storage
    • slow spontaneous release (1 day)
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9
Q

Of the locations serotonin is distributed, where is it not synthesized?

A

Blood platelets

    • stored in vesicles with ATP
    • no synthesis
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10
Q

Where is serotonin located in the CNS?

A

Cell bodides in midbrain raphe nuclei (2%)

– project to hypothalamus, neostriatum, limbic forebrain, neocortex, medulla, and spinal cord

    • synthesis, storage, and release
    • rapid turn over (<4 hours)
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11
Q

Of the serotonin receptors, which is NOT a GPCR?

A

5-HT3 – ligand-gated Cation channel

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12
Q

What is the effector pathway of 5-HT1(A-E)?

A

Inhibition of adenylate cyclase

HT1A also opens K+ channels

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13
Q

What is the effector pathway of 5-HT2(A-C)?

A

Phosphoinositide hydrolysis

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14
Q

What is the effector pathway of 5-HT3?

A

Ligand-gated cation channel

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15
Q

What is the effector pathway of 5-HT4-7?

A

Activation of adenylate cyclase

5-HT5B unknown

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16
Q

What is the function of serotonin auto-receptors and what receptors are they like?

A

Decrease serotonin release

Like 5-HT1A and 5-HT1D

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17
Q

What serotonin receptor results in the inhibition of adenylate cyclase?

A

5-HT1(A-E)

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18
Q

What serotonin receptor results in phosphoinositide hydrolysis?

A

5-HT2(A-C)

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19
Q

What serotonin receptor is a ligand-gated cation channel?

A

5-HT3

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20
Q

What serotonin receptor activates adenylate cyclase?

A

5HT4-7

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21
Q

What is the function of serotonin the in GI system?

A

Causes contraction of G.I. smooth muscle including esophagus, stomach and intestine, increasing tone, peristalsis, and diarrhea

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22
Q

What receptor induces emesis?

A

5-HT3 in GI tract and brain

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23
Q

What is the carcinoid syndrome?

A

Serotonin secreting tumors and bradykinin of enterochromaffin cells

– cause severe diarrhea and asthma

Tx: 5-HT antagonist or somatostatin analog that blocks the secretion of all mediators from tumor

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24
Q

What is the effect of serotonin on large arteries and veins in most vascular beds and cranial blood vessels?

A

Potent vasoconstriction

25
Q

What is the effect of serotonin on smooth muscle cells and the brain?

A

Vasoconstriction

26
Q

What serotonin receptors are found on smooth muscle cells?

A

5-HT2 receptors

27
Q

What serotonin receptors are found in the brain?

A

5-HT1D

28
Q

What is the Bezold-Jarish reflex and what is activated by serotonin?

A

Serotonin is a powerful activator of chemoreceptors in coronary vasculature which activates afferent vagal nerve endings.

The response is bradycardia, hypotension and hypoventilation.

29
Q

What is the effect of serotonin on chemoreceptors in coronary vasculature?

A

Activation!

Bezold-Jarish reflex: Bradycardia, hypotension, and hypoventilation

30
Q

What is the effect of serotonin on platelets?

A

Active uptake of serotonin from circulation results in platelet aggregation

31
Q

As a neurotransmitter, serotonin may be involved in what functions/perceptions/regulations?

A
  • sensory perception (LSD)
  • sleep
  • temperature regulation
  • neuroendocrine regulation (release ACTH, GH, prolactin, TSH, FSH and LH)
  • learning and (short-term) memory
  • pain perception
  • drug abuse
  • emesis (5-HT3 receptors)
  • Mental Illness:
    • Affective disorders
    • Schizophrenia
    • Obsessive-compulsive disorder
    • Anxiety disorders (5-HT1A receptors)
    • Aggressive behavior
32
Q

What types of drugs treat affective disorders?

A

Serotonin Specific Reuptake Inhibitors (SSRIs) and Serotonin Norepinephrine Reuptake inhibitors (SNRIs)

33
Q

What types of drugs treat schizophrenia?

A

Atypical antipsychotics

34
Q

What types of drugs treat obsessive-compulsive disorder?

A

Serotonin Specific Reuptake Inhibitors (SSRIs)

35
Q

Activation of what serotonin receptor results in anxiety?

A

5-HT1A

36
Q

Lysergic Acid Diethylamide

A

Serotonin Agonist

Full or partial agonist at 5-HT2 receptors

– Potent hallucinogen

37
Q

What drug is a full or partial agonist at 5-HT2 receptors and is a potent hallucinogen?

A

Lysergic Acid Diethylamide

38
Q

Buspirone

A

Serotonin Agonist

Partial agonist at 5-HT1A receptors

Tx: Anti-anxiety

39
Q

What drug is a partial agonist at 5-HT1A and is an antianxiety agent?

A

Buspirone

40
Q

Sumatriptan

A

Serotonin Agonist

    • 5-HT1D receptors on cerebral blood vessels
    • inhibit release of vasoactive peptides– Calcitonin gene related peptide (CGRP)
    • promote vasoconstriction

Tx: migraine headaches

Side effects: n/v, angina, dizziness and flushing

41
Q

What drug binds 5-HT1D on cerebral blood vessels to treat migraine headaches?

A

Sumatriptan

42
Q

Fluoxetine

A

Indirect Serotonin Agonist
Serotonin specific Reuptake Inhibitor

  • blocks active reuptake of serotonin into neurons– increases amount of serotonin at synapse

Tx: affective disorders, obsessive-compulsive disorders, panic attacks, etc.

43
Q

What drug blocks the active reuptake of serotonin?

A

Fluoxetine

Serotonin Specific Reuptake Inhibitors (SSRIs)

44
Q

What do SSRIs treat?

A

Ex. Fluoxetine

Tx: affective disorders, obsessive-compulsive disorders, panic attacks, etc.

45
Q

Phenelzine

A

Indirect Serotonin Agonist
Monoamine Oxidase Inhibitors

– block metabolism of serotonin, NE, and DA

Tx: affective disorders and narcolepsy

Side effect: hypertensive crisis

46
Q

What do monoamine oxidase inhibitors block?

A

Black metabolism of serotonin, NE, and DA

47
Q

What indirect serotonin agonist can result in a side effect of hypertensive crisis?

A

Phenelzine

48
Q

What drug can be used to treat narcolepsy and affective disorders?

A

Phenelzine

49
Q

Cyproheptadine

A

Serotonin Antagonist

  • 5-HT2 receptor antagonist; H1 antagonist

Tx: skin allergies, pruritus, and urticaria. Tx of carcinoid

50
Q

What drug is a 5-HT2 receptor antagonist?

A

Cyproheptadine

51
Q

What drug is used in treatment of skin allergies like pruritus and utricaria as well as carcinoid?

A

Cyproheptadine

52
Q

Ondansetron

A

Serotonin antagonist

  • 5-HT3 receptor antagonist
  • acts at both GI and brain receptors

Tx: chemotherapy induced n/v

53
Q

What drug is used to treat chemotherapy induced n/v?

A

Ondansetron

54
Q

What drug works on both 5-HT3 receptors of the CNS and GI?

A

Ondansetron

55
Q

Alosetron

A

Serotonin Antagonist

  • selective 5-HT3 antagonist

Tx: diarrhea predominantly from IBS in women

AEs: severe GI

  • Restricted in women
56
Q

What drug is a selective 5-HT3 antagonist?

A

Alosetron

57
Q

What drug is used to treat diarrhea predominantly from IBS in women?

A

Alosetron

58
Q

What drug is a target for insomnia treatment because it entrains the circadian clock?

A

Melatonin

Pharmacology Block 2 (12 decks)

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