Serotonergic System - Slattery Flashcards

1
Q

What is serotonin? What is it involved in?

A
  • CNS neurotransmitter (5-HT)
  • Peripheral actions
    • smooth muscle in GI tract
    • Cardiovascular system
    • Platelet aggregation
  • Multiple receptor types
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2
Q

How is serotonin synthesized/metabolized?

A
  • Synthesized from tryptophan
  • Strored in axon terminal
  • Metabolized by monoamine oxidase (MAO) after collection by reuptake transporter
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3
Q

What CNS functions is serotonin involved in?

A
  • Sleep-wake cycle regulation
  • Aggression & Impulsivity
  • Cognition
  • Sensory perception
  • Motor Activity
  • Temperature regulation
  • Nociception
  • Mood
  • Appetite
  • Sexual behavior
  • Hormone secretion
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4
Q

What is the cycle of serotonin in the GI tract?

A
  • Produced/Stored in enterochromaffin cells of gastric mucosa
  • Released in response to mechanical stretch
    • eating
    • vagal stimulation
  • Metabolized by monoamine oxidase in liver
  • Uptake by platelets
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5
Q

What action does serotonin have on the cardiovascular system?

A

CONSTRICTION!

  • constriction of cerebral vasculature
  • constriction of splanchnic/renal vasculature
  • constriction of pulmonary vasculature
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6
Q

What is the role of serotonin in migraine headaches?

A
  • concentrations vary in migraine attack
  • increased 5-HT levels = trigger
  • 5-HT receptor agonists = treatment
    • activate pre-synaptic axon terminal receptors that stop serotonin release
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7
Q

What do various serotonin receptors do?

A
  • Transmembrane-signaling system
    • couplet to g-protein –> second messenger system
  • Activate K+ channel, inhibit Ca2+channel
    • Type 1A, 1B, 1D
  • Pre-synaptic axon terminals receptors inhibit serotonin release
    • Type 1B, 1D
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8
Q

What is the MOA of Triptans?

A
  • Serotonin 1B & 1D receptor agonists
    • pre-synaptic axon terminal receptors
    • prevents release of 5HT
  • Vasoconstriction
  • Autoregulation
  • Decreased pro-inflammatory neuropeptide release

(Also lipophilic so they can cross BBB)

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9
Q

How are Triptans metabolized?

A
  • Metabolized by Monoamine oxidsase
  • 1-3 hour half-life
  • Urinary & fecal excretion
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10
Q

What are the contraindications of giving Triptans?

A
  • CAD
  • CVD
  • Hemiplegic or basilar migraine
  • IBD
  • Uncontrolled hypertension
  • Liver disease
  • On ergots or other triptans
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11
Q

What are Ergots?

A
  • Dihydroergotamine (DHE)
  • fungal product used to treat migraine headaches
    • fewer peripheral side effects
    • causes N/V
  • Interacts with cyp3A4
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12
Q

What are the contraindications of giving Ergots?

A
  • Vascular disease
  • Liver disease
  • Renal disease
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