Emesis and migranies (Concepts) Flashcards Preview

Mechanism of Drug Action > Emesis and migranies (Concepts) > Flashcards

Flashcards in Emesis and migranies (Concepts) Deck (16)
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1
Q

What is the process of 5-HT (serotonin) synthesis?

A

Tryptophan →(Tryptophan hydroxylase)→ 5-Hydroxytryptophan →(Dopa decarboxylase)→ 5-HT

2
Q

What is the rate-limiting step in 5-HT syntheses?

A

Tryptophan → 5-Hydroxytryptophan

3
Q

What are the isoforms of tryptophan hydroxylase (Tph) and were are they expressed?

A
  • Tph1 = Enterochromaffin cells
  • Trp2 = Neurones
4
Q

How do platelets acquire 5-HT

A
  • They cannot synthesise it themselves.
  • They load 5-HT using SERT (serotonin transproter) while circulating through intestines
5
Q

How is 5-HT degraded?

A
  1. Oxidative deamination by MAO
  2. Oxidation to 5-HIAA by aldehyde dehydrogenase
6
Q

What are the most important 5-HT receptors?

A
  1. 5-HT1(A-F) (Gi-coupled)
  2. 5-HT2(A-C) (Gq-coupled)
  3. 5-HT3 (ionotropic, LGIC)
7
Q

Which part of the brain mediates vomiting reflex?

A

Vomiting centre (medulla)

8
Q

What are the areas controlling vomiting projecting into the vomiting centre?

A
  1. Cortical centres:
    - Emotional factors
    - Repulsive sight/smell
  2. Chemoreceptor trigger zone (CTZ):
    - Noxious substances in blood
    - Inputs from visceral afferents and vestibular nuclei
  3. Vagal afferents (detection of noxious substances in GI tract):
    - Direct
    - Indirect (via chemoreceptor trigger zone)
  4. Vestibular nuclei (via CTZ)
9
Q

What is the main NT and receptors mediating vomiting?

A

NT = 5-HT

Receptor = 5-HT3

10
Q

What are the symptoms of migranes?

A
  • Severe headache (initially unilateral)
  • Nausea & vomiting
  • Photophobia
  • Prostration (weakness)
11
Q

What are the types of migranes?

A
  • Migranes with aura: Progressive visual disturbance (aura) ~30 minutes preceding headache, followed by headache.
  • Migranes without aura: Headache without visual distubances.
12
Q

What are the theories behind the causes of migranes?

A
  1. Vascular hypothesis
  2. Brain hypothesis
  3. Inflammation hypothesis
13
Q

What is the vascular hypothesis of migranes?

A
  1. Intracerebral vasodilation causes aura
  2. Extracerebral vasodilation causes headache
14
Q

What is the brain hypothesis of migranes?

A
  • Wave if cortical spreading depression (CSD) spreads across the brain at rate of ~2m/s and is responsibe for aura and headache.
  • CSD causes inhibition of neuronal activity by depolarisation.
  • Can be caused by increased [K+]e as a result of neuronal hyperactivity.
15
Q

What is the inflammation hypothesis of migranes?

A
  • Activation of the trigeminal nerve nociceptors in meninges and extracranial vessels causes direct generation of nociceptor signals, causing headache.
  • Neurogenic inflammation is secondary to this event.
16
Q

What evidence suggests there is a strong linke between 5-HT and migrane pathogenesis?

A
  1. There is significant increase in urine 5-HIAA during migrane attacks.
  2. There is a decrease in blood 5-HT during migranes.
  3. Drugs that target 5-HT are very effective in treating migranes.