4.2 - Autocoids - Serotonin Flashcards
Biosynthesis
- Precursor
- Locations
- Steps
- Receptors
- Drugs
Precursor
L-Tryptophan
Locations
• Enterochromaffin cells – GIT – > 90% of 5-HT • Platelets • CNS
Steps
L-tryptophan ➡️1️⃣ 5-hydroxytryptophan ➡️2️⃣ 5-hydroxytryptamine
1️⃣
Hydroxylation
2️⃣
Decarboxylation
Effects
- Central
* Peripheral
Central
- Mood regulation
- BP regulation
- Thermoregulation
- Emesis
Peripheral
- GIT
- Blood vessels
- Platelets
- Brochi
- Uterine SM
GIT
Peristalsis
Blodo vessels
Vasoconstriction
Platelets
Platelet aggregation
Bronchi
Bronchospasm
Uterine SM
Contraction — Oxytosis
Receptors
- 5-HT1a
- 5-HT1B/1D
- 5-HT2a/2B
- 5-HT3
- 5-HT4
5-HT1a
— pre-synaptic (CNS)
INHIBITION of 5-HT release
5-HT1B/1D
— Peripheral Blood vessels
Vasoconstriction
5-HT2a/2B
— Smooth Muscles
Contraction
- Vasoconstriction
- Oxytocic effect
5-HT3
— Area postrema of the brain (CTZ)
Emesis
5-HT4
— GIT
⬆️ GI motility
Drugs
- 5-HT1a
- 5-HT1B/1D
- 5-HT2a/2B
- 5-HT3
- 5-HT4
5-HT1a
Partial Agonist
– Buspirone
- Anxiolytic
5-HT1B/1D: AGONISTS
— -triptan
• Sumatriptan • Zolmitriptan • Naratriptan • Rizatriptan (Vasoconstriction)
⬆️est BA
Naratriptan
Use: 5-HT1B/1D AGONISTS
Mgt of acute migraine HA
S/E: 5-HT1b/1D
⬆️ BP
C/I: 5-HT1b/1D
- HTN
* CAD
5-HT2a/2B
- Antagonist
* Agonists
5-HT2a/2B: AGONIST
Ergotamine (Vasoconstriction) – PO – PR – Nasal – SQ
Use: 5-HT2a/2B Agonist
— Ergotamine
• Mgt of acute migraine HA
- Ergotamine/ Ergonavine
• Mgt of post partum hemorrhage
- Ergonovine
‼️ – Claviceps purpurea – Rye – Vasoconstriction – Ergot Toxicity (St. Anthony's Fire)
Ergot
S/E: Ergot derivatives
- ⬆️ BP
* Oxytocic effect
5-HT2a/2B: ANTAGONIST
- Methysergide
- Ketansiren
– Vasodilation
– Use: Prophylaxis for migraine HA
– S/E: Retroperitoneal fibrosis
Methysergide
– Europe
– Antihypertensive
– a1 antagonist
Ketansiren
5-HT3: ANTAGONISTS
— -setron
— anti-emetics
- Granisetron
- Ondnasetron
- Palonosetron
- Dolasetron
Transdermal patch
Granisetron
– T 1/2: 40 hrs
– Single dose: 5 days
Palonosetron
Use: 5-HT3 ANTAGONISTS
Mgt of Chemotherapy-induced N & V
Route:
- IV
* PO
– GIT
– Mgt of irritable bowel syndrome with diarrhea
Alosetron
5-HT4
- Partial Agonists
* Full Agonist
Partial Agonists
- Tegaserod
* Cisapride
Use: PARTIAL AGONISTS
Mgt of irritable bowel syndrome with predominant constipation
Full Agonist:
— Prucalopride
Mgt of chronic constipation