Serotonin Flashcards
What are 3 areas where serotonin is stored?
Platelets
Neurons
Enterochromaffin cells (GI)
What are 4 stimuli that can cause release of serotonin from enterochromaffin cells?
Mechanical stim
NOR
Hypertonicity
Vagal stimulation
What are 2 events that cause serotonin release from platelets?
Aggregation
Degranulation
How does a carcinoid tumor affect serotonin release?
It enhances 5HT release
All but one of the 5HT receptors (1-7) are GPCRs. What is the exception? What is the function of this exception?
5HT3
Activation - Neuronal activation / NT release
What is the direct effect of serotonin on vascular smooth muscle? Which 2 receptor subtypes mediate this action?
Vasoconstiction
5HT2 and 5HT1D
How can serotonin indirectly cause vasodilation? What receptor subtype mediates this action?
- presynaptic receptor inhibits the release of NOR
- 5HT1
What serotonin receptor mediates platelet aggregation?
5HT2
What are the 2 major roles of serotonin following vascular injury? What receptor subtype mediates these actions?
Platelet aggregation / thrombus formation
Vasoconstriction
5HT2A
What is the bezold Jarisch reflex? What serotonin receptor subtype mediates this effect?
reflex bradycardia due to stimulation of sensory nerve endings - decreased sympathetic stim, increased vagus activity to heart
5HT3
What is the effect of serotonin on the GI and bronchiolar smooth muscle? What is carcinoid syndrome?
- Contraction of those muscles
- Diarrhea because of too much 5HT release
What are the receptor targets of cyproheptadine? What are its actions at these receptors? What is this drug used for? What is a non-specific receptor target of this drug? What are 2 side effects?
- 5hT 1 and 5ht2
- Antagonist
- Carcinoid tumors
- H1 histamine receptor
- Drowsiness, GI disturbance
What is the receptor subtype targeted by ketanserin? What is it used for? What is the mechanism? What is a non selective drug target of this drug?
5HT2 antagonist
Hypertension
Blocks vascular 5HT2
Alpha 1 adrenergics on smooth muscle
What is the action of LSD on serotonin receptors? What is its physiological effect?
5HT2 antagonist
Vascular smooth muscle constrictor
What is the action of ergonivine on serotonin receptors? What is it used to test diagnostically? What is it used to treat? (2)
- 5ht2 partial agonist, weak antagonist
- diagnostic for vasospastic angina
- Post partum and post abortal hemorrhage
What is the action of methysergide on serotonin receptors ? What is it used to treat?
5HT2 antagonist, 5HT1 partial agonist
Carcinoid tumors
What is the action of ergotamine on serotonin receptors? What is its physiological action? What is it used to treat? (2)
Partial 5HT1/2 agonist
VSM constrictor
Migraines, post partum bleeding
Both ergotamine and ergonovine are effective for the treatment of post partum bleeding. Which is preferred and why?
Ergonovine
Less toxic, more active
What are 2 general side effects associated with 5HT2 agonists? What is specific for methysergide?
GI disturbances, prolonged vasospasm
Methy - CNS disturbances (hallucination)
What are the receptor targets of the triptans? What are their actions at these receptors? What are they used to treat (2)?
5HT1B/D/F agonists
Migraines, cluster headaches
What are the 3 triptans provided as examples? What is their mechanism? What is a secondary effect on these drugs on vasculature?
Suma/Zolmi/Riza-triptan
Activate presynaptic 5HTR, block trigem system, block release of inflammatory peptides
Vasoconstriction
How does zolmitriptan compare to sumatriptan (tablet form for both)? (2)
More lipophillic
Longer half life
What are 2 side effects of triptans? What patient population is contraindicated?
Recurrent migraine, coronary spasm (in CV disease)
Hepatic failure patients
While none are on the market yet, what is the expected effect of inverse agonists of the 5HT2A receptor? (3) What would they be used for (2)?
Reduced platelet aggregation
Reduced arterial constriction
Reduced vessel wall thickening
Prevent MI and stroke
