serotonin

Question 1

where is serotonin stored

Answer 1

90% enterochromaffin cells in GI tract, PLT, neurons

Question 2

release of serotonin from enterochromaffin cells

Answer 2

mech stim, hypertonicity, NOR, vagal

Question 3

release of serotonin from PLT

Answer 3

aggregation, degranulation

Question 4

release of serotonin from neurons

Answer 4

NT

Question 5

serotonin and carcinoid tumors

Answer 5

enhancd release

Question 6

all serotonin receptors are _____ except _____

Answer 6

• G Pro coupled receptor

- 5HT3 = ligand gated ion channel

Question 7

5HT3

Answer 7

ligand gated ion channel

-promotes neuronal activation and NT release

Question 8

which serotonin receptors cause direct vasoconstriction on VSM

Answer 8

5HT2 (5HT1D also)

Question 9

which serotonin receptors cause indirect vasodilation on VSM

Answer 9

pre-synaptic 5HT1 receptors on sympathetic neurons inhibit release of the vasoconstrictor NOR
-endothelial cell 5HT1 receptors promote release of NO and PGE

Question 10

serotonin in thrombosis/hemostasis

Answer 10

binds to 5HT2A –> accelerated PLT aggregation, vasoconstriction from VSM
5HT1 can cause endothelial release of NO

Question 11

Bezold-Jarisch reflex

Answer 11

5ht3 receptor (in heart) mediated reflex bradycardia d/t stim of sensory nerve endings resulting in: inhibition of SNS, increased activity of cardiac vagal nerve
-baroreflex will recover MAP, which will initially be higher than baseline d/t constriction from 5HT2, then lower from dilation from 5HT1

Question 12

serotonin in smooth muscle actions

Answer 12

• contracts GI and bronchiolar muscle

- can cause diarrhea assoc with carcinoid syndrome due to effects on GI SM

Question 13

cyproheptadine

Answer 13

• nonselective 5HT1/2 antagonist
• rx symptoms from carcinoid tumors
• blocks PLT aggregation, GI disturbances
• also H1 histamine receptor antagonist and is used for that pupose. SE like H1 antagonist: drowsiness, GI disturbance

Question 14

ketanserin

Answer 14

5HT2 receptor selective (A>C) antagonist

• lowers arterial pressure in HTN, approved in some countries but not US
• blocks 5HT2 receptors on VSM
• blocking alpha 1 adrenergic receptors on VSM

Question 15

LSD

Answer 15

ergot alkaloid

-5HT2 partial agonist, VSM constrictor

Question 16

methylsergide

Answer 16

-antagonist at 5HT2 receptor and partial 5HT1 agonist
-rx carcinoid tumor symptoms
SE: prolonged vasospasm, GI disturbances, CNS disturbances including hallucination

Question 17

ergotamine

Answer 17

partial agonist at 5HT1/2 receptors
-VSM constrictor
-effective for rx acute migraines (probably via 5HT1 receptors)
-control postpartum bleeding via 5HT2, however ergonovine is more active and less toxic
SE: prolonged vasospasm, GI disturbances

Question 18

ergonovine

Answer 18

5HT2 receptor partial agonist, weak antagonist activity
diagnostic tool for vasospastic angina
-used to control postpartum and postabortal hemorrhage (placenta is sensitive to agonist)

Question 19

triptans

Answer 19

sumatriptan, zolmitriptan, rizatriptan
5HT1 (B,D,F) agonists inactive at other receptors
-DOC for migraines, cluster h/a. reduce or abort h/a in over 70% of patients
-activation of prejxn 5HT1B/D receptors on sensory nerves resulting in blockade of trigeminovascular system, leads to inhibited release of inflammatory peptides
-vasoconstriction secondarily, via 5HT1D receptors in cranial BV which promote vasoconstriction
-zolmitriptan is more lipophilic and rapidly absorbed than sumatriptan, has longer t1/2.
SE: recurrent migraine, risk of coronary spasm in pt with CV disease. metabolized by liver, hepatic failure is contraindicated

Question 20

inverse agonists of 5HT receptors

Answer 20

• reducing risk of arterial thrombosis and conditions r/t actions of 5HT on vessel walls
• drugs would impair PLT aggregation, arterial constriction, and thickening of the vessel wall. in clinical trials