Exam 3: serotonergic system (its role in headaches) Slattery

Question 1

What is serotonin (5-HT)?

Answer 1

CNS neurotransmitter

Question 2

What is the peripheral targets of serotonin?

Answer 2

smooth muscle in GI tract, CV system and platelet aggregation

Question 3

What amino acid is serotonin made from?

Answer 3

tryptophan

Question 4

What are the roles of serotonin in the CNS?

Answer 4

sleep-wake cycle regulation, aggression and impulsivity, cognition, sensory perception, motor activity, temp regulation, NOCICEPTION AND MODD, appetite, sexual behavior

Question 5

What is the role of serotonin in the GI tract?

Answer 5

increases GI smooth muscle tone, facilitates peristalsis

Question 6

Where is serotonin stored in the GI tract?

Answer 6

enterochromaffin cells of gastric mucosa

Question 7

Where is serotonin metabolized?

Answer 7

monoamine oxidase in liver

Question 8

What is the role of serotonin in the CV system?

Answer 8

causes contraction of most vascular smooth muscle, dilates blood vessels in heart

Question 9

Describe the mechanism of inducing migraines

Answer 9

1) stress triggers activation of trigeminovascular system. 2) CN V nerve terminal releases vasoactive substances at miningeal blood vessels (CGRP, substance P, neurokinin A). 3) Vasodilation. 4) increased nociceptive neurotransmission within trigeminocervical complex in brainstem and upper spinal cord

Question 10

What are the three neurotransmitters released by trigeminal nerve that lead to increased nociception?

Answer 10

CGRP, substance P, neurokinin A

Question 11

What is the action of activated 5-HT 1A/B/D receptors?

Answer 11

activating K+ channel, Inhibition of calcium channel, hyperpolarizing the neuron

Question 12

What does the 5-HT 1A receptor do, where is it located?

Answer 12

raphe nuclei of brainstem, inhibitory effect on serotonergic neurons

Question 13

What does the 5-HT 1B and 1D receptors do?

Answer 13

inhibit serotonin release

Question 14

What is the mechanism of triptans?

Answer 14

Mimics 5-HT: 5HT 1B and 1D receptor agonists, leading to hyperpolarization of trigeminal nerves decreasing amount of CGRP, Substance P, and neuorkinin A release. They also lead to decreases in cAMP within blood vessels by inhibiting GCPR, also resulting in vasoconstriction

Question 15

Describe the pharmacokinetics of triptans

Answer 15

metabolized by monoamine oxidase, have a 1-3 t1/2, excreted in both urine and feces

Question 16

What are contraindications of triptans?

Answer 16

coronary artery disease, CV disease, hemiplegic of basilar migraine, ischemic bowl, uncontrolled HTN, pt is on ergots or other triptans or MAOIs, liver disease

Question 17

What populations should you avoid giving ergots to?

Answer 17

pregnant women, vascular, hepatic and renal disease patients

Question 18

What liver enzyme do ergots interact with?

Answer 18

CYP3A4