Serotonin

Question 1

5-HT1(A-E)

Answer 1

• inhibition of adenylate cyclase (GPCR)

- 5HT1A also opens K channgel

Question 2

5-HT2(A-C)

Answer 2

-PI hydrolysis (GPCR)

Question 3

5-HT3

Answer 3

• ligand-gated cation channel

- NOT GPCR

Question 4

5-HT4-7

Answer 4

-activation of adenylate cyclase or unknown

Question 5

CV effects of serotonin

Answer 5

• potent vasoconstriction of large arteries and veins, including cranial blood vessels, via 5-HT1D
• vasodilation of coronary, skeletal muscle, and cutaneous blood vessels
• Bezold-Jarisch reflex: coronary chemoreceptors (causes bradycardia, hypotension, hypoventilation)
• platelet aggregation-active uptake of serotonin from circulation

Question 6

CNS effects of serotonin

Answer 6

• sensory perception/LSD and drug abuse
• sleep–slow wave deep sleep
• temperature regulation
• neuroendocrine regulation: release of ACTH, GH, prolactin, TSH, FSH, LH (anterior pituitary hormones)
• learning and memory, particularly short-term
• pain perception
• emesis–5-HT3 receptors
• mental illness–affective disorders, schizophrenia, OCD, anxiety, aggressive behavior

Question 7

Lysergic acid diethylamide

Answer 7

-relatively non-specific; 5HT2 receptor. potent hallucinogen.

Question 8

Buspirone

Answer 8

• 5-HT1A receptor partial agonist

- Antianxiety med

Question 9

Sumatriptan

Answer 9

• and other triptans
• 5-HT1B/D receptors on cerebral blood vessels
• inhibit release of vasoactive peptides (CGRP), promote vasoconstriction, block brainstem pain pathways, inhibit trigeminal nucleus caudalis.
• treatment of migraine headaches; stops existing ones (abortive)
• triptans are major class of drugs used to stop existing migraines (frovatriptan is long-acting; can be used prophylactically)
• side effects: peripheral vasoconstriction, nausea/vomiting, angina, dizziness, flushing
• contraindications: stroke, MI, uncontrolled HTN, ischemic heart disease

Question 10

Other abortive migraine treatment

Answer 10

• ergots: DHE, many routes; ergotamine, oral
• NSAIDS with caffeine
• steroids
• butalbital/caffeine/acetaminophen–base choice because it has potential for abuse and headaches get worse when you stop taking it.

Question 11

Amitryptyline, Nortriptyline

Answer 11

• TCAs used for migraine prophylaxis

- sedating, anticholinergic, effective for many pain sources

Question 12

Antiseizure meds used for migraine prophylaxis

Answer 12

• Divalproex sodium/Valproic acid
• Topiramate
• Gabapentin, Pregabalin, Lamotrigine

Question 13

Vasoactive agents used for migraine prophylaxis

Answer 13

• Beta blockers: propranolol, atenolol

- CCBs: verapamil, diltiazem