Serotonin

Question 0

Serotonin Receptor 5-HT2A

Answer 0

Gq, IP3, Ca
Platelets - when R activated by serotonin, platelets aggregate (serotonin stored by platelets, release reaction causes platelet activation)
Smooth muscle – bronchiolar tone, GI tone (contraction), peristalsis. Powerful vasoconstrictor, EXC in skeletal muscle or heart (DILATES blood vessels instead)
Tox: Serotonin Syndrome

Question 1

Carcinoid Tumor

Answer 1

Neoplasm of enterochromaffin cells -> release SEROTONIN, histamine, bradykinin
Signs: flushing of head and neck, abd cramps and diarrhea, asthmatic wheezing
Dx: urinary 5-HIAA
Tx: 5-HT2 antagonists or surgery

Question 2

Phenoxybenzamine (alpha1 blocker, also 5HT2)
Cyproheptadine (5HT2 blocker, also H1 and M3)
Chlorpromazine (DA2 blocker, also H1, M3, 5 HT2, alpha1)
Ritanserin
(Also H1 blockers)

Answer 2

Competitive antagonist action at 5-HT2A
Smooth muscle action in carcinoid tumor. Cold-induced urticaria
Ritanserin: Platelet stabilizer
Tox: Antimuscarinic, sedation
Note: in asthma and COPD, the action of serotonin is blocked by Beta2 agonists

Question 3

Serotonin Syndrome

Answer 3

This condition is an excess of serotonin due to drugs which block serotonin metabolism (MAOI) and/or drugs which block reuptake of serotonin (SSRI or tricyclic antidepressants) and serotonin agonists
Rapid onset: Hypertension, hyper reflexia, bronchoconstriction, tremor, clonus, hyperthermia, bowel sounds, diarrhea, mydriasis, agitation, coma

Question 4

Synthesis, storage and release of Serotonin occur in:

Answer 4

1) Enterochromaffin Cells of the GI tract
2) Granulated epithelial cells of neuroepithelial bodies (NEB) in the lung
3) CNS, projections in the spinal cord function in motor control and pain perception; forebrain projections control mood and cognition 4)Mast Cells release histamine, serotonin and other cytokines (in RODENTS, NOT HUMANS)

Question 5

5-HIAA

Answer 5

Primary product due to oxidation of serotonin to an acetic acid by MAO. Requires NAD
It can be collected in 24 hr urine and is diagnostic for increases in serotonin. 5-HT containing foods (banana, pineapple and plum) can cause a false positive. Alcohol can cause a false negative

Question 6

5-HT3

Answer 6

Na+, K+ channel activation
GI tract and CTZ, vomiting center of medulla Vomiting Reflex
Tox: Vomiting caused by chemical stimuli, cancer chemotherapy

Question 7

Ondansetron Granisetron Dolasetron Palonosetron Alosetron

Answer 7

Serotonin Antagonist at 5-HT3 receptor
Prevent N/V associated with surgery and cancer chemotherapy Severe Irritable bowel syndrome. Restricted to severe diarrhea- predominant IBS in women
Tox: 30% incidence of constipation, may include hospitalization. Ischemic colitis may be fatal