SEROTONIN

SEROTONIN

Q. 1 Inhibitors of serotonin (5-HT) uptake, such as paroxetine, can cause clinically significant drug interactions with which of the following?

 A Diazepam

 B

Digoxin

 C

Halothane

 D

Tranylcypromine  

Q. 1

Inhibitors of serotonin (5-HT) uptake, such as paroxetine, can cause clinically significant drug interactions with which of the following?

 A

Diazepam

 B

Digoxin

 C

Halothane

 D

Tranylcypromine  

Ans. D

Explanation:

Fatalities have been reported when fluxetine and MAO  inhibitors  (MAOI’s)  such  as tranylcypromine have been given simultaneously. The MAOIs should be stopped at least 2weeks before the administration of fluoxetine or paroxetine. Note that a similar severe interaction can occur between tricyclic antidepressants and MAOIs; the same warning against “overlapping” the two classes of drugs, and allowing one to “Clear” the system completely before starting the other, applies.


Q. 2

Nicotinic acid and serotonin are formed from :

 A

Pyridoxine

 B

Tryptophan

 C

Tyrosine

 D

Methionine

Ans. B

Explanation:

Following hydroxylation of tryptophan to 5-hydroxytryptophan by liver tyrosine hydroxylase, subsequent decarboxylation forms serotonin (5-hydroxytryptamine), a potent vasoconstrictor and stimulator of smooth muscle contraction. 

The amino acid tryptophan can be converted to niacin with an efficiency of 60:1 by weight. Thus, the RDA for niacin is expressed in niacin equivalents. A lower conversion of tryptophan to niacin occurs in vitamin B6 and/or riboflavin deficiencies and in the presence of isoniazid.
 
Ref: Russell R.M., Suter P.M. (2012). Chapter 74. Vitamin and Trace Mineral Deficiency and Excess. In D.L. Longo, A.S. Fauci, D.L. Kasper, S.L. Hauser, J.L. Jameson, J. Loscalzo (Eds), Harrison’s Principles of Internal Medicine, 18e.

 


Q. 3 With help of pyridoxine, serotonin is synthesized from which of the following precursor amino acid?

 A

Tyrosine

 B

Tryptophan

 C

Phenylalanine

 D

Glycine

Ans. B

Explanation:

  • Serotonin is synthesized from the essential amino acid tryptophan.
  • The rate-limiting step is the conversion of the amino acid to 5-hydroxytrptophan by tryptophan hydroxylase. This is then converted to serotonin by the aromatic L-amino acid decarboxylase.
  • 5-hydroxyindoleacetic acid (5-HIAA). This substance is the principal urinary metabolite of serotonin.
  • There are seven classes of 5-HT receptors (from 5-HT1 through 5-HT7 receptors).

Ref: Barrett K.E., Barman S.M., Boitano S., Brooks H.L. (2012). Chapter 7. Neurotransmitters & Neuromodulators. In K.E. Barrett, S.M. Barman, S. Boitano, H.L. Brooks (Eds), Ganong’s Review of Medical Physiology, 24e.


Q. 4

Serotonin is secreted by:

 A

Thyroid

 B

Adrenal cortex

 C

Adrenal medulla

 D

Argentaffin cells

Ans. D

Explanation:

Serotonin is a vasoconstricting hormone, produced in the brain and GI tract. In the GI tract it is produced normally by enterochromaffin cells (argentaffin cells). The principal function is to regulate smooth muscle contraction and peristalsis.

Serotonin: also called 5-hydroxytryptamine, is a chemical substance that is derived from the amino acid tryptophan.
Principally found stored in three main cell types;
  1. Serotonergic neurons in the CNS and in the intestinal myenteric plexus, 
  2. Enterochromaffin cells in the mucosa of the gastrointestinal tract and 
  3. Blood platelets 
Synthesis:
  • Serotonergic neurons and enterochromaffin cells can synthesize serotonin from its precursor amino acid L-tryptophan, whereas platelets rely upon uptake of serotonin for their stores. The biochemical pathway for serotonin synthesis initially involves the conversion of L-tryptophan to 5-hydroxytryptophan by the enzyme L-tryptophan hydroxylase. This enzyme provides the rate limiting step for serotonin synthesis. 
Metabolism of serotonin is carried out primarily by the enzyme monoamine oxidase (MAO), The action of MAO converts serotonin to 5-hydroxyindole acetaldehyde which in turn is readily metabolized by aldehyde dehydrogenase to produce 5-hydroxyindole acetic acid as the major excreted metabolite of serotonin.
 
Carcinoid syndrome: are neuroendocrine tumours (NETs) of predominantly enterochromaffin cell origin (Kulchitsky cells).Carcinoid syndrome is made up of a constellation of symptoms which are caused by the release of a variety of substances (serotonin, histamine, and substance P, among others) by the carcinoid tumor. It may cause trytophan deficiency and causes decrease in  niacin synthesis leading to pellagra.
 
Ref: Principles of medical physiology, By Sabyasachi Sicar, Page 641.

Q. 5 Among the following 5HT3 antagonist is ‑

 A

Cisapride

 B

Ondansetron

 C

Clozapine

 D

Buspirone

Ans. B

Explanation:

Ans. is ‘b’ i.e., Ondansetron

o Stimulation of 5-HT3 receptor is responsible for vomiting induced by anticancer drugs. 5-HT3 receptor antagonists (ondansetron, granisetron and tropisetron) are DOCs for chemotherapy induced vomiting.


Q. 6

Durgs used in migraine prophylaxis are all except

 A

Flunarizine

 B

Propranolol

 C

Cyproheptadine

 D

Sumatriptan

Ans. D

Explanation:

Ans. is ‘d’ i.e., Sumatriptan

Sumatriptan is DOC for acute severe migraine. It is not indicated for prophylaxis of migraine attacks.


Q. 7

Ondansetron acts by –

 A

Acting on CTZ

 B

5-HT3 antagonist

 C

Increases GIT motility

 D

a and b

Ans. D

Explanation:

Ans. is ‘a’ i.e., Acting on CTZ; ‘b’ i.e., 5-HT3 antagonist

o Ondansetron blocks the deoplarizing action of 5HT through 5-HT3 receptors on vagal afferents in the gut as well as in NTS and CTZ. It blocks emetogenic impulses both at their peripheral origin and their central relay.


Q. 8

Which of the following is true regarding 5-HT derivatives:          

March 2009

 A

Cisapride is selective 5-HT4 antagonist

 B

Ondansetron is a 5-HT3 agonist

 C

Cyproheptadine is 5-HT2A agonist

 D

Sumatriptan action is agonistically 5-HT 1B/1D receptor mediated

Ans. D

Explanation:

Ans. D: Sumatriptan action is agonistically 5-HT 113/1D receptor mediated

Cisapride and renzapride are selective 5-HT4 agonists.

  • Ondansetron is a selective 5-HT3 antagonist which inhibits vomiting by blocking these receptors in brainstem as well as in gut wall.
  • Cyproheptadine is 5-HT2A antagonist and has additional H1 antihistaminic, anticholinergic and sedative properties.
  • Sumatriptan and other triptan are selective 5-HT 113/1D agonists, constricts cerebral blood vessels and has emerged as the most effective treatment of acute migraine attacks.

Q. 9 Methysergide is banned as it causes ‑

 A Pulmonary fibrosis

 B

Pleural effusion

 C

Syncope

 D

Myocarditis

Ans. A

Explanation:

Ans. is ‘a’ i.e., Pulmonary fibrosis

Methysergide

  • It is chemically related to ergot alkaloids and antagonizes the action of serotonin on smooth muscles including that of blood vessels, withot producing ergot like effects.
  • It is a potent 5HT2A/2C antagonist.
  • It has been used for migraine prophylaxis, carcinoid and postgastrectomy dumping syndrome.
  • Prolonged use has caused abdominal, pulmonary and endocardial fibrosis, because of which it has gone into disrepute.

Q. 10 With help of the drug shown below, serotonin is synthesized from which of the following precursor amino acid? 

 A Tyrosine.

 B

Tryptophan.

 C

Phenylalanine.

 D

Glycine.

Ans. B

Explanation:

Ans:B.)Tryptophan.

  • Serotonin is synthesized from the essential amino acid tryptophan.
  • The rate-limiting step is the conversion of the amino acid to 5-hydroxytrptophan by tryptophan hydroxylase. 
  • This is then converted to serotonin by the aromatic L-amino acid decarboxylase which needs Pyridoxal Phosphate as a cofactor.

Q. 11 Serotonin is derived from –

 A

Tyrosine

 B

Tryptophan

 C

Phenylalanine

 D

Methionine

Ans. B

Explanation:

Ans. is ‘b’ i.e., Tryptophan 

[Ref Harper 29’/e p. 300]

  • Tryptophan is a precursor for synthesis of niacin (nicotinic acid), serotonin and melatonin.


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