Dr. Sher Mohammad and others focus on Serotonin Syndrome in the Niche of Acute Medical Care and Peri-Anaesthetic Care
(Serotonin received its name from its apparent property of being a vasoconstriction-inducing constituent of serum).
The discovery of serotonin is attributed to Vittorio Erspmarer [1] during his attempt to purify extracts from enterochromaffin cells in 1935. Serotonin, also called 5-hydroxytryptamine(5HT) is a monoamine neurotransmitter which plays role in several biologic functions [2]. Serotonin forms from hydroxylation and decarboxylation of amino acid tryptophan. It is found in hypothalamus, limbic system, cerebellum, spinal cord, retina and in highest concentration in enterochromaffin cells of the gut. The liver metabolises excess serotonin into 5-hydroxy-indol acetic acid(5HIAA). The metabolism begins with the oxidation of the compound to an aldehyde by monoamine oxidase enzyme. The aldehyde is further oxidated by aldehyde dehydrogenase into 5HIAA (excreted in urine). Urinary 5-HIAA is increased with an increase in serotonin levels.
Richest sources of serotonin are salmon fish, eggs, milk, chicken and turkey. Plants and vegetables rich in serotonin include spinach, tomatoes, soy products, seeds and nuts. Fruit sources are plantains, pineapple, bananas, kiwi fruit and plums. Formula of serotonin (5-hydroxytryptamine):C10 H12N2O
Serotonin has a role in many body processes, including the regulation of mood and other emotional behaviours as well as pain perception, aggression, vomiting, the sleep cycle, appetite, sexual function and body temperature control. It acts indirectly via G protein coupled receptors and second messenger.
Inadequate serotonin production can have widespread effects on a person’s attention and emotional states and may be responsible for many cases of severe chronic depression. Fluoxetine, paroxetine, sertraline and related drugs inhibit the reuptake of serotonin by axonal terminals (hence the name selective serotonin reuptake inhibitors or SSRIs). This inhibition leads to increased serotonin concentration at synapses, and over time, the increase may relieve the symptoms of depression.
Predominantly used in the treatment of depression, SSRIs are also used to treat seemingly diverse conditions such as eating disorders, neuropathic pain, sexual behaviour, sleep, aggression and anxiety disorders. An interplay of over-and underactivity of various 5-HT receptor subtypes, including 5-HT1A,5-HT2A and 5-HT2C, as well as other neurotransmitter systems, notably noradrenergic and glutamatergic, are thought to be involved.
The therapy with SSRIs can result in excessive serotonergic activity in the central and peripheral nervous systems which can lead to serotonin toxicity. Classical features include a combination of mental status changes, autonomic instability, and neuromuscular hyperactivity. The intensity of clinical findings reflects the degree of serotonin toxicity-the term serotonin syndrome usually refers to the severe end of toxicity spectrum.
Herbal products which can cause clinically significant inhibition of CYP 450
Grapefruit juice contains bergamottin which inhibits CYP3A49 (70% of this enzyme is present in small gut epithelial cells and 30% in the liver) [3]. A 200 ml of grapefruit juice reduces the activity to a half within 4 hours. This inhibitory effect continues into next day and possibly 2nd day.
Caffeine can inhibit CYP1A2,theoretically it may increase available levels of other serotonergic drugs metabolised by CYP1A2, notably tricyclic antidepressants.
Other important CYP enzyme interactions with serotonergic medications include St. John Wort which inhibits CYP3A4 and it also contains constituents inhibiting several other enzymes (CYP 12A,2C9,2C19,2D6), cigarette smoke (CYP1A2) and alcohol, especially red wine (CYP2E1) [4].
Drugs Triggering Serotonin syndrome:
There are various serotonin-mimetic products which include
Herbs: St. John Wort, Syrian rue, panax, ginseng, nutmeg, yohimbine
Obesity drug: Diethylpropion
Psychedelics :5 Methoxy-di-isopropyltryptamine, Lysergic acid diethylamide (LSD)
Extra: Tryptophan, L-dopa, valproate, Buspirone
The rest of the serotonin-mimetic drugs are briefly mentioned in table-1
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