100 MCQs from Dr. David Browne and Colleagues
David Browne, Selena Morgan Pillay, Guy Molyneaux, Brenda Wright, Bangaru Raju, Ijaz Hussein, Mohamed Ali Ahmed, Michael Reilly in MCQs for the New MRCPsych Paper A, 2017
This woman presents with symptoms that are associated with hyponatraemia. She has several risk factors for hyponatraemia including being female, elderly and receiving co-therapy with a non-steroidal anti-inflammatory drug (NSAID). While she could have delirium as a consequence of hyponatraemia, this vignette does not describe symptoms associated with delirium such as confusion. Symptoms of serotonin syndrome could include restlessness, diaphoresis, tremor, shivering, myoclonus, confusion or convulsions leading to death. Symptoms of hypokalaemia could include muscle weakness, hypotonia, cardiac arrhythmias, cramps and tetany; they are often due to diuretics. The symptoms of neuroleptic malignant syndrome include fever, diaphoresis, rigidity, confusion, fluctuating consciousness, fluctuating blood pressure, tachycardia, elevated creatinine kinase, leucocytosis and altered liver function tests. (2, pp 210–1, 235, 103–5)
Isoniazid
M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson in Kucers’ The Use of Antibiotics, 2017
Symptoms similar to those of histamine poisoning have been observed in patients taking isoniazid after eating various types of fish (Uragoda and Kottegoda, 1977; Uragoda, 1978; Uragoda, 1980). Palpitations, erythema, red eyes, headache, vomiting, wheezing, sweating, diarrhea, urticaria, and itching appear within minutes of eating the fish and resolve within a few hours. During spoilage of scromboid fish (skipjack and tuna), bacteria convert histidine to histamine and ordinary cooking fails to destroy histamine in food. Similar clinical features have been described immediately after eating substances rich in monoamines, especially tyramine, such as cheese and red wine (Kent Smith and Durack, 1978; Lejonc et al., 1979; Uragoda and Lodha, 1979; Toutoungi et al., 1985). Isoniazid is closely related to some of the monoamine oxidase (MAO) inhibitors, and probably precipitates a histamine reaction by inhibiting the enzymes MAO and diamine oxidase (histaminase), which normally rapidly detoxify histamine (Self et al., 1999). Patients who experience flushing with isoniazid should be advised to avoid eating cheese and probably other food and beverages rich in monoamines. A potential for increased risk of serotonin syndrome when administered with other agents such as serotonin reuptake inhibitors has been raised as a possibility (Doyle et al., 2001).
Treatment of Psychological Disorders
Mohamed Ahmed Abd El-Hay in Understanding Psychology for Medicine and Nursing, 2019
The selective serotonin reuptake inhibitors (SSRIs) increase serotonin levels by blocking its reuptake. These involve fluoxetine, paroxetine, sertraline, fluvoxamine, citalopram, and escitalopram. Common side effects of SSRIs include nausea, trouble sleeping, nervousness, tremors, and sexual problems. Co-prescription of SSRIs with other serotonergic drugs and especially MAOIs can lead to serotonin syndrome. This is characterized by a classic triad of mental status changes, neuromuscular abnormalities, and autonomic hyperactivity. These include anxiety, agitation, confusion, hyperreflexia, clonus, tremors, myoclonus, rigidity, increased heart rate, flushing, hyperthermia, and excessive sweating. Death can occur in severe cases of serotonin syndrome.
Monitoring for antidepressant-associated adverse events in the treatment of patients with major depressive disorder: An international consensus statement
Published in The World Journal of Biological Psychiatry, 2018
Seetal Dodd, Philip B. Mitchell, Michael Bauer, Lakshmi Yatham, Allan H. Young, Sidney H. Kennedy, Lana Williams, Trisha Suppes, Carlos Lopez Jaramillo, Madhukar H. Trivedi, Maurizio Fava, A. John Rush, Roger S. McIntyre, Michael E. Thase, Raymond W. Lam, Emanuel Severus, Siegfried Kasper, Michael Berk
Serotonin syndrome is the possible result of excessive serotonin receptor antagonism and not necessarily an idiopathic drug reaction (Boyer and Shannon 2005). Serotonin syndrome is diagnosed by clinical symptoms suggestive of CNS hyper-excitability co-occurring with drug-induced increased serotonin. Symptoms vary between cases and may be mild to life threatening. Common symptoms include; confusion, consciousness impairment, agitation, tremor, hyperreflexia, myoclonus, tachycardia, hypertension and fever. In more severe cases rhabdomyolysis, clonus, rigidity/hypertonicity, elevated temperature, fever or hyperthermia may be evident (Werneke et al. 2016). Treatment of serotonin syndrome requires stopping the serotonergic agent in all cases. Intensity of treatment depends on the severity of illness however, treating clinicians should be aware that some cases may deteriorate without aggressive management. Cardiorespiratory and thermal abnormalities must be aggressively corrected (Boyer and Shannon 2005). Cyproheptadine is a recommended therapy, although other agents have been used (Boyer and Shannon 2005).
Ginsenoside Re attenuates 8-OH-DPAT-induced serotonergic behaviors in mice via interactive modulation between PKCδ gene and Nrf2
Published in Drug and Chemical Toxicology, 2023
Eun-Joo Shin, Ji Hoon Jeong, Bao-Trong Nguyen, Naveen Sharma, Cuong Ngoc Kim Tran, Seung-Yeol Nah, Yi Lee, Jae Kyung Byun, Sung Kwon Ko, Hyoung-Chun Kim
Serotonin syndrome is caused mainly by increases in 5-HT within the central nervous system, and various metabolic pathways can metabolize this excess 5-HT. The majority of 5-HT is catabolized primarily by monoamine oxidase (MAO). In particular, MAO-A has the highest affinity toward 5-HT. MAO-A is located explicitly on the mitochondrial membrane in various cells and oxidatively deaminates several biogenic amines (Squires et al.2006). This process generates H2O2 and reactive aldehydes as a by-product of 5-HT metabolism (Squires et al.2006). Therefore, it is plausible that excessive release of 5-HT by 8-OH-DPAT can be a valid source of oxidative parameters and contributes to the development of oxidative damage. In this study, we observed that 8-OH-DPAT treatment facilitated oxidative burden in the hypothalamus, as shown by the inactivation of Nrf2-related GSH induction. We raise the possibility that GRe-mediated potential on the induction of GPx-1 (Tran et al.2017a) may be implicated in the current findings, although the precise mechanism remains to be explored.
The serotonin toxidrome: shortfalls of current diagnostic criteria for related syndromes
Published in Clinical Toxicology, 2022
Angela L. Chiew, Nicholas A. Buckley
A syndrome of serotonin “hyperstimulation” called serotonin syndrome was initially described in the 1960s [1]. Since these early descriptions and the proposal of diagnostic criteria, there have been increasing reports of serotonin syndrome with an expanding list of drugs implicated. The true incidence of serotonin syndrome is unknown, and this relates to the challenges that still arise with diagnosis and offending agents. However, the incidence is very much higher if those without “hyperstimulation” but with multiple minor side effects of serotonergic agents are diagnosed as having serotonin syndrome. The term serotonin syndrome is also used to describe moderate to severe serotonin toxicity. A syndrome is a group of signs and symptoms characterizing a group of patients, but this can be done whether or not there is a clear mechanism (e.g., Down’s syndrome versus Chronic Fatigue Syndrome). The use of the term “serotonin syndrome” in settings without a clear serotonergic pathophysiological mechanism is all too common. Using clinical symptom/sign criteria to identify possible cases is only useful when other likely diagnoses are excluded. Identifying novel agents that cause serotonin syndrome from such criteria is only possible if the signs are pathognomonic or at least extremely specific.
Related Knowledge Centers
- Fever
- Mydriasis
- Perspiration
- Tachycardia
- Tremor
- Hypertension
- Hyperthermia
- Serotonin
- Recreational Drug Use
- Hyperreflexia