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Neuroleptic Malignant Syndrome

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Description: Neuroleptic malignant syndrome is a life-threatening reaction characterized by fever, muscle rigidity, altered mental status, and autonomic dysfunction, typically triggered by antipsychotic medications.
Type: Neuroleptic malignant syndrome (NMS) is a life-threatening reaction to antipsychotic medications. It is not classified as a genetic disorder, so there is no genetic transmission associated with NMS.
Signs And Symptoms: NMS symptoms include:
Increased body temperature >38 °C (>100.4 °F), or
Confused or altered consciousness
Excessive sweating
Rigid muscles
Autonomic imbalanceThe first symptoms of neuroleptic malignant syndrome are usually muscle cramps and tremors, fever, symptoms of autonomic nervous system instability such as unstable blood pressure, and sudden changes in mental status (agitation, delirium, or coma). Once symptoms appear, they may progress rapidly and reach peak intensity in as little as three days. These symptoms can last anywhere from eight hours to forty days.Symptoms are sometimes misinterpreted by doctors as symptoms of mental illness which can result in delayed treatment. NMS is less likely if a person has previously been stable for a period of time on antipsychotics, especially in situations where the dose has not been changed and there are no issues of noncompliance or consumption of psychoactive substances known to worsen psychosis.
Prognosis: The prognosis is best when identified early and treated aggressively. In these cases NMS is not usually fatal. In earlier studies the mortality rates from NMS ranged from 20%–38%, but by 2009 mortality rates were reported to have fallen below 10% over the previous two decades due to early recognition and improved management. Re-introduction to the drug that originally caused NMS to develop may also trigger a recurrence, although in most cases it does not.Memory impairment is a consistent feature of recovery from NMS, and is usually temporary though in some cases may become persistent.
Onset: Neuroleptic malignant syndrome (NMS) has an onset that typically occurs within days to weeks after starting or increasing the dosage of antipsychotic medications. It can also happen after abruptly stopping dopaminergic treatments. The onset is characterized by symptoms such as hyperthermia, muscle rigidity, altered mental status, and autonomic dysfunction.
Prevalence: The prevalence of Neuroleptic Malignant Syndrome (NMS) is not precisely determined, but estimates suggest that it occurs in about 0.01–0.02% of individuals taking antipsychotic medications. However, these figures can vary based on the population studied and the specific antipsychotic agents used.
Epidemiology: Pooled data suggest the incidence of NMS is between 0.2%–3.23%. However, greater physician awareness coupled with increased use of atypical anti-psychotics have likely reduced the prevalence of NMS. Additionally, young males are particularly susceptible and the male:female ratio has been reported to be as high as 2:1.
Intractability: Neuroleptic Malignant Syndrome (NMS) is potentially fatal but not necessarily intractable. It is a rare and severe reaction to antipsychotic medications. With prompt recognition and treatment, including discontinuation of the offending drug and supportive medical care, the condition can be successfully managed.
Disease Severity: Neuroleptic malignant syndrome (NMS) is a life-threatening condition.
Healthcare Professionals: Disease Ontology ID - DOID:14464
Pathophysiology: The mechanism is commonly thought to depend on decreased levels of dopamine activity due to:

Dopamine receptor blockade
Genetically reduced function of dopamine receptor D2
Sympathoadrenal hyperactivity and autonomic dysfunctionIt has been proposed that blockade of D2-like (D2, D3 and D4) receptors induce massive glutamate release, generating catatonia, neurotoxicity and myotoxicity. Additionally, the blockade of diverse serotonin receptors by atypical antipsychotics and activation of 5-HT1 receptors by certain of them reduces GABA release and indirectly induces glutamate release, worsening this syndrome.The muscular symptoms are most likely caused by blockade of the dopamine receptor D2, leading to abnormal function of the basal ganglia similar to that seen in Parkinson's disease.In the past, research and clinical studies seemed to corroborate the D2 receptor blockade theory in which antipsychotic drugs were thought to significantly reduce dopamine activity by blocking the D2 receptors associated with this neurotransmitter. The introduction of atypical antipsychotic drugs, with lower affinity to the D2 dopamine receptors, was thought to have reduced the incidence of NMS. However, recent studies suggest that the decrease in mortality may be the result of increased physician awareness and earlier initiation of treatment rather than the action of the drugs themselves. NMS induced by atypical drugs also resembles "classical" NMS (induced by "typical" antipsychotic drugs), further casting doubt on the overall superiority of these drugs.However, the failure of D2 dopamine receptor antagonism, or dopamine receptor dysfunction, do not fully explain the presenting symptoms and signs of NMS, as well as the occurrence of NMS with atypical antipsychotic drugs with lower D2 dopamine activity. This has led to the hypothesis of sympathoadrenal hyperactivity (results from removing tonic inhibition from the sympathetic nervous system) as a mechanism for NMS. Release of calcium is increased from the sarcoplasmic reticulum with antipsychotic usage. This can result in increased muscle contractility, which can play a role in the breakdown of muscle, muscle rigidity, and hyperthermia. Some antipsychotic drugs, such as typical antipsychotics, are known to block dopamine receptors; other studies have shown that when drugs supplying dopamine are withdrawn, symptoms similar to NMS present themselves.In support of the sympathoadrenal hyperactivity model, it has been hypothesized that a defect in calcium regulatory proteins within the sympathetic neurons may bring about the onset of NMS. This model of NMS strengthens its suspected association with malignant hyperthermia in which NMS may be regarded as a neurogenic form of this condition which itself is linked to defective calcium-related proteins.There is also thought to be considerable overlap between malignant catatonia and NMS in their pathophysiology, the former being idiopathic and the latter being the drug-induced form of the same syndrome.The raised white blood cell count and creatine phosphokinase (CPK) plasma concentration seen in those with NMS is due to increased muscular activity and rhabdomyolysis (destruction of muscle tissue). The patient may experience hypertensive crisis and metabolic acidosis. A non-generalized slowing on an EEG is reported in around 50% of cases.The fever seen with NMS is believed to be caused by hypothalamic dopamine receptor blockade. The peripheral problems (the high white blood cell and CPK count) are caused by the antipsychotic drugs. They cause an increased calcium release from the sarcoplasmic reticulum of muscle cells which can result in rigidity and eventual cell breakdown. No major studies have reported an explanation for the abnormal EEG, but it is likely also attributable to dopamine blockage leading to changes in neuronal pathways.
Carrier Status: Carrier status for neuroleptic malignant syndrome is not applicable. Neuroleptic malignant syndrome (NMS) is a rare, potentially life-threatening condition related to the use of antipsychotic medications, and it is not a genetic disorder that involves carriers.
Mechanism: Neuroleptic Malignant Syndrome (NMS) is a life-threatening condition often associated with the use of antipsychotic drugs.

**Mechanism:**
NMS primarily occurs due to the blockade of dopamine D2 receptors in the central nervous system, particularly in the hypothalamus and basal ganglia. This blockage disrupts the normal regulation of temperature, muscle tone, and autonomic function, leading to hyperthermia, muscle rigidity, autonomic dysregulation, and altered mental status.

**Molecular Mechanisms:**
1. **Dopamine Receptor Blockade:** Antipsychotic medications block dopamine D2 receptors in the brain, leading to reduced dopaminergic signaling. This is central to the pathogenesis of NMS.
2. **Hypothalamic Dysfunction:** The hypothalamus, responsible for regulating body temperature, becomes dysregulated due to dopamine blockade. This results in hyperthermia.
3. **Muscle Rigidity and Elevated Calcium Levels:** The dopamine blockade can also affect extrapyramidal pathways, leading to muscle rigidity. Additionally, altered calcium homeostasis in muscle cells may contribute to muscle rigidity and subsequent rhabdomyolysis (breakdown of muscle tissue).
4. **Autonomic Dysregulation:** Blockade of central dopamine pathways affects autonomic centers, leading to symptoms such as hypertension, tachycardia, and diaphoresis.

These molecular and physiological disruptions collectively contribute to the development and progression of NMS.
Treatment: NMS is a medical emergency and can lead to death if untreated. The first step is to stop the antipsychotic medication and treat the hyperthermia aggressively, such as with cooling blankets or ice packs to the axillae and groin. Supportive care in an intensive care unit capable of circulatory and ventilatory support is crucial. The best pharmacological treatment is still unclear. Dantrolene has been used when needed to reduce muscle rigidity, and more recently dopamine pathway medications such as bromocriptine have shown benefit.Amantadine is another treatment option due to its dopaminergic and anticholinergic effects.
Apomorphine may be used however its use is supported by little evidence. Benzodiazepines may be used to control agitation. Highly elevated blood myoglobin levels can result in kidney damage, therefore aggressive intravenous hydration with diuresis may be required. When recognized early NMS can be successfully managed; however, up to 10% of cases can be fatal.Should the affected person subsequently require an antipsychotic, trialing a low dose of a low-potency atypical antipsychotic is recommended.
Compassionate Use Treatment: Neuroleptic Malignant Syndrome (NMS) is a life-threatening reaction to antipsychotic medications. While it primarily requires immediate discontinuation of the offending drug, supportive care, and intensive monitoring, certain treatments have been explored for their potential benefits, including:

1. **Dantrolene**: A muscle relaxant commonly used to treat malignant hyperthermia, which may help alleviate hyperthermia and muscle rigidity associated with NMS.

2. **Bromocriptine**: A dopamine agonist that can help counteract dopamine blockade caused by antipsychotics, potentially lessening some symptoms of NMS.

3. **Amantadine**: Another dopaminergic agent that might be beneficial in managing symptoms due to its dopaminergic properties.

These treatments are considered supportive and are used off-label for NMS, as they are not FDA-approved specifically for this syndrome but have shown efficacy in clinical practice.
Lifestyle Recommendations: Neuroleptic Malignant Syndrome (NMS) is a serious and potentially life-threatening reaction to antipsychotic medications. Here are some lifestyle recommendations for managing and preventing NMS:

1. **Medication Adherence**: Always take medications as prescribed by your healthcare provider and never alter the dosage without consulting them. Abruptly stopping medications can precipitate NMS.

2. **Regular Monitoring**: Regular medical check-ups are crucial to monitor for early signs of NMS, such as muscle rigidity, fever, and altered mental status.

3. **Stay Hydrated**: Ensure you maintain proper hydration, as dehydration can exacerbate symptoms.

4. **Healthy Diet**: A well-balanced diet can help maintain overall health and may assist in the management of any side effects related to antipsychotic medications.

5. **Avoid Overexertion**: Try to avoid activities that can excessively increase your body temperature or cause severe physical strain.

6. **Stress Management**: Manage stress through techniques such as mindfulness, meditation, or counseling. High stress levels can contribute to the onset of symptoms.

7. **Informative Support Network**: Educate close family members or caregivers about the signs and symptoms of NMS so they can assist in early detection and seek medical help promptly.

8. **Other Medications**: Be cautious with other medications, including over-the-counter drugs and supplements, and discuss any new medications with your doctor to avoid interactions that could trigger NMS.

9. **Temperature Control**: Avoid environments with extreme temperatures and try to keep your living and working environments cool.

These recommendations can help those at risk of NMS to manage their condition effectively and seek timely help if symptoms develop.
Medication: Neuroleptic Malignant Syndrome (NMS) is a severe reaction most often seen in response to antipsychotic medications. Commonly implicated drugs include:

1. **Typical (First-generation) Antipsychotics**:
- Haloperidol
- Chlorpromazine
- Fluphenazine

2. **Atypical (Second-generation) Antipsychotics**:
- Clozapine
- Risperidone
- Olanzapine

Early recognition and discontinuation of the offending medication are crucial. Supportive treatments may include hydration, cooling, and medications such as dantrolene, bromocriptine, and benzodiazepines to manage symptoms and restore normal function.
Repurposable Drugs: There are currently no officially approved drugs specifically repurposed for the treatment of neuroleptic malignant syndrome (NMS). However, certain medications not originally designed for NMS have been used in its management based on their pharmacological properties. These include:

1. **Dantrolene**: A muscle relaxant that helps reduce muscle rigidity and hyperthermia.
2. **Bromocriptine**: A dopamine agonist used to restore dopamine balance disrupted by antipsychotics.
3. **Amantadine**: Another dopamine agonist that may help alleviate symptoms.

The primary treatment for NMS remains the immediate discontinuation of the triggering antipsychotic medication and supportive care.
Metabolites: Neuroleptic Malignant Syndrome (NMS) is a potentially life-threatening condition often associated with the use of antipsychotic medications. It's characterized by symptoms such as hyperthermia, muscle rigidity, autonomic dysfunction, and altered mental status. Regarding metabolites, antipsychotic drugs can produce various metabolites depending on the specific medication involved. However, the pathological mechanisms of NMS are not directly attributed to specific metabolites but rather to dopamine receptor blockade in the central nervous system. Therefore, the specific role of drug metabolites in NMS remains an area that is not fully understood and is not typically the primary focus in understanding or treating this condition.
Nutraceuticals: Neuroleptic malignant syndrome (NMS) is a rare but life-threatening reaction to neuroleptic or antipsychotic medications. As of now, there is no established evidence to support the use of nutraceuticals in the treatment or management of NMS. The primary treatment involves immediate cessation of the offending medication and supportive care, which may include hydration, cooling, and medications like bromocriptine or dantrolene. Always consult a healthcare professional for management of any medical condition.
Peptides: In the context of neuroleptic malignant syndrome (NMS), the term "peptides" typically refers to small chains of amino acids involved in biological processes. NMS is a life-threatening reaction to antipsychotic medications and is characterized by symptoms like high fever, muscle rigidity, altered mental status, and autonomic dysfunction. Peptides themselves aren't directly involved in the pathogenesis of NMS, but neurotransmitters and their receptors, which can be affected by these medications, play crucial roles. Monitoring and managing biochemical parameters in the body, however, can be essential for treatment.

"Nan" in this context is unclear, as it is not a recognized term related to NMS. If you meant "nan" as an abbreviation, please provide additional details for a more accurate response.