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74-450: Clonazepam , sold under the brand name Klonopin among others, is a benzodiazepine medication used to prevent and treat anxiety disorders , seizures , bipolar mania , agitation associated with psychosis , obsessive–compulsive disorder (OCD), and akathisia . It is a long-acting tranquilizer of the benzodiazepine class. It possesses anxiolytic , anticonvulsant , sedative , hypnotic , and skeletal muscle relaxant properties. It

148-440: A "crawling" feeling, or limbs jerking while awake. The sensations typically begin or intensify during quiet wakefulness, such as when relaxing, reading, studying, or trying to sleep. It is a " spectrum disorder " with some people experiencing only a minor annoyance and others having major disruption of sleep and impairments in quality of life. The sensations—and the need to move—may return immediately after ceasing movement or at

222-431: A dependence on the drug and experience a withdrawal syndrome upon dose reduction. High dosage and long-term use increase the risk and severity of dependence and withdrawal symptoms. Withdrawal seizures and psychosis can occur in severe cases of withdrawal, and anxiety and insomnia can occur in less severe cases of withdrawal. A gradual reduction in dosage reduces the severity of the benzodiazepine withdrawal syndrome . Due to

296-504: A dependence. Physiological dependence was demonstrated by flumazenil -precipitated withdrawal. Use of alcohol or other CNS depressants while taking clonazepam greatly intensifies the effects, including side effects, of the drug. A recurrence of symptoms of the underlying disease should be separated from withdrawal symptoms. Like all benzodiazepines, clonazepam is a GABA-positive allosteric modulator . One-third of individuals treated with benzodiazepines for longer than four weeks develop

370-521: A later time. RLS may start at any age, including childhood, and is a progressive disease for some, while the symptoms may remit in others. In a survey among members of the Restless Legs Syndrome Foundation, it was found that up to 45% of patients had their first symptoms before the age of 20 years. RLS may contribute to higher rates of depression and anxiety disorders in RLS patients. RLS

444-418: A mechanism for high-dose effects on seizures in the study. Clonazepam is a 2'-chlorinated derivative of nitrazepam , which increases its potency due to electron-attracting effect of the halogen in the ortho-position . Clonazepam is lipid-soluble, rapidly crosses the blood–brain barrier , and penetrates the placenta. It is extensively metabolised into pharmacologically inactive metabolites, with only 2% of

518-523: A medical description in 1672. Willis emphasized the sleep disruption and limb movements experienced by people with RLS. Subsequently, other descriptions of RLS were published, including by Theodor Wittmaack  [ de ] (1861) (in relation to whom it is sometimes known as Wittmaack-Ekbom syndrome ). In 1945, Karl-Axel Ekbom (1907–1977) provided a detailed and comprehensive report of this condition in his doctoral thesis, restless legs: clinical study of hitherto overlooked disease . Ekbom coined

592-495: A prevalence from 20% to 57%, while those having kidney transplant improve compared to those treated with dialysis. RLS can occur at all ages, although it typically begins in the third or fourth decade. Genome‐wide association studies have now identified 19 risk loci associated with RLS. Neurological conditions linked to RLS include Parkinson's disease , spinal cerebellar atrophy , spinal stenosis , lumbosacral radiculopathy and Charcot–Marie–Tooth disease type 2. In 2013,

666-437: A role in RLS as part as the limbic system modulated by the dopaminergic system which may affect pain perception. Improvement of RLS symptoms occurs in people receiving low-dose dopamine agonists . There are no specific tests for RLS, but non-specific laboratory tests are used to rule out other causes such as vitamin deficiencies. Five symptoms are used to confirm the diagnosis: The symptoms below are not essential, like

740-698: A role in the prevalence of this syndrome. RLS diagnosed at an older age runs a more severe course. RLS is even more common in individuals with iron deficiency , pregnancy, or end-stage kidney disease . The National Sleep Foundation 's 1998 Sleep in America poll showed that up to 25 percent of pregnant women developed RLS during the third trimester. Poor general health is also linked. There are several risk factors for RLS, including old age, family history, and uremia . The prevalence of RLS tends to increase with age, as well as its severity and longer duration of symptoms. People with uremia receiving renal dialysis have

814-649: A safer choice. The use of clonazepam during pregnancy should only occur if the clinical benefits are believed to outweigh the clinical risks to the fetus . Caution is also required if clonazepam is used during breastfeeding. Possible adverse effects of use of benzodiazepines such as clonazepam during pregnancy include: miscarriage , malformation , intrauterine growth retardation , functional deficits, carcinogenesis , and mutagenesis . Neonatal withdrawal syndrome associated with benzodiazepines include hypertonia , hyperreflexia , restlessness , irritability , abnormal sleep patterns, inconsolable crying, tremors , or jerking of

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888-530: A single 2 mg oral dose of micronized clonazepam in healthy adults. In some individuals, however, peak blood concentrations were reached at 4–8 hours. Clonazepam passes rapidly into the central nervous system, with levels in the brain corresponding with levels of unbound clonazepam in the blood serum. Clonazepam plasma levels are very unreliable amongst patients. Plasma levels of clonazepam can vary as much as tenfold between different patients. Clonazepam has plasma protein binding of 85%. Clonazepam passes through

962-493: A third-line treatment option, as the use of clonazepam is still investigational. Bruxism also responds to clonazepam in the short term. REM sleep behavior disorder responds well to low doses of clonazepam. It is also used for: In September 2020, the U.S. Food and Drug Administration (FDA) required the boxed warning be updated for all benzodiazepine medicines to describe the risks of abuse, misuse, addiction, physical dependence, and withdrawal reactions consistently across all

1036-551: A vibratory counter-stimulation device has been found to help some people with primary RLS to improve their sleep. There is some evidence that intravenous iron supplementation moderately improves restlessness for people with RLS. For those whose RLS disrupts or prevents sleep or regular daily activities, medication may be useful. Evidence supports the use of dopamine agonists including pramipexole , ropinirole , rotigotine , cabergoline , and pergolide . They reduce symptoms, improve sleep quality and quality of life. Levodopa

1110-493: Is also a commonly acknowledged circadian rhythm explanatory mechanism associated with it, clinically shown simply by biomarkers of circadian rhythm, such as body temperature . The interactions between impaired neuronal iron uptake and the functions of the neuromelanin -containing and dopamine-producing cells have roles in RLS development, indicating that iron deficiency might affect the brain dopaminergic transmissions in different ways. Medial thalamic nuclei may also have

1184-402: Is also effective. However, pergolide and cabergoline are less recommended due to their association with increased risk of valvular heart disease. Ropinirole has a faster onset with shorter duration. Rotigotine is commonly used as a transdermal patch which continuously provides stable plasma drug concentrations, resulting in its particular therapeutic effect on patients with symptoms throughout

1258-1152: Is approved by regulatory authorities for the treatment of RLS, whereas gabapentin and pregabalin are used off-label . Data on gabapentinoids in the treatment of RLS are more limited compared to dopamine agonists. However, based on available evidence, gabapentinoids are similarly effective to dopamine agonists in the treatment of RLS. Low doses of opioids are used in the treatment of severe and treatment-resistant cases and are recommended by multiple reputable medical guidelines . The most commonly used agents are prolonged-release oxycodone and methadone , but other opioids, including tramadol , codeine , morphine , and hydrocodone , may also be considered. Opioids are only indicated in severe cases that do not respond to other measures due to their very high abuse liability and high rate of side effects , which may include constipation , fatigue, and headache . However, opioids are said to be highly effective for severe and refractory RLS, and can be helpful in well-selected individuals. Benzodiazepines , such as diazepam or clonazepam , are not generally recommended, and their effectiveness

1332-808: Is categorized as either primary or secondary. While the cause is generally unknown, it is believed to be caused by changes in the neurotransmitter dopamine resulting in an abnormal use of iron by the brain. RLS is often due to iron deficiency (low total body iron status) and could be a sign of anemia caused by internal bleeding or bone marrow issues. Other associated conditions may include end-stage kidney disease and hemodialysis , folate deficiency , magnesium deficiency , sleep apnea , diabetes , peripheral neuropathy , Parkinson's disease , and certain autoimmune diseases , such as multiple sclerosis . RLS can worsen in pregnancy, possibly due to elevated estrogen levels. Use of alcohol, nicotine products, and caffeine may be associated with RLS. A 2014 study from

1406-456: Is effective in the acute control of non-convulsive status epilepticus ; the benefits, though, tended to be transient in many people, and the addition of phenytoin for lasting control was required in these patients. It is also approved for the treatment of typical and atypical absences (seizures) and infantile myoclonic and akinetic seizures . A subgroup of people with treatment-resistant epilepsy may benefit from long-term use of clonazepam;

1480-495: Is generally not recommended for use in elderly people for insomnia due to its high potency relative to other benzodiazepines. Clonazepam is not recommended for use in those under 18. Use in very young children may be especially hazardous. Of anticonvulsant drugs, behavioural disturbances occur most frequently with clonazepam and phenobarbital . Doses higher than 0.5–1 mg per day are associated with significant sedation. Clonazepam may aggravate hepatic porphyria . Clonazepam

1554-542: Is more effective than long-term therapy with clonazepam for the treatment of epilepsy. Many studies have found that tolerance develops to the anticonvulsant properties of clonazepam with chronic use, which limits its long-term effectiveness as an anticonvulsant. Abrupt or over-rapid withdrawal from clonazepam may result in the development of the benzodiazepine withdrawal syndrome, causing psychosis characterised by dysphoric manifestations, irritability, aggressiveness, anxiety, and hallucinations. Sudden withdrawal may also induce

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1628-558: Is not linked to an underlying cause, its frequency may be reduced by lifestyle modifications such as adopting improving sleep hygiene , regular exercise, and stopping smoking . Medications used may include dopamine agonists and gabapentinoids in those with daily restless legs syndrome. In severe or refractory cases, opioids have been used. Treatment of RLS should not be considered until possible medical causes are ruled out. Secondary RLS may be cured if precipitating medical conditions ( anemia ) are managed effectively. Stretching

1702-455: Is not recommended for patients with chronic schizophrenia . A 1982 double-blinded, placebo-controlled study found clonazepam increases violent behavior in individuals with chronic schizophrenia. Clonazepam has similar effectiveness to other benzodiazepines at often a lower dose. Clonazepam decreases the levels of carbamazepine , and, likewise, clonazepam's level is reduced by carbamazepine. Azole antifungals, such as ketoconazole , may inhibit

1776-444: Is not well established. Loss of sleep due to RLS could cause the conditions, or medication used to treat a condition could cause RLS. More than 60% of cases of RLS are familial and are inherited in an autosomal dominant fashion with variable penetrance . Research and brain autopsies have implicated both dopaminergic system and iron insufficiency in the substantia nigra . Iron is well understood to be an essential cofactor for

1850-445: Is outdated usage, as the unambiguous names (WED or RLS) are preferred for clarity. Some doctors express the view that the incidence of restless legs syndrome is exaggerated by manufacturers of drugs used to treat it. Others believe it is an underrecognized and undertreated disorder. Further, GlaxoSmithKline (GSK) ran advertisements that, while not promoting off-licence use of their drug ( ropinirole ) for treatment of RLS, did link to

1924-408: Is recommended that serum levels of clonazepam are monitored and that signs of central nervous system depression and apnea are also checked for. In many cases, non-pharmacological treatments, such as relaxation therapy, psychotherapy, and avoidance of caffeine , can be an effective and safer alternative to the use of benzodiazepines for anxiety in pregnant women. Clonazepam enhances the activity of

1998-454: Is some medical evidence of various malformations (for example, cardiac or facial deformations when used in early pregnancy); however, the data is not conclusive. The data are also inconclusive on whether benzodiazepines such as clonazepam cause developmental deficits or decreases in IQ in the developing fetus when taken by the mother during pregnancy. Clonazepam, when used late in pregnancy, may result in

2072-675: Is typically taken orally (swallowed by mouth) but is also used intravenously . Effects begin within one hour and last between eight and twelve hours in adults. Common side effects may include sleepiness , weakness , poor coordination , difficulty concentrating, and agitation. Clonazepam may also decrease memory formation . Long-term use may result in tolerance , dependence , and life-threatening withdrawal symptoms if stopped abruptly. Dependence occurs in one-third of people who take benzodiazepines for longer than four weeks. The risk of suicide increases, particularly in people who are already depressed. Use during pregnancy may result in harm to

2146-509: Is unknown or contradictory. They, however, are sometimes still used as a second-line treatment, as add-on agents. Other treatments have also been explored, such as valproate , carbamazepine , perampanel , and dipyridamole , but are either not effective or have insufficient data to support their use. Placebos provide a large benefit in terms of reduction of RLS symptoms. This is thought to be due to positive expectancy effects and conditioning, which activate dopamine and opioid pathways in

2220-433: The central nervous system . Benzodiazepines do not have any effect on the levels of GABA in the brain. Clonazepam has no effect on GABA levels and has no effect on gamma-aminobutyric acid transaminase. Clonazepam does, however, affect glutamate decarboxylase activity. It differs from other anticonvulsant drugs it was compared to in a study. Clonazepam's primary mechanism of action is the modulation of GABA function in

2294-648: The idiopathic form of RLS than for people who also have an associated medical condition. Current therapies can control the disorder, minimizing symptoms and increasing periods of restful sleep. In addition, some people have remissions, periods in which symptoms decrease or disappear for days, weeks, or months, although symptoms usually eventually reappear. Being diagnosed with RLS does not indicate or foreshadow another neurological disease, such as Parkinson's disease . RLS symptoms can worsen over time when dopamine -related drugs are used for therapy, an effect called augmentation which may represent symptoms occurring throughout

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2368-557: The American Academy of Neurology also found that reduced leg oxygen levels were strongly associated with restless legs syndrome symptom severity in untreated patients. An association has been observed between attention deficit hyperactivity disorder (ADHD) and RLS or periodic limb movement disorder . Both conditions appear to have links to dysfunctions related to the neurotransmitter dopamine , and common medications for both conditions among other systems, affect dopamine levels in

2442-645: The Ekbom Support Group website. That website contained statements advocating the use of ropinirole to treat RLS. The Association of the British Pharmaceutical Industry (ABPI) ruled against GSK in this case. Different measurements have been used to evaluate treatments in RLS. Most of them are based on subjective rating scores, such as IRLS rating scale (IRLS), Clinical Global Impression (CGI), Patient Global Impression (PGI), and Quality of life (QoL). These questionnaires provide information about

2516-503: The Restless Legs Syndrome Foundation renamed itself the Willis–Ekbom Disease Foundation; however, it reverted to its original name in 2015 “to better support its mission”. A point of confusion is that RLS and delusional parasitosis are entirely different conditions that have both been called "Ekbom syndrome", as both syndromes were described by the same person, Karl-Axel Ekbom . Today, calling WED/RLS "Ekbom syndrome"

2590-650: The Wikimedia System Administrators, please include the details below. Request from 172.68.168.226 via cp1108 cp1108, Varnish XID 760040944 Upstream caches: cp1108 int Error: 429, Too Many Requests at Fri, 29 Nov 2024 05:36:33 GMT Restless legs syndrome Diagnosis of RLS is generally based on a person's symptoms after ruling out other potential causes. Risk factors include low iron levels , kidney failure , Parkinson's disease , diabetes mellitus , rheumatoid arthritis , pregnancy and celiac disease . A number of medications may also trigger

2664-400: The anticonvulsant effects of clonazepam occurs in both animals and humans. In humans, tolerance to the anticonvulsant effects of clonazepam occurs frequently. Chronic use of benzodiazepines can lead to the development of tolerance with a decrease of benzodiazepine binding sites. The degree of tolerance is more pronounced with clonazepam than with chlordiazepoxide . In general, short-term therapy

2738-416: The anticonvulsant effects. Clonazepam has been found effective in treating epilepsy in children, and the inhibition of seizure activity seemed to be achieved at low plasma levels of clonazepam. As a result, clonazepam is sometimes used for certain rare childhood epilepsies, but it is ineffective in the control of infantile spasms. Clonazepam is mainly prescribed for the acute management of epilepsy. Clonazepam

2812-475: The benzodiazepine clorazepate may be an alternative due to its slow onset of tolerance. The effectiveness of clonazepam in the short-term treatment of panic disorder has been demonstrated in controlled clinical trials . Some long-term trials have suggested a benefit of clonazepam for up to three years without the development of tolerance . Clonazepam is also effective in the management of acute mania . Restless legs syndrome can be treated using clonazepam as

2886-423: The blood–brain barrier easily, with blood and brain levels corresponding equally with each other. The metabolites of clonazepam include 7-aminoclonazepam, 7-acetaminoclonazepam and 3-hydroxy clonazepam. These metabolites are excreted by the kidney. It is effective for 6–8 hours in children, and 8–12 in adults. A 2006 US government study of hospital emergency department (ED) visits found that sedative-hypnotics were

2960-503: The brain, by the benzodiazepine receptor, located on GABA A receptors , which, in turn, leads to enhanced GABAergic inhibition of neuronal firing. Benzodiazepines do not replace GABA, but instead enhance the effect of GABA at the GABA A receptor by increasing the opening frequency of chloride ion channels, which leads to an increase in GABA's inhibitory effects and resultant central nervous system depression . In addition, clonazepam decreases

3034-577: The brain. A 2005 study suggested that up to 44% of people with ADHD had comorbid (i.e. coexisting) RLS, and up to 26% of people with RLS had confirmed ADHD or symptoms of the condition. Certain medications may cause or worsen RLS, or cause it secondarily, including: Both primary and secondary RLS can be worsened by surgery of any kind; however, back surgery or injury can be associated with causing RLS. The cause vs. effect of certain conditions and behaviors observed in some patients (ex. excess weight, lack of exercise, depression or other mental illnesses)

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3108-433: The brain. Both dopamine agonists and opioids are used in and effective for the treatment of RLS, which is thought to be related to the effectiveness of placebos for the condition. More than half of the benefit of RLS medications such as pramipexole and gabapentin enacarbil appears to be due to the placebo component based on clinical trial data. RLS symptoms may gradually worsen with age, although more slowly for those with

3182-724: The brand name Rivotril by Roche in Argentina, Australia, Austria, Bangladesh, Belgium, Brazil, Canada, Colombia, Costa Rica, Croatia, the Czech Republic, Denmark, Estonia, Germany, Hungary, Iceland, Ireland, Italy, China, Mexico, the Netherlands, Norway, Portugal, Peru, Pakistan, Romania, Serbia, South Africa, South Korea, Spain, Turkey, and the United States; Emcloz, Linotril, Lonazep, Clotrin and Clonotril in India and other parts of Europe; under

3256-646: The day and affect movements of all limbs. There is no cure for RLS. RLS affects an estimated 2.5–15% of the American population. A minority (around 2.7% of the population) experience daily or severe symptoms. RLS is twice as common in women as in men, and Caucasians are more prone to RLS than people of African descent. RLS occurs in 3% of individuals from the Mediterranean or Middle Eastern regions, and in 1–5% of those from East Asia , indicating that different genetic or environmental factors, including diet, may play

3330-437: The day. A 2008 meta-analysis found pramipexole to be better than ropinirole. There are, however, issues with the use of dopamine agonists including augmentation. This is a medical condition where the drug itself causes symptoms to increase in severity and/or occur earlier in the day. Dopamine agonists may also cause rebound when symptoms increase as the drug wears off. In many cases, the longer dopamine agonists have been used,

3404-442: The development of a severe benzodiazepine withdrawal syndrome in the neonate . Withdrawal symptoms from benzodiazepines in the neonate may include hypotonia , apnoeic spells, cyanosis , and impaired metabolic responses to cold stress. The safety profile of clonazepam during pregnancy is less clear than that of other benzodiazepines, and if benzodiazepines are indicated during pregnancy, chlordiazepoxide and diazepam may be

3478-399: The disorder including antidepressants , antipsychotics , antihistamines , and calcium channel blockers . RLS may either be of early onset, occurring before age 45, or of late onset, occurring after age 45. Early-onset cases tend to progress more slowly and involve fewer comorbidities, while cases in older patients may progress suddenly and alongside other conditions. RLS may resolve if

3552-669: The dopamine agonist treatment has an impact on the resolution or at least improvement of the impulse-control disorder, even though some people can be particularly exposed to dopamine agonist withdrawal syndrome. Gabapentinoids (α 2 δ ligands), including gabapentin , pregabalin , and gabapentin enacarbil , are also widely used in the treatment of RLS. They are used as first-line treatments similarly to dopamine agonists, and as of 2019, guidelines have started to recommend gabapentinoids over dopamine agonists as initial therapy for RLS due to higher known risks of symptom augmentation with long-term dopamine agonist therapy. Gabapentin enacarbil

3626-514: The drug therapeutically. Results from such tests can be used to confirm the diagnosis in potential poisoning victims or to assist in the forensic investigation in a case of fatal overdosage. Both the parent drug and 7-aminoclonazepam are unstable in biofluids, and therefore specimens should be preserved with sodium fluoride, stored at the lowest possible temperature and analyzed quickly to minimize losses. The elderly metabolize benzodiazepines more slowly than younger people and are also more sensitive to

3700-649: The effects of benzodiazepines, even at similar blood plasma levels. Doses for the elderly are recommended to be about half of that given to younger adults and are to be administered for no longer than two weeks. Long-acting benzodiazepines such as clonazepam are not generally recommended for the elderly due to the risk of drug accumulation. The elderly are especially susceptible to increased risk of harm from motor impairments and drug accumulation side effects. Benzodiazepines also require special precaution if used by individuals that may be pregnant, alcohol- or drug-dependent, or may have comorbid psychiatric disorders . Clonazepam

3774-843: The evening and at night, not be triggered by other medical or behavioral conditions, and should impair one's quality of life. Generally, both legs are affected, but in some cases there is an asymmetry. The most common conditions that should be differentiated with RLS include leg cramps, positional discomfort, local leg injury, arthritis, leg edema , venous stasis , peripheral neuropathy , radiculopathy , habitual foot tapping/leg rocking, anxiety , myalgia , and drug-induced akathisia . Peripheral artery disease and arthritis can also cause leg pain but this usually gets worse with movement. There are less common differential diagnostic conditions included myelopathy , myopathy , vascular or neurogenic claudication , hypotensive akathisia , orthostatic tremor , painful legs, and moving toes . If RLS

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3848-420: The extremities, bradycardia , cyanosis , suckling difficulties, apnea , risk of aspiration of feeds, diarrhea and vomiting, and growth retardation . This syndrome can develop between three days to three weeks after birth and can have a duration of up to several months. The pathway by which clonazepam is metabolized is usually impaired in newborns. If clonazepam is used during pregnancy or breastfeeding , it

3922-440: The fetus. Clonazepam binds to GABA A receptors , thus increasing the effect of the chief inhibitory neurotransmitter γ-aminobutyric acid (GABA). Clonazepam was patented in 1960 and went on sale in 1975 in the United States from Roche . It is available as a generic medication . In 2022, it was the 57th most commonly prescribed medication in the United States, with more than 11   million prescriptions. In many areas of

3996-406: The formation of L-dopa , the precursor of dopamine. Six genetic loci found by linkage are known and listed below. Other than the first one, all of the linkage loci were discovered using an autosomal dominant model of inheritance. Three genes, MEIS1 , BTBD9 and MAP2K5 , were found to be associated to RLS. Their role in RLS pathogenesis is still unclear. More recently, a fourth gene, PTPRD

4070-517: The higher the risk of augmentation and rebound as well as the severity of the symptoms. Patients may also develop dopamine dysregulation syndrome , meaning that they can experience an addictive pattern of dopamine replacement therapy. A 2007 study indicated that dopamine agonists used in restless legs syndrome can lead to an increase in compulsive gambling . Patients may also exhibit other impulse-control disorders such as compulsive shopping and compulsive eating. There are some indications that stopping

4144-614: The individual alternating from a comatose state to a hyper-alert state of consciousness, which occurred in a four-year-old boy who overdosed on clonazepam. The combination of clonazepam and certain barbiturates (for example, amobarbital ), at prescribed doses has resulted in a synergistic potentiation of the effects of each drug, leading to serious respiratory depression. Overdose symptoms may include extreme drowsiness, confusion, muscle weakness, and fainting. Clonazepam and 7-aminoclonazepam may be quantified in plasma , serum , or whole blood in order to monitor compliance in those receiving

4218-617: The inhibition of sustained, high-frequency repetitive firing. Benzodiazepines, including clonazepam, bind to mouse glial cell membranes with high affinity. Clonazepam decreases release of acetylcholine in the feline brain and decreases prolactin release in rats. Benzodiazepines inhibit cold-induced thyroid-stimulating hormone (also known as TSH or thyrotropin) release. Benzodiazepines act via micromolar benzodiazepine binding sites as Ca channel blockers and significantly inhibit depolarization-sensitive calcium uptake in experimentation on rat brain cell components. This has been conjectured as

4292-448: The inhibitory neurotransmitter gamma-aminobutyric acid (GABA) in the central nervous system to give its anticonvulsant , skeletal muscle relaxant , and anxiolytic effects. It acts by binding to the benzodiazepine site of the GABA receptors, which enhances the electric effect of GABA binding on neurons, resulting in an increased influx of chloride ions into the neurons. This further results in an inhibition of synaptic transmission across

4366-422: The leg muscles can bring temporary relief. Walking and moving the legs, as the name "restless legs" implies, brings temporary relief. In fact, those with RLS often have an almost uncontrollable need to walk and therefore relieve the symptoms while they are moving. Unfortunately, the symptoms usually return immediately after the moving and walking ceases. Counter-stimulation from massage, a hot or cold compress, or

4440-413: The medication. Clonazepam was approved in the United States as a generic drug in 1997 and is now manufactured and marketed by several companies. Clonazepam is available as tablets and orally disintegrating tablets (wafers) an oral solution (drops), and as a solution for injection or intravenous infusion. In some countries, clonazepam is used by criminals to subdue their victims. It is marketed under

4514-521: The medicines in the class. The long-term effects of clonazepam can include depression, disinhibition , and sexual dysfunction . Clonazepam, like other benzodiazepines, may impair a person's ability to drive or operate machinery. The central nervous system depressing effects of the drug can be intensified by alcohol consumption, so alcohol should be avoided while taking this medication. Benzodiazepines have been shown to cause dependence. Patients dependent on clonazepam should be slowly titrated off under

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4588-626: The metabolism of clonazepam. Clonazepam may affect levels of phenytoin (diphenylhydantoin). In turn, Phenytoin may lower clonazepam plasma levels by increasing the speed of clonazepam clearance by approximately 50% and decreasing its half-life by 31%. Clonazepam increases the levels of primidone and phenobarbital . Combined use of clonazepam with certain antidepressants , anticonvulsants (such as phenobarbital , phenytoin , and carbamazepine ), sedative antihistamines , opiates , and antipsychotics , nonbenzodiazepines (such as zolpidem ), and alcohol may result in enhanced sedative effects. There

4662-654: The most frequently implicated pharmaceutical drug in visits, with benzodiazepines accounting for the majority of these. Clonazepam was the second most frequently implicated benzodiazepine in ED visits. Alcohol alone was responsible for over twice as many ED visits as clonazepam in the same study. The study examined the number of times the non-medical use of certain drugs was implicated in an ED visit. The criteria for non-medical use in this study were purposefully broad, and include, for example, drug abuse , accidental or intentional overdose , or adverse reactions resulting from legitimate use of

4736-480: The name Riklona in Indonesia and Malaysia; and under the brand name Klonopin by Roche in the United States. Other names, such as Antelepsin, Clonoten, Ravotril, Rivotril, Iktorivil, Clonex (Israel), Paxam, Petril, Naze, Zilepam and Kriadex, are used throughout the world. In August 2021, Roche Australia transferred Rivotril to Pharmaco Australia Ltd. Benzodiazepine Too Many Requests If you report this error to

4810-472: The ones above, but occur commonly in RLS patients: According to the International Classification of Sleep Disorders (ICSD-3), the main symptoms have to be associated with a sleep disturbance or impairment in order to support RLS diagnosis. As stated by this classification, RLS symptoms should begin or worsen when being inactive, be relieved when moving, should happen exclusively or mostly in

4884-488: The potentially life-threatening condition, status epilepticus . Anti-epileptic drugs, benzodiazepines such as clonazepam in particular, should be reduced in dose slowly and gradually when discontinuing the drug to mitigate withdrawal effects. Carbamazepine has been tested in the treatment of clonazepam withdrawal but was found to be ineffective in preventing clonazepam withdrawal-induced status epilepticus from occurring. Excess doses may result in: Coma can be cyclic, with

4958-460: The risks of tolerance and withdrawal seizures, clonazepam is generally not recommended for the long-term management of epilepsies. Increasing the dose can overcome the effects of tolerance, but tolerance to the higher dose may occur and adverse effects may intensify. The mechanism of tolerance includes receptor desensitization, down regulation, receptor decoupling, and alterations in subunit composition and in gene transcription coding. Tolerance to

5032-419: The supervision of a qualified healthcare professional to reduce the intensity of withdrawal or rebound symptoms. Benzodiazepines such as clonazepam can be very effective in controlling status epilepticus , but, when used for longer periods of time, some potentially serious side-effects may develop, such as interference with cognitive functions and behavior. Many individuals treated on a long-term basis develop

5106-416: The term "restless legs". Ekbom's work was largely ignored until it was rediscovered by Arthur S. Walters and Wayne A. Hening in the 1980s. Subsequent landmark publications include 1995 and 2003 papers, which revised and updated the diagnostic criteria. RLS sensations range from pain or an aching in the muscles, to "an itch you can't scratch", a "buzzing sensation", an unpleasant "tickle that won't stop",

5180-498: The unchanged drug excreted in the urine. Clonazepam is metabolized extensively via nitroreduction by cytochrome P450 enzymes, including CYP3A4 . Erythromycin , clarithromycin , ritonavir , itraconazole , ketoconazole , nefazodone , cimetidine , and grapefruit juice are inhibitors of CYP3A4 and can affect the metabolism of benzodiazepines. It has an elimination half-life of 19–60 hours. Peak blood concentrations of 6.5–13.5 ng/mL were usually reached within 1–2 hours following

5254-523: The underlying problem is addressed. Otherwise treatment includes lifestyle changes and medication. Lifestyle changes that may help include stopping alcohol and tobacco use, and sleep hygiene . Medications used to treat RLS include dopamine agonists like pramipexole and gabapentinoids (α 2 δ ligands) like gabapentin . RLS affects an estimated 2.5–15% of the American population. Females are more commonly affected than males, and RLS becomes increasingly common with age. Sir Thomas Willis provided

5328-409: The utilization of 5-HT (serotonin) by neurons and has been shown to bind tightly to central-type benzodiazepine receptors. Because clonazepam is effective in low milligram doses (0.5 mg clonazepam = 10 mg diazepam), it is said to be among the class of "highly potent" benzodiazepines . The anticonvulsant properties of benzodiazepines are due to the enhancement of synaptic GABA responses, and

5402-418: The world, it is commonly used as a recreational drug . Clonazepam is prescribed for short-term management of epilepsy , anxiety , obsessive–compulsive disorder (OCD), and panic disorder with or without agoraphobia . Clonazepam, like other benzodiazepines, while being a first-line treatment for acute seizures, is not suitable for the long-term treatment of seizures due to the development of tolerance to

5476-461: Was found to be associated with RLS. There is also some evidence that periodic limb movements in sleep (PLMS) are associated with BTBD9 on chromosome 6p21.2, MEIS1, MAP2K5/SKOR1, and PTPRD. The presence of a positive family history suggests that there may be a genetic involvement in the etiology of RLS. Although it is only partly understood, pathophysiology of restless legs syndrome may involve dopamine and iron system anomalies. There

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