Dantrolene

Dantrolene sodium is a postsynaptic muscle relaxant that lessens excitation-contraction coupling in muscle cells. It achieves this by inhibiting Ca2+ ions release from sarcoplasmic reticulum stores by antagonizing ryanodine receptors.[1] It is the primary drug used for the treatment and prevention of malignant hyperthermia, a rare, life-threatening disorder triggered by general anesthesia. It is also used in the management of neuroleptic malignant syndrome, muscle spasticity (e.g. after strokes, in paraplegia, cerebral palsy, or patients with multiple sclerosis), and 2,4-dinitrophenol poisoning,[2][3] and the related compounds dinoseb and dinoterb.[4]

It is marketed by Par Pharmaceuticals LLC as Dantrium (in North America) and by Norgine BV as Dantrium, Dantamacrin, or Dantrolen (in Europe). A hospital is recommended to keep a minimum stock of 36 dantrolene vials totaling 720 mg, sufficient for a 70-kg person.[5] As of 2015 the cost for a typical course of medication in the United States is 100 to 200 USD.[6]

Dantrolene
Structural formula of dantrolene
Space-filling model of the dantrolene molecule
Clinical data
Trade namesDantrium (in North America)
Dantrolen (in Europe)
Dantamacrin (in Europe , Russia)
AHFS/Drugs.comMonograph
Pregnancy
category
  • US: C (Risk not ruled out)
Routes of
administration
Oral, intravenous
ATC code
Pharmacokinetic data
Bioavailability70%
MetabolismLiver
ExcretionBiliary, renal
Identifiers
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
Chemical and physical data
FormulaC14H10N4O5
Molar mass314.253 g/mol g·mol−1
3D model (JSmol)
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DantroleneSodiumSalt
The sodium salt of dantrolene (shown) is an orange crystalline solid.

History

Dantrolene was first described in the scientific literature in 1967, as one of several hydantoin derivatives proposed as a new class of muscle relaxant.[7] Dantrolene underwent extensive further development, and its action on skeletal muscle was described in detail in 1973.[8]

Dantrolene was widely used in the management of spasticity[9] before its efficacy in treating malignant hyperthermia was discovered by South African anesthesiologist Gaisford Harrison and reported in a landmark 1975 article published in the British Journal of Anaesthesia.[10] Harrison experimentally induced malignant hyperthermia with halothane anesthesia in genetically susceptible pigs, and obtained an 87.5% survival rate, where seven of his eight experiments survived after intravenous administration of dantrolene. The efficacy of dantrolene in humans was later confirmed in a large, multicenter study published in 1982,[11] and confirmed epidemiologically in 1993.[12] Before dantrolene, the only available treatment for malignant hyperthermia was procaine, which was associated with a 60% mortality rate in animal models.[10]

Contraindications

Oral dantrolene cannot be used by:

  • people with a pre-existing liver disease
  • people with compromised lung function
  • people with severe cardiovascular impairment
  • people with a known hypersensitivity to dantrolene
  • pediatric patients under five years of age
  • people who need good muscular balance or strength to maintain an upright position, motoric function, or proper neuromuscular balance

If the indication is a medical emergency, such as malignant hyperthermia, the only significant contraindication is hypersensitivity.

Pregnancy and breastfeeding

If needed in pregnancy, adequate human studies are lacking, therefore the drug should be given in pregnant women only if clearly indicated. It may cause hypotonia in the newborn if given closely before delivery.[4]

Dantrolene should not be given to breastfeeding mothers. If a treatment is necessary, breastfeeding should be terminated.

Adverse effects

Central nervous system side effects are quite frequently noted and encompass speech and visual disturbances, mental depression and confusion, hallucinations, headache, insomnia and exacerbation or precipitation of seizures, and increased nervousness. Infrequent cases of respiratory depression or a feeling of suffocation have been observed. Dantrolene often causes sedation severe enough to incapacitate the patient to drive or operate machinery.

Gastrointestinal effects include bad taste, decreased appetite, nausea, vomiting, abdominal cramps, and diarrhea.

Liver side effects may be seen either as asymptomatic elevation of liver enzymes and/or bilirubin or, most severe, as fatal and nonfatal liver inflammation. The risk of liver inflammation is associated with the duration of treatment and the daily dose. In patients treated for hyperthermia, no liver toxicity has been observed so far. Patients on chronic dantrolene therapy should routinely have LFTs monitored.

Pleural effusion with inflammation of the fibrous sac around the heart (oral treatment only), rare cases of bone marrow damage, diffuse muscle pains, backache, dermatologic reactions, transient cardiovascular reactions, and crystals in the urine have additionally been seen. Muscle weakness may persist for several days following treatment.

Mutagenicity and carcinogenity

It is currently unclear whether Dantrolene has carcinogenic effects.

Mechanism of action

Dantrolene depresses excitation-contraction coupling in skeletal muscle by acting as a receptor antagonist to the ryanodine receptor, and decreasing free intracellular calcium concentration.[4]

Chemistry

Azumolene
Skeletal formula of azumolene. The bromine atom replacing the nitro group found in dantrolene may be seen at left.

Chemically it is a hydantoin derivative, but does not exhibit antiepileptic activity like other hydantoin derivates such as phenytoin.[4]

The poor water solubility of dantrolene leads to certain difficulties in its use.[4][13] A more water-soluble analog of dantrolene, azumolene, is under development for similar indications.[13] Azumolene has a bromine residue instead of the nitro group found in dantrolene, and is 30 times more water-soluble.[4]

Drug interactions

Dantrolene may interact with the following drugs:[14]

Synthesis

The original patent synthesis started with para-nitroaniline which undergoes diazotization followed by a copper(II) chloride catalyzed arylation with furfural (essentially a modified Meerwein arylation). This then reacts with 1-aminohydantoin to form the final product.

Dantrolene synthesis
Dantrolene synthesis:[15] Davis and Snyder; U.S. Patent 3,415,821 (1968 to Norwich Pharma Co).

References

  1. ^ Zucchi, R; Ronca-Testoni, S (March 1997). "The sarcoplasmic reticulum Ca2+ channel/ryanodine receptor: modulation by endogenous effectors, drugs and disease states". Pharmacological Reviews. 49 (1): 1–51. PMID 9085308.
  2. ^ Kumar S, Barker K, Seger D (2002). "Dinitrophenol-Induced Hyperthermia Resolving With Dantrolene Administration. Abstracts of the North American Congress of Clinical Toxicology". Clin Toxicol. 40 (5): 599–673. doi:10.1081/clt-120016859.
  3. ^ Barker K, Seger D, Kumar S (2006). "Comment on "Pediatric fatality following ingestion of Dinitrophenol: postmortem identification of a 'dietary supplement'"". Clin Toxicol. 44 (3): 351. doi:10.1080/15563650600584709. PMID 16749560.
  4. ^ a b c d e f Krause T, Gerbershagen MU, Fiege M, Weisshorn R, Wappler F (2004). "Dantrolene – a review of its pharmacology, therapeutic use and new developments". Anaesthesia. 59 (4): 364–73. doi:10.1111/j.1365-2044.2004.03658.x. PMID 15023108.
  5. ^ Yeung EY, Munroe J (2015). "Development of a malignant hyperthermia protocol" (PDF). BMC Proceedings. 9 (Suppl1): A32. doi:10.1186/1753-6561-9-S1-A32. PMC 4306034.
  6. ^ Hamilton, Richart (2015). Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition. Jones & Bartlett Learning. p. 2. ISBN 9781284057560.
  7. ^ Snyder HR, Davis CS, Bickerton RK, Halliday RP (September 1967). "1-[(5-arylfurfurylidene)amino]hydantoins. A new class of muscle relaxants". J Med Chem. 10 (5): 807–10. doi:10.1021/jm00317a011. PMID 6048486.
  8. ^ Ellis KO, Castellion AW, Honkomp LJ, Wessels FL, Carpenter JE, Halliday RP (June 1973). "Dantrolene, a direct acting skeletal muscle relaxant". J Pharm Sci. 62 (6): 948–51. doi:10.1002/jps.2600620619. PMID 4712630.
  9. ^ Pinder, RM; Brogden, RN; Speight, TM; Avery, GS (January 1977). "Dantrolene sodium: a review of its pharmacological properties and therapeutic efficacy in spasticity". Drugs. 13 (1): 3–23. doi:10.2165/00003495-197713010-00002. PMID 318989.
  10. ^ a b Harrison GG (January 1975). "Control of the malignant hyperpyrexic syndrome in MHS swine by dantrolene sodium". Br J Anaesth. 47 (1): 62–5. doi:10.1093/bja/47.1.62. PMID 1148076. A reprint of the article, which became a "Citation Classic", is available in Br J Anaesth 81 (4): 626–9. PMID 9924249 (free full text).
  11. ^ Kolb ME, Horne ML, Martz R (April 1982). "Dantrolene in human malignant hyperthermia". Anesthesiology. 56 (4): 254–62. doi:10.1097/00000542-198204000-00005. PMID 7039419.
  12. ^ Strazis KP, Fox AW (March 1993). "Malignant hyperthermia: review of published cases". Anesth Analg. 77 (3): 297–304. doi:10.1213/00000539-199377020-00014.
  13. ^ a b Sudo RT, Carmo PL, Trachez MM, Zapata-Sudo G (March 2008). "Effects of azumolene on normal and malignant hyperthermia-susceptible skeletal muscle". Basic Clin Pharmacol Toxicol. 102 (3): 308–16. doi:10.1111/j.1742-7843.2007.00156.x. PMID 18047479.
  14. ^ "Dantrolene Drug Interactions". Epocrates Online. Epocrates. 2008. Retrieved on December 31, 2008.
  15. ^ Snyder, H. R.; Davis, C. S.; Bickerton, R. K.; Halliday, R. P. (1967). "1-[5-Arylfurfurylidene)amino]hydantoins. A New Class of Muscle Relaxants". Journal of Medicinal Chemistry. 10 (5): 807–10. doi:10.1021/jm00317a011. PMID 6048486.

External links

2,4-Dinitrophenol

2,4-Dinitrophenol (2,4-DNP or simply DNP) is an organic compound with the formula HOC6H3(NO2)2. It is a yellow, crystalline solid that has a sweet, musty odor. It sublimes, is volatile with steam, and is soluble in most organic solvents as well as aqueous alkaline solutions. It is a precursor to other chemicals and is biochemically active, inhibiting energy (adenosine triphosphate, ATP) production in cells with mitochondria. Its use in high doses as a dieting aid has been identified with severe side-effects, including a number of deaths.

ATC code M03

ATC code M03 Muscle relaxants is a therapeutic subgroup of the Anatomical Therapeutic Chemical Classification System, a system of alphanumeric codes developed by the WHO for the classification of drugs and other medical products. Subgroup M03 is part of the anatomical group M Musculo-skeletal system.

Codes for veterinary use (ATCvet codes) can be created by placing the letter Q in front of the human ATC code: for example, QM03. ATCvet codes without corresponding human ATC codes are cited with the leading Q in the following list.National issues of the ATC classification may include additional codes not present in this list, which follows the WHO version.

Antispasmodic

An antispasmodic (synonym: spasmolytic) is a pharmaceutical drug or other agent that suppresses muscle spasms.

Brody myopathy

Brody myopathy, also known as Brody disease (BD), is a rare disorder that affects skeletal muscle function. BD was first characterized in 1969 by Dr. Irwin A. Brody at Duke University Medical Center. Individuals with BD have difficulty relaxing their muscles after exercise. This difficulty in relaxation leads to symptoms including cramps, stiffness, and discomfort in the muscles of the limbs and face. Symptoms are heightened by exercise and commonly progress in severity throughout adulthood.Most cases of BD are inherited through autosomal recessive mutations in ATP2A1, where each copy of the affected individual's gene contain a mutation. The gene involved in BD encodes the fast-twitch skeletal muscle ATPase, SERCA1. SERCA1 is a protein pump that uses ATP to pump Ca2+ ions from the cytosol to the sarcoplasmic reticulum in skeletal muscle. In those with BD, SERCA1 pumps are unable to effectively move Ca2+ across the membrane, leading to increased levels of cytoplasmic Ca2+. Increases in cytoplasmic Ca2+ levels interfere with muscle contraction, leading to the characteristic symptoms of BD.In some cases of BD, no mutations in ATP2A1 have been observed. Disease transmission in cases of non-ATP2A1 BD have been characterized as autosomal dominant pattern of inheritance. These cases have revealed that the cause of the disease likely exhibits genetic heterogeneity, meaning the disease involves mutations in other locations within the genome (although no other loci have been identified in the development of BD as of now).

Fever

Fever, also known as pyrexia and febrile response, is defined as having a temperature above the normal range due to an increase in the body's temperature set point. There is not a single agreed-upon upper limit for normal temperature with sources using values between 37.5 and 38.3 °C (99.5 and 100.9 °F). The increase in set point triggers increased muscle contractions and causes a feeling of cold. This results in greater heat production and efforts to conserve heat. When the set point temperature returns to normal, a person feels hot, becomes flushed, and may begin to sweat. Rarely a fever may trigger a febrile seizure. This is more common in young children. Fevers do not typically go higher than 41 to 42 °C (105.8 to 107.6 °F).A fever can be caused by many medical conditions ranging from non serious to life threatening. This includes viral, bacterial and parasitic infections such as the common cold, urinary tract infections, meningitis, malaria and appendicitis among others. Non-infectious causes include vasculitis, deep vein thrombosis, side effects of medication, and cancer among others. It differs from hyperthermia, in that hyperthermia is an increase in body temperature over the temperature set point, due to either too much heat production or not enough heat loss.Treatment to reduce fever is generally not required. Treatment of associated pain and inflammation, however, may be useful and help a person rest. Medications such as ibuprofen or paracetamol (acetaminophen) may help with this as well as lower temperature. Measures such as putting a cool damp cloth on the forehead and having a slightly warm bath are not useful and may simply make a person more uncomfortable. Children younger than three months require medical attention, as might people with serious medical problems such as a compromised immune system or people with other symptoms. Hyperthermia does require treatment.Fever is one of the most common medical signs. It is part of about 30% of healthcare visits by children and occurs in up to 75% of adults who are seriously sick. While fever is a useful defense mechanism, treating fever does not appear to worsen outcomes. Fever is viewed with greater concern by parents and healthcare professionals than it usually deserves, a phenomenon known as fever phobia.

Heat stroke

Heat stroke, also known as sun stroke, is a type of severe heat illness that results in a body temperature greater than 40.0 °C (104.0 °F) and confusion. Other symptoms include red, dry or damp skin, headache, and dizziness. Onset can be sudden or gradual. Complications may include seizures, rhabdomyolysis, or kidney failure.Heat stroke occurs because of high external temperatures or physical exertion. Risk factors include heat waves, high humidity, certain drugs such as diuretics, beta blockers, or alcohol, heart disease, and skin disorders. Cases not associated with physical exertion typically occur in those at the extremes of age or with long term health problems. Diagnosis is based on symptoms. It is a type of hyperthermia. It is distinct from a fever, where there is a physiological increase in the temperature set point.Preventive measures include drinking sufficient fluids and avoiding excessive heat. Treatment is by rapid physical cooling of the body and supportive care. Recommended methods include spraying the person with water and using a fan, putting the person in ice water, or giving cold intravenous fluids. While it is reasonable to add ice packs around a person, this by itself is not routinely recommended.It results in more than 600 deaths a year in the United States. Rates have increased between 1995 and 2015. The risk of death is less than 5% in those with exercise-induced heat stroke and as high as 65% in those with non-exercise induced cases.

Human body temperature

Normal human body temperature, also known as normothermia or euthermia, is the typical temperature range found in humans. The normal human body temperature range is typically stated as 36.5–37.5 °C (97.7–99.5 °F).Individual body temperature depends upon the age, exertion, infection, sex, and reproductive status of the subject, the time of day, the place in the body at which the measurement is made, and the subject's state of consciousness (waking, sleeping or sedated), activity level, and emotional state. It is typically maintained within this range by thermoregulation.

Hydantoin

Hydantoin, or glycolylurea, is a heterocyclic organic compound with the formula CH2C(O)NHC(O)NH. It is a colorless solid that arises from the reaction of glycolic acid and urea. It is an oxidized derivative of imidazolidine. In a more general sense, hydantoins can refer to a groups and a class of compounds with the same ring structure as the parent. For example, phenytoin (mentioned below) has two phenyl groups substituted onto the number 5 carbon in a hydantoin molecule.

Hyperthermia

Hyperthermia is a condition where an individual's body temperature is elevated beyond normal due to failed thermoregulation. The person's body produces or absorbs more heat than it dissipates. When extreme temperature elevation occurs, it becomes a medical emergency requiring immediate treatment to prevent disability or death.

The most common causes include heat stroke and adverse reactions to drugs. The former is an acute temperature elevation caused by exposure to excessive heat, or combination of heat and humidity, that overwhelms the heat-regulating mechanisms. The latter is a relatively rare side effect of many drugs, particularly those that affect the central nervous system. Malignant hyperthermia is a rare complication of some types of general anesthesia.

Hyperthermia differs from fever in that the body's temperature set point remains unchanged. The opposite is hypothermia, which occurs when the temperature drops below that required to maintain normal metabolism. The term is from Greek ὑπέρ, hyper, meaning "above" or "over", and θέρμος, thermos, meaning "hot".

Hypertonia

Hypertonia is a term sometimes used synonymously with spasticity and rigidity in the literature surrounding damage to the central nervous system, namely upper motor neuron lesions. Impaired ability of damaged motor neurons to regulate descending pathways gives rise to disordered spinal reflexes, increased excitability of muscle spindles, and decreased synaptic inhibition. These consequences result in abnormally increased muscle tone of symptomatic muscles. Some authors suggest that the current definition for spasticity, the velocity-dependent over-activity of the stretch reflex, is not sufficient as it fails to take into account patients exhibiting increased muscle tone in the absence of stretch reflex over-activity. They instead suggest that "reversible hypertonia" is more appropriate and represents a treatable condition that is responsive to various therapy modalities like drug and/or physical therapy.

Hypothermia

Hypothermia is reduced body temperature that happens when a body dissipates more heat than it absorbs. In humans, it is defined as a body core temperature below 35.0 °C (95.0 °F). Symptoms depend on the temperature. In mild hypothermia there is shivering and mental confusion. In moderate hypothermia shivering stops and confusion increases. In severe hypothermia, there may be paradoxical undressing, in which a person removes their clothing, as well as an increased risk of the heart stopping.Hypothermia has two main types of causes. It classically occurs from exposure to extreme cold. It may also occur from any condition that decreases heat production or increases heat loss. Commonly this includes alcohol intoxication but may also include low blood sugar, anorexia, and advanced age. Body temperature is usually maintained near a constant level of 36.5–37.5 °C (97.7–99.5 °F) through thermoregulation. Efforts to increase body temperature involve shivering, increased voluntary activity, and putting on warmer clothing. Hypothermia may be diagnosed based on either a person's symptoms in the presence of risk factors or by measuring a person's core temperature.The treatment of mild hypothermia involves warm drinks, warm clothing, and physical activity. In those with moderate hypothermia, heating blankets and warmed intravenous fluids are recommended. People with moderate or severe hypothermia should be moved gently. In severe hypothermia, extracorporeal membrane oxygenation (ECMO) or cardiopulmonary bypass may be useful. In those without a pulse, cardiopulmonary resuscitation (CPR) is indicated along with the above measures. Rewarming is typically continued until a person's temperature is greater than 32 °C (90 °F). If there is no improvement at this point or the blood potassium level is greater than 12 mmol/liter at any time, resuscitation may be discontinued.Hypothermia is the cause of at least 1,500 deaths a year in the United States. It is more common in older people and males. One of the lowest documented body temperatures from which someone with accidental hypothermia has survived is 13.0 °C (55.4 °F) in a near-drowning of a 7-year-old girl in Sweden. Survival after more than six hours of CPR has been described. For those for whom ECMO or bypass is used, survival is around 50%. Deaths due to hypothermia have played an important role in many wars. The term is from Greek ὑπο, hupo, meaning "under", and θερμία, thermía, meaning "heat". The opposite of hypothermia is hyperthermia, an increased body temperature due to failed thermoregulation.

Malignant hyperthermia

Malignant hyperthermia (MH) is a type of severe reaction that occurs to particular medications used during general anesthesia, among those who are susceptible. Symptoms include muscle rigidity, high fever, and a fast heart rate. Complications can include rhabdomyolysis and high blood potassium. Most people who are susceptible are generally otherwise normal when not exposed.The cause of MH is the use of certain volatile anesthetic agents or succinylcholine in those who are susceptible. Susceptibility can occur due to at least six genetic mutations, with the most common one being of the RYR1 gene. Susceptibility is often inherited from a person's parents in an autosomal dominant manner. The condition may also occur as a new mutation or be associated with a number of inherited muscle diseases, such as central core disease.In susceptible individuals, the medications induce the release of stored calcium ions within muscle cells. The resulting increase in calcium concentrations within the cells cause the muscle fibers to contract. This generates excessive heat and results in metabolic acidosis. Diagnosis is based on symptoms in the appropriate situation. Family members may be tested to see if they are susceptible by muscle biopsy or genetic testing.Treatment is with dantrolene and rapid cooling along with other supportive measures. The avoidance of potential triggers is recommended in susceptible people. The condition affects one in 5,000 to 50,000 cases where people are given anesthetic gases. Males are more often affected than females. The risk of death with proper treatment is about 5% while without it is around 75%. While cases that appear similar to MH have been documented since the early 20th century, the condition was only formally recognized in 1960.

Muscle relaxant

A muscle relaxant is a drug that affects skeletal muscle function and decreases the muscle tone. It may be used to alleviate symptoms such as muscle spasms, pain, and hyperreflexia. The term "muscle relaxant" is used to refer to two major therapeutic groups: neuromuscular blockers and spasmolytics. Neuromuscular blockers act by interfering with transmission at the neuromuscular end plate and have no central nervous system (CNS) activity. They are often used during surgical procedures and in intensive care and emergency medicine to cause temporary paralysis. Spasmolytics, also known as "centrally acting" muscle relaxants, are used to alleviate musculoskeletal pain and spasms and to reduce spasticity in a variety of neurological conditions. While both neuromuscular blockers and spasmolytics are often grouped together as muscle relaxants, the term is commonly used to refer to spasmolytics only.

Neuroleptic malignant syndrome

Neuroleptic malignant syndrome (NMS) is a life-threatening reaction that can occur in response to neuroleptic or antipsychotic medication. Symptoms include high fever, confusion, rigid muscles, variable blood pressure, sweating, and fast heart rate. Complications may include rhabdomyolysis, high blood potassium, kidney failure, or seizures.Any medications within the family of neuroleptics can cause the condition, though typical antipsychotics appear to have a higher risk than atypicals. Onset is often within a few weeks of starting the medication but can occur at any time. Risk factors include dehydration, agitation, and catatonia. Rapidly decreasing the use of levodopa may also trigger the condition. The underlying mechanism involves blockage of dopamine receptors. Diagnosis is based on symptoms.Management includes stopping the offending medication, rapid cooling, and starting other medications. Medications used include dantrolene, bromocriptine, and diazepam. The risk of death among those affected is about 10%. Many people can eventually be restarted on a lower dose of antipsychotic.Among those in psychiatric hospitals on neuroleptics about 15 per 100,000 are affected per year. Males appear to be more often affected than females. In the second half of the 20th century rates were higher than present, at about 2% of people in hospital per year. The condition was first described in 1956.

Porcine stress syndrome

Porcine stress syndrome, also known as malignant hyperthermia or PSS, is a condition in pigs. It is characterised by hyperthermia triggered by stress, anaesthesia with halothane or intense exercise. PSS may appear as sudden death in pigs, often after transport. It is an inherited, autosomal recessive disorder due to a defective ryanodine receptor leading to huge calcium influx, muscle contracture and increase in metabolism.

PSS can manifest itself in the abattoir as the production of Pale, Soft and Exudative meat due to a rapid fall in muscle pH and degradation of muscle proteins and structure. This meat is usually rejected after inspection.

This disorder is most common in Landrace, Piétrain and crossbreeds of these breeds of pig. The genes may have been favoured in the past due to a larger muscle bulk in these breeds. However this is not standard protocol in developed countries these days.

RYR1

Ryanodine receptor 1 (RYR-1) also known as skeletal muscle calcium release channel or skeletal muscle-type ryanodine receptor is a protein found primarily in skeletal muscle. In humans, it is encoded by the RYR1 gene.

Suxamethonium chloride

Suxamethonium chloride, also known as suxamethonium or succinylcholine, is a medication used to cause short-term paralysis as part of general anesthesia. This is done to help with tracheal intubation or electroconvulsive therapy. It is given either by injection into a vein or muscle. When used in a vein onset of action is generally within one minute and effects last for up to 10 minutes.Common side effects include low blood pressure, increased saliva production, muscle pain, and rash. Serious side effects include malignant hyperthermia and allergic reactions. It is not recommended in people who are at risk of high blood potassium or a history of myopathy. Use during pregnancy appears to be safe for the baby. Suxamethonium is in the neuromuscular blocker family of medications and is of the depolarizing type. It works by blocking the action of acetylcholine on skeletal muscles.Suxamethonium was described as early as 1906 and came into medical use in 1951. It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system. Suxamethonium is available as a generic medication. The wholesale cost in the developing world is about US$0.45 to US$1.31 a dose. It may colloquially be referred to as "sux".

Wake Up (TV series)

Wake Up (Chinese: 麻醉風暴) is a 2015 Taiwanese television series starring Jag Huang, Wu Kang-jen, Hsu Wei-ning and Michael Huang. Filming began on 29 September 2014 and ended on 11 November. The series was aired on PTS HD from 1 April 2015. Wake Up is based on an original novel, Ferocious Pursuit (惡火追緝), by scriptwriter Huang Jian-ming.

Wake Up has earned praises from Hou Wen Yong, an anaesthesiologist and the author of renowned Taiwanese novel The Hospital. The drama won numerous awards at the 50th Golden Bell Awards, including Best Miniseries, Best Directing for a Miniseries, Best Writing for a Miniseries and Best Supporting Actor in a Miniseries for Wu Kang-jen. Leading Hong Kong newsweekly Yazhou Zhoukan placed the drama in the second spot for the 2015 Top Ten Television Dramas, after China's Nirvana in Fire.Its sequel Wake Up 2 airs on PTS in Taiwan, premiering on September 9, 2017.

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