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Lorazepam: Difference between revisions
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| ''[[Lorazepam/Summary|Summary sheet: Lorazepam]]'' | | ''[[Lorazepam/Summary|Summary sheet: Lorazepam]]'' | ||
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'''Lorazepam''' (trade name '''Ativan''') is an intermediate-duration [[psychoactive]] | '''Lorazepam''' (trade name '''Ativan''') is an intermediate-duration [[psychoactive]] drug of the [[chemical class::benzodiazepine]] class which produces [[anxiolytic]], [[sedative]], [[hypnotic]], [[muscle relaxant]], [[anticonvulsant]], [[Nausea suppression|anti-nausea]], [[psychoactive class::depressant]] and [[amnestic]] effects. This compound is used for the short-term treatment of [[Anxiety|anxiety]], [[insomnia]], [[seizure|acute seizures]], and the sedation of hospitalized patients.<ref>Benzodiazepines and their effects | http://www.benzo.org.uk/hindmarch.htm</ref><ref>An Economic Evaluation of Propofol and Lorazepam for Critically Ill Patients Undergoing Mechanical Ventilation (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2763279/</ref><ref>Status epilepticus: an evidence based guide (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1226249/</ref><ref>Pharmacological Management of Acute Agitation | http://link.springer.com/article/10.2165%2F00003495-200565090-00003</ref> | ||
It's worth noting that [[Benzodiazepine#Discontinuation|the sudden discontinuation of benzodiazepines]] can be potentially dangerous or life-threatening for individuals using regularly for extended periods of time, sometimes resulting in seizures or death.<ref>A fatal case of benzodiazepine withdrawal. (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/19465812</ref> It is highly recommended to [[taper]] one's dose by gradually lowering the amount taken each day for a prolonged period of time instead of stopping abruptly.<ref>Canadian Guideline for Safe and Effective Use of Opioids for Chronic Non-Cancer Pain - Appendix B-6: Benzodiazepine Tapering | http://nationalpaincentre.mcmaster.ca/opioid/cgop_b_app_b06.html</ref> | It's worth noting that [[Benzodiazepine#Discontinuation|the sudden discontinuation of benzodiazepines]] can be potentially dangerous or life-threatening for individuals using regularly for extended periods of time, sometimes resulting in seizures or death.<ref>A fatal case of benzodiazepine withdrawal. (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/19465812</ref> It is highly recommended to [[taper]] one's dose by gradually lowering the amount taken each day for a prolonged period of time instead of stopping abruptly.<ref>Canadian Guideline for Safe and Effective Use of Opioids for Chronic Non-Cancer Pain - Appendix B-6: Benzodiazepine Tapering | http://nationalpaincentre.mcmaster.ca/opioid/cgop_b_app_b06.html</ref> | ||
==Chemistry== | ==Chemistry== | ||
Lorazepam is a | Lorazepam is a drug of the [[benzodiazepine]] class. Benzodiazepine drugs contain a benzene ring fused to a diazepine ring, which is a seven membered ring with the two nitrogen constituents located at R<sub>1</sub> and R<sub>4</sub>. Further, the benzodiazepine ring is bonded at R<sub>5</sub> to a 2-chlorinated phenyl ring. R<sub>7</sub> of the benzyl ring is also substituted with a chlorine group. Additionally, Lorazepam contains a hydroxy (OH-) group substituted at R<sub>3</sub>. It also contains an oxygen group double bonded to R<sub>2</sub> of its diazepine ring to form a ketone. This oxygen substitution at R<sub>2</sub> is shared with other benzodiazepine drugs with the suffix -azepam. | ||
==Pharmacology== | ==Pharmacology== | ||
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{{Preamble/SubjectiveEffects}} | {{Preamble/SubjectiveEffects}} | ||
===Physical effects=== | ===Physical effects=== | ||
*'''[[Effect::Sedation]]''' - In terms of energy level alterations, this | *'''[[Effect::Sedation]]''' - In terms of energy level alterations, this drug has the potential to be extremely sedating and often results in an overwhelmingly lethargic state. At higher levels, this causes users to suddenly feel as if they are extremely sleep deprived and have not slept for days, forcing them to sit down and generally feel as if they are constantly on the verge of passing out instead of engaging in physical activities. This sense of sleep deprivation increases proportional to dosage and eventually becomes powerful enough to force a person into complete unconsciousness. | ||
*'''[[Effect::Motor control loss]]''' | *'''[[Effect::Motor control loss]]''' | ||
*'''[[Effect::Muscle relaxation]] | *'''[[Effect::Muscle relaxation]] | ||
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==Toxicity and harm potential== | ==Toxicity and harm potential== | ||
[[File:harmchart.png|thumb|right|300px|Radar plot showing relative physical harm, social harm, and dependence of benzodiazepines in comparison to other drugs.<ref>Development of a rational scale to assess the harm of | [[File:harmchart.png|thumb|right|300px|Radar plot showing relative physical harm, social harm, and dependence of benzodiazepines in comparison to other drugs.<ref>Development of a rational scale to assess the harm of drugs of potential misuse (ScienceDirect) | http://www.sciencedirect.com/science/article/pii/S0140673607604644</ref>]] | ||
Lorazepam likely has a [[Toxicity::low toxicity]] relative to dose.<ref>Benzodiazepine metabolism: an analytical perspective (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/18855614</ref> However, it is [[Toxicity::potentially [[respiratory depression|lethal]] when mixed with [[depressants]] like [[alcohol]] or [[opioids]]]]. | Lorazepam likely has a [[Toxicity::low toxicity]] relative to dose.<ref>Benzodiazepine metabolism: an analytical perspective (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/18855614</ref> However, it is [[Toxicity::potentially [[respiratory depression|lethal]] when mixed with [[depressants]] like [[alcohol]] or [[opioids]]]]. | ||
It is strongly recommended that one use [[responsible | It is strongly recommended that one use [[responsible drug use|harm reduction practices]] when using this drug. | ||
===Tolerance and addiction potential=== | ===Tolerance and addiction potential=== | ||
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===Dangerous interactions=== | ===Dangerous interactions=== | ||
Although many | Although many drugs are safe on their own, they can become dangerous and even life-threatening when combined with other substances. The list below contains some common potentially dangerous combinations, but may not include all of them. Certain combinations may be safe in low doses of each but still increase the potential risk of death. [https://www.google.com/ Independent research] should always be done to ensure that a combination of two or more substances is safe before consumption. | ||
*'''[[Depressants]]''' (''[[1,4-Butanediol]], [[2-methyl-2-butanol]], [[alcohol]], [[barbiturates]], [[GHB]]/[[GBL]], [[methaqualone]], [[opioids]]'') - This combination can result in dangerous or even fatal levels of [[respiratory depression]]. These substances potentiate the [[muscle relaxation]], [[sedation]] and [[amnesia]] caused by one another and can lead to unexpected loss of consciousness at high doses. There is also an increased risk of vomiting during unconsciousness and death from the resulting suffocation. If this occurs, users should attempt to fall asleep in the [[recovery position]] or have a friend move them into it. | *'''[[Depressants]]''' (''[[1,4-Butanediol]], [[2-methyl-2-butanol]], [[alcohol]], [[barbiturates]], [[GHB]]/[[GBL]], [[methaqualone]], [[opioids]]'') - This combination can result in dangerous or even fatal levels of [[respiratory depression]]. These substances potentiate the [[muscle relaxation]], [[sedation]] and [[amnesia]] caused by one another and can lead to unexpected loss of consciousness at high doses. There is also an increased risk of vomiting during unconsciousness and death from the resulting suffocation. If this occurs, users should attempt to fall asleep in the [[recovery position]] or have a friend move them into it. | ||
*'''[[Dissociatives]]''' - This combination can result in an increased risk of vomiting during unconsciousness and death from the resulting suffocation. If this occurs, users should attempt to fall asleep in the [[recovery position]] or have a friend move them into it. | *'''[[Dissociatives]]''' - This combination can result in an increased risk of vomiting during unconsciousness and death from the resulting suffocation. If this occurs, users should attempt to fall asleep in the [[recovery position]] or have a friend move them into it. | ||
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==Legal issues== | ==Legal issues== | ||
*'''International:''' The | *'''International:''' The drug is a Schedule IV drug under the United Nations Convention on Psychotropic Substances.<ref>List of psychotropic substances under international control | http://www.indiapost.gov.in/Pdf/Customs/List_of_Psychotropic_Substances.pdf</ref> | ||
*'''United States:''' Lorazepam is a Schedule IV | *'''United States:''' Lorazepam is a Schedule IV drug under the Controlled Substances Act in the U.S. | ||
*'''Canada:''' It is a Schedule IV | *'''Canada:''' It is a Schedule IV drug under the Controlled Drugs and Substances Act in Canada. | ||
*'''United Kingdom:''' It is a Class C, Schedule 4 controlled | *'''United Kingdom:''' It is a Class C, Schedule 4 controlled drug under the Misuse of Drugs Regulations 2001.<ref>List of drugs currently controlled under | ||
the misuse of | the misuse of drugs legislation| https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/164222/controlled-drugs-list.pdf</ref> | ||
*'''Germany:''' Preparations containing more than 2.5 mg are controlled under Anlage 3 of the BtMG and require a prescription. | *'''Germany:''' Preparations containing more than 2.5 mg are controlled under Anlage 3 of the BtMG and require a prescription. | ||