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Encyclopedia > Lorazepam
Lorazepam
Systematic (IUPAC) name
9-chloro-6-(2-chlorophenyl)-4-hydroxy-
2,5-diazabicyclo[5.4.0]undeca-
5,8,10,12-tetraen-3-one
Identifiers
CAS number 846-49-1
ATC code N05BA06
PubChem 3958
DrugBank APRD00116
Chemical data
Formula C15H10Cl2N2O2 
Mol. mass 321.2 g/mol
Pharmacokinetic data
Bioavailability 85% of oral dose
Metabolism Hepatic glucuronidation
Half life 10-20 hours
Excretion Renal
Therapeutic considerations
Pregnancy cat.

D(US) Image File history File links This is a lossless scalable vector image. ... Image File history File links Size of this preview: 645 × 600 pixelsFull resolution (1000 × 930 pixel, file size: 179 KB, MIME type: image/png) File links The following pages on the English Wikipedia link to this file (pages on other projects are not listed): Lorazepam ... IUPAC nomenclature is a system of naming chemical compounds and of describing the science of chemistry in general. ... CAS registry numbers are unique numerical identifiers for chemical compounds, polymers, biological sequences, mixtures and alloys. ... The Anatomical Therapeutic Chemical Classification System is used for the classification of drugs. ... A section of the Anatomical Therapeutic Chemical Classification System. ... PubChem is a database of chemical molecules. ... The DrugBank database available at the University of Alberta is a unique bioinformatics and cheminformatics resource that combines detailed drug (i. ... This article or section does not cite any references or sources. ... General Name, symbol, number carbon, C, 6 Chemical series nonmetals Group, period, block 14, 2, p Appearance black (graphite) colorless (diamond) Standard atomic weight 12. ... General Name, Symbol, Number hydrogen, H, 1 Chemical series nonmetals Group, Period, Block 1, 1, s Appearance colorless Atomic mass 1. ... General Name, symbol, number chlorine, Cl, 17 Chemical series halogens Group, period, block 17, 3, p Appearance yellowish green Standard atomic weight 35. ... General Name, Symbol, Number nitrogen, N, 7 Chemical series nonmetals Group, Period, Block 15, 2, p Appearance colorless gas Standard atomic weight 14. ... General Name, Symbol, Number oxygen, O, 8 Chemical series nonmetals, chalcogens Group, Period, Block 16, 2, p Appearance colorless (gas) very pale blue (liquid) Standard atomic weight 15. ... The molecular mass (abbreviated Mr) of a substance, formerly also called molecular weight and abbreviated as MW, is the mass of one molecule of that substance, relative to the unified atomic mass unit u (equal to 1/12 the mass of one atom of carbon-12). ... In pharmacology, bioavailability is used to describe the fraction of an administered dose of unchanged drug that reaches the systemic circulation, one of the principal pharmacokinetic properties of drugs. ... Drug metabolism is the metabolism of drugs, their biochemical modification or degradation, usually through specialized enzymatic systems. ... The liver is an organ present in vertebrates and some other animals. ... Example of glucuronidation Glucuronidation of alcohols and acids Glucuronidation is a major inactivating pathway for a huge variety of exogenous and endogenous molecules, including drugs, polluants, bilirubin, androgens, estrogens, mineralocorticoids, glucocorticoids, fatty acid derivatives, retinoids and bile acids. ... It has been suggested that Effective half-life be merged into this article or section. ... Excretion is the process of eliminating waste products of metabolism and other materials that are of no use. ... The kidneys are organs that filter wastes (such as urea) from the blood and excrete them, along with water, as urine. ... The pregnancy category of a pharmaceutical agent is an assessment of the risk of fetal injury due to the pharmaceutical, if it is used as directed by the mother during pregnancy. ... Motto: (Out Of Many, One) (traditional) In God We Trust (1956 to date) Anthem: The Star-Spangled Banner Capital Washington D.C. Largest city New York City None at federal level (English de facto) Government Federal constitutional republic  - President George Walker Bush (R)  - Vice President Dick Cheney (R) Independence from...

Legal status

Schedule IV(CA) Schedule IV(US) The regulation of therapeutic goods, that is drugs and therapeutic devices, varies by jurisdiction. ... The Controlled Drugs and Substances Act is Canadas federal drug control statute. ... Motto (Latin for From Sea to Sea) Anthem O Canada Royal anthem: God Save the Queen Capital Ottawa Largest city Toronto Official languages English, French Government Parliamentary democracy and federal constitutional monarchy  -  Monarch Queen Elizabeth II  -  Governor General Michaëlle Jean  -  Prime Minister Stephen Harper Establishment  -  Act of Union February... The Controlled Substances Act (CSA) was enacted into law by the Congress of the United States as Title II of the Comprehensive Drug Abuse Prevention and Control Act of 1970. ... Motto: (Out Of Many, One) (traditional) In God We Trust (1956 to date) Anthem: The Star-Spangled Banner Capital Washington D.C. Largest city New York City None at federal level (English de facto) Government Federal constitutional republic  - President George Walker Bush (R)  - Vice President Dick Cheney (R) Independence from...

Routes Oral, I.M., I.V. and transdermal

Lorazepam is a benzodiazepine tranquilizer with short to medium duration of action. It has all five intrinsic benzodiazepine effects: anxiolytic, sedative/hypnotic, amnesic, anticonvulsant and muscle relaxant, to different extents.[1] It is a unique benzodiazepine insofar that it has also found use as an adjunct antiemetic in chemotherapy. Since its introduction in 1971, lorazepam's principal use has been in treating the symptom of anxiety. Compared to other benzodiazepines, lorazepam has relatively high addictive potential. In pharmacology and toxicology, a route of administration is the path by which a drug, fluid, poison or other substance is brought into contact with the body 1. ... Alprazolam 2mg tablets The benzodiazepines (pronounced , or benzos for short) are a class of psychoactive drugs considered as minor tranquilizers with varying hypnotic, sedative, anxiolytic, anticonvulsant, muscle relaxant and amnesic properties, which are brought on by slowing down the central nervous system. ... An anxiolytic is a drug prescribed for the treatment of symptoms of anxiety. ... A sedative is a substance that depresses the central nervous system (CNS), resulting in calmness, relaxation, reduction of anxiety, sleepiness, and slowed breathing, as well as slurred speech, staggering gait, poor judgment, and slow, uncertain reflexes. ... Hypnotic drugs are a class of drugs that induce sleep, used in the treatment of severe insomnia. ... Anterograde amnesia is a form of amnesia, or memory loss, where new events are not transferred to long-term memory. ... The anticonvulsants, sometimes also called antiepileptics, belong to a diverse group of pharmaceuticals used in prevention of the occurrence of epileptic seizures. ... A muscle relaxant is a drug which decreases the tone of a muscle. ... An antiemetic is a drug that is effective against vomiting and nausea. ...

Contents

Uses

Lorazepam has relatively potent anxiolytic effects and its best known indication is the short-term management of severe anxiety. It is less useful in panic disorder.[2] An anxiolytic is a drug prescribed for the treatment of symptoms of anxiety. ...


Lorazepam's sedative/hypnotic effects, and the duration of clinical effects from a single dose, makes it an appropriate choice for the short term treatment of insomnia, particularly in the presence of severe anxiety. A sedative is a substance that depresses the central nervous system (CNS), resulting in calmness, relaxation, reduction of anxiety, sleepiness, and slowed breathing, as well as slurred speech, staggering gait, poor judgment, and slow, uncertain reflexes. ... Hypnotic drugs are a class of drugs that induce sleep, used in the treatment of severe insomnia. ... This article is about the sleeping disorder. ...


Its relatively potent amnesic effect[1], with its anxiolytic and sedative effects, makes lorazepam useful as premedication. It is given prior to a general anaesthetic to reduce the amount of anaesthetic agent required, or before unpleasant awake procedures, such as dentistry or endoscopies, to reduce anxiety, increase compliance and produce varying degrees of amnesia for the procedure. Oral lorazepam is given 90 to 120 minutes before procedures and intravenous lorazepam as late as 10 minutes before procedures.[3][4][5] Premedication refers to a drug treatment given to a patient before a (surgical or invasive) medical procedure. ... Anterograde amnesia is a form of amnesia, or memory loss, where new events are not transferred to long-term memory. ...


The marked anticonvulsant properties of lorazepam, and its pharmacokinetic profile, makes intravenous lorazepam a reliable agent for terminating acute seizures, but it has relatively prolonged sedation after effects. Oral lorazepam, and other benzodiazepines, have a role in long-term prophylactic treatment of resistant forms of petit mal epilepsy but not as first-line therapies, mainly because of the development of resistance to their effects.[6] The anticonvulsants, sometimes also called antiepileptics, belong to a diverse group of pharmaceuticals used in prevention of the occurrence of epileptic seizures. ... Status epilepticus (SE) refers to a life theatening condition in which the brain is in a state of persistent seizure. ... This article is about the neurological disorder as it affects humans. ...


Lorazepam's anticonvulsant, or CNS depressant, properties are useful for the prevention and treatment of alcohol withdrawal symptoms. In this setting it is relevant that impaired liver function is not a hazard with lorazepam since lorazepam does not require oxidation, hepatic or otherwise, for its metabolism.[7][8] Alcohol detoxification or detox for alcoholics is an abrupt stop of alcohol drinking coupled with the substitution of drugs that have similar effects in order to prevent alcohol withdrawal. ...


Where there is need for rapid sedation of violent or agitated patients,[9][10] including acute delirium, lorazepam may be used, but as it can cause paradoxical effects it is preferably given together with haloperidol.[11] Lorazepam is absorbed relatively slowly if given intramuscularly, a common route in restraint situations. Sedation is a medical procedure involving administration of sedative drugs, generally to facilitate a medical procedure, such as endoscopy, vasectomy, or minor surgery with local anaesthesia. ... This article is about the mental state and medical condition. ... Haloperidol (sold under the tradenames Aloperidin, Bioperidolo, Brotopon, Dozic, Duraperidol (Germany), Einalon S, Eukystol, Haldol, Halosten, Keselan, Linton, Peluces, Serenace, Serenase, Sigaperidol) is a conventional, or typical, butyrophenone antipsychotic drug. ...


Catatonia with inability to speak is responsive and sometimes controlled with a single 2 mg oral, or slow intravenous, dose of lorazepam. Symptoms may recur and treatment for some days may be necessary. Catatonia occurring due to abrupt or over-rapid withdrawal from benzodiazepines, as part of the benzodiazepine withdrawal syndrome, should also respond to lorazepam treatment.[12] As lorazepam can have paradoxical effects, haloperidol is sometimes given concomitantly.[13][11] This is a page about catatonic state. ... Benzodiazepine withdrawal syndrome, caused by withdrawal or dosage reduction of benzodiazepines, is the symptoms which appear when a patient who has taken the drug for a period of time stops taking the drug. ... Haloperidol (sold under the tradenames Aloperidin, Bioperidolo, Brotopon, Dozic, Duraperidol (Germany), Einalon S, Eukystol, Haldol, Halosten, Keselan, Linton, Peluces, Serenace, Serenase, Sigaperidol) is a conventional, or typical, butyrophenone antipsychotic drug. ...


Lorazepam is unique among benzodiazepines by having potent anti-emetic properties. It is used as an adjunct antiemetic for treating the nausea and vomiting frequently associated with cancer chemotherapy, usually together with first-line antiemetics such as 5-HT3 antagonists.[14] It is also used as adjunct therapy for cyclic vomiting syndrome. An antiemetic is a drug that is effective against vomiting and nausea. ... For other uses, see Nausea (disambiguation). ... Vomiting (also throwing up or emesis) is the forceful expulsion of the contents of ones stomach through the mouth and sometimes the nose. ... Chemotherapy is the use of chemical substances to treat disease. ... An antiemetic is a drug that is effective against vomiting and nausea. ... Skeletal formula of ondansetron, the prototypical 5-HT3 antagonist The 5-HT3 antagonists are a class of medications which act as receptor antagonists at the 5-hydroxytryptamine-3 receptor (5-HT3 receptor), a subtype of serotonin receptor found in terminals of the vagus nerve and certain areas of the brain. ... // Cyclic vomiting syndrome (US English) or cyclical vomiting syndrome (UK English) (CVS) is a condition whose symptoms are recurring attacks of intense nausea, vomiting and sometimes abdominal pain and/or headaches or migraines. ...


Formulation and Administration

Pure lorazepam is an almost white powder that is nearly insoluble in water and oil. In medicinal form, lorazepam is mainly available as tablets and a solution for injection but in some locations it is also available as a skin patch, an oral solution and a sublingual tablet. Image File history File links No higher resolution available. ... Sublingual, literally under the tongue, from Latin, refers to a pharmacological route of administration in which certain drugs are entered directly into the bloodstream via absorption under the tongue. ...


Lorazepam tablets and syrups are administered by mouth only. The tablets contain either 0.5 mg, 1 mg, or 2 mg lorazepam, with some differences between countries. Lorazepam tablets of the Ativan brand also contain lactose, microcrystalline cellulose, polacrilin potassium, magnesium stearate and colouring agents (Blue tablets: indigo carmine, E132; Yellow tablets: tartrate, E102). Lactose is a disaccharide that consists of β-D-galactose and β-D-glucose molecules bonded through a β1-4 glycosidic linkage. ... Cellulose as polymer of β-D-glucose Cellulose in 3D Cellulose (C6H10O5)n is a polysaccharide of beta-glucose. ... Magnesium stearate, also called Octadecanoic acid,magnesium salt is a white substance, solid at room temperature, chemical formula C36H70MgO4. ... Lump of Indian indigo dye Indigo dye is an important dyestuff with a distinctive blue color (see indigo). ... Tartrazine (otherwise known as E102 or FD&C Yellow 5) is a synthetic yellow azo dye found in fruit squash, fruit cordial, coloured fizzy drinks, instant puddings, cake mixes, custard powder, soups, sauces, ice cream, ice lollies, sweets, chewing gum, marzipan, jam, jelly, marmalade, mustard, yogurt and many convenience foods...


Lorazepam injectable solution is administered either by deep intramuscular injection or by intravenous injection. The injectable solution comes in 1 mL ampoules containing 2 mg or 4 mg lorazepam. The solvents used are polyethylene glycol 400 and propylene glycol. As a preservative, the injectable solution contains benzyl alcohol.[15] Toxicity from propylene glycol has been reported in the case of a patient receiving a continuous lorazepam infusion.[16] Intravenous injections should be given slowly and patients closely monitored for side-effects, such as respiratory depression, hypotension or loss of airway control. Intramuscular injection is the injection of a substance directly into a muscle. ... Intravenous therapy or IV therapy is the giving of liquid substances directly into a vein. ... Pharmaceutical ampoules An ampoule is a small glass vial which is hermetically sealed by melting the thin top usually with a blowtorch flame after filling, and is most commonly used as a container for hypodermic injection solutions (eg. ... Polyethylene glycol (PEG) and polyethylene oxide (PEO) are polymers composed of repeating subunits of identical structure, called monomers, and are the most commercially important polyethers. ... Propylene glycol, also known as 1,2-propanediol, is an organic compound (a diol alcohol), usually a tasteless, odorless, and colorless clear oily liquid that is hygroscopic and miscible with water, acetone, and chloroform. ... Benzyl alcohol, also known as phenylmethanol, is a clear, colorless liquid with a mild pleasant aromatic odor. ... Propylene glycol, also known as 1,2-propanediol, is an organic compound (a diol alcohol), usually a tasteless, odorless, and colorless clear oily liquid that is hygroscopic and miscible with water, acetone, and chloroform. ...


Peak effects roughly coincide with peak serum levels,[17] which occur ten minutes after intravenous injection, up to one hour after intramuscular injection and about 120 minutes after oral administration[18][17], but initial effects are noted before this. A clinically relevant lorazepam dose will normally be effective for 6 - 12 hours, making it unsuitable for regular once-daily administration; it is therefore usually prescribed as two to four daily doses when given regularly.


Pharmacology

Lorazepam is an intermediate acting benzodiazepine and its uniqueness[19], advantages and disadvantages are largely explained by its pharmacokinetic properties (poor water and lipid solubility, high protein binding and non-oxidative metabolism to a pharmacologically inactive glucuronide form) and by its high relative potency (lorazepam 1 mg is equal in effect to diazepam 10 mg[20][21]). Diazepam (IPA: ), first marketed as Valium by Hoffmann-La Roche, is a drug which is a benzodiazepine derivative. ...


Pharmacokinetics

Because of its poor lipid solubility lorazepam is absorbed relatively slowly by mouth and is unsuitable for rectal administration. However, its poor lipid solubility and its high degree of protein binding (85-90%[18]) means that lorazepam's volume of distribution is mainly the vascular compartment. This contrasts with the highly lipid soluble diazepam which, although speedily absorbed orally or rectally, soon redistributes from the serum to other parts of the body, particularly body fat. This explains why one lorazepam dose, despite lorazepam's shorter serum half-life, has longer duration of effect than one diazepam dose.[22] On regular administration diazepam will however accumulate more, having a longer half-life and active metabolites with even longer half-lives. Diazepam (IPA: ), first marketed as Valium by Hoffmann-La Roche, is a drug which is a benzodiazepine derivative. ...

  • Clinical Example: Diazepam has long been a drug of choice for status epilepticus: its high lipid solubility means it gets absorbed with equal speed whether given intravenously, orally or rectally (non-intravenous routes being convenient in non-hospital settings). But diazepam's high lipid solubility also means it does not remain in the vascular space but soon redistributes into other body tissues, and so it may be necessary to repeat diazepam doses to maintain anticonvulsant effects, resulting in excess body accumulation. Lorazepam is the opposite case: its low lipid solubility makes it relatively slowly absorbed by any route other than intravenously, but once given it does not get significantly redistributed beyond the vascular space. Therefore, lorazepam's anticonvulsant effects are more durable, reducing the need for repeated doses. If a patient is known to usually stop convulsing after only one or two diazepam doses, diazepam may be preferable because sedative after-effects will be less than if a single dose lorazepam is given (diazepam anticonvulsant/sedative effects wear off after 15-30 minutes, but lorazepam effects last 12-24 hours.[23]) Prolonged sedative effects from lorazepam may however be an acceptable trade-off for its reliable duration of effects, particularly if the patient needs to be transferred to another facility. Although lorazepam is not necessarily better than diazepam at initially terminating seizures,[24], lorazepam is replacing diazepam as the intravenous agent of choice in status epilepticus.[25][26]

Lorazepam serum levels are proportional to the dose administered. Giving 2 mg oral lorazepam will result in a peak total serum lorazepam level of around 20 nanograms/ml around two hours later,[18][17] half of which is lorazepam, half its inactive metabolite, lorazepam-glucuronide.[27] A similar dose given intravenously will result in an earlier and higher peak serum level, with a higher proportion of unmetabolised (active) lorazepam.[28] On regular administration, maximum lorazepam serum levels are attained after three days. Longer term use, up to six months, does not result in further accumulation.[18] On discontinuation, lorazepam serum levels become negligible after 3 days and undetectable after about a week. Lorazepam is metabolised in the liver by conjugation into inactive lorazepam-glucuronide. This metabolism does not involve hepatic oxidation and therefore is relatively unaffected by reduced liver function. Lorazepam-glucuronide is more lipid-soluble than its precursor and therefore gets more widely distributed in the body leading to a longer half-life than lorazepam. Lorazepam-glucuronide is excreted by the kidneys[18] and remains detectable - particularly in the urine - for substantially longer than lorazepam.


Pharmacodynamics

Relative to other benzodiazepines, lorazepam is thought to have high affinity for GABA receptors,[29] which may also explain its marked[1] amnesic effects. The main pharmacological effects of lorazepam are the enhancement of GABA at the GABAA receptor.[30] The GABA receptors are a group of receptors with γ-aminobutyric acid (GABA) as their endogenous ligand. ... Gaba may refer to: Gabâ or gabaa (Philippines), the concept of negative karma of the Cebuano people GABA, the gamma-amino-butyric acid neurotransmitter GABA receptor, in biology, receptors with GABA as their endogenous ligand Gaba 1 to 1, an English conversational school in Japan Marianne Gaba, a US model...


The magnitude and duration of lorazepam effects are dose related, meaning that larger doses have stronger and longer-lasting effects. This is because the brain has spare benzodiazepine drug receptor capacity, with single, clinical doses leading only to an occupancy of some 3% of the available receptors[31].


The anticonvulsant properties of lorazepam and other benzodiazepines may be, in part or entirely, due to binding to voltage-dependent sodium channels rather than benzodiazepine receptors. Sustained repetitive firing seems to get limited, by the benzodiazepine effect of slowing recovery of sodium channels from inactivation.[32] Sodium channels are integral membrane proteins that exist in a cells plasma membrane and regulate the flow of sodium (Na+) ions into it. ...

1987 Ativan advertisement. "In a world where certainties are few...no wonder Ativan® (lorazepam)C-IV is prescribed by so many caring clinicians."
1987 Ativan advertisement. "In a world where certainties are few...no wonder Ativan® (lorazepam)C-IV is prescribed by so many caring clinicians."

Image File history File links No higher resolution available. ... Image File history File links No higher resolution available. ...

Contraindications and Special Considerations

Contraindications

Lorazepam must be avoided in patients with the following conditions:

  • Allergy or hypersensitivity. Past hypersensitivity or allergy to lorazepam, to any benzodiazepine or to any of the ingredients in lorazepam tablets or injections.
  • Severe respiratory failure. Benzodiazepines, including lorazepam, may depress central nervous system respiratory drive and are contraindicated in severe respiratory failure. An example would be the inappropriate use to relieve anxiety associated with acute severe asthma. The anxiolytic effects may also be detrimental to a patient's willingness and ability to fight for breath. However, if mechanical ventilation becomes necessary, lorazepam may be used to facilitate deep sedation.
  • Acute intoxication. Lorazepam may interact synergistically with the effects of alcohol, narcotics, or other psychoactive substances. It should therefore not be administered to a drunk or intoxicated person.
  • Ataxia. This is a neurological clinical sign, consisting of unsteady and clumsy motion of the limbs and torso, due to failure of gross muscle movement coordination, most evident on standing and walking. Benzodiazepines should not be administered to ataxic patients for the same reasons that they are not given alcohol.
  • Acute narrow-angle glaucoma. Lorazepam has pupil-dilating effects which may further interfere with the drainage of aqueous humour from the anterior chamber of the eye, thus worsening narrow-angle glaucoma.
  • Sleep apnoea. Sleep apnoea may be worsened by lorazepam's central nervous system depressant effects.
  • Myasthenia gravis. This condition is characterised by muscle weakness and a muscle relaxant may exacerbate symptoms.
  • Pregnancy and breast feeding. Lorazepam belongs to the Food and Drug Administration (FDA) pregnancy category D which means that it is likely to cause harm to the unborn baby if taken during the first trimester of pregnancy. Lorazepam given to pregnant women antenatally may cause floppy infant syndrome in the neonate, respiratory depression necessitating ventilation, and neonatal withdrawal symptoms. Lorazepam may also inbibit foetal liver bilirubin glucuronidation, leading to neonatal jaundice. Lorazepam is present in breast milk so caution must be exercised about breast feeding.

An allergy is an abnormal, acquired sensitivity to a given substance, including pollen, drugs, or numerous environmental triggers. ... Hypersensitivity refers to undesirable (damaging, discomfort-producing and sometimes fatal) reactions produced by the normal immune system. ... Respiratory failure is a medical term for inadequate gas exchange by the respiratory system. ... Status asthmaticus is an acute exacerbation of asthma that does not respond to standard treatments of bronchodilators and corticosteroids. ... mechanical or forced ventilation is the use of powered equipment, e. ... ... For other uses, see Ataxia (disambiguation). ... Human eye cross-sectional view. ... Sleep apnea (alternatively sleep apnoea) is a sleep disorder in which breathing is interrupted during sleep. ... Myasthenia gravis (sometimes abbreviated MG; from the Greek myastheneia, lit. ... A pregnant woman near the end of her term Pregnancy is the carrying of one or more offspring in an embryonal or fetal stage of development by female mammals, including humans, inside their bodies, between the stages of conception and birth. ... A breastfeeding infant Breastfeeding is the practice of a woman feeding an infant (or sometimes a toddler or a young child) with milk produced from her mammary glands, usually directly from the nipples. ... hi “FDA” redirects here. ... Hypotonia is a condition of abnormally low muscle tone (the amount of tension or resistance to movement in a muscle), often involving reduced muscle strength. ...

Special groups and situations

  • Children and the elderly. The safety and effectiveness of lorazepam is not well determined in children under 16 years of age, but it is used to treat serial seizures. Dose requirements have to be individualized, especially in the elderly and debilitated patients in whom the risk of oversedation is greater. Long term therapy may lead to cognitive deficits, especially in the elderly, but this is reversible after a period of discontinuation.
  • Liver or Kidney failure. Lorazepam may be safer than most benzodiazepines in patients with impaired liver function. Like oxazepam it does not require hepatic oxidation, but only hepatic glucuronidation into lorazepam-glucuronide. Therefore, impaired liver function is unlikely to result in lorazepam accumulation to an extent causing adverse reactions.[7] Lorazepam-glucuronide and a small amount of unchanged lorazepam are excreted by the kidneys, so in renal failure small increases in lorazepam levels may occur.
  • Premedication. Informed consent for medical or surgical procedures must be obtained before lorazepam is administered, or consent may be invalidated. Health workers should take sensible precautions (chaperoning, avoiding ambiguous language and gestures) against patients later making unfounded allegations of abuse during treatment, due to impaired memory and drug-induced disinhibition/misinterpretations. After a lorazepam injection, or a single oral premedication sized dose, patients should normally not be discharged from hospital settings without an accompanying care-giver (parent, spouse, etc.) before 24 hours have elapsed, due to variable residual effects like sleepiness, vertigo, hypotension, amnesia, etc. Patients should also not drive a car or handle machines for 24 hours.

Liver failure is the final stage of liver disease. ... Oxazepam (marketed under brand names Alepam, Murelax, Oxascand, Serax, Serepax, Seresta, Sobril) is a drug which is a benzodiazepine derivative. ... Informed consent is a legal condition whereby a person can be said to have given consent based upon an appreciation and understanding of the facts and implications of an action. ...

Tolerance, dependence and abuse

Tolerance to benzodiazepine effects develops with regular use. This is desirable with amnesic and sedative effects, undesirable with anxiolytic, hypnotic and anticonvulsant effects. Patients at first experience drastic relief from e.g. anxiety or sleeplessness, but symptoms gradually return, relatively soon in the case of insomnia but slower in the case of anxiety symptoms. After four to six months of regular benzodiazepine use, there is little evidence of continued efficacy. If regular treatment is continued for longer than this, dose increases may be necessary to maintain effects, but treatment resistant symptoms may in fact be benzodiazepine withdrawal symptoms.[33] On abrupt, or overly rapid discontinuation of lorazepam, anxiety and signs of physical withdrawal have been observed, similar to those seen on withdrawal from alcohol and barbiturates. The likelihood of dependence is relatively high with lorazepam compared to other benzodiazepines. Because of lorazepam's relatively short serum half-life, confinement mainly to the vascular space and an inactive metabolite, with resultant interdose withdrawal phenomenon and next dose craving, which may reinforce psychological dependence. Because of lorazepam's high potency, the smallest tablet strength of 0.5 mg is also a significant dose reduction (in the UK, the smallest tablet strength is 1.0 mg, which accentuates this difficulty). To minimise the risk of physical/psychological dependence, lorazepam is best used only short-term and at the smallest effective dose. If a benzodiazepine has been used long-term, the recommendation is a gradual dose taper over a period of weeks, months or longer, according to dose and duration of use, degree of physical dependence and the individual. Coming off long-term lorazepam may be more realistically achieved by a gradual switch to an equivalent dose of diazepam, a period of stabilisation on this and only then initiating dose reductions. The advantage of switching to diazepam is that dose reductions are felt less acutely, because of the longer half lives (20-200 hours) of diazepam and its active metabolites.[34] Benzodiazepine withdrawal syndrome, caused by withdrawal or dosage reduction of benzodiazepines, is the symptoms which appear when a patient who has taken the drug for a period of time stops taking the drug. ... Alprazolam 2mg tablets The benzodiazepines (pronounced , or benzos for short) are a class of psychoactive drugs considered as minor tranquilizers with varying hypnotic, sedative, anxiolytic, anticonvulsant, muscle relaxant and amnesic properties, which are brought on by slowing down the central nervous system. ... Physical dependence refers to a state resulting from habitual use of a drug, where negative physical withdrawal symptoms result from abrupt discontinuation. ...


Prescribers of lorazepam must be alert to the possibility of abuse or diversion for illegitimate use when prescribing for unsupervised out-patients. This applies particularly to patients with past or present substance abuse disorders, as persons with addictive personalities are likelier to abuse medications such as lorazepam. In addition to recreational use, benzodiazepines may be diverted and used to facilitate crime: criminals may take them to deliberately seek disinhibition prior to committing crimes[35] (which increases their potential for violence) or they may give them to unwitting victims as date rape drugs, notably with alcohol. Date rape drugs are substances added to a drink to render a victim unconscious or compliant and able to be easily raped or sexually assaulted, perhaps adding to the effect of an alcoholic drink, generally unknown to the person drinking it. ...


Adverse effects

Any of the five intrinsic benzodiazepine effects possessed by lorazepam (sedative/hypnotic, muscle relaxant, anxiolytic, amnesic and anticonvulsant) may be considered as "adverse effects", or "side effects", if unwanted.[1] Lorazepam's effects are dose-dependent, meaning that the higher the dose, the stronger the effects (and side effects) will be. Using the smallest dose needed to achieve desired effects lessens the risk of adverse effects.


Lorazepam has an advantage of being non-sedative relative to its potent anxiolytic effects, but sedation is still the most complained-of side effect. In a group of around 3500 patients treated for anxiety, the commonest side effects complained of from lorazepam were sedation (15.9%), dizziness (6.9%), weakness (4.2%), and unsteadiness (3.4%). Side effects such as sedation and unsteadiness increased with age.[36]

  • Paradoxical effects. In some cases there can be paradoxical effects with benzodiazepines, such as increased hostility and aggression, which is thought to be at least partially due to disinhibition. It is more likely to occur with higher doses, in patients with pre-existing personality disorders and those with a psychiatric illness. The latter is relevant since frustrating stimuli - something which the drug may be prescribed to help the patient cope with - may in fact trigger such reactions. Since paradoxical effects are dose-related they usually subside on dose reduction or complete withdrawal of lorazepam.[37][38][39][35][40][41]
  • Suicidality. Benzodiazepines in general may sometimes unmask suicidal ideation in depressed patients (indirectly, through disinhibition or fear reduction, rather than through any known direct effect). Though relatively non-toxic in themselves, the concern is that benzodiazepines may inadvertently become facilitators of suicidal behaviour.[42] Lorazepam should therefore not be prescribed alone in depression but only together with an appropriate antidepressant and at the minimal dose required.
  • Amnesic effects. Among benzodiazepines, lorazepam has relatively strong amnesic effects,[1][43] but patients soon develop tolerance to this with regular use. To avoid amnesia (or excess sedation) being a problem, the initial total daily lorazepam dose should not exceed 2 mg. This also applies to use for night sedation. Five participants in a sleep study were prescribed lorazepam 4 mg at night and the next evening three subjects unexpectedly volunteered memory gaps for parts of that day, an effect which subsided completely after 2-3 days use.[44] Amnesic effects cannot be estimated from the degree of sedation present, since the two effects are unrelated.

For full lists of lorazepam side effects, refer to the manufacturers' data sheets. Note that some may list side effects for the entire benzodiazepine class, not the specific side-effect profile for lorazepam. Look up paradox in Wiktionary, the free dictionary. ... 1. ... Personality disorder, formerly referred to as a Characterological disorder is a class of mental illness characterized by rigid and on-going patterns of thought and action. ... Anterograde amnesia is a form of amnesia, or memory loss, where new events are not transferred to long-term memory. ...


Interactions

  • Alcohol. Lorazepam is not usually fatal in overdose, but may cause fatal respiratory depression if taken in overdose with alcohol. The combination also causes synergistic enhancement of the disinhibitory and amnesic effects of both drugs, with potentially embarrassing or forensic consequences. Some experts advise patients should be warned against taking alcohol while on lorazepam treatment,[1][45] but such clear warnings are not universal.[46]

1. ... Anterograde amnesia is a form of amnesia, or memory loss, where new events are not transferred to long-term memory. ...

Overdose

In cases of a suspected lorazepam overdose, it is important to establish if the patient is a regular user of lorazepam or other benzodiazepines, since regular use causes tolerance to develop. Also, one must ascertain if other drugs were also ingested.


Signs of overdose range through mental confusion, dysarthria, paradoxical reactions, drowsiness, hypotonia, ataxia, hypotension, hypnotic state, coma, cardiovascular depression, respiratory depression and death.


Early management of alert patients includes emetics, gastric lavage and activated charcoal. Otherwise, management is by observation, including of vital signs, support and - only if necessary, considering the hazards of doing so - giving intravenous flumazenil. Wikipedia does not yet have an article with this exact name. ... Gastric lavage, also commonly called a stomach pump, is the process of cleaning out the contents of the stomach. ... Activated carbon (also called activated charcoal) is the more general term which includes material mostly derived from charcoal. ... Flumazenil (flumazepil, Anexate®, Lanexat®, Mazicon®, Romazicon®) is a benzodiazepine antagonist, used as an antidote in the treatment of benzodiazepine overdose. ...


Patients are ideally nursed in a kind, non-frustrating environment since, when given or taken in high doses, benzodiazepines are more likely to cause paradoxical reactions. If shown sympathy, even quite crudely feigned, patients may respond solicitously, but they may respond with disproportionate aggression to frustrating cues.[47] Opportunistic counseling has limited value here, as the patient is unlikely to recall this later due to drug-induced anterograde amnesia. The word counseling or counselling comes from the Middle English counseil, from Old French conseil, from Latin cōnsilium; akin to cōnsulere, to take counsel, consult. ... Anterograde amnesia is a form of amnesia, or memory loss, where new events are not transferred to long-term memory. ...


History and Legal status

Early lorazepam marketing, a 1977 direct-to-patient advertisement implying its positive effects: "Now it can be yours - The Ativan Experience."
Early lorazepam marketing, a 1977 direct-to-patient advertisement implying its positive effects: "Now it can be yours - The Ativan Experience."

Lorazepam was first introduced by Wyeth Pharmaceuticals in 1971 under the brand names of Ativan and Temesta. Wyeth's original patent on lorazepam is expired in the United States but the drug continues to be commercially viable. As a measure of its ongoing success, it has been marketed under more than seventy generic brands since then: Image File history File links No higher resolution available. ... Image File history File links No higher resolution available. ... Wyeth, formerly known as American Home Products, is one of the largest pharmaceutical companies in the world. ... Wyeth, formerly known as American Home Products, is one of the largest pharmaceutical companies in the world. ... For other uses, see Patent (disambiguation). ... A generic brand product is one made by a manufacturer the customer doesnt know much about who may or may not put thier name on the product. ...


Almazine, Alzapam, Anxiedin, Anxira, Anzepam, Aplacasse, Aplacassee, Apo-Lorazepam, Aripax, Azurogen, Bonatranquan, Bonton, Control, Donix, Duralozam, Efasedan, Emotion, Emotival, Idalprem, Kalmalin, Larpose, Laubeel, Lopam, Lorabenz, Loram, Lorans, Lorapam, Lorat, Lorax, Lorazene, Lorazep, Lorazepam, Lorazin, Lorazon, Lorenin, Loridem, Lorivan, Lorsedal, Lorzem, Lozepam, Merlit, Nervistop L, Nervistopl, NIC, Novhepar, Novolorazem, Orfidal, Piralone, Placidia, Placinoral, Punktyl, Quait, Renaquil, Rocosgen, Securit, Sedarkey, Sedatival, Sedizepan, Sidenar, Silence, Sinestron, Somnium, Stapam, Tavor, Titus, Tolid, Tranqil, Tranqipam, Trapax, Trapaxm, Trapex, Upan, Wintin and Wypax.


In 2000, the U.S. drug company Mylan agreed to pay $147 million to settle accusations by the F.T.C. that they had raised the price of generic lorazepam by 2600 percent and generic clorazepate by 3200 percent in 1998 after having obtained exclusive licensing agreements for certain ingredients.[48] Year 2000 (MM) was a leap year starting on Saturday (link will display full 2000 Gregorian calendar). ... Motto: (Out Of Many, One) (traditional) In God We Trust (1956 to date) Anthem: The Star-Spangled Banner Capital Washington D.C. Largest city New York City None at federal level (English de facto) Government Federal constitutional republic  - President George Walker Bush (R)  - Vice President Dick Cheney (R) Independence from... Mylan Laboratories Inc. ... FTC headquarters, Washington, D.C. The Federal Trade Commission (or FTC) is an independent agency of the United States government, established in 1914 by the Federal Trade Commission Act. ... Clorazepate (marketed under the brand names Tranxene® and Tranxilium®) is a drug which is a benzodiazepine derivative. ...


Lorazepam is a Schedule IV drug under the Controlled Substances Act in the U.S. and internationally under the United Nations Convention on Psychotropic Substances.[49] Lorazepam is a Schedule IV drug under the Controlled Drugs and Substances Act in Canada. In the United Kingdom, lorazepam is a Class 4 Controlled Drug under the Misuse of Drugs Regulations 2001. The Controlled Substances Act (CSA) was enacted into law by the Congress of the United States as Title II of the Comprehensive Drug Abuse Prevention and Control Act of 1970. ... Convention on Psychotropic Substances Opened for signature February 21, 1971 in Vienna Entered into force August 16, 1976 Conditions for entry into force 40 ratifications Parties 175 The Convention on Psychotropic Substances is a United Nations treaty designed to control psychoactive drugs such as amphetamines, barbiturates, and psychedelics. ... The Controlled Drugs and Substances Act is Canadas federal drug control statute. ... The Controlled Drugs and Substances Act is Canadas federal drug control statute. ...


In popular culture

Lorazepam has been mentioned in several contemporary media in recent years, with various clinical aspects highlighted. It is seen in medical situations, such as the TV series House, MD as the drug of choice for the cessation of seizures. A similar use is depicted in the movie Saw III where "Jigsaw" is being operated on and begins to convulse: the character performing the surgery yells many times for Ativan, but discovers that none is available in the limited operating area. Lorazepam, as an anxiolytic, is portrayed in the 2006 movie The Departed, where Vera Farmiga's character, Madolyn prescribes it to Leonardo DiCaprio's character, Billy. Blue October mentions Lorazepam in their song "HRSA", where it is being prescribed in a psychiatric ward for a similar use. The dependency problem is portrayed in William Gibson's 2007 book Spook Country, in which the character Milgrim is addicted to Ativan and the character Brown exploits Milgrim's addiction, in order to control him, through a steady supply of Ativan and Rize (a brand of the benzodiazepine clotiazepam). House, also known as House, M.D., is a critically-acclaimed American medical drama television series created by David Shore and executive produced by Shore and film director Bryan Singer. ... Saw III is the third installment in the Saw horror film series. ... Year 2006 (MMVI) was a common year starting on Sunday of the Gregorian calendar. ... The Departed is an Academy Award-winning 2006 film directed by Martin Scorsese and starring Leonardo DiCaprio, Matt Damon and Jack Nicholson. ... Vera Ann Farmiga (born August 6, 1973) is an American actress. ... Leonardo Wilhelm DiCaprio (born November 11, 1974[1]) is a three-time Academy Award-nominated and Golden Globe Award-winning American actor well known for his roles in blockbuster movies such as William Shakespeares Romeo + Juliet (1996), Titanic (1997), The Beach (2000), Catch Me If You Can (2002), Gangs... This article is about the American band. ... There are a number of people who have been (or are) named William Gibson. ... Spook Country is a novel by William Gibson, released on August 2, 2007 in the UK and on August 7, 2007 in the US by publisher Penguin Putnam. ... Clotiazepam (marketed under brand name Trecalmo) is a drug which is a benzodiazepine derivative. ...


In 2005, Fall Out Boy member Pete Wentz overdosed on lorazepam; he included references to the episode in the songs "I've Got a Dark Alley and a Bad Idea That Says You Should Shut Your Mouth (Summer Song)" and "7 Minutes in Heaven (Atavan Halen)",[50] on the album From Under the Cork Tree. Fall Out Boy (commonly abbreviated as FOB) is an American band from Wilmette, Illinois (a suburb of Chicago) that formed in 2001. ... Pete Wentz (born June 5, 1979) is the bassist, back-up vocalist, and primary lyricist of Chicago-based band Fall Out Boy. ... Alternate cover Limited Black Clouds and Underdogs Edition (2005) Singles from From Under the Cork Tree Released: 2005 Released: 2005 Released: June 6, 2006 From Under the Cork Tree is the third full album from Fall Out Boy and their major label debut on Island Records. ...

  • In Gym Class Hero's "Pillmatic", the chorus refers to the drug as part of a chemical escape cocktail: "This world is crazy so I stay medicated / Percocet, Ativan, and Klonopin."
  • Minus the Bear mentions the drug in their song "Get Me Naked 2: Electric Boogaloo"

Minus the Bear is a Seattle, Washington-based band. ...

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is the 30th day of the year in the Gregorian calendar. ... For the band, see 1997 (band). ... Year 2007 (MMVII) is the current year, a common year starting on Monday of the Gregorian calendar and the AD/CE era. ... is the 133rd day of the year (134th in leap years) in the Gregorian calendar. ... The Portable Document Format (PDF) is the file format created by Adobe Systems in 1993 for document exchange. ... PubMed Central grew from the online Entrez PubMed biomedical literature search system. ... The Portable Document Format (PDF) is the file format created by Adobe Systems in 1993 for document exchange. ... The Portable Document Format (PDF) is the file format created by Adobe Systems in 1993 for document exchange. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... June 4 is the 155th day of the year (156th in leap years) in the Gregorian calendar. ... This article is about the year. ... Year 2007 (MMVII) is the current year, a common year starting on Monday of the Gregorian calendar and the AD/CE era. ... is the 133rd day of the year (134th in leap years) in the Gregorian calendar. ... The Portable Document Format (PDF) is the file format created by Adobe Systems in 1993 for document exchange. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... A letter to the editor (sometimes abbreviated LTTE or LTE) is a letter sent to a publication about issues of concern to its readers. ... The logo of the association. ... The Royal Pharmaceutical Society of Great Britain (RPSGB) is the regulatory and professional body for pharmacists in England, Scotland and Wales. ... Otherwise known as the doctors prescribing Bible the British National Formulary (BNF) contains a wide spectrum of information on prescribing and pharmacology, among others indications, side effects and costs of the prescription of all medication drugs available on the National Health Service. ... Year 2007 (MMVII) is the current year, a common year starting on Monday of the Gregorian calendar and the AD/CE era. ... is the 133rd day of the year (134th in leap years) in the Gregorian calendar. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... The Portable Document Format (PDF) is the file format created by Adobe Systems in 1993 for document exchange. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... PubMed Central grew from the online Entrez PubMed biomedical literature search system. ... Year 2007 (MMVII) is the current year, a common year starting on Monday of the Gregorian calendar and the AD/CE era. ... is the 152nd day of the year (153rd in leap years) in the Gregorian calendar. ... Year 2007 (MMVII) is the current year, a common year starting on Monday of the Gregorian calendar and the AD/CE era. ... is the 222nd day of the year (223rd in leap years) in the Gregorian calendar. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... is the 21st day of the year in the Gregorian calendar. ... Year 1998 (MCMXCVIII) was a common year starting on Thursday (link will display full 1998 Gregorian calendar). ... Year 2007 (MMVII) is the current year, a common year starting on Monday of the Gregorian calendar and the AD/CE era. ... May 14 is the 134th day of the year (135th in leap years) in the Gregorian calendar. ... is the 298th day of the year (299th in leap years) in the Gregorian calendar. ... Year 2006 (MMVI) was a common year starting on Sunday of the Gregorian calendar. ... Year 2007 (MMVII) is the current year, a common year starting on Monday of the Gregorian calendar and the AD/CE era. ... May 14 is the 134th day of the year (135th in leap years) in the Gregorian calendar. ... The New York Times is a daily newspaper published in New York City by Arthur Ochs Sulzberger Jr. ... is the 194th day of the year (195th in leap years) in the Gregorian calendar. ... Year 2000 (MM) was a leap year starting on Saturday (link will display full 2000 Gregorian calendar). ... Year 2007 (MMVII) is the current year, a common year starting on Monday of the Gregorian calendar and the AD/CE era. ... May 14 is the 134th day of the year (135th in leap years) in the Gregorian calendar. ... Mr. ... The Portable Document Format (PDF) is the file format created by Adobe Systems in 1993 for document exchange. ... A mebibyte (a contraction of mega binary byte) is a unit of information or computer storage, abbreviated MiB. 1 MiB = 220 bytes = 1,048,576 bytes = 1,024 kibibytes 1 MiB = 1024 (= 210) kibibytes (KiB), and 1024 MiB equal one gibibyte (GiB). ... The Chicago Sun-Times is an American daily newspaper published in Chicago. ... April 8 is the 98th day of the year (99th in leap years) in the Gregorian calendar. ... Year 2007 (MMVII) is the current year, a common year starting on Monday of the Gregorian calendar and the AD/CE era. ... Year 2007 (MMVII) is the current year, a common year starting on Monday of the Gregorian calendar and the AD/CE era. ... May 14 is the 134th day of the year (135th in leap years) in the Gregorian calendar. ...

External links


  Results from FactBites:
 
lorazepam (Ativan) - drug class, medical uses, medication side effects, and drug interactions by MedicineNet.com (687 words)
Because lorazepam is removed from the blood more rapidly than many other benzodiazepines, there is less chance that lorazepam concentrations in blood will reach high levels and become toxic.
PRESCRIBED FOR: Lorazepam is used for the management of anxiety disorders, the short-term relief of the symptoms of anxiety or anxiety associated with depression.
Lorazepam also has been shown to be effective for improving sleep in people with insomnia, for panic attacks, and as an adjunct (i.e., when added to other medications) to prevent nausea and vomiting in patients receiving cancer chemotherapy.
Lorazepam - definition of Lorazepam in Encyclopedia (209 words)
Lorazepam is classified as a sedative-hypnotic and a member of the group of drugs known as benzodiazepines.
A dose equivalent to 5 mg of diazepam is 500 micrograms (0.5 mg) of lorazepam.
Safety and effectiveness of lorazepam is not well determined in children under 18 years of age, but it is used to treat serial seizures.
  More results at FactBites »

 
 

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