Lorazepam

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Lorazepam is a benzodiazepine used as an anti-anxiety agent with few side effects. It also has hypnotic, anticonvulsant, and considerable sedative properties and has been proposed as a preanesthetic agent.

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
ChemSpider	3821
Chemical data
Formula	C15H10Cl2N2O2
Mol. mass	321.2 g/mol
Pharmacokinetic data
Bioavailability	85% of oral dose
Metabolism	Hepatic glucuronidation
Half life	9–16 hours[1][2][3]
Excretion	Renal
Therapeutic considerations
Pregnancy cat.	D(US)
Legal status	Schedule IV(CA) Schedule IV(US)
Routes	Oral, I.M., I.V. and transdermal

Contents 1 Indication 2 Pharmacology 3 Mechanism of Action 4 Overdosage Lorazepam 5 Drug Interactions 6 Absorption 7 Toxicity 8 Protein Binding 9 Biotransformation 10 Half Life 11 Brand names for Lorazepam 11.1 U.S. Brand Names 12 History and legal status 13 In popular culture 13.1 Canadian Brand Names 13.2 International Brand names for Lorazepam

Indication

For the management of anxiety disorders or for the short-term relief of the symptoms of anxiety or anxiety associated with depressive symptoms

Pharmacology

Lorazepam, a benzodiazepine not transformed to active metabolites, is used to treat anxiety, status epilepticus, and for sedation induction and anterograde amnesia.

Mechanism of Action

Lorazepam binds to central benzodiazepine receptors which interact allosterically with GABA receptors. This potentiates the effects of the inhibitory neurotransmitter GABA, increasing the inhibition of the ascending reticular activating system and blocking the cortical and limbic arousal that occurs following stimulation of the reticular pathways.

Overdosage Lorazepam

Symptoms of overdose include confusion, coma, hypoactive reflexes, dyspnea, labored breathing. Note: Prolonged infusions have been associated with toxicity from propylene glycol and/or polyethylene glycol. Treatment for benzodiazepine overdose is supportive. Flumazenil has been shown to selectively block the binding of benzodiazepines to CNS receptors, resulting in a reversal of benzodiazepine-induced CNS depression but not respiratory depression

Drug Interactions

CNS depressants: Sedative effects and/or respiratory depression may be additive with CNS depressants; includes ethanol, barbiturates, narcotic analgesics, and other sedative agents.

Levodopa: Lorazepam may decrease the antiparkinsonian efficacy of levodopa.

Loxapine: There are rare reports of significant respiratory depression, stupor, and/or hypotension with concomitant use of loxapine and lorazepam; use caution if concomitant administration of loxapine and CNS drugs is required

Scopolamine: May increase the incidence of sedation, hallucinations, and irrational behavior; reported only with parenteral lorazepam

Theophylline: May partially antagonize some of the effects of benzodiazepines; monitor for decreased response; may require higher doses for sedation Ethanol/Nutrition/Herb Interactions:

Ethanol: Avoid or limit ethanol (may increase CNS depression).

Herb/Nutraceutical: Avoid valerian, St John's wort, kava kava, gotu kola (may increase CNS depression).

Absorption

Readily absorbed with an absolute bioavailability of 90%.

Toxicity

Somnolence, confusion, and coma, LD50=3178mg/kg (orally in mice).

Protein Binding

85%

Biotransformation

Hepatic

Half Life

12 hours

Brand names for Lorazepam

U.S. Brand Names

• Ativan®
• Lorazepam Intensol®

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."

Historically, lorazepam is one of the "classical" benzodiazepines. Other classical benzodiazepines include diazepam, clonazepam, oxazepam, nitrazepam, flurazepam, bromazepam and clorazepate. Lorazepam was first introduced by Wyeth Pharmaceuticals in 1971 under the brand names of Ativan and Temesta. The drug was developed by President of Research, D.J. Richards. 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:

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.

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. 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.

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. Usage for seizures is also 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. 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). In Martin Scorsese's recent film, The Departed, Billy Costigan--an edgy, bitter, intelligent undercover cop for the Massachusetts State Police--suffers from frequent anxiety, claims to have panic attacks, and is prescribed lorazepam by a police psychologist. Blair Waldorf, of the CW's TV show Gossip Girl, mentioned Lorazepam and some other drugs in the fifth episode of the first season. In 2005, Fall Out Boy member Pete Wentz attempted to overdose on lorazepam when attempting suicide; 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)", on the album From Under the Cork Tree. In Season 6, Episode 2 of The Sopranos, Tony Soprano is also given Ativan for the seizure when he first awakes from his coma, and is subsequently kept in an induced coma using Ativan.

Canadian Brand Names

• Apo-Lorazepam®
• Ativan®
• Novo-Lorazepam
• Nu-Loraz
• PMS-Lorazepam
• Riva-Lorazepam

International Brand names for Lorazepam

• Abinol® (CL)
• Amparax® (CL)
• Amparax Sublingual® (CL)
• Ansilor® (PT)
• Anta® (TH)
• Anxira® (TH)
• Aplacasse® (AR)
• Apo-Lorazepam® (CA, SG)
• Ativan® (AU, CA, CO, CR, CY, DO, EG, GB, GT, HK, HN, ID, IE, IN, JO, KW, LB, MT, MX, NZ, PA, SG, SV, TH, TR, ZA)
• Bonton® (IL)
• Calmamed® (BE)
• Calmese® (IN)
• Control® (IT)
• Docloraze® (BE)
• Doclormeta® (BE)
• Donix® (ES)
• duralozam® (DE)
• durazolam® (DE)
• Emotival® (AR)
• Idalprem® (ES)
• Kalmalin® (AR)
• Larpose® (IN)
• Laubeel® (DE)
• Lauracalm® (BE, LU)
• Lonza® (TH)
• Lorabenz® (DK)
• Lorafen® (PL)
• Loramed® (TH)
• Loram® (RU, SI, YU)
• Lorans® (CY, IT, JO, RO, SG)
• Lorapam® (NZ, TH)
• Lora-P® (TH)
• Lorasifar® (CH)
• Lora Tabs® (NZ)
• Lora® (TH)
• Lorax® (BR)
• Lorazemed® (BE)
• Lorazene® (TH)
• Lorazepam® (BR, CL, CO, GB, YU)
• Lorazepam Dorom® (IT)
• Lorazepam-Efeka® (LU)
• Lorazepam Efka (BE)
• Lorazepam EG® (BE, IT)
• Lorazepam-Eurogenerics® (LU)
• Lorazepam Fabra® (AR)
• Lorazepam Genericon® (AT)
• Lorazepam Lannacher® (AT)
• Lorazepam L.CH.® (CL)
• Lorazepam Macrophar® (TH)
• Lorazepam Medical® (ES)
• Lorazepam MK® (CR, DO, GT, HN, PA, SV)
• Lorazepam-neuraxpharm® (DE)
• Lorazepam Normon® (ES)
• Lorazepam-ratiopharm® (BE, DE, IT)
• Lorazepam Richet® (AR)
• Lorazepam Teva® (IT)
• Lorazepan Chobet® (AR)
• Lorazep® (TH)
• Lorazetop® (BE)
• Lorenin® (PT)
• Loridem® (BE, LU)
• Lorium® (BR)
• Lorivan® (CY, HK, IL, RO)
• Lorsedal® (PT)
• Lorsilan® (HR, SI)
• Lorzem® (NZ)
• Max Pax® (BR)
• Merlit® (AT, RO, RU)
• Mesmerin® (BR)
• Microzepam® (AR)
• Milinda Tolid® (DE)
• Nervistop L® (AR)
• Novo-Lorazepam (CA)
• Nu-Loraz (CA)
• Ora® (TH)
• Orfidal Wyeth® (ES)
• Placinoral® (ES)
• PMS-Lorazepam (CA)
• Razepam® (TH)
• Renaquil® (ID)
• Riva-Lorazepam (CA)
• Sedatival® (AR)
• Sedazin® (CH)
• Sedicepan® (ES)
• Serenase® (BE)
• Sidenar® (AR)
• Sinestron® (DO, GT, HN, MX, SV)
• Somagerol® (DE)
• Tavor® (CZ, DE, IT)
• Temesta® (AT, BE, CH, DK, FI)
• Témesta® (FR)
• Temesta® (LU, NL, SE)
• Tolid® (DE)
• Tranqipam® (ZA)
• Trapax® (AR)
• Tratenamin® (AR)
• Trisedan® (AR)
• Vigiten® (BE, LU)
• Wypax® (JP)

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