Description

Simple

A sedative medication used to help with panic attacks, anxiety, and seizures.

Clinical

A long-acting benzodiazepine commonly used to treat panic disorders, severe anxiety, and seizures.

Overview

Lorazepam is a short-acting and rapidly cleared benzodiazepine used commonly as a sedative and anxiolytic.[6] It was developed by DJ Richards, presented and marketed initially by Wyeth Pharmaceuticals in the USA in 1977. The first historic FDA label approval is reported in 1985 by the company Mutual Pharm.[14]

Pharmacology

Indication

Lorazepam is FDA-approved for the short-term relief of anxiety symptoms related to anxiety disorders and anxiety associated with depressive symptoms such as anxiety-associated insomnia. It is as well used as an anesthesia premedication in adults to relieve anxiety or to produce sedation/amnesia and... Read more

Pharmacodynamic

The effect of lorazepam in GABA-A receptors produces an increase in the frequency of opening of the chloride ion channel. However, for its effect to generate, the neurotransmitter is required.[ Read more

Mechanism of action

Lorazepam allosterically binds on the benzodiazepine receptors in the post-synaptic GABA-A ligand-gated chloride channel in different sites of the central nervous system (CNS). This binding will result in an increase on the GABA inhibitory effects which is translated as an increase in the flow of ch... Read more

Absorption

Readily absorbed with an absolute bioavailability of 90% when given orally. When intramuscularly administered a dose of 4 mg, lorazepam is completely and rapidly absorbed and achieves a maximal serum concentration of 48 ng/ml in 15-30 minutes. When administered orally, the time to attained maximum c... Read more

Protein binding

Reports indicate that 85% of lorazepam administered dose is protein bound.[12]

Volume of distribution

The reported volume of distribution of lorazepam is 1.3 L/kg.[12] It is important to mention that due to the lipophilicity of lorazepam, it... Read more

Clearance

_In vivo_ studies with lorazepam have shown a clearance rate of 5.8 ml.min/kg.[ Read more

Half life

When administered parentally, the registered half-life of lorazepam is of 14 hours.[11]

Route of elimination

When a single 2 mg oral dose is given to healthy subjects, 88% of the administered dose is recovered in urine and 7% was recovered in feces. From the excreted dose in urine, the major form is the glucuronide version that represents 74% while only 0.3% of the dose is recovered as unchanged lorazepam.... Read more

Toxicity

The LD50 observed by oral administration in a mouse is of 1850 mg/kg.[15] When an overdose administration is registered, signs of CNS and respiratory depression are rapidly observed. An overdose stage can result in prof... Read more

Adverse Effects

Contraindications

  • Hypersensitivity:
    • true
  • Regions: US
  • Route:
    • Oral
    • Intramuscular
    • Intravenous
  • Dose Form:
    • Injection
  • Regions: US
  • Patient Conditions:
      • Name: Acute narrow-angle glaucoma
      • Drugbank Id: DBCOND0097823
      • Modification Of:
        • Base:
          • Name: Narrow-angle glaucoma
          • Drugbank Id: DBCOND0095646
        • Severity:
          • Includes:
            • acute
  • Route:
    • Intramuscular
    • Intravenous
  • Dose Form:
    • Injection
  • Regions: US
  • Patient Conditions:
      • Name: Severe respiratory insufficiency
      • Drugbank Id: DBCOND0107490
      • Modification Of:
        • Base:
          • Name: Respiratory Insufficiency
          • Drugbank Id: DBCOND0029091
        • Severity:
          • Includes:
            • severe
  • Route:
    • Intramuscular
    • Intravenous
  • Dose Form:
    • Injection
  • Regions: US
  • Patient Conditions:
      • Name: Sleep Apnea Syndrome
      • Drugbank Id: DBCOND0028401
  • Regions: US
  • Patient Conditions:
      • Name: Intraarterial administration
      • Drugbank Id: DBCOND0107491

Food Interactions

  • Avoid alcohol.
  • Limit caffeine intake.
  • Take with food.

Interactions

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  • Paracetamol(acetaminophen)
  • Paxil(paroxetine)
  • Pamelor(nortriptyline)
  • Panadol(acetaminophen)
  • Patanol(olopatadine ophthalmic)
  • Pataday(olopatadine ophthalmic)
  • Parnate(tranylcypromine)
  • Pazeo(olopatadine ophthalmic)
2,5-Dimethoxy-4-ethylthioamphetamine
The risk or severity of adverse effects can be increased when Lorazepam is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
3-isobutyl-1-methyl-7H-xanthine
The therapeutic efficacy of Lorazepam can be decreased when used in combination with 3-isobutyl-1-methyl-7H-xanthine.
4-Bromo-2,5-dimethoxyamphetamine
The risk or severity of adverse effects can be increased when Lorazepam is combined with 4-Bromo-2,5-dimethoxyamphetamine.
4-hydroxycoumarin
The metabolism of 4-hydroxycoumarin can be decreased when combined with Lorazepam.
4-Methoxyamphetamine
The risk or severity of adverse effects can be increased when Lorazepam is combined with 4-Methoxyamphetamine.
5-methoxy-N,N-dimethyltryptamine
The risk or severity of adverse effects can be increased when Lorazepam is combined with 5-methoxy-N,N-dimethyltryptamine.
6-Deoxyerythronolide B
The metabolism of Lorazepam can be decreased when combined with 6-Deoxyerythronolide B.
6-O-benzylguanine
The therapeutic efficacy of Lorazepam can be decreased when used in combination with 6-O-benzylguanine.
7-Deazaguanine
The therapeutic efficacy of Lorazepam can be decreased when used in combination with 7-Deazaguanine.
7-ethyl-10-hydroxycamptothecin
The metabolism of Lorazepam can be decreased when combined with 7-ethyl-10-hydroxycamptothecin.
7-Nitroindazole
The risk or severity of adverse effects can be increased when Lorazepam is combined with 7-Nitroindazole.
7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline
The risk or severity of adverse effects can be increased when Lorazepam is combined with 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline.
7,9-Dimethylguanine
The therapeutic efficacy of Lorazepam can be decreased when used in combination with 7,9-Dimethylguanine.
8-azaguanine
The therapeutic efficacy of Lorazepam can be decreased when used in combination with 8-azaguanine.
8-chlorotheophylline
The therapeutic efficacy of Lorazepam can be decreased when used in combination with 8-chlorotheophylline.
9-aminocamptothecin
The metabolism of 9-aminocamptothecin can be decreased when combined with Lorazepam.
9-Deazaguanine
The therapeutic efficacy of Lorazepam can be decreased when used in combination with 9-Deazaguanine.
9-Methylguanine
The therapeutic efficacy of Lorazepam can be decreased when used in combination with 9-Methylguanine.
Abacavir
Lorazepam may decrease the excretion rate of Abacavir which could result in a higher serum level.
Abatacept
The metabolism of Lorazepam can be increased when combined with Abatacept.
15 References
  1. 1 . Kemper N, Poser W, Poser S: [Benzodiazepine dependence: addiction potential of the benzodiazepines is greater than previously assumed (author's transl)]. Dtsch Med Wochenschr. 1980 Dec 5;105(49):1707-12.PubMed: 7439058
  2. 2 . Lader M: Short-term versus long-term benzodiazepine therapy. Curr Med Res Opin. 1984;8 Suppl 4:120-6.PubMed: 6144459
  3. 3 . Maltais F, Laberge F, Laviolette M: A randomized, double-blind, placebo-controlled study of lorazepam as premedication for bronchoscopy. Chest. 1996 May;109(5):1195-8.PubMed: 8625666
  4. 4 . Heisterkamp DV, Cohen PJ: The effect of intravenous premedication with lorazepam (ativan), pentobarbitone or diazepam on recall. Br J Anaesth. 1975 Jan;47(1):79-81.PubMed: 238548
  5. 5 . Milligan DW, Howard MR, Judd A: Premedication with lorazepam before bone marrow biopsy. J Clin Pathol. 1987 Jun;40(6):696-8.PubMed: 3611398
  6. 6 . Authors unspecified: Systematic review of the benzodiazepines. Guidelines for data sheets on diazepam, chlordiazepoxide, medazepam, clorazepate, lorazepam, oxazepam, temazepam, triazolam, nitrazepam, and flurazepam. Committee on the Review of Medicines. Br Med J. 1980 Mar 29;280(6218):910-2.PubMed: 7388368
  7. 7 . Li C, Liu T, Cui X, Uss AS, Cheng KC: Development of in vitro pharmacokinetic screens using Caco-2, human hepatocyte, and Caco-2/human hepatocyte hybrid systems for the prediction of oral bioavailability in humans. J Biomol Screen. 2007 Dec;12(8):1084-91. doi: 10.1177/1087057107308892. Epub 2007 Nov 7.PubMed: 17989424
  8. 8 . Riss J, Cloyd J, Gates J, Collins S: Benzodiazepines in epilepsy: pharmacology and pharmacokinetics. Acta Neurol Scand. 2008 Aug;118(2):69-86. doi: 10.1111/j.1600-0404.2008.01004.x. Epub 2008 Mar 31.PubMed: 18384456
  9. 9 . McLean MJ, Macdonald RL: Benzodiazepines, but not beta carbolines, limit high frequency repetitive firing of action potentials of spinal cord neurons in cell culture. J Pharmacol Exp Ther. 1988 Feb;244(2):789-95.PubMed: 2450203
  10. 10 . Kamal MA, Smith DE, Cook J, Feltner D, Moton A, Ouellet D: Pharmacodynamic differentiation of lorazepam sleepiness and dizziness using an ordered categorical measure. J Pharm Sci. 2010 Aug;99(8):3628-41. doi: 10.1002/jps.22093.PubMed: 20213833
  11. 11 . Ghiasi N. and Marwaha R. (2018). Lorazepam.. Treasure Island, FL.
  12. 12 . Pagliaro L. and Pagliaro A. (1999). Psychologists' psychotropic drug reference. Taylor and Francis.
  13. 13 . Volpe J. (2008). Neurology of the Newborn (5th ed.). Saunders Elsevier.
  14. 14 . FDA approvals Link
  15. 15 . Lorazepam monograph Link