Lorazepam


Description

Lorazepam is a short-acting and rapidly cleared benzodiazepine used commonly as a sedative and anxiolytic.[

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Pharmacology

Indication

Lorazepam is FDA-approved for the short-term relief of anxiety symptoms related to anxiety disorders... Read more

Pharmacodynamic

The effect of lorazepam in GABA-A receptors produces an increase in the frequency of opening of the... Read more

Mechanism of action

Lorazepam allosterically binds on the benzodiazepine receptors in the post-synaptic GABA-A ligand-ga... Read more

Absorption

Readily absorbed with an absolute bioavailability of 90% when given orally. When intramuscularly adm... Read more

Protein binding

Reports indicate that 85% of lorazepam administered dose is protein bound.[ Read more

Volume of distribution

The reported volume of distribution of lorazepam is 1.3 L/kg.[ 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.[ Read more

Route of elimination

When a single 2 mg oral dose is given to healthy subjects, 88% of the administered dose is recovered... Read more

Toxicity

The LD50 observed by oral administration in a mouse is of 1850 mg/kg.[ Read more


Adverse Effects

Effect Regions Age Groups Incidences Evidence Type
Injection site pain US
  • Kind: experimental
    • Percent: 17%
  • Clinical Trial
    Sedation US
  • Kind: experimental
    • Percent: 15.9%
  • Clinical Trial
    Dizziness US
  • Kind: experimental
    • Percent: 6.9%
  • Clinical Trial
    Weakness US
  • Kind: experimental
    • Percent: 4.2%
  • Clinical Trial
    Somnolence US
  • Kind: experimental
    • Percent: 1.5-3.5%
  • Clinical Trial
    Unsteadiness US
  • Kind: experimental
    • Percent: 3.4%
  • Clinical Trial
    Respiratory Failure US
  • Kind: experimental
    • Percent: 1.5-2.4%
  • Clinical Trial
    Hypotension US
  • Kind: experimental
    • Percent: 1.5-2.4%
  • Clinical Trial
    Injection site pain US
  • Kind: experimental
    • Percent: 1.6%
  • Clinical Trial
    Headache US
  • Kind: experimental
    • Percent: 1.2%
  • Clinical Trial
    Stupor US
  • Kind: experimental
    • Percent: 1.2%
  • Clinical Trial
    Hypoventilation US
  • Kind: experimental
    • Percent: <1-1.2%
  • Clinical Trial
    Apnea US
  • Kind: experimental
    • Percent: 1.2%
  • Clinical Trial
    Respiratory disorder US
  • Kind: experimental
    • Percent: 1.2%
  • Clinical Trial
    Abnormal Liver Function Tests US
  • Kind: experimental
    • Percent: <1%
  • Clinical Trial
    Infection US
  • Kind: experimental
    • Percent: <1%
  • Clinical Trial
    Vomiting US
  • Kind: experimental
    • Percent: <1%
  • Clinical Trial
    Acidosis US
  • Kind: experimental
    • Percent: <1%
  • Clinical Trial
    Nausea US
  • Kind: experimental
    • Percent: <1%
  • Clinical Trial
    Brain Edema US
  • Kind: experimental
    • Percent: <1%
  • Clinical Trial
    Coma US
  • Kind: experimental
    • Percent: <1%
  • Clinical Trial
    Abnormal thinking US
  • Kind: experimental
    • Percent: <1%
  • Clinical Trial
    Convulsion US
  • Kind: experimental
    • Percent: <1%
  • Clinical Trial
    Hyperventilation US
  • Kind: experimental
    • Percent: <1%
  • Clinical Trial
    Injection site reaction US
  • Kind: experimental
    • Percent: <1%
  • Clinical Trial
    Cystitis US
  • Kind: experimental
    • Percent: <1%
  • Clinical Trial
    Anaphylactic/oid reactions US
    Hypersensitivity reactions US
    Increase in ALP US
    Increase in transaminases US
    SIADH US
    Alopecia US
    Allergic skin reactions US
    Dermatological symptoms US
    Pancytopenia US
    Agranulocytosis US
    Thrombocytopenia US
    Hyponatremia US
    Paradoxical excitation US
    Paradoxical anxiety US
    Autonomic manifestations US
    Hypothermia US
    Paradoxical aggression US
    Paradoxical rage US
    Paradoxical agitation US
    Paradoxical hostility US
    Paradoxical sexual arousal US
    Paradoxical hallucinations US
    Paradoxical sleep disturbances US
    Paradoxical insomnia US

    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.
    • Avoid excessive quantities of coffee or tea (Caffeine).
    • Take with food.

    Interactions

    Type in a drug name to check for interaction with Lorazepam

    The metabolism of (R)-warfarin can be decreased when combined with Lorazepam.
    The metabolism of (S)-Warfarin can be decreased when combined with Lorazepam.
    The risk or severity of adverse effects can be increased when Lorazepam is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
    The therapeutic efficacy of Lorazepam can be decreased when used in combination with 3-isobutyl-1-methyl-7H-xanthine.
    The metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Lorazepam.
    The risk or severity of adverse effects can be increased when Lorazepam is combined with 4-Bromo-2,5-dimethoxyamphetamine.
    The metabolism of 4-hydroxycoumarin can be decreased when combined with Lorazepam.
    The risk or severity of adverse effects can be increased when Lorazepam is combined with 4-Methoxyamphetamine.
    The metabolism of 5-androstenedione can be decreased when combined with Lorazepam.
    The risk or severity of adverse effects can be increased when Lorazepam is combined with 5-methoxy-N,N-dimethyltryptamine.
    The metabolism of Lorazepam can be decreased when combined with 6-Deoxyerythronolide B.
    The therapeutic efficacy of Lorazepam can be decreased when used in combination with 6-O-benzylguanine.
    The therapeutic efficacy of Lorazepam can be decreased when used in combination with 7-Deazaguanine.
    The metabolism of Lorazepam can be decreased when combined with 7-ethyl-10-hydroxycamptothecin.
    The risk or severity of adverse effects can be increased when Lorazepam is combined with 7-Nitroindazole.
    The risk or severity of adverse effects can be increased when Lorazepam is combined with 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline.
    The therapeutic efficacy of Lorazepam can be decreased when used in combination with 7,9-Dimethylguanine.
    The therapeutic efficacy of Lorazepam can be decreased when used in combination with 8-azaguanine.
    The therapeutic efficacy of Lorazepam can be decreased when used in combination with 8-chlorotheophylline.
    The metabolism of 9-aminocamptothecin can be decreased when combined with Lorazepam.

    References

    • 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 . Lader M: Short-term versus long-term benzodiazepine therapy. Curr Med Res Opin. 1984;8 Suppl 4:120-6. [PubMed: 6144459]
    • 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 . 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 . 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 . 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 . 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 . 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 . 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 . 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 . Ghiasi N. and Marwaha R. (2018). Lorazepam.. Treasure Island, FL.
    • 12 . Pagliaro L. and Pagliaro A. (1999). Psychologists' psychotropic drug reference. Taylor and Francis.
    • 13 . Volpe J. (2008). Neurology of the Newborn (5th ed.). Saunders Elsevier.
    • 14 . FDA approvals [Link]
    • 15 . Lorazepam monograph [Link]

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