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Lorazepam Metabolization

Lorazepam is an anxiolytic that belongs to the group of benzodiazepines. Lorazepam is prescribed to relieve anxiety as a short-term treatment in periods of anxiety and tension. It is also prescribed to treat sleep disorders, insomnia, hyperemotivity and neurosis. Benzodiazepines are only indicated for the treatment of severe disorders that limit the patient's activity or make them to suffer significant stress.

Lorazepam has hypnotic, anticonvulsant, sedative, muscle relaxant, and amnesic activity.

ACTION MECHANISM

Lorazepam works by increasing the activity of gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter located in the brain, by facilitating its binding to the GABAergic receptor. In this way, lorazepam reduces anxiety levels.

CONTRAINDICATIONS

Lorazepam is contraindicated in the following cases: Hypersensitivity, myasthenia gravis, sleep apnea syndrome, severe respiratory failure, severe liver failure (risk of encephalopathy).

Lorazepam is contraindicated in simultaneous treatment with opiates, barbiturates or neuroleptics.

Lorazepam should not be used during pregnancy. If it is prescribed to a woman who could become pregnant during treatment, it will be recommended that when planning a pregnancy or detecting that she is pregnant, contact the doctor to proceed with the withdrawal of treatment. The use of benzodiazepines seems to be related to a possible increased congenital risk of malformations in the first trimester of pregnancy. The presence of benzodiazepines and glucuronic metabolites in human umbilical cord blood has been detected, this fact indicating the passage of this drug through the placenta.

Because benzodiazepines are secreted in maternal milk, their use is contraindicated in nursing mothers unless the actual benefit to the woman outweighs the potential risk to the child.

CAUTIONS

Precautions should be taken when prescribing lorazepam in the elderly, in patients with mild or moderate renal and/or hepatic impairment, in children, in patients with mild or moderate respiratory impairment, in patients with dependence on alcohol or other drugs, and in patients with closed angle glaucoma.

Treatment with lorazepam carries some risk of anterograde amnesia and the development of psychiatric and paradoxical reactions, more frequently in children and elderly patients.

After prolonged use of lorazepam there is a risk of tolerance and of developing physical and mental dependence. Abrupt discontinuation after continued use causes withdrawal syndrome. Do not use in anxiety associated with depression or as a primary treatment for psychotic illness.

Lorazepam should be discontinued if angioedema in the tongue, glottis or larynx appears.

PHARMACOLOGIC INTERACTIONS

The sedative effect of lorazepam is increased by alcohol consumption.

The depressant effect of lorazepam is enhanced by: neuroleptics, hypnotics, anxiolytics/sedatives, antidepressants, narcotic analgesics, antiepileptics, anesthetics, sedative antihistamines and barbiturates.

The activity of lorazepam is enhanced by taking cytochrome P450 inhibitors.

Plasma concentrations of lorazepam are increased and its total clearance (elimination) decreased with: valproate, probenecid (if taken concomitantly reduce the dose to 50%).

SIDE EFFECTS

Sedation, affective dullness, reduced alertness, fatigue, headache, drowsiness, feeling of suffocation, ataxia, diplopia, confusion, depression, unmasking depression, dizziness, asthenia, muscle weakness, psychiatric and paradoxical reactions.

If lorazepam overdose occurs, flumazenil may act as an antidote.

BRAND NAMES

  • Orfidal®
  • Donix®
  • Idalprem®
  • Placinoral®

Gene or region studied

  • UGT2B15
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