ロラゼパム

DEA NFLIS-Drug Category -> Benzodiazepines

DEA Schedule IV Controlled Substance -> Depressants

Pharmaceuticals -> Synthetic Cannabinoids or Psychoactive Compounds

Pharmaceuticals -> Benzodiazepines

Pharmaceuticals

3.5

2.37

Breast Feeding; Lactation; Milk, Human; Hypnotics and Sedatives; Anti-Anxiety Agents; Benzodiazepines

FDA approved drugs -> Active ingredient

FDA approved drugs -> Active ingredient

Pharmaceuticals

Antiseizure medicines

192-194

166 - 168 °C

165.8 Ų [M+H]+ [CCS Type: TW; Method: Major Mix IMS/Tof Calibration Kit (Waters)]

169.42 Ų [M-H]-

Warning

H361 (93.1%): Suspected of damaging fertility or the unborn child [Warning Reproductive toxicity]

P203, P280, P318, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 102 reports by companies from 11 notifications to the ECHA C&L Inventory.

Hazard Traits - Developmental Toxicity

DEA schedule IV controlled substance

Lorazepam: Does not have an individual approval but may be used under an appropriate group standard

General supportive and symptomatic measures are recommended. Vital signs must be monitored and the patient closely observed. When there is a risk of aspiration, induction of emesis is not recommended. Gastric lavage may be indicated if performed soon after ingestion or in symptomatic patients. Administration of activated charcoal may also limit drug absorption. (L1712)

They cause slurred speech, disorientation and "drunken" behavior. They are physically and psychologically addictive. May cause a potentially dangerous rash that may develop into Stevens Johnson syndrome, an extremely rare but potentially fatal skin disease.

Lorazepam, as with other benzodiazepines, is rarely associated with serum ALT or alkaline phosphatase elevations during therapy, and considering its widescale use, clinically apparent liver injury from lorazepam is extremely rare. There has been only a single case report of symptomatic, acute liver injury from lorazepam. The latency to onset was 9 months and the clinical pattern that of a self-limited cholestatic hepatitis that resolved within 2 months of stopping. Similar isolated single cases of clinically apparent hepatitis have been reported with other benzodiazepines including alprazolam, chlordiazepoxide, clonazepam, diazepam, flurazepam and triazolam. The clinical pattern of acute liver injury from benzodiazepines is typically cholestatic and mild-to-moderate in severity with a latency of 1 to 6 months. Fever and rash are not common nor is autoantibody formation.

Parenteral (intravenous, sublingual); oral. Readily absorbed with an absolute bioavailability of 90% when given orally. When intramuscularly administered, lorazepam is completely and rapidly absorbed. It achieves max serum concentration in 3 hours. The max serum concentration of a 4 mg dose is 48 ng/mL.

Signs and Symptoms of Overdose

Lorazepam binds to an allosteric site on GABA-A receptors, which are pentameric ionotropic receptors in the CNS. Binding potentiates the effects of the inhibitory neurotransmitter GABA, which upon binding opens the chloride channel in the receptor, allowing chloride influx and causing hyperpolerization of the neuron.

Drug Induced Liver Injury Rank (DILIrank 2.0)

Lorazepam

vLess-DILI-concern

3

Warnings & precautions

DOI:10.1016/j.drudis.2016.02.015

◉ Summary of Use during Lactation

◈ What is lorazepam?

Lorazepam

Pharmaceutical

Smith, C.D. and Nowell, L.H., 2024. Health-Based Screening Levels for evaluating water-quality data (3rd ed.). DOI:10.5066/F71C1TWP

N05BA06

N - Nervous system

QN - Nervous system

N05BA06

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. The anticonvulsant properties of lorazepam are thought to be related to the binding to voltage-dependent sodium channels in which the sustained repetitive firing gets limited by the slow recovery of sodium channels due to the benzodiazepine effect. The effect of lorazepam seems to be very compartmental which was observed with a different generation of sleepiness and a dizziness effect.

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 chloride ions into the cell causing hyperpolarization and stabilization of the cellular plasma membrane. According to the binding site of lorazepam, we can observe different activities as the binding in the amygdala is known to help mainly in anxiety disorders while the binding in the cerebral cortex helps in seizure disorders.

When administered parentally, the registered half-life of lorazepam is of 14 hours. Following the administration of 1 mg of lorazepam in healthy adult male volunteers and using a multi-doses equation based on a one-compartment model, the average elimination half-life of lorazepam was estimated to be 11 hours and 8 hours for sublingual and oral doses respectively. The absorption half-life was calculated to be 55 minutes for oral doses and 15 minutes for sublingual doses.

Lorazepam is hepatically metabolized by CYP450 isoenzymes and extensively conjugated to the 3-0-phenolic glucuronide. This is an inactive metabolite and is eliminated mainly by the kidneys.

Lorazepam has known human metabolites that include Lorazepam glucuronide.

Lorazepam is hepatically metabolized and is extensively conjugated to the 3-0-phenolic glucuronide. This is an inactive metabolite and is eliminated mainly by the kidneys. Route of Elimination: When a single 2 mg oral dose is give to healthy subjects, 88±4% of the administered dose was recovered in urine and 7±2% was recovered in feces. The percent of administered dose recovered in urine as lorazepam glucuronide was 74±4%. Only 0.3% of the dose was recovered as unchanged lorazepam, and the remainder of the radioactivity represented minor metabolites. Half Life: Parenteral administration = 14±5 hours; Oral administration = 2 hours.

O26FZP769L

LORAZEPAM

Established Pharmacologic Class [EPC] - Benzodiazepine

Chemical Structure [CS] - Benzodiazepines

Lorazepam is a Benzodiazepine.

LORAZEPAM

Drugs used to prevent SEIZURES or reduce their severity.

Drugs used to prevent NAUSEA or VOMITING.

Drugs used to induce drowsiness or sleep or to reduce psychological excitement or anxiety.

Agents that alleviate ANXIETY, tension, and ANXIETY DISORDERS, promote sedation, and have a calming effect without affecting clarity of consciousness or neurologic conditions. ADRENERGIC BETA-ANTAGONISTS are commonly used in the symptomatic treatment of anxiety but are not included here.

Substances that do not act as agonists or antagonists but do affect the GAMMA-AMINOBUTYRIC ACID receptor-ionophore complex. GABA-A receptors (RECEPTORS, GABA-A) appear to have at least three allosteric sites at which modulators act: a site at which BENZODIAZEPINES act by increasing the opening frequency of GAMMA-AMINOBUTYRIC ACID-activated chloride channels; a site at which BARBITURATES act to prolong the duration of channel opening; and a site at which some steroids may act. GENERAL ANESTHETICS probably act at least partly by potentiating GABAergic responses, but they are not included here.

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 concentration is observed to be of 2 hours.

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.

The reported volume of distribution of lorazepam is 1.3 L/kg. It is important to mention that due to the lipophilicity of lorazepam, it does not redistribute as fast in the brain.

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

Use (kg; approx.) in Germany (2009): >100

For the management of anxiety disorders, and for treatment of status epilepticus.