Lorazepam

Lorazepam
ATC Code N05BA06
Formula C15H10Cl2N2O2
Molar Mass (g·mol−1) 321,16
Physical State solid
Melting Point (°C) 166–168
PKS Value 13
CAS Number 846-49-1
PUB Number 3958
Drugbank ID DB00186
Solubility sparingly soluble in water

Basics

Lorazepam is a drug from the group of benzodiazepines. It has antianxiety, sedative and sleep-inducing properties. Its main use is in the treatment of anxiety and panic disorders. In some cases, it is used in emergency medicine to break life-threatening epileptic seizures. It is also used for the short-term treatment of sleep disorders.

Lorazepam requires a prescription and is mainly taken in tablet form. In emergencies it can also be given intravenously or intramuscularly.

Pharmacology

Pharmacodynamics

The action of lorazepam and other benzodiazepines is due to binding to GABA-A receptors in the brain. These receptors play a role in the depressant (e.g.: sleep or sedation) processes in the brain. However, lorazepam is not an agonist of this receptor, but a so-called allosteric modulator. The receptor itself is a ligand-gated chloride channel that isopenedby its agonist GABA (gamma-aminobutyric acid). Lorazepam binds to a separate site on the receptor and increases sensitivity to GABA. This increases the opening probability of the channel and results in the depressant effects of the drug.

Pharmacokinetics

When administered orally, the bioavailability is approximately 90%. Plasma protein binding in the blood is about 85% and the half-life of the drug is about 14 hours. Due to this extremely long half-life, a single daily dose is sufficient for many applications. Lorazepam is broken down in the liver by enzymes of the CYP450 family and about 90% is excreted in the urine and 10% in the intestine.

Drug interactions

Especially together with opioids and alcohol life-threatening side effects such as respiratory depression or coma are to be expected. Severe side effects and an increased risk of suicide have also been observed together with other benzodiazepines. Other interactions are possible with psychotropic drugs such as certain antidepressants.

Toxicity

Signs of overdose include increased drowsiness, respiratory depression or arrest, and coma. Without prompt medical countermeasures, overdose can lead to death.

In

pregnant women, use should be avoided as fetal death is a possible outcome.

Benzodiazepines are at risk of abuse and have an increased potential for addiction, so dispensing must be monitored particularly closely.

Side effectsPossible side

effects include sedation, drowsiness, fatigue, weakness, depression, gait disturbance, drowsiness, hallucinations, dizziness, tremors, sexual dysfunction and respiratory depression.

Toxikologische Daten 

LD50: 1850 mg/kg (Maus, oral)