From the Guidelines
Lorazepam works by activating γ-aminobutytic acid A (GABA) neuronal receptors in the brain, producing anxiolytic, sedating, hypnotic, and anticonvulsant effects. This mechanism of action is based on the most recent and highest quality study available 1. The activation of GABA receptors by lorazepam increases chloride ion conductance through the neuronal cell membrane, resulting in hyperpolarization of neurons and decreased neuronal excitability.
Key Points
- Lorazepam has a relatively rapid onset of action and an intermediate duration of action 1
- The typical oral dosage ranges from 0.5 to 2 mg, taken 2-3 times daily for anxiety 2
- Patients should be aware that lorazepam can cause physical dependence with prolonged use, and abrupt discontinuation may lead to withdrawal symptoms 1
- It should be used cautiously in elderly patients and those with respiratory conditions, as it can cause respiratory depression, especially when combined with other central nervous system depressants 1
Dosage and Administration
The recommended dosage of lorazepam is 0.5-1 mg orally four times a day as required, with a maximum of 4 mg in 24 hours 2. In elderly or debilitated patients, the dose should be reduced to 0.25-0.5 mg, with a maximum of 2 mg in 24 hours 2. Oral tablets can be used sublingually, although this is an off-label use 2.
Special Considerations
Lorazepam clearance is reduced in patients with hepatic dysfunction, renal failure, and other disease states, as well as in elderly patients 1. The elimination half-life and duration of clinical effect of lorazepam are also increased in patients with renal failure 1. Therefore, caution should be exercised when using lorazepam in these patient populations.
From the FDA Drug Label
Studies in healthy volunteers show that in single high doses lorazepam has a tranquilizing action on the central nervous system with no appreciable effect on the respiratory or cardiovascular systems. The mechanism of action for Lorazepam (Ativan) is a tranquilizing action on the central nervous system.
- The exact mechanism is not explicitly described in the label, but it is known to have an effect on the central nervous system (CNS). 3
From the Research
Mechanism of Action for Lorazepam (Ativan)
The mechanism of action for Lorazepam (Ativan) can be understood through its interaction with the gamma-aminobutyric acid (GABA) receptors in the central nervous system. Key points include:
- Lorazepam, like other benzodiazepines, potentiates the neural inhibition mediated by GABA, leading to sedative, hypnotic, anxiolytic, and muscle relaxant effects 4, 5.
- Benzodiazepines, including Lorazepam, do not activate GABA(A) receptors directly but require the presence of GABA to exert their effects 4.
- The action of Lorazepam on GABA(A) receptors results in a slowing of neurotransmission, which is responsible for its therapeutic effects 5, 6.
- The specific interaction of Lorazepam with GABA(A) receptors involves allosteric modulation, enhancing the activity of GABA and leading to the aforementioned effects 5, 6.
Pharmacokinetics and Pharmacodynamics
- Lorazepam undergoes glucuronide conjugation and is not metabolized by cytochrome P450 (CYP) enzymes, unlike some other benzodiazepines like midazolam and diazepam 4.
- The duration of action of Lorazepam is dependent on the duration of its administration, with its recovery profile being shorter than that of diazepam but longer than midazolam 4.
- Lorazepam, being a benzodiazepine, has synergistic interactions with other hypnotics and opioids, which can lead to enhanced sedative effects and potential for abuse 4, 7.
Clinical Use and Abuse Potential
- Lorazepam is widely used for sedation, induction, and maintenance of anesthesia, as well as for the treatment of anxiety and insomnia 4, 5.
- Despite its therapeutic benefits, Lorazepam has a potential for dependence and abuse, similar to other benzodiazepines, with its reinforcing properties, maladaptive behaviors related to its use, and potential for tolerance and dependence 7.
- Research into the specific GABA(A) receptor subtypes involved in the effects of Lorazepam and other benzodiazepines may provide insights into reducing the abuse potential while maintaining therapeutic efficacy 6, 7.