Lorazepam description and background information

Lorazepam is a drug from the benzodiazepine group, which owns all as an anxiolytic benzodiazepines (anxiolytic), anticonvulsant (epileptic potentials oppressive), sedative (sleep-induced leader) and muscle-relaxing effect, in that order from strong to weak. Lorazepam has a relatively long half-life. Therefore, it is mainly used as a sedative for anxiety and panic disorders, since here the longer duration of action (for example, a whole day), is desired. In the intensive care and emergency medicine, it is used for the perforation of a long-lasting, life-threatening epileptic seizure (status epilepticus) and for prophylaxis of seizures. Rarely is there an indication for the treatment of insomnia.

(R)-form (left) and (S)-form (right)

. The synthesis is described in the literature [3] Lorazepam is a chiral drug with a chiral center and is a racemate, ie as a 1:1 mixture of the mirror image (R) - and (S)-form, used medicinally [4th ] In general, such enantiomers have different pharmacokinetic and pharmacological properties, which is relevant for lorazepam, however, since in aqueous solution very fast racemization occurs, the application of pure enantiomers is not possible [5].
Pharmacological properties

Uptake and distribution in the body (pharmacokinetics)
Lorazepam is the body after any kind of application (oral, sublingual, intravenous, intramuscular) was added rapidly and almost completely. The onset of action is one to two minutes after sublingual intravenous injections, approximately five to ten minutes after application and 30 to 45 minutes after ingestion (tablet) and in up to one hour after intramuscular injections.
The duration of action depends on the dosage and the stomach contents and is normally from five to nine hours. The half-life of lorazepam in patients with normal liver function is 11 to 18 hours. Therefore, often two to four daily doses are needed.
Clinical Data

Applications (indications)
Lorazepam is a benzodiazepine with the mean plasma half-life of 12-16 hours. The effect is a relatively fast (absorption half 11-40 minutes for oral administration). However, this is also a greatly increased risk of dependence.
Lorazepam is administered to:
Treatment of anxiety disorders (particularly panic attacks)
Short-term treatment of insomnia, particularly if these are associated with strong agitation
Treatment of symptoms associated with Alkoholentzügen and Opiatentzügen
Long-term treatment of otherwise resistant forms of epilepsy and general acute care
Intensive therapy of status epilepticus
Intensive therapy of catatonic states alone / or with haloperidol
Treatment of acute delirium, preferably together with haloperidol
Supportive therapy of nausea / vomiting often associated with cancer chemotherapy, usually together with firstline antiemetics like 5-HT3 antagonists
Supportive therapy for nausea and vomiting regular
As a premedication,
to facilitate unpleasant procedures such as endoscopy and dental surgery
to increase the effect of the main anesthetic drug
to achieve an anterograde amnesia for the period of intervention
Posology and method of administration
The daily dose varies widely from 7.5 to 0.25 mg to mg.
Catatonia with inability to speak to speak lorazepam orally or intravenously to slowly injected. Catatonia may recur and treatment for several days may be necessary. Sometimes haloperidol is given concomitantly.
The control of status epilepticus requires slow intravenous injections, taking into account the possible occurrence of respiratory distress (hypoventilation) and low blood pressure (hypotension).
In any case, the dosage must be done individually, especially in elderly and debilitated patients in whom the risk is greater, to sedate the patient too much. The safety and effectiveness of lorazepam in children under 18 years is not well understood, but it is used to treat consecutive seizures. At higher doses (preferably iv) the patient is often not able to recall unpleasant events (anterograde amnesia) as to therapeutic interventions (endoscopies, etc.). This effect is desired. In palliative care, v.a. for use in the hospice service, lorazepam can be used for anxiolysis, sedation and relaxation shielding can be administered.
Lorazepam may have a hard foreseeable residual effects such as fatigue, dizziness and low blood pressure, within twelve hours still can lead to significant restrictions in daily life.
Use in pregnancy and lactation
There is clear evidence for risks attributable to benzodiazepines on the human fetus, which restricts the application to only absolute necessity.
Adverse effects
Lorazepam, like other benzodiazepines, making mental and / or physically dependent. Most severe withdrawal symptoms, similar in appearance to that of alcohol, barbiturates and heroin, have been observed after abrupt adjustment (particularly after prolonged dosing). Therefore, a gradual discontinuation (tapering off) over a period of weeks or months, depending on the time in which it was taken, and the dosage necessary.
The likelihood of abuse, dependence and withdrawal symptoms lorazepam is due to its rather short half-life, higher potency and stronger binding to the GABA receptor complex is much higher than with other benzodiazepines. In this context, it behaves like alprazolam (short half-life and high potency) and clonazepam (long half-life and high potency). Alprazolam has, however, in contrast to lorazepam at least one active metabolite, which the user perceives completion duration of action of the drug as less unpleasant and therefore the coupling between the drug and the patient is less pronounced. This leads to a lower probability of psychological dependence.
Long-term therapy may lead to cognitive deficits that are reversible upon treatment discontinuation.
Lorazepam can, if taken during pregnancy, may harm the unborn child, but was rarely observed. Administered near the time of birth can cause lorazepam withdrawal symptoms in infants.
In some cases, benzodiazepines may cause paradoxical effects such as increased power and aggression. Some doctors think that these effects could be caused by a disinhibition and therefore in patients who are due to pre-existing personality disorders may be below the average of disinhibition, occur frequently. Paradoxical effects are observed most frequently during use in mania and schizophrenia. Following abrupt cessation or fast tapering often occur the same effects (anxiety, panic attacks, sometimes severe epileptic seizures - but more pronounced) to still start taking, which again leads to situations that required treatment.

pharmacology of lorazepam

Infornation on the pharmacology of lorazepam counter indications and side effects included.