Lorazepam is a substance in the benzodiazepine group. It is used as an anxiolytic, sedative, hypnotic, anticonvulsant, and muscle relaxant. Furthermore, lorazepam is misused in the drug scene. It is subject to narcotics laws when the amount of active ingredient exceeds 2.5 mg per unit.
What is lorazepam?
Lorazepam is a drug present as a solid that belongs to the benzodiazepine group and exerts anxiolytic, sedative, anticonvulsant, hypnotic, and muscle relaxant effects. Its indications mainly include anxiety and panic disorders. In addition, lorazepam is used for the therapy of status epilepticus and for the prophylaxis of epileptic seizures. In sleep disorders, the use of lorazepam is rare. The chemical formula of lorazepam is C15H10Cl2N2O2. The melting point of the substance is about 166-168 degrees Celsius. The lethal dose 50 is 4500 mg x kg^-1 in the rat when administered orally, and 1810 mg x kg^-1 when administered intraperitoneally. The molar mass of lorazepam is 321.16 g x mol^-1. With lorazepam, as with all benzodiazepines, there is a risk of abuse. Preparations with active ingredient amounts of more than 2.5 mg lorazepam per unit therefore fall under the Narcotics Act. Lorazepam is available only on prescription.
Pharmacologic effect
Lorazepam is rapidly and almost completely absorbed regardless of route of administration. With oral administration, the average absorption half-life ranges from 10.8 to 40.4 minutes. After intravenous injection, the effect occurs very quickly – after just one to two minutes. This is due to the fact that the substance does not have to be absorbed first, but is applied directly into the bloodstream. The duration of action of lorazepam is relatively long: the effect lasts for five to nine hours. Specifically, the duration of action depends on the dosage and on the type and amount of stomach contents. The half-life of the substance is eleven to eighteen hours with normal liver function. Because of its long duration of action, lorazepam is well suited for the treatment of panic disorder. Lorazepam is able to cross the blood–brain barrier. The substance then binds to specific receptors in the brain. Binding to the membrane receptor enhances the effect of the neurotransmitter GABA. GABA has an overall inhibitory effect – the administration of lorazepam enhances this effect and the overall state of excitation of the nervous system is lowered.
Medical use and application
The dosage of lorazepam depends on the specific application and usually ranges from 0.25 mg to 7.5 mg daily. When using lorazepam, the dosage should always be individualized to the patient. There is a risk of excessive sedation, especially in elderly and debilitated patients. In individuals under 18 years of age, lorazepam is used only for therapy of epileptic seizures to prevent multiple consecutive seizures. At higher doses, especially after intravenous administration, anterograde amnesia often occurs. The patient is then unable to remember things that happened during the period of action. This effect is desirable and is used during unpleasant therapeutic interventions. Indications for lorazepam include treatment of panic attacks, treatment of severe anxiety and panic disorders, treatment of acute delirium (in combination with haloperidol), treatment of severe fasciculations (involuntary muscle twitching), emergency treatment of status epilepticus, treatment of acute catatonia, and treatment of epilepsy when other antiepileptic drugs are not effective. Furthermore, lorazepam is administered as a premedication before some diagnostic and therapeutic procedures and is used for anxiolysis in cardiac arrhythmias. Lorazepam is also used in addiction treatment.
Risks and side effects
Lorazepam interacts with various other drugs and with stimulants.With concomitant use of sleeping pills and sedatives, antiepileptic drugs, neuroleptics, morphine-containing agents, AT-1 receptor antagonists (used to lower blood pressure), H2 receptor antagonists (used to inhibit gastric acid secretion), Erythromycin, clozapine, anticoagulants, oral contraceptives, proton pump inhibitors, valproic acid, muscle relaxants, alcohol, and antihypertensives. Various side effects may occur during treatment with lorazepam. These include severe fatigue, impaired reaction, drowsiness, loss of libido, hypotension (low blood pressure), muscle weakness, skin reactions, and dry mouth. Very rarely, psychosis, unsteadiness of gait, confusion, muscle spasms, visual disturbances, sensitivity to light, an increase in liver enzymes, impaired concentration, agranulocytosis, reaction such as anger and aggressiveness, a decrease in hemoglobin, impotence, anorgasmia, and suicidal thoughts may also occur. Other side effects are possible. Participation in road traffic, operation of heavy machinery, and work without safe footing should not be performed or only after medical consultation. Therapy with lorazepam should not be stopped abruptly, otherwise tremors, sweating, palpitations, and agitation may occur, which may even lead to a life-threatening seizure. Lorazepam can lead to dependence. Long-term therapy may cause cognitive deficits, but these are reversible after discontinuation of the medication. There is a risk of abuse. During pregnancy and lactation, lorazepam should not be used or should be used only when absolutely necessary, as it may harm the child in the womb. Furthermore, withdrawal symptoms may occur in an infant if the mother was treated with lorazepam near the time of delivery.
