Lorazepam is a drug that has anxiolytic, sedative, anticonvulsant and muscle relaxant properties. From the chemical point of view, lorazepam is a benzodiazepine. It was marketed in Italy for the first time under the name Tavor ®.
Indications
For what it uses
Lorazepam - Chemical Structure
The therapeutic indications of lorazepam vary according to the pharmaceutical form and - consequently - to the route of administration through which it is taken.
Injectable Lorazepam
The use of injectable lorazepam is indicated in the following cases:
- Anesthetic premedication to relieve anxiety;
- Symptomatic relief of acute neurotic or psychotic anxiety;
- Treatment of epileptic states due to different types of partial and generalized epilepsy.
Lorazepam for oral administration
In this case, the use of lorazepam is indicated for the treatment of:
- Anxiety;
- Tension and somatic or psychiatric manifestations associated with anxiety syndrome;
- Insomnia.
Warnings
Lorazepam should be used with extreme caution in patients who have a history of alcohol and / or drug abuse.
The use of lorazepam can cause respiratory depression with fatal results. Therefore, patients must be carefully monitored.
Tolerance to lorazepam may develop after repeated use and for a long time. In other words, there is a decrease in the hypnotic effects induced by the drug.
Lorazepam can cause blood dyscrasia and increase levels of liver enzymes in the bloodstream. Therefore, periodic blood tests are recommended.
Since lorazepam may cause hypotension, great caution should be used when administering the drug in patients in whom lowering blood pressure could give rise to severe cardiac and cerebrovascular complications.
Due to the disorders of the upper gastrointestinal tract that lorazepam can cause, regular checks are necessary.
Although injectable lorazepam is indicated for the treatment of epileptic conditions, great caution should be used when administering the drug in epilepsy patients, as respiratory arrest or partial airway obstruction may occur. Therefore, this category of patients must be closely monitored.
However, lorazepam is not indicated for epilepsy maintenance therapy. Once control of epileptic seizures is achieved, it is necessary to administer more suitable drugs to prevent new attacks.
Injectable lorazepam should be administered with caution in elderly patients, in patients with limited pulmonary reserve and in patients with cardiocirculatory lability, as apnea and / or hypoxic cardiac arrest may arise.
Injectable lorazepam should not be administered intra-arterially, as it can cause a spasm of the artery that can lead to gangrene.
Patients who received injectable lorazepam should be observed for at least 24 hours after the last administration.
Caution should be exercised when administering lorazepam in elderly patients, in debilitated patients and in patients with hepatic and / or renal dysfunction.
Lorazepam should not be used on its own to treat anxiety associated with depression.
Lorazepam can induce effects that can alter the ability to drive or use machines, therefore, these activities should be avoided.
Interactions
Concomitant use of lorazepam and haloperidol (an antipsychotic) can cause apnea, bradycardia, cardiac arrest, coma and death.
The sedative effect of lorazepam is increased by the simultaneous intake of alcohol, therefore, this association should be avoided.
The central nervous system depressive effect induced by lorazepam is increased by concomitant administration of the following drugs:
- Barbiturates ;
- Antipsychotic drugs;
- Hypnotic, sedative and anxiolytic drugs;
- Antidepressant drugs;
- Opioid analgesics ;
- Anesthetic drugs;
- Antiepileptic drugs;
- Sedative antihistamine drugs.
However, the concomitant administration of lorazepam and opioid analgesics could also favor an increase in euphoria and - consequently - an increase in psychic dependence.
Co-administration of injectable lorazepam and scopolamine (a muscarinic receptor antagonist) may result in increased sedation, hallucinations and irrational behavior.
Concomitant administration of lorazepam and loxapine (an antipsychotic) can cause excessive stupor, reduced respiratory rate and hypotension.
Concomitant use of lorazepam and clozapine (an antipsychotic) may induce marked sedation, hypersalivation and ataxia.
Concomitant use of lorazepam and valproic acid (a drug used to treat epilepsy) or probenecid (a drug used to treat hyperuricemia) may cause an increase in the plasma concentration of lorazepam itself. Therefore, it is necessary to reduce the dose of lorazepam administered.
Side effects
Lorazepam can cause various types of side effects, although not all patients experience them. This is due to the different sensitivity that each individual has towards the drug.
Below are the main side effects that may occur during lorazepam therapy.
Addiction
Lorazepam can lead to the development of physical and mental dependence. The risk of developing dependence is directly proportional to the dose of drug administered and to the duration of the treatment.
Patients who have a history of alcohol and drug abuse are at greater risk of developing addiction.
Once physical dependence is established, abrupt termination of treatment causes withdrawal symptoms. These symptoms are:
- Depression;
- derealization;
- depersonalization;
- Anxiety;
- Confusion;
- Nervousness;
- Restlessness;
- Irritability;
- dysphoria;
- Hallucinations;
- Delusions;
- Epileptic shocks;
- Insomnia;
- Mood changes;
- Sweating;
- Diarrhea;
- Headache;
- Muscle pains;
- Hypersensitivity and intolerance to sounds (hyperacusis);
- Hypersensitivity to light and physical contact.
Therefore, it is advisable to gradually stop the treatment.
Anterograde amnesia
Therapy with lorazepam can cause anterograde amnesia.
The development of this type of amnesia usually takes place a few hours after taking the drug. Therefore, after taking the drug, patients should be able to sleep continuously for at least 8 hours.
Memory can be compromised if the patient wakes up at the time of maximum activity of the drug.
However, when injectable lorazepam is used in anesthetic premedication, this effect can be beneficial.
Psychiatric disorders
Paradoxical reactions may occur during lorazepam treatment, such as:
- agitation;
- Restlessness;
- Irritability;
- Aggression;
- Anger;
- Hallucinations;
- Psychosis;
- Nightmares;
- Disappointment;
- Abnormal behavior.
Paradox symptoms occur more often in elderly patients and children.
Furthermore, confusion, reduced alertness, suicidal ideation and behavior and disinhibition can occur.
Insomnia or rebound anxiety
Insomnia or rebound anxiety may occur upon discontinuation of lorazepam therapy. That is to say, we are witnessing the recurrence in an aggravated form of the symptoms that made the use of the drug necessary.
Rebound symptoms may be accompanied by mood swings and restlessness.
The risk of developing these symptoms is greater when the treatment is stopped abruptly, therefore, the interruption of therapy must take place gradually.
Nervous system disorders
Treatment with lorazepam may cause:
- Drowsiness;
- Sedation;
- Ataxia;
- Tremors;
- Dizziness;
- Headache;
- Dysarthria;
- Speech disorders;
- Convulsions or seizures;
- Balance disorders;
- Compromise of concentration;
- Disorientation;
- Coma.
Blood and lymphatic system disorders
Therapy with lorazepam can cause disorders in the system responsible for the production of blood cells. These disorders can cause thrombocytopenia (decrease in the number of platelets in the blood), agranulocytosis (lack of granulocytes in the bloodstream) and pancytopenia (decreased levels of all blood cells).
Endocrine disorders
Treatment with lorazepam may trigger the syndrome of inappropriate secretion of the antidiuretic hormone (SIADH).
Eye disorders
Lorazepam therapy can cause blurred vision and diplopia (double vision).
Metabolism and nutrition disorders
Treatment with lorazepam may cause changes in appetite and hyponatremia (decrease in blood concentration of sodium).
Cardiovascular disorders
Therapy with lorazepam may induce tachycardia and hypotension.
Gastrointestinal disorders
During treatment with lorazepam various gastrointestinal disorders may occur, including nausea and constipation.
Lung and respiratory tract disorders
Therapy with lorazepam can cause apnea, worsening of sleep apnea, respiratory depression and worsening of obstructive pulmonary disease.
Hepatobiliary disorders
Treatment with lorazepam may increase the plasma concentration of bilirubin, hepatic transaminases and alkaline phosphatase and may promote the onset of jaundice.
Skin and subcutaneous tissue disorders
Therapy with lorazepam can cause skin rashes, rashes and alopecia.
Pathologies and conditions related to the site of administration
During the administration of injectable lorazepam, the following may occur:
- Injection site pain;
- Burning and redness at the injection site;
- Local phlebitis.
Other side effects
Other side effects that may occur following lorazepam therapy are:
- Allergic reactions, even serious, in sensitive subjects;
- Fatigue;
- Asthenia;
- Changes in libido;
- Urinary incontinence;
- Hypothermia;
- Muscle weakness.
Overdose
The symptoms that may occur following an overdose of lorazepam are:
- Lethargy;
- lightheadedness;
- Mental confusion;
- Drowsiness;
- Dysarthria;
- Changes in coordination;
- Ataxia;
- hypotonia;
- Hypotension;
- Respiratory depression;
- Coma.
In case of overdose, patients' breathing, blood pressure and heart rate must be constantly monitored.
If the patient is conscious, vomiting should be induced within an hour of taking the drug. If, on the other hand, the patient is unconscious, a gastric lavage should be performed.
If no improvement is noted following gastric lavage, the administration of activated charcoal may be useful to reduce drug absorption.
Flumazenil, a benzodiazepine receptor antagonist, may also be used for the treatment of lorazepam overdose.
In any case, if you suspect you have taken an overdose of medication, you must contact a doctor immediately and contact the nearest hospital.
Action mechanism
Lorazepam is a benzodiazepine and - as such - stimulates the GABAergic system, ie the γ-aminobuttiric acid system which is the main inhibitory neurotransmitter of the brain.
GABA performs its biological functions by binding to its specific receptors: GABA-A, GABA-B and GABA-C.
A binding site for benzodiazepines is present on the GABA-A receptor.
Lorazepam binds to this specific site and activates the receptor, thus promoting the cascade of inhibitory signals induced by GABA.
Mode of Use - Posology
Lorazepam is available as oral drops and tablets for oral administration and as vials for intramuscular and intravenous administration.
The dosage of lorazepam must be established by the doctor according to the pathology to be treated.
The doses of drug normally used are given below.
In elderly patients and in patients with hepatic and / or renal diseases, a reduction in the dose of lorazepam usually administered may be necessary.
Anesthetic premedication
When lorazepam is used in anesthetic premedication, the usual intravenous dose of drug is 0.044 mg / kg of body weight, up to a maximum of 2 mg total, to be administered twenty minutes before surgery.
If necessary, the dosage can be increased to 0.05 mg / kg of body weight, up to a maximum of 4 mg total of drug.
When administered intramuscularly, by contrast, the dose of lorazepam usually used is 0.05 mg / kg of body weight, up to a maximum of 4 mg total, to be administered at least two hours before surgery.
Acute neurotic or psychotic anxiety
The recommended dose of lorazepam is 0.05 mg / kg of body weight, up to a maximum of 2-4 mg total, to be administered intravenously or intramuscularly.
Epileptic states due to various types of partial or generalized epilepsy
The usual starting dose of lorazepam is 4 mg of drug for slow intravenous infusion.
Within twelve hours a maximum of 8 mg of lorazepam can be administered.
Anxiety
For the treatment of anxiety, lorazepam is administered orally.
The dose of medication usually used is 2-3 mg a day.
In elderly patients, the recommended starting dose is 1-2 mg of drug per day.
Treatment should be as short as possible and normally should not exceed 8-12 weeks, including the period of gradual interruption of therapy.
Insomnia
Again, lorazepam is administered orally.
The usual dose is 1-2 mg of drug to be taken before bedtime. If necessary, the doctor may decide to increase the amount of drug administered.
The duration of treatment varies from a few days to two weeks.
Pregnancy and breastfeeding
Since lorazepam can cause harm to the fetus, the drug should not be used during pregnancy, especially during the first trimester of gestation.
If - for reasons of real need - lorazepam is administered during the last period of pregnancy or during labor, adverse effects may occur in the newborn, including hypothermia, hypotonia, respiratory depression, sedation and inability to eat.
Because lorazepam is excreted in breast milk, breastfeeding mothers should not take the medicine.
Contraindications
The use of lorazepam is contraindicated in the following cases:
- Known hypersensitivity to lorazepam or other benzodiazepines;
- In patients with myasthenia gravis;
- In patients suffering from severe respiratory failure;
- In patients with sleep apnea syndrome;
- In patients with severe hepatic impairment;
- In patients with narrow-angle glaucoma;
- Pregnant;
- During breastfeeding.
