Diazepam

Diazepam is a benzodiazepine that has anxiolytic, sedative, anticonvulsant and muscle relaxant properties. Probably, diazepam is best known under the trade name Valium®.

Indications

For what it uses

Diazepam - Chemical Structure

Diazepam can be used for the treatment of various diseases. Therapeutic indications may vary depending on the pharmaceutical form and - consequently - the chosen method of administration.

Oral administration

When administered orally, diazepam is indicated for the treatment of:

Anxiety;
Voltage;
Psychiatric or somatic manifestations associated with anxiety syndrome;
Insomnia.

Intravenous or intramuscular administration

In this case, diazepam is indicated for the treatment of:

States of agitation;
States of motor excitation in paranoid-hallucinatory clinical pictures;
States of epileptic illness;
Severe muscle spasms of both central and peripheral origin;
Tetanus.

Rectal administration

When diazepam is administered rectally, it is indicated for the treatment of:

Convulsions;
Febrile convulsions in children;
As a sedative before undergoing exploratory examinations and treatments (eg colonoscopy).

Warnings

Diazepam should be used with great caution in patients who have abused alcohol and / or drugs.

Patients who make prolonged use of diazepam may develop tolerance. In other words, there may be a decrease in the effects induced by diazepam itself.

Extreme caution should be used when administering diazepam in patients with cardiorespiratory failure.

Much attention must also be paid to the administration of the drug in patients suffering from hepatic and / or renal diseases.

Outpatients given parenteral diazepam should be monitored for at least an hour after taking the drug and should be discharged only if accompanied by someone.

Abrupt discontinuation of diazepam treatment causes withdrawal symptoms, so gradual discontinuation of therapy is recommended.

In elderly and debilitated patients adjustment of the administered diazepam dose may be necessary.

In elderly patients and in patients who are concomitantly using other sedatives, there is an increased risk of falls and subsequent fractures.

Diazepam may impair the ability to drive and use machines. Therefore, these activities must be avoided.

Interactions

The central nervous system depressive effect induced by diazepam is increased when it is given concomitantly with:

Alcohol ;
Antipsychotic drugs;
Other hypnotic, sedative or anxiolytic drugs;
Antidepressant drugs;
Antiepileptic drugs;
Anesthetics ;
Sedative antihistamine drugs.

The combination of diazepam and opioid analgesics may promote an increase in euphoria and psychic dependence.

The activity of diazepam can be increased by the simultaneous administration of drugs, such as:

Ketoconazole, itraconazole and other antifungal drugs with azolic structure;
Cimetidine and omeprazole, drugs used to reduce acid secretion of the stomach;
Fluvoxamine and fluoxetine, antidepressant drugs, serotonin reuptake inhibitors (SSRIs);
Ritonavir, indinavir and other antiviral agents;
Isoniazid, an antituberculous drug;
Oral contraceptives ;
Disulfiram, a drug used to treat alcoholism.

The therapeutic efficacy of diazepam may be reduced by concomitant administration of drugs, such as:

Rifampicin, an antibiotic;
Carbamazepine, phenytoin and phenobarbital, drugs used in the treatment of epilepsy;
Corticosteroids .

Simultaneous use of diazepam and levodopa (a drug used to treat Parkinson's disease) leads to a decrease in the effects of levodopa itself.

Diazepam potentiates the effect of ketamine (an anesthetic).

Side effects

Diazepam can induce many types of side effects, although not all patients experience them. This is due to the different sensitivity that each individual has towards the drug. Therefore it is not said that all adverse effects occur with the same intensity in each patient.

The following are the main side effects that may occur following treatment with diazepam.

Amnesia

Diazepam therapy can cause anterograde amnesia.

The development of this type of amnesia usually takes place a few hours after taking the drug. Therefore, patients - after taking diazepam - 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.

Addiction

Diazepam 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 abused alcohol and drugs 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;
Hallucinations;
Epileptic shocks;
Rebound insomnia;
Mood changes;
Sweating;
Diarrhea;
Headache;
Muscle pains;
Hypersensitivity and intolerance to sounds (hyperacusis);
Hypersensitivity to light and physical contact.

It is therefore recommended to gradually stop the treatment.

Psychiatric disorders

So-called paradox symptoms can occur during diazepam treatment. These symptoms are:

Restlessness and agitation;
Irritability;
Aggression;
Anger;
Disappointment;
Hallucinations;
Nightmares;
Psychosis;
Abnormal behavior.

If these symptoms appear, treatment with diazepam should be stopped. Paradoxical reactions occur mainly in elderly and pediatric patients.

Furthermore, the drug can cause emotional poverty, depression and reduced alertness.

Nervous system disorders

Diazepam therapy can cause drowsiness, headache, tremors, dizziness, vertigo, ataxia, dysarthria and impaired motor skills.

Gastrointestinal disorders

Treatment with diazepam can cause various gastrointestinal disorders, including nausea, hypersalivation, constipation or diarrhea and dry mouth.

Eye disorders

Diazepam therapy can cause visual disturbances, such as blurred vision, diplopia (double vision) and nystagmus (ie a rapid movement of the eyeball which is caused by the spasm of the related muscles).

Cardiovascular disorders

Diazepam treatment can cause hypotension, heart failure, heart rate changes and cardiac arrest.

Furthermore, when diazepam is administered rectally, it can cause cardiorespiratory depression.

Renal and urinary tract disorders

Diazepam therapy may cause incontinence or urinary retention.

Hepatobiliary disorders

Treatment with diazepam can cause changes in the levels of liver enzymes in the bloodstream and can promote the onset of jaundice.

Skin and subcutaneous tissue disorders

Diazepam therapy can cause skin rashes, rashes and itching.

Alteration of diagnostic tests

Treatment with diazepam may cause increases in blood levels of alkaline phosphatase and transaminases.

Pathologies and conditions related to the site of administration

When diazepam is administered intravenously, the following may occur:

Irritation at the injection site level;
Local swelling;
Venous thrombosis;
Phlebitis.

Furthermore, occasionally hiccups can appear and very rarely vascular changes can occur.

When diazepam is administered intramuscularly, however, local pain may occur accompanied by erythema at the injection site.

Overdose

Generally, an overdose of diazepam should not be life-threatening for patients, unless other drugs that depress the central nervous system, drugs or alcohol have been taken at the same time.

The symptoms that may arise from taking an overdose are:

Drowsiness;
Ataxia;
Dysarthria;
nystagmus;
areflexia;
Apnea;
Hypotension;
Cardiorespiratory depression;
Coma.

In case of oral diazepam overdosage, if the patient is conscious, vomiting should be induced within one hour of taking the drug. If the patient, on the other hand, is unconscious, gastric lavage should be performed. The administration of activated charcoal could also be useful.

If necessary, a benzodiazepine antagonist can be given, flumazenil .

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

Diazepam exerts its action by stimulating 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.

Diazepam - because it is a benzodiazepine - binds to this specific site and activates the receptor, thereby promoting the cascade of inhibitory signals induced by GABA.

Mode of Use - Posology

As mentioned above, diazepam is available for oral, rectal, intravenous and intramuscular administration.

For oral administration, diazepam is available as tablets, capsules or oral drops.

For rectal administration, however, it is available as a solution.

The dosage of diazepam must be established by the doctor on an individual basis. The dose of drug administered varies according to the type and severity of the pathology to be treated and according to the route of administration chosen. In any case, the duration of the treatment must be as short as possible.

The following are the usual diazepam dosages.

Oral administration

The dose of diazepam usually given in adult patients is 2-5 mg once or twice a day.

In elderly patients the usual drug dose is 2 mg twice a day.

The children are given oral drops. The usual dose for children up to 3 years is 1-6 mg of drug per day. In children between 4 and 12 years of age, the dose is 4-12 mg of diazepam per day.

In hospitalized patients suffering from anxiety states, the usual diazepam dose is 10-20 mg of drug, to be administered three times a day.

Intramuscular or intravenous administration

The doses of drug administered vary according to the pathology to be treated:

States of agitation : the usual dose is 10-20 mg of diazepam three times a day, until the acute symptoms disappear;
States of epileptic illness : the initial dose of diazepam is 10-20 mg intravenously; subsequent doses are 20 mg of drug, to be administered intravenously or intramuscularly;
Muscle spasms : the dose of diazepam usually used is 10 mg, administered once or twice intramuscularly;
Tetanus : the usual dose of diazepam is 10 mg intravenously. This dosage is able to cancel the spastic state induced by the tetanus for a period of about 8 hours.

Rectal administration

In adults and children over three years of age, the usual dose of diazepam is 10 mg.

In children up to three years and in elderly and debilitated patients, the usual dose of diazepam is 5 mg.

Pregnancy and breastfeeding

Diazepam should not be administered in the first trimester of pregnancy.

If for reasons of absolute necessity, diazepam is administered during the last periods of pregnancy or during labor it can cause the following side effects in the fetus or newborn:

Irregularity in the fetal heart rate;
Hypothermia;
hypotonia;
Respiratory depression;
Possibility of development of physical dependence and withdrawal symptoms in the post-natal period.

Since diazepam is excreted in breast milk, mothers taking the drug should not breast-feed.