drugs

Alprazolam

Alprazolam is a benzodiazepine with an anxiolytic action. Most likely, it is best known under the trade name Xanax®.

Alprazolam - Chemical Structure

Indications

For what it uses

The use of alprazolam is indicated for the treatment of:

  • Anxiety;
  • Tension and other somatic or psychiatric manifestations associated with anxiety syndrome;
  • Panic attacks, with or without agoraphobia.

Warnings

The duration of treatment with alprazolam should be as short as possible.

Extreme caution should be used when administering alprazolam in patients who have a history of alcohol and / or drug abuse.

In elderly and debilitated patients, the minimum effective dose of medication should be used, in order to avoid excessive sedation or the onset of ataxia.

Patients with cardiorespiratory insufficiency should undergo regular checkups for the duration of alprazolam therapy, due to the respiratory depression that the drug can induce.

Alprazolam should not be used alone for the treatment of anxiety associated with depression, since - in this category of patients - suicidal ideations and behaviors can worsen. Therefore, these patients must be kept under strict control.

In depressed patients, the use of alprazolam could lead to the onset of mania or hypomania.

Alprazolam should not be used in patients with psychomotor difficulties, in patients suffering from endogenous depression, bipolar disorder or psychotic symptoms.

Following abrupt cessation of treatment with alprazolam seizures may occur, therefore gradual interruption of therapy is recommended, especially in those patients with pre-existing epilepsy.

Following the reduction in the dose of alprazolam administered, withdrawal symptoms may arise, therefore, gradual dose reduction is recommended.

Caution should be exercised when administering alprazolam in patients with impaired hepatic and / or renal function.

Following repeated use and for a long period of time tolerance to aprazolam may develop. That is, the hypnotic effects induced by the drug may be reduced.

Alprazolam may impair the ability to drive or use machines, so these activities should be avoided.

The use of alprazolam in children and adolescents under 18 years of age is not recommended.

Interactions

The effect of alprazolam is increased by concomitant alcohol intake .

Simultaneous use of alprazolam and the following drugs may increase the depressive action on the central nervous system induced by the alprazolam itself:

  • Antipsychotic drugs;
  • Hypnotic, sedative or anxiolytic drugs;
  • Antidepressant drugs;
  • Opioid analgesics ;
  • Anesthetic drugs;
  • Antiepileptic drugs;
  • Sedative antihistamine drugs.

The concomitant administration of alprazolam and the following drugs may increase the plasma concentration of alprazolam itself:

  • Azole antifungal drugs, such as - for example - ketoconazole, itraconazole, posaconazole and voriconazole ;
  • Antiviral drugs protease inhibitors, such as - for example - ritonavir ;
  • Macrolide antibiotics, such as - for example - erythromycin, clarithromycin and telithromycin ;
  • Antidepressant drugs, such as nefazodone, fluvoxamine and fluoxetine ;
  • Cimetidine, a drug used to reduce acid secretion of the stomach;
  • Propoxyphene, an opioid analgesic;
  • Oral contraceptives .

The association with these drugs should be avoided or, however, carried out with extreme caution. The dose of alprazolam administered may need to be reduced.

Concomitant use of alprazolam and diltiazem (a calcium channel blocker used to treat cardiovascular diseases) is not recommended.

Alprazolam may increase the plasma concentration of digoxin (a drug used to increase the strength of cardiac contraction), therefore, patients on these two drugs should be monitored to identify any side effects due to digoxin.

The concomitant and long-term use of alprazolam and St. John's wort (a plant with antidepressant properties) may decrease the therapeutic efficacy of alprazolam.

Co-administration of alprazolam and clozapine (an antipsychotic) increases the risk of respiratory and / or cardiac arrest.

In any case, it is necessary to inform your doctor if you are taking - or have recently been taken - drugs of any kind, including over-the-counter drugs and herbal and / or homeopathic products.

Side effects

Alprazolam can cause many adverse effects, but not all patients experience them. This depends on the different sensitivity that each individual has towards the drug.

The main side effects that may occur during treatment with alprazolam are listed below.

Addiction

Treatment with alprazolam may result in 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 with a history of alcohol and / or 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;
  • 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 advised to stop the treatment gradually.

Insomnia or rebound anxiety

Insomnia or rebound anxiety may occur when treatment with alprazolam is stopped. That is, the symptoms that made the use of the drug necessary (anxiety and insomnia) reappear in aggravated form. 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.

Psychiatric disorders

So-called paradox symptoms can occur during alprazolam therapy. These symptoms are:

  • agitation;
  • Anxiety;
  • Aggression;
  • Anger;
  • Sleep disorders;
  • Nightmares;
  • Insomnia;
  • Panic attacks
  • Nervousness;
  • Irritability;
  • Hallucinations;
  • Depressive state;
  • Abnormal thoughts;
  • Hostile behavior.

Furthermore, alprazolam can cause confusion, disorientation, decreased or increased libido, psychomotor hyperactivity, euphoria, mania or hypomania.

Nervous system disorders

Treatment with alprazolam may cause:

  • Sedation;
  • Drowsiness;
  • Lethargy;
  • Ataxia;
  • dizziness;
  • Headache;
  • Tremors;
  • Impairment of memory and balance;
  • Dizziness;
  • Disorders of coordination and attention;
  • Alterations in the sense of taste;
  • Changes in gait;
  • Convulsions;
  • Partial epileptic accesses.

Anterograde amnesia

Alprazolam therapy can cause anterograde amnesia.

The development of this type of amnesia usually occurs after hours of taking the drug. Therefore, patients should be able to sleep continuously for at least 8 hours after taking the drug.

Memory can be compromised if the patient wakes up at the time of maximum activity of the drug.

Cardiovascular disorders

Treatment with alprazolam can cause palpitations and flushes.

Gastrointestinal disorders

During alprazolam therapy, abdominal pain, nausea, vomiting, diarrhea or constipation, dry mouth, stomach pain and necrotizing enterocolitis may occur.

Respiratory disorders

Treatment with alprazolam may cause respiratory problems and suffocation.

Hepatobiliary disorders

Alprazolam therapy can induce liver function abnormalities, increase bilirubin blood concentration and promote the occurrence of hepatitis and jaundice.

Skin and subcutaneous tissue disorders

Dermatitis, skin rash, itching, increased sweating and photosensitivity reactions may occur during treatment with alprazolam.

Musculoskeletal disorders

During alprazolam therapy, muscle weakness, myalgia, pain in the limbs, arthralgia and muscle cramps may occur.

Reproductive system disorders

Treatment with alprazolam can cause sexual dysfunction, irregular menstruation, erectile dysfunction and ejaculation disorders.

Other side effects

Other adverse effects that may occur during alprazolam therapy are:

  • Hyperprolactinemia (increase in the blood concentration of the hormone prolactin);
  • Blurring of sight;
  • Increased intraocular pressure;
  • Tinnitus, that is an auditory disorder characterized by the perception of rustling, buzzing, whistling, etc .;
  • Angioedema;
  • Loss of appetite;
  • Increase or decrease in body weight;
  • Fatigue;
  • Weakness;
  • slow;
  • Chest pain;
  • Influenza syndrome;
  • Sense of thirst;
  • Foreign body sensation.

Overdose

The symptoms that may occur following an overdose of alprazolam are:

  • Lethargy;
  • lightheadedness;
  • Mental confusion;
  • Drowsiness;
  • Dysarthria;
  • Changes in coordination;
  • Ataxia;
  • hypotonia;
  • Hypotension;
  • Respiratory depression;
  • Coma.

Some cases of death have been reported following the intake of an overdose of alprazolam, either alone or in combination with alcohol.

In case of overdose of alprazolam - if the patient is conscious - vomiting should be induced within an hour of taking the drug. If the patient, on the other hand, is unconscious, gastric lavage should be performed.

If - following gastric lavage - no improvement is noted, the administration of activated charcoal may be useful.

Flumazenil, a benzodiazepine antagonist, may also be used for the treatment of alprazolam overdose.

However - in case of overdose - patients' breathing, blood pressure and heart rate must be constantly monitored.

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

Alprazolam is a benzodiazepine and - as such - it exerts its anxiolytic action by enhancing the GABAergic signal, ie the signal of γ-aminobuttiric acid (GABA).

GABA is the main inhibitory neurotransmitter of the brain and carries out its biological functions by binding to its specific receptors: GABA-A, GABA-B and GABA-C.

The GABA-A receptor has a specific binding site for benzodiazepines. Alprazolam binds to this site by activating the receptor. In this way, it promotes the cascade of inhibitory signals induced by GABA thus exerting an anxiolytic action.

Mode of Use - Posology

Alprazolam is available for oral administration in the form of tablets and oral drops.

The dosage of the drug must be established by the doctor on an individual basis, depending on the type and severity of the disease to be treated and according to the patient's response to therapy.

In any case, the treatment must be as short as possible.

The doses of drug usually given are given below.

Anxiety disorders

The usual starting dose of alprazolam is 0.25-0.50 mg of drug three times a day.

The dose can be increased up to a maximum of 4 mg of alprazolam per day.

The duration of treatment should not exceed 8-12 weeks, including the period of gradual interruption of therapy. In any case, the doctor may decide to extend the treatment beyond the maximum period.

In elderly patients, in patients with severe liver disease and in debilitated patients, the dose of alprazolam usually administered is 0.25 mg of drug two or three times a day.

Panic attacks, with or without agoraphobia

The starting dose of alprazolam usually administered is 0.5-1 mg of drug, to be taken in the evening before bedtime, for one or two days. Thereafter, the dose should be adjusted based on the response to therapy by each patient.

Pregnancy and breastfeeding

Alprazolam should not be administered during the first trimester of pregnancy due to the risk of developing birth defects in the fetus.

Since alprazolam is excreted in breast milk, the drug should not be taken by breast-feeding mothers.

Contraindications

The use of alprazolam is contraindicated in the following cases:

  • Known hypersensitivity to alprazolam or other benzodiazepines;
  • In patients with myasthenia gravis (a neuromuscular disease);
  • In patients suffering from severe respiratory failure;
  • In patients with sleep apnea syndrome;
  • In patients with severe hepatic impairment;
  • In patients with acute angle-closure glaucoma;
  • In children and adolescents under 18 years of age;
  • During the first trimester of pregnancy;
  • During breastfeeding.