Alprazolam

Alprazolam is a drug which is a benzodiazepine derivative. It is classified as short-acting, and is used to treat anxiety disorders and insomnia.

Pharmacology
Alprazolam is a triazolobenzodiazepine, that is, a benzodiazepine with a triazolo-ring attached to its structure. Alprazolam binds to the GABAA subtype of the GABA receptor, increasing inhibitory effects of GABA within the central nervous system. The binding site for benzodiazepines is distinct from the binding site for GABA on the GABA receptor.

Unlike other benzodiazepines, alprazolam may also have some antidepressant activity, although clinical evidence of this is lacking.

Pharmacokinetics
The mechanism of action is not fully understood; However, Alprazolam is readily absorbed from the gastrointestinal tract. The peak plasma concentration is achieved in 1-2 hours. Most of the drug is bound to plasma protein, mainly albumin. Alprazolam is hydroxylated in the liver to &alpha;-hydroxyalprazolam, which is also pharmacologically active. This and other metabolites are later excreted in urine as glucuronides. Some of the drug is also excreted in unchanged form.

Indications
The main medical uses for alprazolam include:


 * Treatment of panic disorder, with or without agoraphobia. Alprazolam is very effective in preventing panic attacks. However, despite its efficacy, many psychiatrists are reluctant to use alprazolam for this condition because of the possibility of dependence and interdose anxiety due to its short-acting nature. An extended-release formulation of alprazolam known as Xanax XR® was introduced in 2001 and is often preferred.


 * Treatment of panic attacks. Alprazolam is taken as needed (PRN); 4 to 6 doses per month are the acceptable limit. If dependence seems to develop and/or the limit is exceeded, therapy may be reconsidered and/or discontinued.


 * Long-term treatment of severe generalized anxiety disorders. Alprazolam may be used for long-term treatment of anxiety if other therapies either do not work or are contraindicated. Duration of therapy in this case is often four months or longer. The decision to use alprazolam for this purpose must be carefully made by a specialized psychiatrist, taking into account the individual's suffering, quality of life, loss of social performance and risk of dependence.


 * Adjunctive treatment of depression. Alprazolam is sometimes used together with SSRIs such as paroxetine, sertraline, or fluoxetine to alleviate initial SSRI-induced anxiety while waiting for the antidepressant to begin working. However, clinical experience has shown that SSRIs may actually provoke panic attacks in otherwise healthy individuals, and cause sexual dysfunction. In these cases, a tricyclic antidepressant may be used instead. Buspirone may also be useful in conjunction with alprazolam in cases of generalized anxiety disorder.


 * Other uses. Alprazolam may be used by specialists to treat severe cases of Borderline Personality Disorder. Some studies have shown positive results.

Availability
Alprazolam is generally sold in generic form in the United States. It is also sold under many other brand names, depending on the country:
 * Xanax&reg; - United States, Australia, United Kingdom, Turkey, Portugal, Ireland, Greece
 * Xanax XR&reg; - (an extended release formulation) United States
 * Niravam&reg; - (formulary that dissolves on the tongue) United States
 * Apo-Alpraz&reg; - Canada (also made by other companies under different names)
 * Xanor&reg; - Finland, Philippines, South Africa, Sweden, Norway
 * Kalma&reg; - Australia, New Zealand
 * Ralozam&reg; - Australia, New Zealand
 * Zamhexal&reg; - Australia
 * Alplax&reg; - Argentina
 * Alviz&reg; - Indonesia
 * Alzolam&reg; - India, Malaysia
 * Alprax&reg; - India
 * Tranax&reg; - India
 * Restyl&reg; - Bahrain, Cyprus, Egypt, Iran, Iraq, Jordan, Kuwait, Lebanon, Libya, Oman, Qatar, Republic of Yemen, Saudi Arabia, Syria, United Arab Emirates
 * Tranquinal&reg; - Ecuador, Peru
 * Trankimazin&reg; - Spain
 * Tafil&reg; - Costa Rica, Denmark, El Salvador, Germany, Guatemala, Honduras, Mexico, Nicaragua, Panama, Venezuela
 * Tafil AP&reg; - (an extended release formulation) Mexico
 * Constan&reg; - Japan
 * Solanax&reg; - Japan
 * Zolarem&reg; - Bahrain, Benin, Burkina-Faso, Cyprus, Egypt, Ethiopia, Gambia, Ghana, Guinea, Iran, Iraq, Israel, Ivory Coast, Jordan, Kenya, Kuwait, Lebanon, Liberia, Libya, Malawi, Mali, Mauritania, Mauritius, Morocco, Niger, Nigeria, Oman, Qatar, Republic of Yemen, Saudi Arabia, Senegal, Seychelles, Sierra-Leone, South Africa, Sudan, Syria, Tanzania, Tunia, Uganda, United Arab Emirates, Zambia, Zimbabwe
 * Zoldac&reg; - Benin, Burkina-Faso, Ethiopia, Gambia, Ghana, Guinea, India, Ivory Coast, Kenya, Liberia, Malawi, Mali, Mauritania, Mauritius, Morocco, Niger, Nigeria, Senegal, Seychelles, Sierra-Leone, South Africa, Sudan, Tanzania, Tunia, Uganda, Zambia, Zimbabwe
 * Calmax&reg; - Ireland

Side Effects
Common side effects of alprazolam can include:
 * Somnolence (drowsiness)
 * Impaired motor functions
 * Dizziness
 * Clumsiness

Less common side effects can include:
 * Fatigue
 * Headache

Rare side effects can include:
 * Sleep apnea
 * Hypoventilation (Respiratory depression)
 * Blurred vision
 * Difficulty in depth perception
 * Slurred speech or dysarthria
 * Changes in personality
 * Confusion
 * Disorientation
 * Amnesia (memory impairment)
 * Vivid dreams and/or nightmares
 * Jaundice
 * Tachycardia
 * Bradycardia
 * Changes in plasma cortisol and ACTH levels
 * Blood dyscrasias
 * Decreased salivation
 * Increased salivation
 * Diarrhea
 * Constipation
 * Nausea
 * Elevated hepatic (liver) enzymes
 * Incontinence

Rare paradoxical side effects can include:
 * Nervousness
 * Anxiety
 * Agitation
 * Rage
 * Insomnia
 * Muscle spasms and rigidity

Long-term treatment with alprazolam may lead to physical and/or psychological dependence. Users often develop a tolerance to the drug's sedative effects, although its anxiolytic efficacy remains intact.

There is now a general consensus among many psychiatrists that alprazolam (a so-called 'high-potency' benzodiazepine) poses a particularly high risk for misuse, abuse and dependence. Withdrawal after long-term treatment should be done slowly over a period of weeks (or even months) to avoid serious withdrawal symptoms such as agitation, rebound anxiety, muscle cramps and seizures. Some patients may benefit from a substitution with diazepam.

Contraindications
Use of alprazolam should be avoided in individuals with the following conditions:
 * Myasthenia gravis
 * Acute intoxication with alcohol, narcotics, or other psychoactive substances
 * Ataxia
 * Severe hypoventilation
 * Acute narrow-angle glaucoma
 * Severe liver deficiencies (e.g. hepatitis and cirrhosis)
 * Severe sleep apnea
 * Hypersensitivity or allergy to any drug in the benzodiazepine class

Patients at a High Risk for Abuse and Dependence
At a particularly high risk for misuse, abuse, and dependence are:
 * Patients with a history of alcohol or drug abuse and/or dependence
 * Emotionally unstable patients
 * Patients with severe personality disorders
 * Patients with chronic pain or other physical disorders

Patients from the aforementioned group should be monitored very closely during therapy for signs of abuse and development of dependence. Discontinue therapy if any of these signs are noted. Long-term therapy in these patients is not recommended.

Recreational use
Alprazolam, like all benzodiazepines, has the potential for abuse, especially in individuals prone to addiction. Although it is not manufactured illegally, it is often diverted to the black market. The state of relaxation, anxiolysis, disinhibition and euphoria induced by benzodiazepines is the main reason for their illicit use.

For recreational effects, alprazolam is generally administered orally. Nasal insufflation (often called "snorting") sometimes occurs, but due to the drug's chemical structure, it is not absorbed through the mucous membranes. Instead, the powdered tablets and mucous drip down the back of the throat into the stomach, where they are absorbed as they would have been if taken orally. Therefore, insufflation of the drug is no more potent than when taken orally, and it often severely irritates the nasal passages. Furthermore, nasal insufflation may be significantly less potent than other means of administrations on a dosage-per-time basis, because the mucous drip enters the stomach at a slower rate than traditional ingestion.

Alprazolam is sometimes used with other recreational drugs to relieve the panic or distress of dysphoric reactions to psychedelics such as LSD and also to promote sleep in the "come-down" period following use of recreational drugs with stimulant or insomniac properties (such as LSD, cocaine, amphetamines, and MDMA). It is also often used in conjuction with marijuana for an even more relaxing effect. Also, Alprazolam is often combined with the drug Methadone to produce a unique, Heroin-like "high".

Legal Status
In the United States, alprazolam is a prescription drug and is assigned to Schedule IV of the Controlled Substances Act by the Drug Enforcement Administration. Internationally, alprazolam is included under the United Nations Convention on Psychotropic Substances.