Alprazolam icon is a short-acting
anxiolyticAn anxiolytic is a drug used for the treatment of anxiety, and its related psychological and physical symptoms...
of the
benzodiazepineA benzodiazepine is a psychoactive drug whose core chemical structure is the fusion of a benzene ring and a diazepine ring...
classChemical classification systems attempt to classify as elements or compounds according to certain chemical functional or structural properties. Whereas the structural properties are largely intrinsic, functional properties and the derived classifications depend to a certain degree on the type of...
of psychoactive drugs. Alprazolam, like other benzodiazepines, binds to specific sites on the GABA
A gamma-amino-butyric acid receptor. Alprazolam is commonly used and FDA approved for the treatment of
panic disorderPanic disorder is an anxiety disorder characterized by recurring severe panic attacks. It may also include significant behavioral change lasting at least a month and of ongoing worry about the implications or concern about having other attacks. The latter are called anticipatory attacks...
, and
anxiety disorderAnxiety disorder is a blanket term covering several different forms of abnormal and pathological fear and anxiety. Conditions now considered anxiety disorders only came under the aegis of psychiatry at the end of the 19th century. Gelder, Mayou & Geddes explains that anxiety disorders are...
s, such as generalized anxiety disorder (GAD) or
social anxiety disorderSocial anxiety disorder , also known as social phobia, is an anxiety disorder characterized by intense fear in social situations causing considerable distress and impaired ability to function in at least some parts of daily life...
(SAD). Alprazolam is available for
oral administrationOral administration is a route of administration where a substance is taken through the mouth.-Terminology:Per os is an adverbial phrase meaning literally from Latin "by mouth" or "by way of the mouth." The expression is used in medicine to describe a treatment that is taken orally. The...
in
compressed tabletA tablet is a pharmaceutical dosage form. It comprises a mixture of active substances and excipients, usually in powder form, pressed or compacted from a powder into a solid dose...
(CT) and extended-release
capsule-Anatomy:* an eggshell* Articular capsules - every diarthrodial joint possesses a fibrous or ligamentous capsule, lined with synovial membrane, attached to the adjacent ends of the articulating bones* the sac that encloses the crystalline lens of the eye...
(XR) formulations. Alprazolam possesses
anxiolyticAn anxiolytic is a drug used for the treatment of anxiety, and its related psychological and physical symptoms...
,
sedativeA sedative or tranquilizer is a substance that induces sedation by reducing irritability or excitement....
,
hypnoticHypnotic drugs are a class of psychoactives whose primary function is to induce sleep and to be used in the treatment of insomnia and in surgical anesthesia...
, skeletal muscle relaxant,
anticonvulsantThe anticonvulsants are a diverse group of pharmaceuticals used in the treatment of epileptic seizures. Anticonvulsants are also increasingly being used in the treatment of bipolar disorder, since many seem to act as mood stabilizers, and in the treatment of neuropathic pain. The goal of an...
, and amnestic properties.
Alprazolam has a fast onset of action and symptomatic relief. 90% of peak benefits are achieved within the first hour of using either preparation for
panic disorderPanic disorder is an anxiety disorder characterized by recurring severe panic attacks. It may also include significant behavioral change lasting at least a month and of ongoing worry about the implications or concern about having other attacks. The latter are called anticipatory attacks...
, and full peak benefits are achieved in 1.5 and 1.6 hours respectively. Peak benefits achieved for generalized anxiety disorder (GAD) may take up to a week. Tolerance does not appear to develop to the
anxiolyticAn anxiolytic is a drug used for the treatment of anxiety, and its related psychological and physical symptoms...
effects but may develop to the
sedativeA sedative or tranquilizer is a substance that induces sedation by reducing irritability or excitement....
effects within a couple of days. Withdrawal symptoms or rebound symptoms may occur after ceasing treatment abruptly following a few weeks or longer of steady dosing, and may necessitate a gradual dose reduction.
Alprazolam is the most prescribed, and the most misused
benzodiazepineA benzodiazepine is a psychoactive drug whose core chemical structure is the fusion of a benzene ring and a diazepine ring...
on the U.S. retail market. The potential for abuse is low and is similar to that of other benzodiazepine drugs. Compared to the large number of prescriptions, relatively few individuals increase their dose on their own initiative or engage in drug-seeking behavior. Alprazolam is classified as a schedule C IV controlled substance by the U.S. Drug Enforcement Agency (DEA).
Medical uses
Alprazolam is primarily used to treat
anxiety disorderAnxiety disorder is a blanket term covering several different forms of abnormal and pathological fear and anxiety. Conditions now considered anxiety disorders only came under the aegis of psychiatry at the end of the 19th century. Gelder, Mayou & Geddes explains that anxiety disorders are...
s,
panic disorderPanic disorder is an anxiety disorder characterized by recurring severe panic attacks. It may also include significant behavioral change lasting at least a month and of ongoing worry about the implications or concern about having other attacks. The latter are called anticipatory attacks...
s, and
nauseaNausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...
due to
chemotherapyChemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....
. The FDA label advises that the physician should periodically reassess the usefulness of the drug.
Panic disorder
In the US alprazolam is FDA-approved for the treatment of
panic disorderPanic disorder is an anxiety disorder characterized by recurring severe panic attacks. It may also include significant behavioral change lasting at least a month and of ongoing worry about the implications or concern about having other attacks. The latter are called anticipatory attacks...
with or without
agoraphobiaAgoraphobia is an anxiety disorder defined as a morbid fear of having a panic attack or panic-like symptoms in a situation from which it is perceived to be difficult to escape. These situations can include, but are not limited to, wide-open spaces, crowds, or uncontrolled social conditions...
. Alprazolam is effective in the relief of moderate to severe
anxietyAnxiety is a psychological and physiological state characterized by somatic, emotional, cognitive, and behavioral components. The root meaning of the word anxiety is 'to vex or trouble'; in either presence or absence of psychological stress, anxiety can create feelings of fear, worry, uneasiness,...
and panic attacks. Systematic clinical studies of effectiveness in treating panic disorder have been limited to 4 to 10 weeks. However, patients with panic disorder have been treated on an open basis for up to 8 months without apparent loss of benefit.
Alprazolam is recommended by the World Federation of Societies of Biological Psychiatry (WFSBP) for treatment resistant cases of panic disorder where there is no history of tolerance or dependence, as of 2002.
Anxiety disorders
In the US alprazolam is FDA-approved for the management of anxiety disorders (a condition corresponding most closely to the APA
Diagnostic and Statistical Manual DSM-III-R diagnosis of generalized anxiety disorder) or the short-term relief of symptoms of anxiety. Anxiety associated with depression is responsive to alprazolam. Demonstrations of the effectiveness by systematic clinical study are limited to 4 months duration for anxiety disorder.
In the UK, alprazolam is recommended for the short-term treatment (2–4 weeks) of severe acute anxiety.
Long term users of alprazolam may develop
depressionMajor depressive disorder is a mental disorder characterized by an all-encompassing low mood accompanied by low self-esteem, and by loss of interest or pleasure in normally enjoyable activities...
.
Nausea due to chemotherapy
Alprazolam may be used in combination with other medications for
chemotherapy-induced nausea and vomitingChemotherapy-induced nausea and vomiting is a common side-effect of many cancer treatments. Nausea and vomiting are two of the most feared cancer treatment-related side effects for cancer patients and their families. In 1983, Coates et al. found that patients receiving chemotherapy ranked nausea...
.
Pregnancy and lactation
Benzodiazepines cross the placenta, enter into the fetus and are also excreted with breast milk. The use of benzodiazepines during
pregnancyPregnancy refers to the fertilization and development of one or more offspring, known as a fetus or embryo, in a woman's uterus. In a pregnancy, there can be multiple gestations, as in the case of twins or triplets...
or
lactationLactation describes the secretion of milk from the mammary glands and the period of time that a mother lactates to feed her young. The process occurs in all female mammals, however it predates mammals. In humans the process of feeding milk is called breastfeeding or nursing...
has potential risks. The use of alprazolam in pregnancy is believed to be associated with congenital abnormalities.
DiazepamDiazepam , first marketed as Valium by Hoffmann-La Roche is a benzodiazepine drug. Diazepam is also marketed in Australia as Antenex. It is commonly used for treating anxiety, insomnia, seizures including status epilepticus, muscle spasms , restless legs syndrome, alcohol withdrawal,...
and
chlordiazepoxideChlordiazepoxide, is a sedative/hypnotic drug and benzodiazepine. It is marketed under the trade names Angirex, Klopoxid, Librax , Libritabs, Librium, Mesural, Multum, Novapam, Risolid, Silibrin, Sonimen and Tropium.Chlordiazepoxide was the first benzodiazepine to be synthesised and...
have a better safety profile in pregnancy than alprazolam.
Women who are pregnant or are planning on becoming pregnant should avoid starting alprazolam. Use in the last trimester may cause fetal drug dependence and withdrawal symptoms in the post-natal period as well as neonatal flaccidity and respiratory problems. However, in long-term users of benzodiazepines abrupt discontinuation due to concerns of teratogenesis has a high risk of causing extreme withdrawal symptoms and a severe
rebound effectThe rebound effect, or rebound phenomenon, is the tendency of some medications, when discontinued suddenly, to cause a return of the symptoms it relieved, and that, to a degree stronger than they were before treatment first began...
of the underlying mental health disorder. Spontaneous abortions may also result from abrupt withdrawal of psychotropic medications including benzodiazepines.
Benzodiazepines, including alprazolam, are known to be excreted in human milk. Chronic administration of diazepam to nursing mothers has been reported to cause their infants to become lethargic and to lose weight.
Contraindications
Benzodiazepines require special precaution if used in children and in alcohol- or drug-dependent individuals. Particular care should be taken in pregnant or elderly patients, patients with substance abuse history, particularly alcohol dependence and patients with comorbid psychiatric disorders. Use of alprazolam should be avoided or carefully monitored by medical professionals in individuals with the following conditions:
myasthenia gravisMyasthenia gravis is an autoimmune neuromuscular disease leading to fluctuating muscle weakness and fatiguability...
, acute narrow-angle
glaucomaGlaucoma is an eye disorder in which the optic nerve suffers damage, permanently damaging vision in the affected eye and progressing to complete blindness if untreated. It is often, but not always, associated with increased pressure of the fluid in the eye...
, severe liver deficiencies (e.g.,
cirrhosisCirrhosis is a consequence of chronic liver disease characterized by replacement of liver tissue by fibrosis, scar tissue and regenerative nodules , leading to loss of liver function...
), severe
sleep apneaSleep apnea is a sleep disorder characterized by abnormal pauses in breathing or instances of abnormally low breathing, during sleep. Each pause in breathing, called an apnea, can last from a few seconds to minutes, and may occur 5 to 30 times or more an hour. Similarly, each abnormally low...
, pre-existing respiratory depression, marked neuromuscular respiratory weakness including unstable
myasthenia gravisMyasthenia gravis is an autoimmune neuromuscular disease leading to fluctuating muscle weakness and fatiguability...
, acute pulmonary insufficiency, chronic
psychosisPsychosis means abnormal condition of the mind, and is a generic psychiatric term for a mental state often described as involving a "loss of contact with reality"...
, hypersensitivity or
allergyAn Allergy is a hypersensitivity disorder of the immune system. Allergic reactions occur when a person's immune system reacts to normally harmless substances in the environment. A substance that causes a reaction is called an allergen. These reactions are acquired, predictable, and rapid...
to alprazolam or other drugs in the
benzodiazepineA benzodiazepine is a psychoactive drug whose core chemical structure is the fusion of a benzene ring and a diazepine ring...
class,
borderline personality disorderBorderline personality disorder is a personality disorder described as a prolonged disturbance of personality function in a person , characterized by depth and variability of moods.The disorder typically involves unusual levels of instability in mood; black and white thinking, or splitting; the...
(may induce suicidality and
dyscontrolEpisodic dyscontrol syndrome , is a pattern of abnormal, episodic, and frequently violent and uncontrollable social behavior in the absence of significant provocation; it can result from limbic system diseases, disorders of the temporal lobe, or abuse of alcohol or other psychoactive substances.EDS...
).
Like all
central nervous systemThe central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
depressants, including
alcoholIn chemistry, an alcohol is an organic compound in which the hydroxy functional group is bound to a carbon atom. In particular, this carbon center should be saturated, having single bonds to three other atoms....
, alprazolam in larger-than-normal doses can cause significant deterioration in
alertnessAlertness is the state of paying close and continuous attention, being watchful and prompt to meet danger or emergency, or being quick to perceive and act. It is related to psychology as well as to physiology...
, combined with increased feelings of drowsiness, especially in those unaccustomed to the drug's effects. People driving or conducting activities that require vigilance should exercise caution in using alprazolam or any other depressant.
Elderly individuals should be cautious in the use of alprazolam due to the possibility of increased susceptibility to side-effects, especially loss of coordination and drowsiness.
Adverse effects
Although the side-effect profile of alprazolam is, in general, benign, side-effects may occur in some patients and are more likely the higher the dosage taken. Some side-effects may disappear with continued treatment. If signs of an allergic reaction occur - such as hives; difficulty breathing;
swellingIn medical parlance, swelling is the transient enlargement or protuberance in the body and may include tumors. According to cause, it may be congenital, traumatic, inflammatory, neoplastic or miscellaneous....
of face, lips, tongue, or throat - medical attention should be sought immediately. Medical attention should also be sought immediately if signs of
jaundiceJaundice is a yellowish pigmentation of the skin, the conjunctival membranes over the sclerae , and other mucous membranes caused by hyperbilirubinemia . This hyperbilirubinemia subsequently causes increased levels of bilirubin in the extracellular fluid...
appear: yellowing of the skin or eyes. Other side-effects that may occur are as follows:
- Drowsiness
Somnolence is a state of near-sleep, a strong desire for sleep, or sleeping for unusually long periods . It has two distinct meanings, referring both to the usual state preceding falling asleep, and the chronic condition referring to being in that state independent of a circadian rhythm...
, dizzinessDizziness refers to an impairment in spatial perception and stability. The term is somewhat imprecise. It can be used to mean vertigo, presyncope, disequilibrium, or a non-specific feeling such as giddiness or foolishness....
, lightheadednessLight-headedness is a common and often unpleasant sensation of dizziness and/or feeling that one may be about to faint, which may be transient, recurrent, or occasionally chronic. In some cases, the individual may feel as though his or her head is weightless. The individual may also feel as...
, fatigue, unsteadiness and impaired coordinationthumb|right|Motor coordination is shown in this animated sequence by [[Eadweard Muybridge]] of himself throwing a diskMotor coordination is the combination of body movements created with the kinematic and kinetic parameters that result in intended actions. Such movements usually smoothly and...
, vertigoVertigo is a type of dizziness, where there is a feeling of motion when one is stationary. The symptoms are due to a dysfunction of the vestibular system in the inner ear...
- Skin rash, respiratory depression, constipation
Constipation refers to bowel movements that are infrequent or hard to pass. Constipation is a common cause of painful defecation...
- Disinhibition
Disinhibition is a term in psychology used to describe a lack of restraint manifested in several ways, including disregard for social conventions, impulsivity, and poor risk assessment. Disinhibition affects motor, instinctual, emotional, cognitive and perceptual aspects with signs and symptoms...
- Suicidal ideation
Suicidal ideation is a common medical term for thoughts about suicide, which may be as detailed as a formulated plan, without the suicidal act itself. Although most people who undergo suicidal ideation do not commit suicide, some go on to make suicide attempts...
(rare)
- Urinary retention
Urinary retention, also known as ischuria, is a lack of ability to urinate. It is a common complication of benign prostatic hyperplasia , although it can also be caused by nerve dysfunction, constipation, infection, or medications...
(infrequent)
- Hallucination
A hallucination, in the broadest sense of the word, is a perception in the absence of a stimulus. In a stricter sense, hallucinations are defined as perceptions in a conscious and awake state in the absence of external stimuli which have qualities of real perception, in that they are vivid,...
s (rare)
- Ataxia
Ataxia is a neurological sign and symptom that consists of gross lack of coordination of muscle movements. Ataxia is a non-specific clinical manifestation implying dysfunction of the parts of the nervous system that coordinate movement, such as the cerebellum...
, slurred speech
- Anterograde amnesia
Anterograde amnesia is a loss of the ability to create new memories after the event that caused the amnesia, leading to a partial or complete inability to recall the recent past, while long-term memories from before the event remain intact. This is in contrast to retrograde amnesia, where memories...
and concentrationAttention is the cognitive process of paying attention to one aspect of the environment while ignoring others. Attention is one of the most intensely studied topics within psychology and cognitive neuroscience....
problems
- Change in libido
Libido refers to a person's sex drive or desire for sexual activity. The desire for sex is an aspect of a person's sexuality, but varies enormously from one person to another, and it also varies depending on circumstances at a particular time. A person who has extremely frequent or a suddenly...
- Dry mouth
Xerostomia is the medical term for the subjective complaint of dry mouth due to a lack of saliva. Xerostomia is sometimes colloquially called pasties, cottonmouth, drooth, or doughmouth. Several diseases, treatments, and medications can cause xerostomia. It can also be exacerbated by smoking or...
(infrequent)
- Jaundice
Jaundice is a yellowish pigmentation of the skin, the conjunctival membranes over the sclerae , and other mucous membranes caused by hyperbilirubinemia . This hyperbilirubinemia subsequently causes increased levels of bilirubin in the extracellular fluid...
(very rare)
Paradoxical reactions
Although unusual, if the following paradoxical reactions occur, the prescribing physician or other healthcare professional should be alerted and the medication gradually discontinued:
- Twitches and tremor
A tremor is an involuntary, somewhat rhythmic, muscle contraction and relaxation involving to-and-fro movements of one or more body parts. It is the most common of all involuntary movements and can affect the hands, arms, eyes, face, head, vocal folds, trunk, and legs. Most tremors occur in the...
- Aggression
In psychology, as well as other social and behavioral sciences, aggression refers to behavior between members of the same species that is intended to cause humiliation, pain, or harm. Ferguson and Beaver defined aggressive behavior as "Behavior which is intended to increase the social dominance of...
- Rage
Rage is a feeling of intense anger. It is associated with the Fight-or-flight response and oftentimes activated in response to an external cue, such as the murder of a loved one. The phrase, 'thrown into a fit of rage,' expresses the immediate nature of rage that occurs before deliberation. If left...
, hostility
- Mania
Mania, the presence of which is a criterion for certain psychiatric diagnoses, is a state of abnormally elevated or irritable mood, arousal, and/ or energy levels. In a sense, it is the opposite of depression...
, agitationPsychomotor agitation is a series of unintentional and purposeless motions that stem from mental tension and anxiety of an individual. This includes pacing around a room, wringing one's hands, pulling off clothing and putting it back on and other similar actions...
, hyperactivity and restlessness
Food and drug interactions
Alprazolam is primarily metabolised via
CYP3A4Cytochrome P450 3A4 , a member of the cytochrome P450 mixed-function oxidase system, is one of the most important enzymes involved in the metabolism of xenobiotics in the body. CYP3A4 is involved in the oxidation of the largest range of substrates of all the CYPs. As a result, CYP3A4 is present in...
. Combining
CYP3A4Cytochrome P450 3A4 , a member of the cytochrome P450 mixed-function oxidase system, is one of the most important enzymes involved in the metabolism of xenobiotics in the body. CYP3A4 is involved in the oxidation of the largest range of substrates of all the CYPs. As a result, CYP3A4 is present in...
inhibitors with alprazolam can lead to profound sedating effects.
CimetidineCimetidine INN is a histamine H2-receptor antagonist that inhibits the production of acid in the stomach. It is largely used in the treatment of heartburn and peptic ulcers. It is marketed by GlaxoSmithKline under the trade name Tagamet...
,
erythromycinErythromycin is a macrolide antibiotic that has an antimicrobial spectrum similar to or slightly wider than that of penicillin, and is often used for people who have an allergy to penicillins. For respiratory tract infections, it has better coverage of atypical organisms, including mycoplasma and...
,
fluoxetineFluoxetine is an antidepressant of the selective serotonin reuptake inhibitor class. It is manufactured and marketed by Eli Lilly and Company...
,
fluvoxamineFluvoxamine is an antidepressant which functions as a selective serotonin reuptake inhibitor . Fluvoxamine was first approved by the U.S. Food and Drug Administration in 1993 for the treatment of obsessive compulsive disorder . Fluvoxamine CR is approved to treat social anxiety disorder...
,
itraconazoleItraconazole , invented in 1984, is a triazole antifungal agent that is prescribed to patients with fungal infections. The drug may be given orally or intravenously.-Medical uses:...
,
ketoconazoleKetoconazole is a synthetic antifungal drug used to prevent and treat fungal skin infections, especially in immunocompromised patients such as those with AIDS or those on chemotherapy. Ketoconazole is sold commercially as an anti-dandruff shampoo, topical cream, and oral tablet.Ketoconazole is...
,
nefazodoneNefazodone is an antidepressant marketed by Bristol-Myers Squibb. Its sale was discontinued in 2003 in some countries due to the rare incidence of hepatotoxicity , which could lead to the need for a liver transplant, or even death. The incidence of severe liver damage is approximately 1 in every...
, propoxyphene, and
ritonavirRitonavir, with trade name Norvir , is an antiretroviral drug from the protease inhibitor class used to treat HIV infection and AIDS....
all interact with alprazolam leading to a delayed clearance of alprazolam, which may result in excessive accumulation of alprazolam. This may result in excessive sedation and other adverse effects associated with excessive intake of alprazolam.
ImipramineImipramine , also known as melipramine, is an antidepressant medication, a tricyclic antidepressant of the dibenzazepine group...
and
desipramineDesipramine is a tricyclic antidepressant . It inhibits the reuptake of norepinephrine and to a lesser extent serotonin. It is used to treat depression, but not considered a first line treatment since the introduction of SSRI antidepressants...
have been reported to be increased an average of 31% and 20%, respectively, by the concomitant administration of alprazolam tablets in doses up to 4 mg/day. Combined oral contraceptive pills reduce the clearance of alprazolam, which may lead to increased plasma levels of alprazolam and accumulation.
AlcoholEthanol, also called ethyl alcohol, pure alcohol, grain alcohol, or drinking alcohol, is a volatile, flammable, colorless liquid. It is a psychoactive drug and one of the oldest recreational drugs. Best known as the type of alcohol found in alcoholic beverages, it is also used in thermometers, as a...
is one of the most important and common interactions. Alcohol and benzodiazepines such as alprazolam taken in combination have a synergistic effect on one another, which can cause severe sedation, behavioral changes, and intoxication. The more alcohol and alprazolam taken the worse the interaction. Combination of alprazolam with the herb
kavaKava or kava-kava is a crop of the western Pacific....
can result in the development of a semi-
comaIn medicine, a coma is a state of unconsciousness, lasting more than 6 hours in which a person cannot be awakened, fails to respond normally to painful stimuli, light or sound, lacks a normal sleep-wake cycle and does not initiate voluntary actions. A person in a state of coma is described as...
tose state.
HypericumHypericum is a genus of about 400 species of flowering plants in the family Hypericaceae ....
conversely can lower the plasma levels of alprazolam and reduce its therapeutic effect.
Overdose
Overdoses of alprazolam can be mild to severe depending on how much of the drug is taken and any other drugs that have been taken.
Alprazolam overdoses cause excess
central nervous systemThe central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
(CNS) depression and may include one or more of the following symptoms:
- Somnolence
Somnolence is a state of near-sleep, a strong desire for sleep, or sleeping for unusually long periods . It has two distinct meanings, referring both to the usual state preceding falling asleep, and the chronic condition referring to being in that state independent of a circadian rhythm...
(sleepy state)
- Hypotension
In physiology and medicine, hypotension is abnormally low blood pressure, especially in the arteries of the systemic circulation. It is best understood as a physiologic state, rather than a disease. It is often associated with shock, though not necessarily indicative of it. Hypotension is the...
(low blood pressure)
- Hypoventilation
In medicine, hypoventilation occurs when ventilation is inadequate to perform needed gas exchange...
(shallow breathing)
- Impaired motor functions
- Dizziness
Dizziness refers to an impairment in spatial perception and stability. The term is somewhat imprecise. It can be used to mean vertigo, presyncope, disequilibrium, or a non-specific feeling such as giddiness or foolishness....
- Impaired balance
- Muscle weakness
Muscle weakness or myasthenia is a lack of muscle strength. The causes are many and can be divided into conditions that have true or perceived muscle weakness...
- Impaired or absent reflexes
- Fainting
- Coma
In medicine, a coma is a state of unconsciousness, lasting more than 6 hours in which a person cannot be awakened, fails to respond normally to painful stimuli, light or sound, lacks a normal sleep-wake cycle and does not initiate voluntary actions. A person in a state of coma is described as...
- Death
Death is the permanent termination of the biological functions that sustain a living organism. Phenomena which commonly bring about death include old age, predation, malnutrition, disease, and accidents or trauma resulting in terminal injury....
(very rare)
In a study of deaths in Palm Beach County where the drug alprazolam was detected, approx. 50% of cases were attributed to poly-drug use (the combined toxicity of two or more drugs). The majority of these cases included either
cocaineCocaine is a crystalline tropane alkaloid that is obtained from the leaves of the coca plant. The name comes from "coca" in addition to the alkaloid suffix -ine, forming cocaine. It is a stimulant of the central nervous system, an appetite suppressant, and a topical anesthetic...
or
methadoneMethadone is a synthetic opioid, used medically as an analgesic and a maintenance anti-addictive for use in patients with opioid dependency. It was developed in Germany in 1937...
. Alprazolam alone caused only 1% of the deaths. These results indicate alprazolam has a very low incidence of causing death when taken alone.
Dependence and withdrawal
Alprazolam, like other benzodiazepines, binds to specific sites on the GABA
A gamma-amino-butyric acid receptor. When bound to these sites, which are referred to as benzodiazepine receptors, it modulates the effect of GABA A receptors and, thus, GABAergic neurons. Long-term use causes adaptive changes in the benzodiazepine receptors, making them less sensitive to stimulation and less powerful in their effects.
WithdrawalWithdrawal can refer to any sort of separation, but is most commonly used to describe the group of symptoms that occurs upon the abrupt discontinuation/separation or a decrease in dosage of the intake of medications, recreational drugs, and alcohol...
and rebound symptoms occur commonly and necessitate a gradual reduction in dosage to minimize withdrawal effects when discontinuing.
Not all withdrawal effects are evidence of true dependence or withdrawal. Recurrence of symptoms such as anxiety may simply indicate that the drug was having its expected anti-anxiety effect and that, in the absence of the drug, the symptom has returned to pretreatment levels. If the symptoms are more severe or frequent, the patient may be experiencing a
rebound effectThe rebound effect, or rebound phenomenon, is the tendency of some medications, when discontinued suddenly, to cause a return of the symptoms it relieved, and that, to a degree stronger than they were before treatment first began...
due to the removal of the drug. Either of these can occur without the patient's actually being drug-dependent.
Alprazolam and other benzodiazepines may also cause the development of
physical dependencePhysical dependence refers to a state resulting from chronic use of a drug that has produced tolerance and where negative physical symptoms of withdrawal result from abrupt discontinuation or dosage reduction...
, tolerance, and benzodiazepine withdrawal symptoms during rapid dose reduction or cessation of therapy after long-term treatment. There is a higher chance of withdrawal reactions if the drug is administered in a higher dosage than recommended, or if a patient stops taking the medication altogether without slowly allowing the body to adjust to a lower-dosage regimen.
In 1992, Romach and colleagues reported that dose escalation is not a characteristic of long-term alprazolam users, and that the majority of long-term alprazolam users change their initial pattern of regular use to one of symptom control only when required.
Some common symptoms of alprazolam discontinuation include malaise, weakness, insomnia, tachycardia, lightheadedness, and dizziness.
Patients taking a dosing regimen larger than 4 mg per day have an increased potential for dependence. This medication may cause withdrawal symptoms upon abrupt withdrawal or rapid tapering, which in some cases have been known to cause seizures. The discontinuation of this medication may also cause a reaction called
rebound anxiety. Grand mal seizures have occurred after abrupt withdrawal after only short-term use. Therefore, even short-term users of alprazolam should taper off of their medication slowly to avoid serious withdrawal reactions including seizures.
DeliriumDelirium or acute confusional state is a common and severe neuropsychiatric syndrome with core features of acute onset and fluctuating course, attentional deficits and generalized severe disorganization of behavior...
and seizures have been anecdotally reported in the medical literature from abrupt alprazolam discontinuation.
In a 1983 study of patients who had taken long-acting benzodiazepines, e.g.,
clorazepateClorazepate , also known as clorazepate dipotassium, is a drug that is a benzodiazepine derivative. It possesses anxiolytic, anticonvulsant, sedative, hypnotic and skeletal muscle relaxant properties. Clorazepate is a prodrug for desmethyldiazepam, which is rapidly produced as an active metabolite...
, for extended periods, the medications were stopped abruptly. Only 5% of patients who had been taking the drug for less than 8 months demonstrated withdrawal symptoms, but 43% of those who had been taking them for more than 8 months did. With alprazolam - a short-acting benzodiazepine - taken for 8 weeks, 35% of patients experienced significant rebound anxiety. To some degree, these older benzodiazepines are self-tapering.
The benzodiazepines
diazepamDiazepam , first marketed as Valium by Hoffmann-La Roche is a benzodiazepine drug. Diazepam is also marketed in Australia as Antenex. It is commonly used for treating anxiety, insomnia, seizures including status epilepticus, muscle spasms , restless legs syndrome, alcohol withdrawal,...
(Valium) and
oxazepamOxazepam , is a drug which is a short to intermediate acting 3-hydroxy benzodiazepine derivative...
(Serepax) have been found to produce fewer withdrawal reactions than alprazolam (Xanax),
temazepamTemazepam is an intermediate-acting 3-hydroxy benzodiazepine. It is mostly prescribed for the short-term treatment of sleeplessness in patients who have difficulty maintaining sleep...
(Restoril/Normison), or
lorazepamLorazepam is a high-potency short-to-intermediate-acting 3-hydroxy benzodiazepine drug that has all five intrinsic benzodiazepine effects: anxiolytic, amnesic, sedative/hypnotic, anticonvulsant, antiemetic and muscle relaxant...
(Temesta/Ativan). Factors that determine the risk of
psychological dependenceThe section about substance dependence in the Diagnostic and Statistical Manual of Mental Disorders does not use the word addiction at all. It explains:...
or
physical dependencePhysical dependence refers to a state resulting from chronic use of a drug that has produced tolerance and where negative physical symptoms of withdrawal result from abrupt discontinuation or dosage reduction...
and the severity of the benzodiazepine withdrawal symptoms experienced during dose reduction of alprazolam include: dosage used, length of use, frequency of dosing, personality characteristics of the individual, previous use of cross-dependent/cross-tolerant drugs (alcohol or other sedative-hypnotic drugs), current use of cross-dependent/-tolerant drugs, use of other short-acting, high-potency benzodiazepines, and method of discontinuation.
Detection in body fluids
Alprazolam may be quantitated in blood or plasma to confirm a diagnosis of poisoning in hospitalized patients, provide evidence in an impaired driving arrest or to assist in a medicolegal death investigation. Blood or plasma alprazolam concentrations are usually in a range of 10-100 μg/L in persons receiving the drug therapeutically, 100-300 μg/L in those arrested for impaired driving and 300-2000 μg/L in victims of acute overdosage. Most commercial immunoassays for the benzodiazepine class of drugs will cross-react with alprazolam, but confirmation and quantitation is usually performed using chromatographic techniques.
Pharmacology
Alprazolam is classed as a high-potency benzodiazepine and is a triazolobenzodiazepine more specifically–a benzodiazepine with a
triazole ring1,2,3-Triazole is one of a pair of isomeric chemical compounds with molecular formula C2H3N3, called triazoles, which have a five-membered ring of two carbon atoms and three nitrogen atoms...
attached to its structure. Benzodiazepines produce a variety of therapeutic and adverse effects by binding to the benzodiazepine receptor site on the
GABAAThe GABAA receptor is an ionotropic receptor and ligand-gated ion channel. Its endogenous ligand is γ-aminobutyric acid , the major inhibitory neurotransmitter in the central nervous system. Upon activation, the GABAA receptor selectively conducts Cl- through its pore, resulting in...
receptor and modulating the function of the
GABA receptorThe GABA receptors are a class of receptors that respond to the neurotransmitter gamma-aminobutyric acid , the chief inhibitory neurotransmitter in the vertebrate central nervous system...
, the most prolific inhibitory receptor within the brain. The GABA chemical and receptor system mediates inhibitory or calming effects of alprazolam on the nervous system. The GABA
A receptor is made up of 5 subunits out of a possible 19, and GABA
A receptors made up of different combinations of subunits have different properties, different locations within the brain, and, importantly, different activities with regard to benzodiazepines. Benzodiazepines and in particular alprazolam causes a marked suppression of the hypothalamicpituitary-adrenal axis. The therapeutic properties of alprazolam are similar to other benzodiazepines and include
anxiolyticAn anxiolytic is a drug used for the treatment of anxiety, and its related psychological and physical symptoms...
,
anticonvulsantThe anticonvulsants are a diverse group of pharmaceuticals used in the treatment of epileptic seizures. Anticonvulsants are also increasingly being used in the treatment of bipolar disorder, since many seem to act as mood stabilizers, and in the treatment of neuropathic pain. The goal of an...
,
muscle relaxantA muscle relaxant is a drug which affects skeletal muscle function and decreases the muscle tone. It may be used to alleviate symptoms such as muscle spasms, pain, and hyperreflexia. The term "muscle relaxant" is used to refer to two major therapeutic groups: neuromuscular blockers and spasmolytics...
,
hypnoticHypnotic drugs are a class of psychoactives whose primary function is to induce sleep and to be used in the treatment of insomnia and in surgical anesthesia...
and amnesic.
Pharmacokinetics
Alprazolam is readily absorbed from the gastrointestinal tract with a bioavailability of 80–100%. The peak
plasmaBlood plasma is the straw-colored liquid component of blood in which the blood cells in whole blood are normally suspended. It makes up about 55% of the total blood volume. It is the intravascular fluid part of extracellular fluid...
concentration is achieved in 1–2 hours. Most of the drug is bound to plasma protein, mainly
serum albuminSerum albumin, often referred to simply as albumin is a protein that in humans is encoded by the ALB gene.Serum albumin is the most abundant plasma protein in mammals. Albumin is essential for maintaining the osmotic pressure needed for proper distribution of body fluids between intravascular...
. Alprazolam is
hydroxylatedHydroxylation is a chemical process that introduces a hydroxyl group into an organic compound. In biochemistry, hydroxylation reactions are often facilitated by enzymes called hydroxylases. Hydroxylation is the first step in the oxidative degradation of organic compounds in air...
in the liver to α-hydroxyalprazolam, which is also pharmacologically active but much less so than the parent compound. This and other
metaboliteMetabolites are the intermediates and products of metabolism. The term metabolite is usually restricted to small molecules. A primary metabolite is directly involved in normal growth, development, and reproduction. Alcohol is an example of a primary metabolite produced in large-scale by industrial...
s are later excreted in urine as
glucuronideA glucuronide, also known as glucuronoside, is any substance produced by linking glucuronic acid to another substance via a glycosidic bond...
s. Some of the drug is also excreted in unchanged form. The elderly clear alprazolam more slowly than younger adults.
Chemistry
Alprazolam is a chemical analog of
triazolamTriazolam is a benzodiazepine drug. It possesses pharmacological properties similar to that of other benzodiazepines, but it is generally only used as a sedative to treat severe insomnia...
that differs by the absence of a chlorine atom in the
o-position of the 6-phenyl ring. The same scheme that was used to make
triazolamTriazolam is a benzodiazepine drug. It possesses pharmacological properties similar to that of other benzodiazepines, but it is generally only used as a sedative to treat severe insomnia...
can be used to make alprazolam, with the exception that it begins with 2-amino-5-chlorobenzophenone. However, a non-standard way of making alprazolam has been suggested, which comes from 2,6-dichloro-4-phenylquinoline, the reaction of which with hydrazine gives 6-chloro-2-hydrazino-4-phenylquinoline. Boiling this with
triethyl orthoacetateTriethyl orthoacetate is the ethyl orthoester of acetic acid. It is also known as 1,1,1-triethoxyethane, and is an oily liquid with a colour that is anywhere from yellow to colorless. It is also known for its pungent odour....
in
xyleneXylene encompasses three isomers of dimethylbenzene. The isomers are distinguished by the designations ortho- , meta- , and para- , which specify to which carbon atoms the two methyl groups are attached...
leads to the heterocyclization into a
triazoleTriazole refers to either one of a pair of isomeric chemical compounds with molecular formula C2H3N3, having a five-membered ring of two carbon atoms and three nitrogen atoms.The two isomers are:*1,2,3-Triazole 100px*1,2,4-Triazole 100px...
derivative. The resulting product undergoes oxidative cleavage using
sodium periodateSodium periodate is the sodium salt of periodic acid. It can refer to two different chemical compounds, sodium metaperiodate , which has the formula NaIO4, and sodium orthoperiodate , which has the formula Na2H3IO6...
and ruthenium dioxide in an
acetoneAcetone is the organic compound with the formula 2CO, a colorless, mobile, flammable liquid, the simplest example of the ketones.Acetone is miscible with water and serves as an important solvent in its own right, typically as the solvent of choice for cleaning purposes in the laboratory...
–
waterWater is a chemical substance with the chemical formula H2O. A water molecule contains one oxygen and two hydrogen atoms connected by covalent bonds. Water is a liquid at ambient conditions, but it often co-exists on Earth with its solid state, ice, and gaseous state . Water also exists in a...
system to give 2-[4-(3′-methyl-1,2,4-triazolo)]-5-chlorobenzophenone. Oxymethylation of the last using
formaldehydeFormaldehyde is an organic compound with the formula CH2O. It is the simplest aldehyde, hence its systematic name methanal.Formaldehyde is a colorless gas with a characteristic pungent odor. It is an important precursor to many other chemical compounds, especially for polymers...
and subsequent substitution of the resulting hydroxyl group by
phosphorus tribromidePhosphorus tribromide is a colourless liquid with the formula PBr3. It fumes in air due to hydrolysis and has a penetrating odour. It is widely used in the laboratory for the conversion of alcohols to alkyl bromides.-Preparation:...
,gives 2-[4-(3′-methyl-5′-bromomethyl-1,2,4-triazolo)]-5-chlorobenzophenone. Substitution of the
bromineBromine ") is a chemical element with the symbol Br, an atomic number of 35, and an atomic mass of 79.904. It is in the halogen element group. The element was isolated independently by two chemists, Carl Jacob Löwig and Antoine Jerome Balard, in 1825–1826...
atom with an amino group using
ammoniaAmmonia is a compound of nitrogen and hydrogen with the formula . It is a colourless gas with a characteristic pungent odour. Ammonia contributes significantly to the nutritional needs of terrestrial organisms by serving as a precursor to food and fertilizers. Ammonia, either directly or...
and the spontaneous, intramolecular heterocyclization following that reaction gives alprazolam.
History
Alprazolam was first released by
UpjohnThe Upjohn Company was a pharmaceutical manufacturing firm founded in 1886 in Kalamazoo, Michigan by Dr. William E. Upjohn, an 1875 graduate of the University of Michigan medical school. The company was originally formed to make friable pills, which were specifically designed to be easily digested...
(now a part of
PfizerPfizer, Inc. is an American multinational pharmaceutical corporation. The company is based in New York City, New York with its research headquarters in Groton, Connecticut, United States...
). It is covered under , which was filed on October 29, 1969, granted on October 19, 1976, and expired in September 1993. Alprazolam was released in 1981. The first approved indication was panic disorder. Upjohn took this direction at the behest of a young
psychiatristA psychiatrist is a physician who specializes in the diagnosis and treatment of mental disorders. All psychiatrists are trained in diagnostic evaluation and in psychotherapy...
, David Sheehan. Sheehan's suggestion was to use the new distinction the
DSM-IIIThe Diagnostic and Statistical Manual of Mental Disorders is published by the American Psychiatric Association and provides a common language and standard criteria for the classification of mental disorders...
created in the classification of anxiety disorders between generalized anxiety disorder (GAD) and
panic disorderPanic disorder is an anxiety disorder characterized by recurring severe panic attacks. It may also include significant behavioral change lasting at least a month and of ongoing worry about the implications or concern about having other attacks. The latter are called anticipatory attacks...
in order to market alprazolam specifically for the latter. Panic disorder was, at that point, perceived to be rare and treatable only with
tricyclic antidepressantTricyclic antidepressants are heterocyclic chemical compounds used primarily as antidepressants. The TCAs were first discovered in the early 1950s and were subsequently introduced later in the decade; they are named after their chemical structure, which contains three rings of atoms...
s; benzodiazepines were thought to be ineffective.
However, from his clinical experience, Sheehan knew panic disorder to be both widespread among the populace and responsive to benzodiazepines. He suggested to Upjohn that marketing alprazolam for panic disorder would both cover new diagnostic territory and emphasize the unique potency of this drug. Sheehan describes the first group of patients treated by alprazolam as so impressed by its action that the company knew outright that the drug was going to be a hit. A few of those patients actually pooled their money and purchased stock in Upjohn. Several months later, when alprazolam was approved by the United States Food and Drug Administration, they sold out and made a profit.
Soon after its introduction a number of case reports were published in the
medical literatureMedical literature refers to articles in journals and texts in books devoted to the field of medicine.Contemporary and historic views regarding diagnosis, prognosis and treatment of medical conditions have been documented for thousands of years. The Edwin Smith papyrus is the first known medical...
of severe withdrawal symptoms, including
psychosesPsychosis means abnormal condition of the mind, and is a generic psychiatric term for a mental state often described as involving a "loss of contact with reality"...
,
seizureAn epileptic seizure, occasionally referred to as a fit, is defined as a transient symptom of "abnormal excessive or synchronous neuronal activity in the brain". The outward effect can be as dramatic as a wild thrashing movement or as mild as a brief loss of awareness...
s and intense rebound anxiety, upon discontinuation of alprazolam. Several studies found that initial treatment of panic disorder with alprazolam was significantly superior but after 8 weeks of use alprazolam lost its effectiveness and was no more effective than placebo. It was found that behavioral therapy and the drug
imipramineImipramine , also known as melipramine, is an antidepressant medication, a tricyclic antidepressant of the dibenzazepine group...
however, proved superior to both placebo and alprazolam. It has been argued that placebo is superior than alprazolam after 8 weeks of use due to lack of rebound withdrawal effects and side effects. Controversy exists in that there are allegations that the drug manufacturer suppressed these negative findings regarding lack of sustained efficacy.
Recreational use
Most prescribed alprazolam users do not misuse their medication, and the long-term use of benzodiazepines doesn't generally collaborate with the need for dose escalation. However, based on US findings from the Treatment Episode Data Set (TEDS), an annual compilation of patient characteristics in substance abuse treatment facilities in the United States, admissions due to "primary tranquilizer" (including, but not limited to, benzodiazepine-type) drug use increased 79% from 1992 to 2002, suggesting that misuse of benzodiazepines may be on the rise.
Alprazolam is one of the most commonly prescribed and misused benzodiazepines in the United States. A large-scale nationwide U.S. government study conducted by SAMHSA found that, in the U.S., benzodiazepines are recreationally the most frequently used pharmaceuticals due to their widespread availability, accounting for 35% of all drug-related visits to hospital emergency and urgent care facilities. Men use benzodiazepines recreationally as commonly as women. The report found that alprazolam is the most common benzodiazepine for recreational use followed by
clonazepamClonazepamis a benzodiazepine drug having anxiolytic, anticonvulsant, muscle relaxant, and hypnotic properties. It is marketed by Roche under the trade name Klonopin in the United States and Rivotril in Australia, Brazil, Canada and Europe...
,
lorazepamLorazepam is a high-potency short-to-intermediate-acting 3-hydroxy benzodiazepine drug that has all five intrinsic benzodiazepine effects: anxiolytic, amnesic, sedative/hypnotic, anticonvulsant, antiemetic and muscle relaxant...
, and
diazepamDiazepam , first marketed as Valium by Hoffmann-La Roche is a benzodiazepine drug. Diazepam is also marketed in Australia as Antenex. It is commonly used for treating anxiety, insomnia, seizures including status epilepticus, muscle spasms , restless legs syndrome, alcohol withdrawal,...
.
At a particularly high risk for misuse and dependence are people with a history of
alcoholismAlcoholism is a broad term for problems with alcohol, and is generally used to mean compulsive and uncontrolled consumption of alcoholic beverages, usually to the detriment of the drinker's health, personal relationships, and social standing...
or drug abuse and/or dependence and people with
borderline personality disorderBorderline personality disorder is a personality disorder described as a prolonged disturbance of personality function in a person , characterized by depth and variability of moods.The disorder typically involves unusual levels of instability in mood; black and white thinking, or splitting; the...
.
Alprazolam, along with other benzodiazepines, is often used with other recreational drugs. These uses include aids to relieve the panic or distress of
dysphoricDysphoria is medically recognized as a mental and emotional condition in which a person experiences intense feelings of depression, discontent and indifference to the world around them.Mood disorders can induce dysphoria, often with a heightened risk of suicide, especially in...
("
bad tripBad trip is a disturbing experience sometimes associated with use of a psychedelic drug such as LSD, Salvinorin A, DXM, mescaline, psilocybin, DMT and sometimes even other drugs including cannabis, alcohol and MDMA....
") reactions to psychedelic drugs, such as
LSDLysergic acid diethylamide, abbreviated LSD or LSD-25, also known as lysergide and colloquially as acid, is a semisynthetic psychedelic drug of the ergoline family, well known for its psychological effects which can include altered thinking processes, closed and open eye visuals, synaesthesia, an...
, and is often used in the "
comedownComedown refers to the after effects of heavy recreational stimulant use, usually ecstasy, amphetamine, methylphenidate, cocaine, alcohol, and occasionally cannabis. It can be characterized by depression, apathy, dysphoria, anxiety, fatigue, intense hunger, paranoia and insomnia. These effects are...
" stages of
stimulantStimulants are psychoactive drugs which induce temporary improvements in either mental or physical function or both. Examples of these kinds of effects may include enhanced alertness, wakefulness, and locomotion, among others...
use, such as
amphetamineAmphetamine or amfetamine is a psychostimulant drug of the phenethylamine class which produces increased wakefulness and focus in association with decreased fatigue and appetite.Brand names of medications that contain, or metabolize into, amphetamine include Adderall, Dexedrine, Dextrostat,...
, in order to help relieve drug-induced
agitationPsychomotor agitation is a series of unintentional and purposeless motions that stem from mental tension and anxiety of an individual. This includes pacing around a room, wringing one's hands, pulling off clothing and putting it back on and other similar actions...
and
insomniaInsomnia is most often defined by an individual's report of sleeping difficulties. While the term is sometimes used in sleep literature to describe a disorder demonstrated by polysomnographic evidence of disturbed sleep, insomnia is often defined as a positive response to either of two questions:...
, allowing sleep. Alprazolam may also be used in conjunction with other
depressant drugsA depressant, or central depressant, is a drug or endogenous compound that depresses the function or activity of a specific part of the brain...
, such as
alcoholIn chemistry, an alcohol is an organic compound in which the hydroxy functional group is bound to a carbon atom. In particular, this carbon center should be saturated, having single bonds to three other atoms....
,
marijuanaCannabis, also known as marijuana among many other names, refers to any number of preparations of the Cannabis plant intended for use as a psychoactive drug or for medicinal purposes. The English term marijuana comes from the Mexican Spanish word marihuana...
,
heroin or other opiates, in an attempt to enhance the psychological effect of these drugs.
The poly-drug use of powerful depressant drugs poses the highest level of health concerns due to a significant increase in the likelihood of experiencing an
overdoseThe term drug overdose describes the ingestion or application of a drug or other substance in quantities greater than are recommended or generally practiced...
which may result in fatal respiratory depression.
A 1990 study claimed that diazepam has a higher misuse potential relative to other benzodiazepines, and that some data suggests that alprazolam and lorazepam resemble diazepam in this respect.
Anecdotally injection of alprazolam has been reported, causing dangerous damage to blood vessels, closure of blood vessels (embolization) and decay of muscle tissue (rhabdomyolysis). Alprazolam is practically not soluble in water, when crushed in water it will not fully
dissolveSolubility is the property of a solid, liquid, or gaseous chemical substance called solute to dissolve in a solid, liquid, or gaseous solvent to form a homogeneous solution of the solute in the solvent. The solubility of a substance fundamentally depends on the used solvent as well as on...
(40 µg/ml of
H2OWater is a chemical substance with the chemical formula H2O. A water molecule contains one oxygen and two hydrogen atoms connected by covalent bonds. Water is a liquid at ambient conditions, but it often co-exists on Earth with its solid state, ice, and gaseous state . Water also exists in a...
at pH 7). There have also been anecdotal reports of alprazolam being
snortedInsufflation is the practice of inhaling a substance. Insufflation has limited medical use, but is a common route of administration with many respiratory drugs used to treat conditions in the lungs and paranasal sinus .The technique is common for many recreational drugs and is also used for some...
. Due to the low weight of a dose, alprazolam in one case was found to be distributed on blotter paper in a manner similar to LSD.
Availability
Alprazolam instant release (IR) is available in 0.125 mg, 0.25 mg, 0.5 mg, 1 mg and 2 mg strength regular and orally disintegrating tablets.
Alprazolam Extended Release (XR) is available in 0.5 mg, 1 mg, 2 mg, and 3 mg strength oral.
Alprazolam is available in English-speaking countries under the following brand names:
- Alganax
- Alzolam
- Alprax
- Alprose
- Alprox
- Alzam
- Anxirid
- Apo-Alpraz
- Calmax
- Gerax
- Helex
- Kalma
- Mylan
- Nervin
- Niravam
- Novo-Alprazol
- Nu-Alpraz
- Onax
- Restyl
- Tafil
- Texidep
- Trika
- Tranax
- Xanax
- Xanor
- Zamhexal
- Zolam
- Zopax
Legal status
In the
United StatesThe United States of America is a federal constitutional republic comprising fifty states and a federal district...
, alprazolam is a prescription drug and is assigned to Schedule IV of the
Controlled Substances ActThe Controlled Substances Act was enacted into law by the Congress of the United States as Title II of the Comprehensive Drug Abuse Prevention and Control Act of 1970. The CSA is the federal U.S. drug policy under which the manufacture, importation, possession, use and distribution of certain...
by the
Drug Enforcement AdministrationThe Drug Enforcement Administration is a federal law enforcement agency under the United States Department of Justice, tasked with combating drug smuggling and use within the United States...
. Under the UK drug misuse classification system benzodiazepines are class C drugs (Schedule 4). In the UK, alprazolam is not available on the
NHSThe National Health Service is the shared name of three of the four publicly funded healthcare systems in the United Kingdom. They provide a comprehensive range of health services, the vast majority of which are free at the point of use to residents of the United Kingdom...
and can only be obtained on private prescription. Internationally, alprazolam is included under the United Nations
Convention on Psychotropic SubstancesThe Convention on Psychotropic Substances of 1971 is a United Nations treaty designed to control psychoactive drugs such as amphetamines, barbiturates, benzodiazepines, and psychedelics signed at Vienna on February 21, 1971...
as Schedule IV. In
IrelandIreland is an island to the northwest of continental Europe. It is the third-largest island in Europe and the twentieth-largest island on Earth...
, alprazolam is a Schedule 4 medicine. In
SwedenSweden , officially the Kingdom of Sweden , is a Nordic country on the Scandinavian Peninsula in Northern Europe. Sweden borders with Norway and Finland and is connected to Denmark by a bridge-tunnel across the Öresund....
, alprazolam is a prescription drug in List IV (Schedule 4) under the Narcotics Drugs Act (1968). In the
NetherlandsThe Netherlands is a constituent country of the Kingdom of the Netherlands, located mainly in North-West Europe and with several islands in the Caribbean. Mainland Netherlands borders the North Sea to the north and west, Belgium to the south, and Germany to the east, and shares maritime borders...
, alprazolam is a List 2 substance of the
Opium LawThe Opium Law is the section of the Dutch law which covers nearly all psychotropic drugs. All non-psychotropic, but prescription-only drugs are covered by the Medicine Act.- Origin and history :...
and is available for prescription.
External links