Alprazolam (Xanax)
Jessica J. Miguel
Benzodiazepines are antianxiety (anxiolytic) drugs, and
probably the most frequently prescribed psychotropic in the
United States (Doweiko, 2002). It is estimated that
approximately 10-20% of adults in the Western part of the world
have used benzodiazepines at least once. In 1960, one of the
first members of the benzodiazepines, chlordiazepoxide, was
introduced as an antianxiety drug. Since then, 3000 or so
different benzodiazepines have been developed in the world, and
about 12 of them are prescribed in the United States.
Benzodiazepines were introduced as fairly safe replacement
drugs for the highly addicting barbituates. The benzodiazepines
have also become the most commonly used antianxiety drugs
because they don't have to be taken on an ongoing basis in order
to be effective.
Of those Benzodiazepines prescribed in the United States,
Alprazolam (Xanax) has been commonly preferred over other
benzodiazepines, such as chlordiazepoxide, because alprazolam
has a relatively shorter half-life (11 hours) and does not have
active metabolites that can lead to accumulation, particularly
of concern in elderly benzodiazepine users (Vaults of Erowid,
2003). Alprazolam was approved by the FDA in 1981 and has been
classified by the DEA as a Schedule IV Controlled Substance.
Alprazolam (generic name) has hundreds of brand names around the
world, Xanax being the most common in the United States.
Alprazolam is a triazolo analog of the 1,4 benzodiazepine
class of central nervous system active compounds (Vaults of
Erowid, 2003;Dobbs et. al, 1995). The chemical name for
alprazolam is 8 Chloro 1 methyl 6 phenyl 4H s triazolo (4,3
a)(1,4). Addition of the triazole ring to the basic
benzodiazepine chemical structure makes up the chemical
structure for alprazolam. The chemical formula for alprazolam is
C17H13CIN4 and its molecular weight is 308.7695. Alprazolam is a
white crystalline powder, soluble in methanol or ethanol, but
has no appreciable solubility in water at physiological pH.
Alprazolam is administered orally and is quickly absorbed.
Alprazolam tablets contain either 0.25, 0.5, 1, or 2 mg of
alprazolam. There is also an oral solution in concentrates of
0.5mg/5ml, or 1mg/1ml. Alprazolam is indicated primarily for the
management and treatment of anxiety disorders or for the short-
term relief of mild to moderate anxiety and nervous tension
(mentalhealth.com, 2005; psyweb.com, 2005; Vaults of Erowid,
2003). Alprazolam has also been found to be effective in the
treatment of activity depression and panic disorder, with or
without agoraphobia. In addition, it has been found useful in
treating irritable bowel syndrome, premenstrual syndrome, some
cancer pains (in combination with various narcotics), and in
some cases doctors prescribe alprazolam to treat alcohol
withdrawal. Alprazolam has a reportedly calming and relaxing
effect on the user. While there appears to be numerous symptoms
and problems that have clinically shown to be successfully
treated with alprazolam, there are many precautions and warnings
that must be taken into consideration before using alprazolam.
Clinical studies showing safety and efficacy in patients
under the age of 18 has not been established, therefore
alprazolam is not recommended for those under the age of 18
(mentalhealth.com, 2005; psyweb.com, 2005). Extreme caution must
be taken when prescribing alprazolam to elderly patients and
those with debilitating illnesses. These populations are prone
to the CNS depressant activity of benzodiazepines, even after
low dosages. Studies have shown an increased risk of congenital
malformations in pregnant women in association with
benzodiazepine use, therefore it is not recommended for pregnant
women to use alprazolam. Women breastfeeding their infants
should also not use alprazolam because it is secreted through
the breast milk. Other patient populations for which Alprazolam
use is contraindicated is patients with myasthenia gravis,
narrow angle glaucoma, and those with organic brain syndrome.
Alprazolam is not recommended for treating psychotic or
depressive disorders. Caution must be taken in individuals prone
to grand mal seizures because abrupt withdrawal from Alprazolam
may exacerbate seizures in epileptic patients.
Like all benzodiazepines, alprazolam is a CNS depressant
that when taken with other drugs that are also depressants, such
as alcohol, narcotics, barbituates, nonbarbituate hypnotics,
anticonvulsants, antihistamines, phenothiazines, butyrophenones,
MAO inhibitors, and tricyclic antidepressants, there may be
additive or potentiating effects, even fatalities (Vaults of
Erowid, 2003; mentalhealth.com, 2005). Grapefruit juice has also
been clinically shown to potentiate the effects of alprazolam.
While benzodiazepines were meant to be a safer replacement
for the highly addicting barbituates, benzodiazepines have their
own potential for misuse and dependence. Physical dependence to
alprazolam can occur, even with short-term use (Vaults of
Erowid, 2003; mentalhealth.com, 2005). It is cautioned that
alprazolam should not be administered to individuals prone to
drug abuse, or to those considered to have potential for
psychological dependence (mentalhealth.com, 2005).Data suggests
that the risk of dependence is higher in those taking doses
greater than 4mg per day (Vaults of Erowid, 2003). It should be
carefully considered when alprazolam is administered for the
treatment of panic disorder because clinical studies have shown
that the successful treatment of panic disorder in many patients
has required doses of alprazolam greater than 4mg per day.
Misuse of alprazolam does occur. One case report of a 30
year old woman with a history of depression, died after
ingesting alprazolam, tramadol (an analgesic), and alcohol
(Michaud et al., 1999). This case highlights the warnings of
mixing other drugs with alprazolam, as well as using alprazolam
in the treatment of primary depression. Other ways in which
alprazolam has been misused is exemplified in the case of a 12
year old girl who was sexually assaulted by her father from the
time she was six years old (Kintz et al, 2004). In this case the
father had been giving the little girl alprazolam (Xanax) in
pill form. In another case of a 16 year old girl, she was given
alprazolam and was battered and forced to prostitute. In both of
these cases alprazolam was used to sedate the victims to make
the perpetrators crimes easier. In both of these cases,
alprazolam was detected through hair analysis of the victims'
hairs.
Like all drugs, prescribed and illegal, there are many
precautions to be taken. Any prescription drug should be used
only as intended by a prescribing physician. Because of the many
cautions to be considered with alprazolam use, dosages must be
individualized, beginning at the lowest possible effective dose,
and carefully monitored. Alprazolam should never be stopped
abruptly, this may cause severe withdrawal symptoms. Patients
should be monitored during the phase of cessation from
alprazolam, and doses should become gradually lower (Vaults of
Erowid, 2003; mentalhealth.com, 2005).
References
Dobbs et al. (1995). Studies with 11c Alprazolam; An agonist for
the benzodiazepine receptor. Nuclear Medicine and Biology, 22.
Pages 459 to 466.
Doweiko, H, (2002). Concepts of chemical dependency. Brooks and
Cole, Australia. Pages 105 to 120.
Kintz et al. (2004). Identification of alprazolam in hair in two
cases of drug-facilitated incidents. Forensic Science
International.
http://www.mentalhealth.com/drug/p30 x01.html
Michaud, K, et al. (1999). Fatal overdose of tramadol and
alprazolam. Forensic Science International, 105. Pages 185 to
189.
http://www.psyweb.com/Drughtm/xanax.html
http://www.erowid.org/pharms/alprazolam/alprazolam faq.shtml
Erin C. Villa
Inhibitory/Excitatory changes
Ion channels effected
Physiological changes
Benzodiazepines, such as diazepam (Valium),
chlordiazepoxide HCI (Librium), and alprazolam (Xanax), can be
prescribed to treat anxiety, acute stress reactions, and panic
attacks; the more sedating benzodiazepines, such as triazolam
(Haricion) and estazolam (ProSom) can be prescribed for short-
term treatment or sleep disorders (HYPERLINK
http://www.homedrugtestingkit.com). Although benzodiazepines
have many beneficial effects, such drugs as Xanax have the
potential for abuse. Like all drugs, one must look closely see
if the benefits out weigh the negative aspects.
To refresh your memory, an ion is an atom that has lost one
or more electrons to another atom or has stolen them from
another atom. But stealing electrons, it acquires a negative
charge, because it now has a surplus. By losing them, it
acquires a positive charge. (Palfai & Jankiewicz, 2001). In
discussing ions and their changes, one must look at water-
soluble and/or lipid-soluble drugs.
Water soluble drugs ionize in body fluids and lipid-soluble
drugs, then, ionize and can cross through membranes. Lipid-
03soluble drugs normally cross through membranes, but if they
ionize, the ionized portion loses its lipid-solubility (Palfai &
Jankiewicz, 2001). Benzodiazepines such as Xanax are highly fat
or lipid-soluble. They actually accumulate in the fatty tissue.
The benzodiazepines augment the GABAergic action by
increasing the frequency of the channel opening (Palfai &
Jankiewicz, 2001). Chlorine ions enter through the post-
synaptic membrane, making the cell interior more negative and
raising the threshold for excitation (Palfai & Jankiewicz,
2001). As a consequence of the enhancement of GABA's inhibitory
activity caused by benzodiazepines, the brain's output of
excitatory neurotransmitters, including norepinephrine
(noradrenalin), serotonin, acetylcholine and dopamine, is
reduced (HYPERLINK http://www.oxyabusekills.com/xanax.html).
Benzodiazepines enhance the affinity of the recognition site for
GABA by inducing conformational changes that make GABA binding
more efficacious. Activation of the benzodiazepine-GABA-
chloride ionophor complex is responsible for producing the
therapeutic anxiolytic effects of benzodiazepines (HYPERLINK
http://www.aafp.org). These excitatory neurotransmitters are
necessary for normal alertness, memory, muscle tone and
coordination, emotional responses, endocrine gland secretions,
heart rate, and blood pressure control and a host of other
functions, all of which may be impaired by benzodiazepines.
Other benzodiazepine receptors, not linked to GABA, are present
in the kidney, colon, blood cells and adrenal cortex and these
may also be affected by some benzodiazepines (HYPERLINK
http://www.oxyabusekills.com/xanax.html). As you will read
later in the side effects, these actions, whether indirect or
direct, are responsible for many of the "popular" adverse
effects of benzodiazepines.
When benzodiazepines bind to a specific site on a GABA
receptor, they do not stimulate it directly. Instead, they make
it more efficient by increasing the frequency with which the
chlorine channel opens when GABA binds to its own site on this
receptor. The resulting increase in the concentration of CL-
ions in the post-synaptic neuron immediately hyperpolarizes this
neuron, thus making it less excitable. Barbiturates bind to
another site on the GABA receptor, with similar effects. But
the advantage of benzodiazepines is that, unlike barbiturates,
they do not open the CL- directly, but instead act more subtly
by potentiating the effect of GABA (HYPERLINK
http://www.thebrain.mcgill.ca/flash/i/i_03/i_03_m/i_03-m-
par/i_03-m-par_benzodiazepines.html). Mixing benzodiazepines
with alcohol is dangerous because their respective effects on
the Cl- channels can be addictive.
Physiological Changes
Benzodiazepines (Xanax) are a sedative-hypnotic that affect the
central nervous system through depression. Benzodiazepines are
widely prescribed, with four of them: alprozolam (Xanax),
clonazepam (Klonopin), diazepam (Valium), and lorazepam (Ativan)
listed among the top 100 most commonly prescribed medications
(HYPERLINK http://www.aafp.org).
These category of drugs slow normal brain function. With
Xanax and other benzodiazepines, the activity in the central
nervous system slows down. As we discussed in the beginning of
the paper, there are numerous CNS depressants; most act on the
brain by affecting the neurotransmitter gamma-aminobutric acid
(GABA) (HYPERLINK http://www.homedrugtestingkit.com).
When considering doses, small amounts of the drug relieve
tension, which the why many individuals reach to this drug.
When large amounts are taken, the body may react in several
different ways. A large dose produces staggering, blurred
vision, impaired thinking, slurred speech, impaired perception
of time and space, slowed reflexes and breathing, reduced
sensitivity to pain (HYPERLINK
"http://www.homedrugtestingkit.com"). With the extreme being
unconsciousness, coma and possible death.
All of the benzodiazepines displays five chief effects,
which vary in degree from agent to agent (Palfai & Jankiewicz,
2001). These include anxiolytic effects (reduction of anxiety),
muscle relaxant effects, hypnotic effect (sleep induction),
anticonvulsant effects, amnesic effects (memory loss). When
considering Xanax, one must look at the anxiolytic effects.
The anxiolytic effects of the benzodiazepines are most
likely mediated by circuits in the neocortex, where the
concentration of benzodiazepine receptors is highest. Although
brain stem concentrations are low, circuits involving GABA there
appear to mediate the potentiation of fear and the acoustic
startle reflex- the automatic jumping at a sudden loud sound.
Also implications are limbic structures such as the hippocampus
and amygdale, which contribute to anxiolytic effects and taming
effects. (Palfai & Jankiewicz, 2001).
Psychomotor slowing may be especially profound following
initial administration of a benzodiazepine or with a sudden
dosage increase (HYPERLINK "http://www.aafp.org"). These
psychomotor symptoms include drowsiness, poor concentration,
ataxia, dysarthria, motor in coordination, diplopia, muscle
weakness, vertigo and mental confusion. Studies of the
psychomotor effects suggest that benzodiazepines slow reaction
time and impair driving skills, increasing the risk of motor
vehicle crashes in patients who are taking these agents
(HYPERLINK http://www.aafp.org").
Another area in which benzodiazepines interfere with normal
body functioning is memory impairment. Benzodiazepines induce
anterograde amnesia, which accounts for the beneficial effects
of benzodiazepines such as midazolam for presurgical medication.
These specific amnestic effects appear to be separate from
sedation. (HYPERLINK http://www.aafp.org.). Specific deficits
in visuospatial ability and sustained attention have also been
described in patients who have taken therapeutic doses of
benzodiazepines regularly for longer than one year.
(HYPERLINK"http://www.aafp.org.).
As stated before, an individual must look at all aspects of
a drug and its interaction with the body to come to a well-
educated conclusion if this is the right route to take in
controlling certain ailments, disorders, etc.
References
About Benzodiazepines (n.d.). Retrieved April 29, 2005 from
http://wwwoxyabuse kills.com.
Addiction: Part I. Benzodiazepines- side effects, abuse risks,
and alternatives. Retrieved April 29, 2005 from
http://www.aafp.org.
Benzodiazepines (n.d.). Retrieved April 29, 2005 from
http://www.thebrain.mcgill.ca.
Palfai, T. & Jankiewicz, H. (2001) Drugs and Human Behavior
(2nd edition). New York, NY: McGraw Hill Primis.
The Benzodiazepines (2005). Retrieved April 29, 2005 from
http://www.benzo.org.
Xanax Definition (n.d.). Retrieved April 29, 2005 from
http://www.homedrugtestingkit.com.
Eric West
Xanax (Alprazolam): Primary behavior changes, side effects,
effects reported by users.
Anxiolitics, e.g. benzodiazepines, such as Xanax, appear to
be the most common anxiety-reducing medications prescribed to
date. Though they are the drug of choice for treating anxiety
related disorders, there are a number of drawbacks to their use
in addition to the beneficial effects experienced by people who
use them. Beneficial effects include the relief of anxiety
symptoms, such as panic response, sweaty hands, dry mouth, and
rapid heart-beat, as well as relief from some symptoms of
depression. However, virtually all the literature on first and
second generation benzodiazepines include warnings of potential
effects that should be duly noted by prescribing physicians and
patients alike, as benzodiazepines are Central Nervous System
(CNS) intoxicants.
Among those effects that Xanax can produce are behavioral
changes that may seriously affect the users ability to function
safely and effectively while using the drug. Though Xanax is
used enthusiastically for treating both anxiety disorders and
depression, the user must beware of the possibility of
experiencing these changes, which include physical dependence
and tolerance, conditions which prompt many prescribing
physicians to use Xanax only as a short-term treatment option.
The dependence, which occurs fairly quickly (at 4mg/day for more
than 12 weeks, according to Russell Katz, M.D., and a director
in the Center for Drug Evaluation and Research), can be both
physical and psychological, suggesting that Xanax should be
prescribed in conjunction with psychotherapy (see Beutler,
et.al, 1987), and should be prescribed at the lowest possible
affective dosage for the shortest possible duration. Withdrawal
symptoms, some of which may be life-threatening, especially
following abrupt discontinuance of use, may include mild
dysphoria and insomnia, to a more severe syndrome that includes
serious abdominal and muscle cramps. On the contrasting side,
Xanax appears to be quite effective at reducing anxiety
symptoms, as well as those associated with depression, allowing
the patient to function more effectively and comfortably in his
or her daily activities, from the home to the job, and in the
community.
Abuse has also been associated with the use of
benzodiazepines, and behaviors associated with abuse should be
duly noted. Reports of benzodiazepine abuse arose within just a
few years of their introduction to the pharmaceutical market
(Doweiko, 2002, 109). As with abuse of any drug, overdose can be
a danger. Overdose of Xanax may manifest symptoms such as
somnolence, confusion, loss of coordination, diminished
reflexes, and coma. Death has been associated with overdoses of
Xanax alone, as with other benzodiazepines, as well as when used
in conjunction with other substances, such as alcohol.
Behavioral changes such as altering one's daily routine in order
to obtain and use the substance are also associated with abuse,
in addition to the time one spends under the influence of the
drug.
Side effects of the use of Xanax are varied and numerous.
Some appear to be more severe than others, but many are
potentially debilitating, and some potentially fatal. Among the
more common side effects are clumsiness or unsteadiness,
dizziness, lightheadedness, drowsiness and slurred speech. Less
common side effects include abdominal or stomach cramps, pain,
blurred vision, changes in sexual desire or ability,
constipation, diarrhea, dryness of mouth or increased thirst,
false sense of well-being, headache, muscle spasm,
nausea/vomiting, problems with urinating, trembling or shaking,
unusual tiredness or weakness. In addition, more severe less
common and rare side effects may include anxiety (rare),
confusion, fast, pounding, or irregular heartbeat, mental
depression. Among more rare effects are thought problems
including disorientation, delusions, loss of a sense of reality,
agitation, aggression, bizarre behavior, lack of inhibition,
angry outbursts, convulsions, hallucinations, hypotension, and
sleep disturbances (see references, web 1). Other reported side
effects include difficulty breathing, closing of your throat,
swelling of lips, face, or tongue, or hives, sores in the mouth
or throat, jaundice, rashes and hallucinations. (see references,
web 2). Another side effect is anterograde amnesia (Palfai &
Jankiewicz, 2001, 223-229), which goes away after a period of
time. According to these authors, some users experience
"paradoxical effects," such as wakefulness rather than the
tranquilizing effect expected, and irritability and euphoria.
In the Katz report (as mentioned above), patients treated
with Xanax for panic disorder reported events which were
analyzed according to percentages by the author. This analysis
was labeled "Discontinuation-Emergent Symptom Incidence," and is
separated according to categories, including body/system event,
psychiatric, gastrointestinal, metabolic-nutritional,
dermatological, cardiovascular, and special senses. The
breakdown of these events experienced and reported by users of
Xanax are as follows:
Body Systems: Insomnia, 29.5%;
Light-headedness, 19.3%;
Abnormal involuntary movement, 17.3%;
Headache, 17%,
Muscular twitching, 6.9%;
Impaired coordination, 6.6%;
Muscle tone disorders, 5.9%;
Weakness, 5.8%.
Psychiatric: Anxiety, 19.2%;
Fatigue and tiredness, 18.4%;
Irritability, 10.5%;
Cognitive disorder, 10.3%;
Memory impairment, 5.5%;
Depression, 5.1%,
confused state, 5%.
Gastrointestinal: Nausea/Vomiting, 16.5%;
Diarrhea, 13.6%;
decreased salivation, 10.6%.
Metabolic/Nutritional: Weight loss, 13.3%,
Decreased appetite, 12.8%.
Dermatological: Sweating, 14.4%.
Cardiovascular: Tachycardia, 12.2%.
Special Senses: Blurred vision, 10%.
As a CNS intoxicant, Xanax effects neural networks that are
essential to the normal functioning of many physical parts of
our anatomy. Voluntary movement may be sufficiently impaired to
render simple tasks such as walking difficult, or in the
extreme, untenable. Impaired vision could render problems with
reading or driving a car, or operating other equipment.
Increased number of visits to a doctor or emergency room may
occur as a result of internal symptom manifestations inherent to
the use of Xanax.
In conclusion, though Xanax may be a very popular drug of
choice for treating anxiety and depression, as well as bi-polar
disorder, there appear to be many considerations that need to be
addressed before and during use, and upon cessation of use. The
beneficial qualities of Xanax appear to be preferable to other
benzodiazepines/anxiolitics, but the risks inherent to use of
the drug are considerable, and potentially dangerous or lethal.
The balance between the risks and benefits should be taken into
serious consideration before prescribing or using this
substance.
References:
Katz, R., May 2, 2000. Letter of reply to Pharmacia & Upjohn
Company in response to a supplemental drug application to the
Division of Neuropharmacological Drug Products, Office of Drug
Evaluation 1, Center for Drug Evaluation and Research.
Beutler, L. E., Scogin, F., Kirkish, P., Schretlen, D.,
Corbishley, A., Hamblin, D., Meredith, K., Potter, R., Bamford,
C. R., and Levenson, A. I. (1987). Group cognitive therapy and
alprazolam in the treatment of depression in older adults.
Journal of Consulting and Clinical Psychology, 55 (4), 550 to
556. Retrieved from: http://gateway.ut.ovid/gw1/ovidweb.cgi?, on
4/21/05
Doweiko, H. E. (2002). Concepts of Chemical Dependency, 5th ed.
Web 1: Retrieved from:
http://bipolar.about.com/cs/sfx/a/sfx_xanax.htm, on 4/21/05.
Side Effects Alprazolam/Xanax Bipolar Disorder Medications.
Web 2: Retrieved from: http://www.anxiety-and-depression-
solutions.com/xanax.htm, on 4/21/05. Xanax (Alprazolam)
Information What does it do to you? Xanax Side Effects and
More.
Palfai, T. and Jankiewicz, H. (2001). Drugs and Human Behavior,
2nd ed.
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Copyright © 2005, Dr. John M. Morgan, All rights reserved -
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