Alprazolam
General Information
(All names are trademark of the respective manufacturer)
Slang / Street Names:
Common Methods / Routes of Administration:
Drug Evaluation & Classification Program Category:
Federal (DEA) Schedule:
May be found as a metabolite of:
Therapeutic Blood Concentrations
|
Micrograms per liter (μg/L) or Nanograms per milliliter (ng/mL) |
Milligrams per liter (mg/L) or Micrograms per milliliter (μg/mL) |
|
|---|---|---|
| Baselt (2020) | 25 - 102 | 0.025 - 0.102 |
| Schulz, et al. (2020) | 5 - 50 | 0.005 - 0.050 |
| Winek, et al. (2001) | 25 - 102 | 0.025 - 0.102 |
References for Therapeutic Ranges
Schulz M, Schmoldt A, Andresen-Streichert H, Iwersen-Bergmann S. Revisited: Therapeutic and toxic blood concentrations of more than 1100 drugs and other xenobiotics. Crit Care. 2020 May 6;24(1):195. doi: 10.1186/s13054-020-02915-5. PMID: 32375836; PMCID: PMC7201985.
Winek CL, Wahba WW, Winek CL Jr, Balzer TW. Drug and chemical blood-level data 2001. Forensic Sci Int. 2001 Nov 1;122(2-3):107-23. doi: 10.1016/s0379-0738(01)00483-2. PMID: 11672964.
Note Regarding Schulz, et al. values: When a value is expressed in brackets or parentheses, it typically indicates an extension of the corresponding lower or upper parameter based upon unique or unusual conditions (e.g., very old or very young patients, high or low body mass, adapted tolerance to the drug, etc.) See page 84 of the attachment to Shulz et al. for a more complete description.
Caution: Refer to source text for further details of values provided. Be cognizant of sample matrix (e.g., serum vs. whole blood) and dosing regimen that resulted in stated values, when such information is available and disclosed. See ANSI / ASB Best Practice Recommendation 037: Guidelines for Opinions and Testimony in Forensic Toxicology for further guidance on appropriate application of such information.
Pharmacology
Mechanism of Action
Nervous system function requires transmission of excitatory and inhibitory signals. One of the primary neurotransmitters responsible for inhibitory signaling is γ-aminobutyric acid (GABA), which exerts significant effects on the central nervous systems (CNS) at a receptor known as GABA-A (among others). The primary effects of benzodiazepines are thought to result from attaching to a peripheral site on the GABA-A complex, potentiating (increasing) the action of GABA. Primary therapeutic benefits from this mechanism include reduction in anxiety (anxiolysis), sedation, and easier induction of sleep (hypnosis).
Notable Metabolites
Notable Drug Interactions
FDA boxed warning: “Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing for use in patients for whom alternative treatment options are inadequate; limit dosages and durations to the minimum required; and follow patients for signs and symptoms of respiratory depression and sedation.”
Additive CNS depressant effects may occur when combined with other CNS depressing drugs, such as alcohol, barbiturates, anxiolytics, antidepressants, antipsychotics, sedative-hypnotics, sedating antihistamines, anticonvulsants, and anesthetics.
Combining with drugs that inhibit Cytochrome 3A enzymes may increase the concentration of alprazolam (and its effects on the patient).
Half-Life
Baselt (2020)
Schulz, et al. (2020)
Effects on Performance & Behavior
Ocular Effects
Gaze Nystagmus: Under normal conditions, people use “smooth pursuit” eye movements to maintain a moving visual target over the foveal region of the retina – where visual acuity is highest. Similarly, when gazing at an object away from center, the eyes can normally fixate (hold steady) on a target to keep it over the fovea as well. Certain drugs, including this one, may cause reduced performance of smooth pursuit eye movements and induce gaze nystagmus in the horizontal or vertical plane. Involuntary spontaneous eye movements may cause difficulty maintaining a visual target steadily over the foveal region of the retina. This can lead to impaired visual perception and may also result in the illusion of movement in the environment when/where it does not exist.
Reaction to Light: Under normal conditions, pupils react briskly to increased light exposure. When that response is slowed, the over-exposure of light may result in glare and reduced visual acuity. The alterations in visual perception may be very brief if the pupil does reach an appropriate size, but may persist if the pupil remains enlarged (mydriasis). Appropriate reaction to light is required in conditions of low light where exposures to bright light may occur – such as driving at night and passing other vehicles’ headlights or emergency lights.
Performance Effects
Alprazolam can significantly affect performance, including:
- Reduced divided attention capacity
- Poor vigilance
- Slowed reaction times
- Reduced concentration and cognitive skills
- Impaired psychomotor performance and coordination
- Impaired eye/hand coordination
These effects can adversely impact driving, including:
- Difficulty maintaining lane position
- Reduced alertness
- Slowed braking / reaction times
- Difficulty attending to multiple tasks
- Impaired tracking ability
- Altered decision making and execution capacity
Manufacturer Warnings
General Indicators
- May appear similar to a person intoxicated by alcohol
- Drowsiness
- Slow / sluggish demeanor and reactions
- Slurred speech
- Ptosis (droopy eyelids)
- Impaired / unsteady walking
- Poor coordination
- Disorientation / confusion
Other
Benzodiazepines do not generally create notable changes in body temperature. Relaxed / flaccid muscle tone and a reduction in pulse rate and blood pressure may be observed.
Drug Evaluation & Classification Program Major Indicators
HGN
Present
VGN
Present*
LOC
Present
Pupil Size
Normal**
RTL
Slow
Pulse
Down***
BP
Down
Body Temp
Normal
Muscle Tone
Flaccid
HGN: Horizontal Gaze Nystagmus, VGN: Vertical Gaze Nystagmus, LOC: Lack of Convergence, RTL: Reaction to Light, BP: Blood Pressure
*High Doses.
**Soma, quaaludes, and some antidepressants usually dilate pupils.
***Quaaludes, ETOH and some antidepressants may elevate.
Note: The symptomatology chart shown above is for the associated category of drugs. Actual manifestations of intoxicated / impairment are more variable than can be fully encapsulated in this syndromic reference. Partial or atypical presentations do not necessarily imply less significance, and may still prove valuable to identifying drug impairment and potential causes. This is of particular relevance in cases of multi-substance impairment.
External Links
Drug Images:
Click Here to view images from the Drugs.com Pill Identifier.
Prescriber’s Digital Reference:
Click Here for prescriber reference material, indications, dosages, and more detailed drug interaction information.
NCTR: FDA Label Search:
Click Here for FDA Labels
Click Here for a more extensive repository of drug labels.
Bibliography
These references have been reviewed by the SOFT Drugs & Driving Committee and placed on their DUI-D literature page.
Leufkens, T.R., et al. Cognitive, psychomotor and actual driving performance in healthy volunteers after immediate and extended release formulations of alprazolam 1 mg. Psychopharmacology 191:951-959 (2007)
Moffat, A.C., et al. Alprazolam. In: Clarke’s Analysis of Drugs and Poisons (3rd ed.), Grayslake, IL: Pharmaceutical Press; 605-606 (2004)
Stone, B.T., et al. Behavioral and neurophysiological signatures of benzodiazepine-related driving impairments. Front Psychol 6:1799 (2015)
Verster, J.C., et al. Effects of alprazolam on driving ability, memory functioning and psychomotor performance: a randomized, placebo-controlled study. Neuropsychopharmacology 27:260-269 (2002)
Verster, J.C. and Volkerts, E.R. Clinical pharmacology, clinical efficacy, and behavioral toxicity of alprazolam: a review of the literature. CNS Drugs Rev 10:45-76 (2004)
Dubois S, Bédard M, Weaver B. The impact of benzodiazepines on safe driving. Traffic Inj Prev. 2008 Oct;9(5):404-13. doi: 10.1080/15389580802161943. PMID: 18836950.
Drummer OH. Benzodiazepines – Effects on Human Performance and Behavior. Forensic Sci Rev. 2002 Feb;14(1-2):1-14. PMID: 26256485.
Hindmarch I, Patat A, Stanley N, Paty I, Rigney U. Residual effects of zaleplon and zolpidem following middle of the night administration five hours to one hour before awakening. Hum Psychopharmacol. 2001 Mar;16(2):159-167. doi: 10.1002/hup.282. PMID: 12404586.
van der Sluiszen NNJJM, Vermeeren A, Verster JC, van de Loo AJAE, van Dijken JH, Veldstra JL, Brookhuis KA, de Waard D, Ramaekers JG. Driving performance and neurocognitive skills of long-term users of benzodiazepine anxiolytics and hypnotics. Hum Psychopharmacol. 2019 Nov;34(6):e2715. doi: 10.1002/hup.2715. PMID: 31837049; PMCID: PMC7003498.
Verster JC, Roth T. Blood drug concentrations of benzodiazepines correlate poorly with actual driving impairment. Sleep Med Rev. 2013 Apr;17(2):153-9. doi: 10.1016/j.smrv.2012.05.004. Epub 2012 Aug 9. PMID: 22884949.
Willumeit HP, Ott H, Neubert W. Simulated car driving as a useful technique for the determination of residual effects and alcohol interaction after short- and long-acting benzodiazepines. Psychopharmacology Suppl. 1984;1:182-92. doi: 10.1007/978-3-642-69659-6_16. PMID: 6147840.
These are additional references that members may find relevant to the subject of this guide. DrugImpairment.com does not vouch for credibility or completeness of any source, and users should be familiar with details of a study before offering it in support of opinions or testimony. We are, however, available to answer specific questions or provide feedback / guidance as needed via the Ask an Expert form.
Vinckenbosch FRJ, Vermeeren A, Vuurman EFPM, van der Sluiszen NNJJM, Verster JC, van de Loo AJAE, van Dijken JH, Veldstra JL, Brookhuis KA, De Waard D, Ramaekers JG. An explorative approach to understanding individual differences in driving performance and neurocognition in long-term benzodiazepine users. Hum Psychopharmacol. 2021 Jul;36(4):e2778. doi: 10.1002/hup.2778. Epub 2021 Feb 6. PMID: 33547849; PMCID: PMC8365705.
Smith RB, Kroboth PD. Influence of dosing regimen on alprazolam and metabolite serum concentrations and tolerance to sedative and psychomotor effects. Psychopharmacology (Berl). 1987;93(1):105-12. doi: 10.1007/BF02439595. PMID: 3114808.
Griffin CE 3rd, Kaye AM, Bueno FR, Kaye AD. Benzodiazepine pharmacology and central nervous system-mediated effects. Ochsner J. 2013 Summer;13(2):214-23. PMID: 23789008; PMCID: PMC3684331.
O’Hanlon JF, Vermeeren A, Uiterwijk MM, van Veggel LM, Swijgman HF. Anxiolytics’ effects on the actual driving performance of patients and healthy volunteers in a standardized test. An integration of three studies. Neuropsychobiology. 1995;31(2):81-8. doi: 10.1159/000119177. PMID: 7760989.
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