Therapeutic index (English Wikipedia)

"Benzodiazepines (benzos, diazepam, valium)". NHS Information Authority. Archived from the original on February 18, 2025. Mixing benzodiazepines with other drugs increases the risk of harm. Mixing benzodiazepines with alcohol and other depressants like heroin increases their effects and can increase toxicity. They slow down the central nervous system, increasing the risk of overdose.
"Benzodiazepines and Opioids". National Institute on Drug Abuse. 7 November 2022. Archived from the original on February 18, 2025. Retrieved February 18, 2025. Taking opioids in combination with other central nervous system depressants—like benzodiazepines, alcohol, or xylazine—increases the risk of life-threatening overdose.
"Benzodiazepines in Combination with Opioid Pain Relievers or Alcohol: Greater Risk of More Serious ED Visit Outcomes". Substance Abuse and Mental Health Services Administration. December 18, 2014. Archived from the original on September 23, 2020. Combining benzodiazepines with opioid pain relievers or alcohol significantly increases the risk of a more serious ED [Emergency Department] visit outcome.
Mir, Soodaba; Wong, Jean; Ryan, Clodagh M.; Bellingham, Geoff; Singh, Mandeep; Waseem, Rida; Eckert, Danny J.; Chung, Frances (2020). "Concomitant benzodiazepine and opioids decrease sleep apnoea risk in chronic pain patients". ERJ Open Research. 6 (3): 00093–2020. doi:10.1183/23120541.00093-2020. PMC 7445118. PMID 32864381. Archived from the original on February 18, 2025. In chronic pain patients on opioids, administration of certain benzodiazepine sedatives induced a mild respiratory depression but paradoxically reduced sleep apnoea risk and severity by increasing the respiratory arousal threshold.
Quote: "Benzos enhance the opioid high but actually dampen the rewarding effects of stimulants (Lile JA et al, Drug Alcohol Depend 2011;119(3):187–193). That is particularly true with oxazepam, which is unique among the benzos for its ability to raise neurosteroids that block the rewarding properties of drugs of abuse (Spence AL et al, Drug Alcohol Depend 2016;166:209–217). Oxazepam also has a lower abuse liability than most benzodiazepines when used on its own. On the other hand, amphetamines can lead to benzodiazepine abuse, as patients often turn to benzodiazepines to ease anxiety and other undesirable effects of amphetamines (Darke S et al, Addiction 1994;89(12):1683–1690). That pattern also shows up in practice when clinicians prescribe one drug to manage the side effects of the other." Chris Eiken, MD (September 25, 2022). "The Benzodiazepine-Stimulant Combo: What Could Go Wrong?". Archived from the original on February 18, 2025.} (via: The Carlat Psychiatry Report)

books.google.com

Goodman, Louis S. (2011). Brunton, Laurence L.; Chabner, Bruce; Knollmann, Björn C. (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics (12 ed.). New York: McGraw-Hill. ISBN 9780071624428.

cancer.gov

"Ataxia Telangiectasia". National Cancer Institute. Retrieved 2016-04-11.
"maximum tolerated dose". Dictionary of Cancer Terms. National Cancer Institute. Retrieved 26 July 2010.

ccohs.ca

"CCOHS: What is a LD₅₀ and LC₅₀?". www.ccohs.ca. Canadian Centre for Occupational Health and Safety. 2024-05-10. Retrieved 2024-07-25.

doi.org

Muller PY, Milton MN (October 2012). "The determination and interpretation of the therapeutic index in drug development". Nature Reviews. Drug Discovery. 11 (10): 751–61. doi:10.1038/nrd3801. PMID 22935759. S2CID 29777090.
Filloon, T. G. (May 1995). "Estimating the minimum therapeutically effective dose of a compound via regression modelling and percentile estimation". Statistics in Medicine. 14 (9–10): 925–932, discussion 933. doi:10.1002/sim.4780140911. ISSN 0277-6715. PMID 7569511.
"IUPAC - median lethal dose (M03810)". goldbook.iupac.org. The International Union of Pure and Applied Chemistry (IUPAC). doi:10.1351/goldbook.M03810. Retrieved 2024-07-25.
Stanley TH (January 2000). "Anesthesia for the 21st century". Proceedings. 13 (1): 7–10. doi:10.1080/08998280.2000.11927635. PMC 1312206. PMID 16389318.
Gable RS (June 2004). "Comparison of acute lethal toxicity of commonly abused psychoactive substances" (PDF). Addiction. 99 (6): 686–96. doi:10.1111/j.1360-0443.2004.00744.x. PMID 15139867.
Bertolini A, Ferrari A, et al. (2006). "Paracetamol New Vistas of an Old Drug". CNS Drug Reviews. 12 (3–4): 250–275. doi:10.1111/j.1527-3458.2006.00250.x. PMC 6506194. PMID 17227290. Vol. 12, No. 3–4, pp. 250–275
Becker DE (Spring 2007). "Drug therapy in dental practice: general principles. Part 2 – pharmacodynamic considerations". Anesthesia Progress. 54 (1): 19–23, quiz 24–25. doi:10.2344/0003-3006(2007)54[19:DTIDPG]2.0.CO;2. PMC 1821133. PMID 17352523.
Thoms J, Bristow RG (October 2010). "DNA repair targeting and radiotherapy: a focus on the therapeutic ratio". Seminars in Radiation Oncology. 20 (4): 217–22. doi:10.1016/j.semradonc.2010.06.003. PMID 20832013.
Yokoya A, Shikazono N, Fujii K, Urushibara A, Akamatsu K, Watanabe R (2008-10-01). "DNA damage induced by the direct effect of radiation". Radiation Physics and Chemistry. The International Symposium on Charged Particle and Photon Interaction with Matter – ASR 2007. 77 (10–12): 1280–85. Bibcode:2008RaPC...77.1280Y. doi:10.1016/j.radphyschem.2008.05.021.
Soriani RR, Satomi LC, Pinto Td (2005-07-01). "Effects of ionizing radiation in ginkgo and guarana". Radiation Physics and Chemistry. 73 (4): 239–42. doi:10.1016/j.radphyschem.2005.01.003.
Russell, Cayley; Law, Justine; Bonn, Matthew; Rehm, Jürgen; Ali, Farihah (2023). "The increase in benzodiazepine-laced drugs and related risks in Canada: The urgent need for effective and sustainable solutions". International Journal of Drug Policy. 111. doi:10.1016/j.drugpo.2022.103933. PMID 36529033. For example, a recent study conducted in Canada showed that concurrent use of opioids and benzodiazepines carried a 13% higher risk of hospitalization or emergency department visits, and almost doubled the risk of death (Citing Sharma, Vishal; Simpson, Scot H.; Samanani, Salim; Jess, Ed; Eurich, Dean T. (2020). "Concurrent use of opioids and benzodiazepines/Z-drugs in Alberta, Canada and the risk of hospitalisation and death: A case cross-over study". BMJ Open. 10 (11): e038692. doi:10.1136/bmjopen-2020-038692. PMID 33444187.)
Jones, Jermaine D.; Mogali, Shanthi; Comer, Sandra D. (2012). "Polydrug abuse: A review of opioid and benzodiazepine combination use". Drug and Alcohol Dependence. 125 (1–2): 8–18. doi:10.1016/j.drugalcdep.2012.07.004. PMID 22857878. Our search found approximately 200 articles appropriate for inclusion...The co-abuse of BZDs and opioids is substantial and has negative consequences for general health, overdose lethality, and treatment outcome.
Mir, Soodaba; Wong, Jean; Ryan, Clodagh M.; Bellingham, Geoff; Singh, Mandeep; Waseem, Rida; Eckert, Danny J.; Chung, Frances (2020). "Concomitant benzodiazepine and opioids decrease sleep apnoea risk in chronic pain patients". ERJ Open Research. 6 (3): 00093–2020. doi:10.1183/23120541.00093-2020. PMC 7445118. PMID 32864381. Archived from the original on February 18, 2025. In chronic pain patients on opioids, administration of certain benzodiazepine sedatives induced a mild respiratory depression but paradoxically reduced sleep apnoea risk and severity by increasing the respiratory arousal threshold.

ersnet.org

publications.ersnet.org

Mir, Soodaba; Wong, Jean; Ryan, Clodagh M.; Bellingham, Geoff; Singh, Mandeep; Waseem, Rida; Eckert, Danny J.; Chung, Frances (2020). "Concomitant benzodiazepine and opioids decrease sleep apnoea risk in chronic pain patients". ERJ Open Research. 6 (3): 00093–2020. doi:10.1183/23120541.00093-2020. PMC 7445118. PMID 32864381. Archived from the original on February 18, 2025. In chronic pain patients on opioids, administration of certain benzodiazepine sedatives induced a mild respiratory depression but paradoxically reduced sleep apnoea risk and severity by increasing the respiratory arousal threshold.

files.wordpress.com

rgable.files.wordpress.com

Gable RS (June 2004). "Comparison of acute lethal toxicity of commonly abused psychoactive substances" (PDF). Addiction. 99 (6): 686–96. doi:10.1111/j.1360-0443.2004.00744.x. PMID 15139867.

fs.blog

Street, Farnam (2014-02-13). "The Minimum Effective Dose: Why Less is More". Farnam Street. Retrieved 2023-05-23.

harvard.edu

ui.adsabs.harvard.edu

Yokoya A, Shikazono N, Fujii K, Urushibara A, Akamatsu K, Watanabe R (2008-10-01). "DNA damage induced by the direct effect of radiation". Radiation Physics and Chemistry. The International Symposium on Charged Particle and Photon Interaction with Matter – ASR 2007. 77 (10–12): 1280–85. Bibcode:2008RaPC...77.1280Y. doi:10.1016/j.radphyschem.2008.05.021.

iupac.org

goldbook.iupac.org

"IUPAC - median lethal dose (M03810)". goldbook.iupac.org. The International Union of Pure and Applied Chemistry (IUPAC). doi:10.1351/goldbook.M03810. Retrieved 2024-07-25.

ncseonline.org

This article incorporates public domain material from Jasper Womach. Report for Congress: Agriculture: A Glossary of Terms, Programs, and Laws, 2005 Edition (PDF). Congressional Research Service.

nhsinform.scot

"Benzodiazepines (benzos, diazepam, valium)". NHS Information Authority. Archived from the original on February 18, 2025. Mixing benzodiazepines with other drugs increases the risk of harm. Mixing benzodiazepines with alcohol and other depressants like heroin increases their effects and can increase toxicity. They slow down the central nervous system, increasing the risk of overdose.

nih.gov

pubmed.ncbi.nlm.nih.gov

Muller PY, Milton MN (October 2012). "The determination and interpretation of the therapeutic index in drug development". Nature Reviews. Drug Discovery. 11 (10): 751–61. doi:10.1038/nrd3801. PMID 22935759. S2CID 29777090.
Ratanajamit C, Soorapan S, Doang-ngern T, Waenwaisart W, Suwanchavalit L, Suwansiri S, Jantasaro S, Yanate I (November 2006). "Appropriateness of therapeutic drug monitoring for lithium". Journal of the Medical Association of Thailand = Chotmaihet Thangphaet. 89 (11): 1954–60. PMID 17205880.
Filloon, T. G. (May 1995). "Estimating the minimum therapeutically effective dose of a compound via regression modelling and percentile estimation". Statistics in Medicine. 14 (9–10): 925–932, discussion 933. doi:10.1002/sim.4780140911. ISSN 0277-6715. PMID 7569511.
Stanley TH (January 2000). "Anesthesia for the 21st century". Proceedings. 13 (1): 7–10. doi:10.1080/08998280.2000.11927635. PMC 1312206. PMID 16389318.
Gable RS (June 2004). "Comparison of acute lethal toxicity of commonly abused psychoactive substances" (PDF). Addiction. 99 (6): 686–96. doi:10.1111/j.1360-0443.2004.00744.x. PMID 15139867.
Bertolini A, Ferrari A, et al. (2006). "Paracetamol New Vistas of an Old Drug". CNS Drug Reviews. 12 (3–4): 250–275. doi:10.1111/j.1527-3458.2006.00250.x. PMC 6506194. PMID 17227290. Vol. 12, No. 3–4, pp. 250–275
Becker DE (Spring 2007). "Drug therapy in dental practice: general principles. Part 2 – pharmacodynamic considerations". Anesthesia Progress. 54 (1): 19–23, quiz 24–25. doi:10.2344/0003-3006(2007)54[19:DTIDPG]2.0.CO;2. PMC 1821133. PMID 17352523.
Thoms J, Bristow RG (October 2010). "DNA repair targeting and radiotherapy: a focus on the therapeutic ratio". Seminars in Radiation Oncology. 20 (4): 217–22. doi:10.1016/j.semradonc.2010.06.003. PMID 20832013.
Russell, Cayley; Law, Justine; Bonn, Matthew; Rehm, Jürgen; Ali, Farihah (2023). "The increase in benzodiazepine-laced drugs and related risks in Canada: The urgent need for effective and sustainable solutions". International Journal of Drug Policy. 111. doi:10.1016/j.drugpo.2022.103933. PMID 36529033. For example, a recent study conducted in Canada showed that concurrent use of opioids and benzodiazepines carried a 13% higher risk of hospitalization or emergency department visits, and almost doubled the risk of death (Citing Sharma, Vishal; Simpson, Scot H.; Samanani, Salim; Jess, Ed; Eurich, Dean T. (2020). "Concurrent use of opioids and benzodiazepines/Z-drugs in Alberta, Canada and the risk of hospitalisation and death: A case cross-over study". BMJ Open. 10 (11): e038692. doi:10.1136/bmjopen-2020-038692. PMID 33444187.)
Jones, Jermaine D.; Mogali, Shanthi; Comer, Sandra D. (2012). "Polydrug abuse: A review of opioid and benzodiazepine combination use". Drug and Alcohol Dependence. 125 (1–2): 8–18. doi:10.1016/j.drugalcdep.2012.07.004. PMID 22857878. Our search found approximately 200 articles appropriate for inclusion...The co-abuse of BZDs and opioids is substantial and has negative consequences for general health, overdose lethality, and treatment outcome.
Mir, Soodaba; Wong, Jean; Ryan, Clodagh M.; Bellingham, Geoff; Singh, Mandeep; Waseem, Rida; Eckert, Danny J.; Chung, Frances (2020). "Concomitant benzodiazepine and opioids decrease sleep apnoea risk in chronic pain patients". ERJ Open Research. 6 (3): 00093–2020. doi:10.1183/23120541.00093-2020. PMC 7445118. PMID 32864381. Archived from the original on February 18, 2025. In chronic pain patients on opioids, administration of certain benzodiazepine sedatives induced a mild respiratory depression but paradoxically reduced sleep apnoea risk and severity by increasing the respiratory arousal threshold.

ncbi.nlm.nih.gov

Stanley TH (January 2000). "Anesthesia for the 21st century". Proceedings. 13 (1): 7–10. doi:10.1080/08998280.2000.11927635. PMC 1312206. PMID 16389318.
Bertolini A, Ferrari A, et al. (2006). "Paracetamol New Vistas of an Old Drug". CNS Drug Reviews. 12 (3–4): 250–275. doi:10.1111/j.1527-3458.2006.00250.x. PMC 6506194. PMID 17227290. Vol. 12, No. 3–4, pp. 250–275
Becker DE (Spring 2007). "Drug therapy in dental practice: general principles. Part 2 – pharmacodynamic considerations". Anesthesia Progress. 54 (1): 19–23, quiz 24–25. doi:10.2344/0003-3006(2007)54[19:DTIDPG]2.0.CO;2. PMC 1821133. PMID 17352523.
Mir, Soodaba; Wong, Jean; Ryan, Clodagh M.; Bellingham, Geoff; Singh, Mandeep; Waseem, Rida; Eckert, Danny J.; Chung, Frances (2020). "Concomitant benzodiazepine and opioids decrease sleep apnoea risk in chronic pain patients". ERJ Open Research. 6 (3): 00093–2020. doi:10.1183/23120541.00093-2020. PMC 7445118. PMID 32864381. Archived from the original on February 18, 2025. In chronic pain patients on opioids, administration of certain benzodiazepine sedatives induced a mild respiratory depression but paradoxically reduced sleep apnoea risk and severity by increasing the respiratory arousal threshold.

nida.nih.gov

"Benzodiazepines and Opioids". National Institute on Drug Abuse. 7 November 2022. Archived from the original on February 18, 2025. Retrieved February 18, 2025. Taking opioids in combination with other central nervous system depressants—like benzodiazepines, alcohol, or xylazine—increases the risk of life-threatening overdose.

samhsa.gov

"Benzodiazepines in Combination with Opioid Pain Relievers or Alcohol: Greater Risk of More Serious ED Visit Outcomes". Substance Abuse and Mental Health Services Administration. December 18, 2014. Archived from the original on September 23, 2020. Combining benzodiazepines with opioid pain relievers or alcohol significantly increases the risk of a more serious ED [Emergency Department] visit outcome.

semanticscholar.org

api.semanticscholar.org

Muller PY, Milton MN (October 2012). "The determination and interpretation of the therapeutic index in drug development". Nature Reviews. Drug Discovery. 11 (10): 751–61. doi:10.1038/nrd3801. PMID 22935759. S2CID 29777090.

thecarlatreport.com

Quote: "Benzos enhance the opioid high but actually dampen the rewarding effects of stimulants (Lile JA et al, Drug Alcohol Depend 2011;119(3):187–193). That is particularly true with oxazepam, which is unique among the benzos for its ability to raise neurosteroids that block the rewarding properties of drugs of abuse (Spence AL et al, Drug Alcohol Depend 2016;166:209–217). Oxazepam also has a lower abuse liability than most benzodiazepines when used on its own. On the other hand, amphetamines can lead to benzodiazepine abuse, as patients often turn to benzodiazepines to ease anxiety and other undesirable effects of amphetamines (Darke S et al, Addiction 1994;89(12):1683–1690). That pattern also shows up in practice when clinicians prescribe one drug to manage the side effects of the other." Chris Eiken, MD (September 25, 2022). "The Benzodiazepine-Stimulant Combo: What Could Go Wrong?". Archived from the original on February 18, 2025.} (via: The Carlat Psychiatry Report)

vcu.edu

www2.courses.vcu.edu

"FAQs: Dr. Damaj". Retrieved 4 October 2015.

worldcat.org

search.worldcat.org

Filloon, T. G. (May 1995). "Estimating the minimum therapeutically effective dose of a compound via regression modelling and percentile estimation". Statistics in Medicine. 14 (9–10): 925–932, discussion 933. doi:10.1002/sim.4780140911. ISSN 0277-6715. PMID 7569511.