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Another group of substances that have R<10 are sex hormone modulators indicated as antineoplastics. Examples in this group are estrogen receptor antagonists and estrogen receptor modulators, which can cause adverse effects on reproduction and EFD. In this group, estrogen receptor agonists, in addition to the EFD effects, were found to also have carcinogenic potential. Aromatase and androgen receptor inhibitors, as well as antiandrogens, are also consistently found in the group where R<10. For example, tamoxifen citrate is a selective estrogen receptor modulator (SERM). Tamoxifen and several of its metabolites are thought to act as estrogen antagonists by competitively binding to estrogen receptors on tumor and other tissue targets, producing a nuclear complex that decreases DNA synthesis. This mechanism appears to cause cells to accumulate in G0 and G1 phases and may induce apoptosis independent of estrogen receptor expression. It is also recognized that tamoxifen acts as an estrogen agonist on endometrium, bone, and lipids. Primary uses of tamoxifen are brain tumors, breast cancer, melanoma, and soft tissue sarcoma. Other uses are carcinoid tumor, endometrial cancer, and pancreatic cancer. Reproductive toxicity and non-genotoxic carcinogenicity have been reported for other SERMs such as raloxifene hydrochloride and lasofoxifene tartrate. Raloxifene and lasofoxifene have been shown to be teratogenic whereas tamoxifen may be potentially teratogenic (15).

References

  1. JEVTANA Prescribing Information. Bridgewater, NJ: sanofi-aventis . LLC; September 2017.
  2. Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version ). Eur J Cancer . 2009;45(2):228-247.
  3. Data on file. Clinical study report (TROPIC). A randomized, open label multicenter study of XRP6258 at 25 mg/m 2 in combination with prednisone every 3 weeks compared to mitoxantrone in combination with prednisone for the treatment of hormone refractory metastatic prostate cancer previously treated with a Taxotere-containing regimen. Study number EFC6193. Sanofi-aventis. March 18, 2010.
  4. National Comprehensive Cancer Network ® . Clinical Practice Guidelines in Oncology™: Prostate Cancer. V2. 2017

REFERENCES: 1. BELBUCA ® (Prescribing Information). Raleigh, NC: BioDelivery Sciences International, Inc.; December 2016. 2. Data on file, DOF-BL-20. BioDelivery Sciences International, Inc.; 2016. 3. Data on file, DOF-BL-03. BioDelivery Sciences International, Inc.; 2015. 4. Gimbel J, Spierings ELH, Katz N, Xiang Q, Tzanis E, Finn A. Efficacy and tolerability of buccal buprenorphine in opioid-experienced patients with moderate to severe chronic low back pain: results of a phase 3, enriched enrollment, randomized withdrawal study. Pain. 2016;157(11):2517-2526. 5. Data on file, DOF-BL-01. BioDelivery Sciences International, Inc.; 2016. 6. Data on file, DOF-BL-11. BioDelivery Sciences International, Inc.; 2016. 7. Therapeutic Research Center. Equianalgesic dosing of opioids for pain management. New Hampshire Medical Society website. https:///sites/default/files/Pdfs/Opioid-Comparison-Chart-Prescriber-Letter-. Published 2012. Accessed May 9, 2017. 8. McPherson ML. Transdermal and parenteral fentanyl dosage calculations and conversions. In: McPherson ML, ed. Demystifying Opioid Conversion Calculations: A Guide to Effective Dosing. 1st ed. Bethesda, MD: AHSP; 2009:83-106. 9. Drug Enforcement Administration. Questions & Answers – Prescriptions. US Department of Justice website. https:///faq/. Accessed May 9, 2017. 10. Drug Enforcement Administration. Controlled Substances – by CSA Schedule. US Department of Justice website.

At sub-anesthetic doses, dissociatives alter many of the same cognitive and perceptual processes affected by other hallucinogenic drugs such as mescaline , LSD , and psilocybin ; hence they are also considered hallucinogenic , and psychedelic . [11] [12] [13] [14] Perhaps the most significant subjective differences between dissociatives and the classical hallucinogens (such as LSD and mescaline ) are the dissociative effects, including: depersonalization , the feeling of being unreal, disconnected from one's self, or unable to control one's actions; and derealization , the feeling that the outside world is unreal or that one is dreaming. [15]

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At sub-anesthetic doses, dissociatives alter many of the same cognitive and perceptual processes affected by other hallucinogenic drugs such as mescaline , LSD , and psilocybin ; hence they are also considered hallucinogenic , and psychedelic . [11] [12] [13] [14] Perhaps the most significant subjective differences between dissociatives and the classical hallucinogens (such as LSD and mescaline ) are the dissociative effects, including: depersonalization , the feeling of being unreal, disconnected from one's self, or unable to control one's actions; and derealization , the feeling that the outside world is unreal or that one is dreaming. [15]

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