The Metabolism of Opioid Agents and the Clinical Impact of Their Active Metabolites

Smith, Howard S.

doi:10.1097/ajp.0b013e31821d8ac1

Cited by 104 publications

(69 citation statements)

References 155 publications

(186 reference statements)

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“…PCA [27]. Additionally, sufentanil is not processed into active metabolites, while morphine and hydromorphone produce active glucuronide intermediates which may accumulate to a greater degree than their parent drugs and may cause adverse effects [24,[40][41]. In a Phase III study comparing SSTS and iv.…”

Section: • Pharmacodynamics (Sufentanil)mentioning

confidence: 97%

“…PCA, has a drug offset time that increases with infusion durations of greater than 4 h [22], potentially exposing the patient to prolonged drug effects [23]. Furthermore, opioids may be processed into active metabolites that may increase the risk for prolonged sedation or other adverse events (see table 1) [24]. Recent analyses showed that opioid-induced adverse drug reactions led to complications that increased treatment costs and hospital stays [25,26].…”

Section: Practice Pointsmentioning

confidence: 98%

“…Sufentanil is processed in the liver by a CY P450 (CY P) enzyme, CY P3A4 [24] . Co-administration of drugs that affect CYP3A4 function may, therefore, interfere with sufentanil metabolism.…”

Section: Drug Interactionsmentioning

confidence: 99%

“…PCA usage, a novel approach to PCA was developed to reduce the risk of dosestacking-, pump-and iv.-related complications by pairing an opioid optimized for on-demand analgesia with a noninvasive route of delivery. This article focuses on the development of the sufentanil sublingual tablet system (SSTS) for the control of moderate-to-severe pain following major orthopedic (total knee arthroplasty [TKA] [24] Fentanyl 277 [27] 6.6 [28] None Hydromorphone 232 [29,30] 46 [20] H3G; Morphine 71 [27] 168 [19] M3G; M6G Sufentanil 26,716 [27] 6.2 [28] None †…”

Section: Practice Pointsmentioning

confidence: 99%

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A Review of Sufentanil and the Sufentanil Sublingual Tablet System for Acute Moderate to Severe Pain

Minkowitz¹

2015

Pain Manag.

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The sufentanil sublingual tablet system (SSTS) is a novel patient-controlled analgesia (PCA) system that is pending approval from the US FDA for the management of moderate to severe acute pain in hospitalized patients. SSTS offers a noninvasive alternative to intravenous (iv.) PCA and optimized on-demand analgesia with the rapid onset and titratibility of sublingual sufentanil. Phase III clinical trials have demonstrated that SSTS has greater efficacy for the treatment of pain during the 72-h postoperative period after open abdominal and major orthopedic (total knee or total hip arthroplasty) surgery compared with iv. PCA with morphine sulfate (MS) or a placebo system. Safety assessments indicate that adverse events are typical for postoperative patients taking opioid analgesics. While the frequency of adverse events is comparable between patients using SSTS and iv. PCA MS, the incidence of oxygen desaturation is lower in those using SSTS.

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Section: • Pharmacodynamics (Sufentanil)mentioning

confidence: 97%

Section: Practice Pointsmentioning

confidence: 98%

Section: Drug Interactionsmentioning

confidence: 99%

Section: Practice Pointsmentioning

confidence: 99%

See 2 more Smart Citations

A Review of Sufentanil and the Sufentanil Sublingual Tablet System for Acute Moderate to Severe Pain

Minkowitz¹

2015

Pain Manag.

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“…One of the most common non-CYP enzymes associated with pain medications is UDP-glucuronosyltransferase (UGT) [44]. UGT is the main metabolizer of morphine, creating morphine-6-glucuronide (M3G), which contributes to pain relief, and morphine-3-glucuronide (M3G), which is hyperalgesic (causing increased pain).…”

Section: Opioid Metabolismmentioning

confidence: 99%

Genetic Testing for Opioid Pain Management: A Primer

2017

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Patients see their primary care physicians (PCPs) for a variety of medical conditions, chronic pain being one of the most common. An increased use of prescription medications (especially opioids) has led to an increase in adverse drug reactions and has heightened our awareness of the variability in response to medications. Opioids and other pain adjuvants are widely used, and drug–drug interactions involving these analgesics can be problematic and potentially lethal. Pharmacogenetics has improved our understanding of drug efficacy and response, opened doors to individual tailoring of medical management, and created a series of ethical and economic considerations. Since it is a relatively new field, genetic testing has not been fully integrated into the primary care setting. The purpose of this paper is to review the metabolism of commonly prescribed opioids, discuss the economic and ethical issues, and provide PCPs with an understanding of how to incorporate genetic testing into routine use to improve clinical practice and patient management.

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Reconsidering Reliance on Confirmatory Drug Testing in a Patient With Repeated Positive Urine Drug Screen Results

2021

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A 40-year-old woman with a history of polysubstance use presented to a methadone clinic with opioid use disorder and housing instability. The patient, who reported injecting intermittent cocaine and 2 to 3 g of what she believed to be fentanyl per day, was initiated on methadone therapy. Results of a urine drug screen (UDS) on her presentation day were positive for fentanyls and confirmed by liquid chromatography-mass spectrometry (parent fentanyl = 20.0 ng/mL, metabolite norfentanyl = 337.0 ng/mL). On day 23, results of her UDS and confirmatory testing were again positive for fentanyls, although no parent fentanyl was detected on confirmation, and the norfentanyl metabolite concentration (0.7 ng/mL) was barely above the detection threshold (0.5 ng/mL). This result was misinterpreted as the patient having relapsed, and she was discharged from clinic-associated housing despite her disavowal of new fentanyl use. Results of UDS on days 30 and 45 were negative for fentanyls. The patient struggled to maintain sobriety owing to

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The Metabolism of Opioid Agents and the Clinical Impact of Their Active Metabolites

Abstract: A greater appreciation of the metabolism of commonly prescribed opioid analgesics and the impact of their active metabolites on efficacy and safety may aid prescribers in tailoring care for optimal outcomes.

Cited by 104 publications

References 155 publications

A Review of Sufentanil and the Sufentanil Sublingual Tablet System for Acute Moderate to Severe Pain

A Review of Sufentanil and the Sufentanil Sublingual Tablet System for Acute Moderate to Severe Pain

Genetic Testing for Opioid Pain Management: A Primer

Reconsidering Reliance on Confirmatory Drug Testing in a Patient With Repeated Positive Urine Drug Screen Results

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