DDInter1042 DDInter1166
Leuprolide is a synthetic 9-residue peptide analogue of gonadotropin-releasing hormone (GnRH). Unlike the endogenous decapeptide GnRH, leuprolide contains a single D-amino acid (D-leucyl) residue, which helps to increase its circulating half-life from three to four minutes to approximately three hours. As a GnRH mimic, leuprolide is capable of binding to the GnRH receptor (GnRHR) and inducing downstream modulation of both gonadotropin hormone and sex steroid levels. Prolonged activation of GnRHR results in significant downregulation of sex steroid levels, which is primarily responsible for the clinical efficacy of leuprolide in diverse conditions, including advanced prostate cancer, endometriosis, and central precocious puberty.[A203126, A203132] Leuprolide was first approved in 1985 as a daily subcutaneous injection under the tradename
Methadone is a potent synthetic analgesic that works as a full µ-opioid receptor (MOR) agonist and N-methyl-d-aspartate (NMDA) receptor antagonist. As a full MOR agonist, methadone mimics the natural effects of the body's opioids, endorphins, and enkephalins through the release of neurotransmitters involved in pain transmission. It also has a number of unique characteristics that have led to its increased use in the last two decades; in particular, methadone has a lower risk of neuropsychiatric toxicity compared to other opioids (due to a lack of active metabolites), minimal accumulation in renal failure, good bioavailability, low cost, and a long duration of action.[F4685,F4688,F4691,A185885,A185900,A185903] Due to its unique mechanism of action, methadone is particularly useful for the management of hard to treat pain syndromes such as neuropathic pain and cancer pain requiring higher and more frequent doses of shorter-acting opioids.[A185888,A185891,A185897] Compared with [morphine], the gold standard reference opioid, methadone also acts as an agonist of κ- and σ-opioid receptors, as an antagonist of the N-methyl-D-aspartate (NMDA) receptor, and as an inhibitor of serotonin and norepinephrine uptake.[A497,A5344] Specifically by inhibiting the NMDA receptor, methadone dampens a major excitatory pain pathway within the central nervous system. Compared to other opioids, methadone's effects on NMDA inhibition may explain it's improved analgesic efficacy and reduced opioid tolerance.[A185891,A185894] Methadone shares similar effects and risks of other opioids such as [morphine], [hydromorphone], [oxycodone], and [fentanyl]. However, it also has a unique pharmacokinetic profile. Compared with short-acting and even extended-release formulations of [morphine], methadone displays a comparatively longer duration of action and half-life. These effects make methadone a good option for the treatment of severe pain and addiction as fewer doses are needed to maintain analgesia and prevent opioid withdrawal symptoms. However, methadone also has an unpredictable half-life with interindividual variability, which leads to an unpredictable risk of respiratory depression and overdose when initiating or titrating therapy. Overall, methadone's pharmacological actions result in analgesia, suppression of opioid withdrawal symptoms, sedation, miosis, sweating, hypotension, bradycardia, nausea and vomiting (via binding within the chemoreceptor trigger zone), and constipation. At higher doses, methadone use can result in respiratory depression, overdose, and death.[F4685,F4688,F4691] Treatment of opioid addiction with methadone, [buprenorphine], or slow-release oral [morphine] (SROM) is termed Opioid Agonist Treatment (OAT) or Opioid Substitution Therapy (OST). The intention of substitution of illicit opioids with the long-acting opioids used in OAT is to prevent withdrawal symptoms for 24-36 hours following dosing to ultimately reduce cravings and drug-seeking behaviours. Use of OAT is also intended to lead to social stabilization by reducing crime rates, incarceration, use of illicit opioids such as [heroin] or [fentanyl], and ultimately marginalization. Illegally purchased opioids present many other harms in addition to overdose as they can be injected and may be laced with other substances that increase the risk of harm or overdose. Provision of OAT is often combined with education about harm reduction including use of clean needles and injection supplies in an effort to reduce the risks associated with injection drug use such as contraction of HIV and Hepatitis C and other complications including skin infections, abscesses, or endocarditis.
Methadone {u} (Compound) resembles {v} (Compound) Diphenoxylate
Methadone {u} (Compound) resembles {v} (Compound) Ethopropazine
Methadone {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Trospium
Methadone {u} (Compound) binds {v} (Gene) CYP2B6
Methadone {u} (Compound) is included by {v} (Pharmacologic Class) Full Opioid Agonists
Methadone {u} (Compound) causes {v} (Side Effect) Cardiomyopathy
Methadone {u} may cause a minor interaction that can limit clinical effects when taken with {v} Ammonium chloride
Methadone {u} may cause a minor interaction that can limit clinical effects when taken with {v} Peginterferon alfa-2a
Methadone {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Alpelisib
Methadone {u} may lead to a major life threatening interaction when taken with {v} Naltrexone
Methadone (Compound) resembles Diphenoxylate (Compound)
Methadone (Compound) resembles Ethopropazine (Compound)
Methadone may cause a moderate interaction that could exacerbate diseases when taken with Trospium
Methadone (Compound) binds CYP2B6 (Gene)
Methadone (Compound) is included by Full Opioid Agonists (Pharmacologic Class)
Methadone (Compound) causes Cardiomyopathy (Side Effect)
Methadone may cause a minor interaction that can limit clinical effects when taken with Ammonium chloride
Methadone may cause a minor interaction that can limit clinical effects when taken with Peginterferon alfa-2a
Methadone may cause a moderate interaction that could exacerbate diseases when taken with Alpelisib
Methadone may lead to a major life threatening interaction when taken with Naltrexone