DDInter458 DDInter1166
Cyclosporine is a calcineurin inhibitor known for its immunomodulatory properties that prevent organ transplant rejection and treat various inflammatory and autoimmune conditions. It is isolated from the fungus _Beauveria nivea_. Initially manufactured by Sandoz and approved for use by the FDA in 1983, cyclosporine is now available in various products by Novartis (previously known as Sandoz).[L11097,L3734,L11118]
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.
Cyclosporine {u} (Compound) binds {v} (Gene) CYP2C9
CYP2C9 {u} (Gene) is bound by {v} (Compound) Methadone
Cyclosporine {u} (Compound) causes {v} (Side Effect) Somnolence
Somnolence {u} (Side Effect) is caused by {v} (Compound) Methadone
Cyclosporine {u} (Compound) binds {v} (Gene) CYP2C9
CYP2C9 {u} (Gene) is bound by {v} (Compound) Clotrimazole
Clotrimazole {u} (Compound) resembles {v} (Compound) Methadone
Cyclosporine {u} (Compound) causes {v} (Side Effect) Somnolence
Somnolence {u} (Side Effect) is caused by {v} (Compound) Darifenacin
Darifenacin {u} (Compound) resembles {v} (Compound) Methadone
Cyclosporine {u} (Compound) causes {v} (Side Effect) Amenorrhoea
Amenorrhoea {u} (Side Effect) is caused by {v} (Compound) Ifosfamide
Ifosfamide {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Methadone
Cyclosporine {u} (Compound) causes {v} (Side Effect) Lacrimation increased
Lacrimation increased {u} (Side Effect) is caused by {v} (Compound) Metronidazole
Metronidazole {u} may cause a minor interaction that can limit clinical effects when taken with {v} Methadone
Cyclosporine {u} (Compound) binds {v} (Gene) CYP3A5
CYP3A5 {u} (Gene) is bound by {v} (Compound) Modafinil
Modafinil {u} (Compound) resembles {v} (Compound) Methadone
Cyclosporine {u} (Compound) causes {v} (Side Effect) Anxiety
Anxiety {u} (Side Effect) is caused by {v} (Compound) Trimipramine
Trimipramine {u} (Compound) resembles {v} (Compound) Methadone
Cyclosporine {u} (Compound) causes {v} (Side Effect) Hypomagnesaemia
Hypomagnesaemia {u} (Side Effect) is caused by {v} (Compound) Bexarotene
Bexarotene {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Methadone
Cyclosporine {u} (Compound) causes {v} (Side Effect) Fracture
Fracture {u} (Side Effect) is caused by {v} (Compound) Abiraterone
Abiraterone {u} may lead to a major life threatening interaction when taken with {v} Methadone
Cyclosporine (Compound) binds CYP2C9 (Gene) and CYP2C9 (Gene) is bound by Methadone (Compound)
Cyclosporine (Compound) causes Somnolence (Side Effect) and Somnolence (Side Effect) is caused by Methadone (Compound)
Cyclosporine (Compound) binds CYP2C9 (Gene) and CYP2C9 (Gene) is bound by Clotrimazole (Compound) and Clotrimazole (Compound) resembles Methadone (Compound)
Cyclosporine (Compound) causes Somnolence (Side Effect) and Somnolence (Side Effect) is caused by Darifenacin (Compound) and Darifenacin (Compound) resembles Methadone (Compound)
Cyclosporine (Compound) causes Amenorrhoea (Side Effect) and Amenorrhoea (Side Effect) is caused by Ifosfamide (Compound) and Ifosfamide may cause a moderate interaction that could exacerbate diseases when taken with Methadone
Cyclosporine (Compound) causes Lacrimation increased (Side Effect) and Lacrimation increased (Side Effect) is caused by Metronidazole (Compound) and Metronidazole may cause a minor interaction that can limit clinical effects when taken with Methadone
Cyclosporine (Compound) binds CYP3A5 (Gene) and CYP3A5 (Gene) is bound by Modafinil (Compound) and Modafinil (Compound) resembles Methadone (Compound)
Cyclosporine (Compound) causes Anxiety (Side Effect) and Anxiety (Side Effect) is caused by Trimipramine (Compound) and Trimipramine (Compound) resembles Methadone (Compound)
Cyclosporine (Compound) causes Hypomagnesaemia (Side Effect) and Hypomagnesaemia (Side Effect) is caused by Bexarotene (Compound) and Bexarotene may cause a moderate interaction that could exacerbate diseases when taken with Methadone
Cyclosporine (Compound) causes Fracture (Side Effect) and Fracture (Side Effect) is caused by Abiraterone (Compound) and Abiraterone may lead to a major life threatening interaction when taken with Methadone