+<unk>  at opioid receptors Affinities () Ratio MOR:DOR:KOR 0.47 nM 18.5 nM 24.9 nM 1:39:53 + Equianalgesic doses Compound Route Dose Codeine 200 mg Hydrocodone 20–30 mg<unk>  7.5 mg<unk>  1.5 mg Morphine 30 mg Morphine 10 mg Oxycodone 20 mg Oxycodone 10 mg Oxymorphone 10 mg Oxymorphone 1 mg<unk>  is a semi-synthetic μ-opioid agonist. As a hydrogenated ketone of morphine, it shares the pharmacologic properties typical of opioid analgesics.<unk>  and related opioids produce their major effects on the central nervous system and gastrointestinal tract. These include analgesia, drowsiness, mental clouding, changes in mood, euphoria or dysphoria, respiratory depression, cough suppression, decreased gastrointestinal motility, nausea, vomiting, increased cerebrospinal fluid pressure, increased biliary pressure, and increased pinpoint constriction of the pupils. Formulations<unk>  is available in parenteral, rectal, subcutaneous, and oral formulations, and also can be administered via epidural or intrathecal injection.<unk>  also has been administered via nebulization to treat shortness of breath, but it is not used as a route for pain control due to low bioavailability. Transdermal delivery systems are also under consideration to induce local skin analgesia. Concentrated aqueous solutions of<unk>  hydrochloride have a visibly different refractive index from pure water, isotonic 9‰ (0·9 per cent) saline and the like, especially when stored in clear ampoules and phials may acquire a slight clear amber discolouration upon exposure to light; this reportedly has no effect on the potency of the solution, but 14-dihydromorphinones such as<unk> , oxymorphone, and relatives come with instructions to protect from light. Ampoules of solution which have developed a precipitate should be discarded. Battery-powered intrathecal drug delivery systems are implanted for chronic pain when other options are ruled out, such as surgery and traditional pharmacotherapy, provided that the patient is considered a suitable fit in terms of any contraindications, both physiological and psychological. An extended-release (once-daily) version of<unk>  is available in the United States. Previously, an extended-release version of<unk> , Palladone, was available before being voluntarily withdrawn from the market after a July 2005 FDA advisory warned of a high overdose potential when taken with alcohol. As of March 2010, it is still available in the United Kingdom under the brand name Palladone SR, Nepal under the brand name Opidol, and in most other European countries. Pharmacokinetics The chemical modification of the morphine molecule to<unk>  results in higher lipid solubility and greater ability to cross the blood–brain barrier to produce more rapid and complete central nervous system penetration. On a per milligram basis,<unk>  is considered to be five times as potent as morphine; although the conversion ratio may vary from 4–8 times, five times is in typical clinical usage. The development of tolerance also may vary among individuals. Patients with renal abnormalities must exercise caution when dosing<unk> . In those with renal impairment, the half-life of<unk>  may increase to as much as 40 hours. The typical half-life of intravenous<unk>  is 2.3 hours. Peak plasma levels usually occur between 30 and 60 minutes after oral dosing. The onset of action for<unk>  administered intravenously is less than 5 minutes and within 30 minutes of oral administration (immediate release). Metabolism While other opioids in its class, such as codeine or oxycodone, are metabolized via CYP450 enzymes,<unk>  is not.<unk>  is extensively metabolized in the liver to<unk> -3-glucoronide, which has no analgesic effects. As similarly seen with the morphine metabolite, morphine-3-glucoronide, a build-up in levels of<unk> -3-glucoronide may produce excitatory neurotoxic effects such as restlessness, myoclonus and hyperalgesia. Patients with compromised kidney function and older patients are at higher risk for metabolite accumulation.
Hydromorphone
Oxymorphone
Morphine
Nalorphine
Ropivacaine
Butorphanol
Oxymorphol
Sufentanil