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 hydromorphone is available in the United States. Previously, an extended-release version of hydromorphone, Palladone, was available before being voluntarily withdrawn from the market after a July 2005 FDA advisory warned of a high overdose potential when taken with alcohol.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 hydromorphone 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, hydromorphone 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 hydromorphone. In those with renal impairment, the half-life of hydromorphone may increase to as much as 40 hours. The typical half-life of intravenous hydromorphone is 2.3 hours. Peak plasma levels usually occur between 30 and 60 minutes after oral dosing. The onset of action for hydromorphone 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, hydromorphone is not. Hydromorphone is extensively metabolized in the liver to hydromorphone-3-glucuronide, which has no analgesic effects. As similarly seen with the morphine metabolite, morphine-3-glucuronide, a build-up in levels of hydromorphone-3-glucuronide 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. Chemistry With a formula of C17H19NO3 and a molecular weight of 285.343, both identical to morphine, hydromorphone can be considered a structural isomer of morphine and is a hydrogenated ketone thereof. Hydromorphone is made from morphine either by direct re-arrangement (made by reflux heating of alcoholic or acidic aqueous solution of morphine in the presence of platinum or palladium catalyst) or reduction to dihydromorphine (usually