Morphine dextropropoxyphene

The prototypical opioid is morphine (A.137) (Figure A.39). Isolated in a crude form, called opium, morphine has been recognized as a potent pain killer for thousands of years. Although effective, morphine has a low oral availability (F = 25%). Two common derivatives of morphine include hydrocodone (Vicodin, A.138) and oxycodone (A.139), both of which have oral availabilities of greater than 75%. Oxycodone is often sold in an oral continuous-release form under the trade name of OxyContin. Not all opioids are semisynthetic derivatives of morphine. Dextropropoxyphene (Darvon, A.140) and tramadol (Tramal, A.141) are fully synthetic opioids. Both compounds preserve the pharmacophore of morphine as described in the morphine rule (see Chapter 11). Dextropropoxyphene and tramadol are depicted in Figure A.39 to highlight possible pharmacologically active conformations that resemble morphine. 

The most known narcotics are the opium alkaloids such as morphine, codeine, thebaine, papaverine, noscapine and their derivatives and modified compounds such as nalmorphine, apomorphine, apomopholcodine, dihydrocodeine, hydro-morphone and heroine, also known as diamorphine. Synthetic narcotics share the structural skeleton of morphine and include dextromethorphan, pentazocine, phenazocine meperidine (pethidine), phentanyl, anfentaitil, remifentalin, methadone, dextropropoxyphene, levoproxyphene, dipipanone, dextromoramide, meptazinol and tramadol. Thebaine derivatives are also modified narcotics and include oxycodone, oxymorphone, etorphine, buprenorphine, nalbuphine, naloxone or naltrexone. Narcotics can be semi-synthesized or totally synthesized from the morphine and thebaine model. The compounds serve various purposes in clinical practise. 

Opioid receptor binding Dextropropoxyphene has a lower p-opioid receptor binding capacity than morphine. Binding at other opioid receptors is even weaker. 

O Neill, W.M. et al., The cognitive and psychomotor effects of morphine in healthy subjects a randomized controlled trial of repeated (four) oral doses of dextropropoxyphene, morphine, lorazepam and placebo, Pain, 85, 209, 2000. 

Drugs in this therapeutic group include morphine, heroin, pethidine, methadone, codeine, dihydrocodeine, dextropropoxyphene, pentazocine, phenazocine, levorphanol and buprenorphine. The principal antagonists in clinical use are naloxone and naltrexone (see Figure 15.3). 

In common with other opioids, dextropropoxyphene can produce dependence (11). However, it has also been used to withdraw patients from morphine (12). 

Dextropropoxyphene 65 mg Oral 6-32 (norpropoxyphene Moderate pain As morphine cardiotoxicity, not... 

Renal insufficiency can result in clinically significant accumulation of pharmacologically active opioid metabolites and prolonged narcosis such patients must be monitored for signs of toxicity (SEDA-17, 79) (SEDA-21, 85) (98,99). To date, this effect has only been reported with codeine, morphine, and pethidine. Dextropropoxyphene is not recommended in renal insufficiency, as its metabolite norpropoxyphene, which is eliminated by the kidneys, accumulates, causing cardiac depression (SEDA-17, 79) (SEDA-21, 85). 

In general the opioid analgesics can enhance the CNS depressant effects of alcohol, which has been fatal in some cases this appears to be a particular problem with dextropropoxyphene. Alcohol has been associated with rapid release of hydromorphone and morphine from extended-release preparations, which could result in potentially fatal doses. Acute administration of alcohol and methadone appears to increase the blood levels of methadone. The bioavailability of dextropropoxyphene is increased by alcohol... 

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