oceanview88

Dex is an NMDA receptor blocker. This receptor is believed to control pain tolerance and opiate tolerance. Methadone and levodromoran are the only opiates that have this ability to block the receptor.

There is a new OTC med called Dexalone that is a dex capsule that some docs are adding to peoples mix.

Drugs that bind rather than block this receptor have shown to cause hyperanelgesia "more pain" so by blocking the NMDA receptor you can give morphine or oxy the same quality that methadone has as far as slow tolerance, and increased efficacy on neuro pain.

Search for info on the NMDA receptor and you will find what your looking for. Ocean
Article:
Methadone Rediscovered

Methadone is a potent synthetic opioid agonist that has been available for over 50 years. Methadone has been somewhat stigmatized by the medical and lay public as the “heroin addict’s drug”, but it is a very useful, cost-effective agent for treating chronic pain and cancer pain that is non-responsive or refractory to high doses of other opioid agonists (morphine, hydromorphone, oxycodone, fentanyl) due to tolerance or disease progression. Methadone is also useful for the treatment of severe neuropathic pain requiring high-dose opioid therapy where the addition of tricyclic antidepressants and anticonvulsants has been ineffective. It also has a role when high doses of other opioids produce significant financial impact to the patient or the patient experiences intolerable adverse effects from other opioids.

Methadone is a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist and mu-receptor agonist. NMDA – receptor activation results in central sensitization, which is implicated in hyperalgesia, allodynia, and opioid tolerance. Blocking the NMDA receptors may reduce tolerance to opioids and improve neuropathic pain control, thus the current interest in methadone therapy for chronic pain syndromes. Methadone historically has not been utilized because of the risk of cumulative toxicity but more knowledge about its pharmacokinetics and equianalgesic dosing when switching from other opioids has led to its rediscovery.

Methadone is a basic and lipophilic agent that has a large initial volume of distribution. Tissue levels greatly exceed plasma levels with repeated dosing. It has a long elimination half-life that can reach 128 hours with continued dosing. This is due to a slow release from tissues into the bloodstream. This slow tissue release sustains the plasma level, which decreases in a biexponential fashion. The long half-life explains the cumulative toxicity and allows methadone to be administered once or twice daily. Methadone has an oral biovailability of approximately 80%. The oral route is preferred although methadone may be administered by the intravenous, rectal, epidural, intramuscular, and subcutaneous routes. The analgesic effect of oral methadone after single dose administration begins within 30 to 60 minutes and lasts for 4 to 6 hours. As mentioned previously, the long terminal half-life with repeated dosing results in a longer duration of action and subsequent dose changes take time to reach an effect, which makes methadone less suitable as an agent for breakthrough pain. Methadone has no known active metabolites and can be used safely in patients with renal dysfunction. It can be used in patients with chronic stable hepatic disease, but should be titrated to effect.

Once the pharmacokinetics of methadone is appreciated, one has to become familiar with the equianalgesic dosing conversion from other opioids to methadone. Currently, published equianalgesic dosing tables grossly underestimate the potency of methadone and are based on single dose conversions. Most tables for morphine to methadone conversion suggest a 1:1 or 1:4 ratio. The equianalgesic dose of methadone is much lower in patients treated previously with high doses of opioids:

Morphine – methadone conversion ratios

Daily oral morphine dose Approximate conversion ratio

< 100 mg 3:1

101-300 mg 5:1

301-600 mg 10:1

601-800 mg 12:1

801-1000 mg 15:1

>1001 mg 20:1

To initiate methadone therapy, a loading dose of 25% to 50% extra is used during the first 2 days to allow for saturation of body tissues. This should be avoided in the frail and elderly and in those on other sedating medications. For instance, a patient is taking sustained release morphine 300 mg twice a day. The predicted maintenance dose of methadone is 60 mg daily. A loading dose of 80 mg per day is given as 20 mg four times a day for the first 2 days, reduced to 20 mg three times a day on day three, simplified to 30 mg twice a day on day five. To highlight cost savings, the cost difference based on average wholesale price is $39.48 per day for MS Continâ 600 mg compared to $0.87 for 60 mg of methadone. Immediate release opioids (e.g. morphine, oxycodone) should be provided for breakthrough pain. Dose adjustments of methadone should be performed in the morning for monitoring purposes. Dose reductions should be initiated whenever indicated using standard assessment parameters.

Methadone shares all of the common toxicities associated with other opioid agonists. Patients over 65 years of age have reduced methadone clearance and need cautious dosing and supervision. Methadone, when dosed properly, is a valuable addition for clinicians treating severe cancer pain, cancer pain with a neuropathic component, pain that is poorly responsive to other opioids, or when finances dictate a change based on other high-dose therapies.



[This message has been edited by oceanview88 (edited 07-15-2003).]