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Old 09-28-2006, 11:50 AM
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mrsD mrsD is offline
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Join Date: Aug 2006
Location: Great Lakes
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mrsD mrsD is offline
Wisest Elder Ever
mrsD's Avatar
 
Join Date: Aug 2006
Location: Great Lakes
Posts: 33,508
15 yr Member
Post Critical Methadone warnings:

I had this information up on the chronic pain board, at OBT.
So I am moving it here as well.

In the news just this week is the tragic death of Anna Nicole Smith's 20yr old
son. 2 days ago I saw the Cyril Wecht who was hired by Ms Smith to do the
autopsy reported on Court TV that the death is being called a Torsade de Pointes or in English a Prolongation of QT and sudden cardiac death.
Daniel Smith had Zoloft, Lexapro (why both is confusing) and METHADONE in
his tox screen results. Methadone is the only opiate to cause this interaction and effect on the heart. So patients who are using this opiate for pain
management need to be aware that 1) they should be evaluated for prolongation of QT with an EKG before treatment is started, and 2) use of
drugs that appear on the lists for causing this could be additive with methadone.

Some new papers have surfaced in the medical community warning physicians to screen their patients for cardiac risk.
http://jama.ama-assn.org/cgi/content/extract/290/8/1025
But not all doctors read the newest findings. So I am putting them here
for readers on this board.

Quote:
Pharmacotherapy. 2005 Nov;25(11):1523-9. Related Articles, Links

Effects of Methadone on QT-Interval Dispersion.

Krantz MJ, Lowery CM, Martell BA, Gourevitch MN, Arnsten JH.

1. Department of Medicine, Denver Health Medical Center, Denver, Colorado.

Study Objective. To evaluate the effects of methadone on QT-interval dispersion. Design. Single-center, prospective, cohort study. Setting. Methadone maintenance treatment facility. Patients. One hundred eighteen patients who were newly admitted to the facility. Intervention. Twelve-lead electrocardiograms (ECGs) were performed in patients at both baseline and 6 months after the start of methadone therapy. Measurements and Main Results. The ECGs were manually interpreted, and investigators were blinded to time interval and methadone dose. At least eight discernible ECG leads were required for study inclusion. Mean differences between baseline and follow-up rate-corrected QT (QTc) interval and QT dispersion were compared. Multivariate associations between clinical characteristics and magnitude of change in QT dispersion were assessed using linear regression. Mean +/- SD baseline QT dispersion was 32.9 +/- 12 msec, which increased to 42.4 +/- 15 msec (+9.5 +/- 18.6 msec, p<0.0001) after 6 months of therapy. The QTc increased by a similar magnitude (+14.1 msec, p<0.0001). No QT dispersion value exceeded 100 msec. The only variable associated with a greater increase in QT dispersion was antidepressant therapy (20 vs 8.5 msec, p=0.04). Conclusion. Methadone modestly increased both QTc interval and QT dispersion. Increased QT dispersion reflects heterogeneous cardiac repolarization and occurs with nonantiarrhythmic agents, such as synthetic opioids. However, the magnitude of this effect appears to be substantially less with methadone than with antiarrhythmic drugs.

PMID: 16232014 [PubMed - in process]
And:
Quote:
Tidsskr Nor Laegeforen. 2005 Aug 11;125(15):2021-2. Related Articles, Links
Click here to read
[Methadone-induced heart arrhythmia]

[Article in Norwegian]

Ostvold C, Topper M.

Hjerteseksjonen, Medisinsk avdeling, Sykehuset Telemark, 3710 Skien.

There is an ongoing debate over whether it is necessary to screen patients with an ECG before and during therapy with methadone. We present two patients who developed QT prolongation and sustained ventricular arrhythmias during treatment. Our experience as well as a literature survey indicate that an ECG should be performed before and during long-term methadone treatment.

Publication Types:

* Case Reports


PMID: 16100543 [PubMed - indexed for MEDLINE]
and
Quote:
Swiss Med Wkly. 2005 May 14;135(19-20):282-5. Related Articles, Links
Click here to read
Methadone-induced Torsade de pointes tachycardias.

Sticherling C, Schaer BA, Ammann P, Maeder M, Osswald S.

University Hospital Basel, Div. of Cardiology, Basel, Switzerland. csticherling@uhbs.ch

Methadone is a synthetic opioid frequently used in drug maintenance programs for heroin addicts. It prolongs the QT-interval and is mainly metabolized by the isoenzyme CYP3A4 of the hepatic cytochrome-P450-system, which is used by numerous other QT-prolonging agents. Its most severe side effect is the development of life-threatening Torsade de pointes ventricular tachycardia in the setting of a prolonged QT-interval. Since drug addicts are prone to concomitant medical conditions requiring additional medication as well as to continued abuse of cocaine, they are at higher risk for developing this major complication of methadone therapy. Before subjecting patients on methadone to other drugs, the QT-interval should be determined and it should be ascertained whether the new agent has the property to prolong the QT-interval or is metabolised by the cytochrome-P450 system.

Publication Types:

* Review


PMID: 15986265 [PubMed - indexed for MEDLINE]
At risk are people who are magnesium deficient or low in potassium, who genetically inherited this trait, who use multiple drugs that can cause this in an additive or synergistic manner, anorexics or who are poor metabolizers (this is genetic also).

It is difficult to find illustrations of the electrocardiogram that illustrate the QT tracing. I used to have a good link here, but it closed.
Most people watch TV and see doctor shows, which show this tracing on the monitors. All of the separate parts of the graph have labels, from Q, R, S, T, and the timing for this can be measured. When the timing gets prolonged, the heart cannot maintain its built in rhythm and the ventricles begin to beat independently, and may go into a fib condition (trembling) and the heart must be reset with a shock, using the paddles.


The University of Arizona keeps a good up to date list on four categories of drugs involving QT issues. Here is their new website:
http://www.azcert.org/
The 4 lists of drugs are on PDF files and don't have links.

Anyone on Methadone should print out what I have posted here and take to their doctor, if cardiac concerns have not been discussed. Not all doctors understand the new methadone data or have read it. There is still a general
assumption that all opiates are not QT risks. And that is no longer true.

Adding a link here:
http://www.ptcommunity.com/ptjournal...PTJ3103159.pdf
This link discusses the common use of proton pump inhibitors (Prilosec, Nexium, Aciphex, Prevacid, Protonix) and how these
drugs affect other medications and absorption. Listed is methadone, which is enhanced by these drugs. So people on methadone for pain could have dosage problems if taking a PPI at the same time. Be careful

adding a link re FDA warning on Haldol and QT
http://www.fda.gov/cder/drug/InfoShe...aloperidol.htm

This link is to a site that explains the genetics of drug metabolism.
People who are "slow metabolizers" are at greater risk for drug interactions or negative responses to certain drugs:
http://www.dnadirect.com/web/article...s/186/ancestry
and
http://www.dnadirect.com/web/article...574439B11AEAF2
__________________
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These forums are for mutual support and information sharing only. The forums are not a substitute for medical advice, diagnosis or treatment provided by a qualified health care provider. Always consult your doctor before trying anything you read here.

Last edited by mrsD; 05-21-2009 at 04:51 AM. Reason: fixing old links
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