s Methadone induced long QTc and "torsade de pointe". Bittar P, Piguet V, Kondo-Oestreicher J et al. Swiss Medical Forum 2002 S4;P | I2P: Information to Pharmacists - Archive
Publication Date 01/07/2009         Volume. 1 No. 2   
Information to Pharmacists

Editorial

From the desk of the editor

Welcome to the July edition of i2P, and of course, the first week of the new financial year.

Note that we are developing a new range of categories for you to follow e.g. health politics, hospital news, an expanded IT offer and we will be developing the category of anti-ageing medicine

Also, out of interest, could I refer you to the e-publications category located immediately below our columnists. If you click on the link contained there, you will find a range of e-publications that are recommended reading.

The first publication noted is the Pharmacist Activist written by Dr Daniel A. Hussar of the faculty of the Philadelphia College of Pharmacy at the University of the Sciences in Philadelphia. He is a pharmacy advocate.

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Recent Comments

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I’ve seen the future…….and I’m not happy, Jan!

Chris Wright

The ubiquitous Mrs Wright, in her quest to unearth a new erotic shopping experience, ushered this writer to a new Coles store located at the all very nice and leafy suburb of Ivanhoe in Melbourne recently.
This is contemporary retailing at its best, no doubt influenced by the gurus at Westfarmers and the rapidly changing retail climate in Australia, which of course involves the future of Pharmacy in some way….but more about Pharmacy later.

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Pharmacists losing their mojo

Neil Retallick

I read some market research recently that ought to concern community pharmacists across the country, as well as the Pharmacy Guild of Australia.
Groups of average Australians were brought together for a series of focus groups to discuss the community pharmacy landscape as they see it.
Some of the feedback was disconcerting.

Comments: 3

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Has the horse bolted?

Ken Stafford

Some twenty years ago uneasy tremors were running through hospital pharmacy here in Perth. Hospital management had suggested to one of my fellow Chief Pharmacists that the hospital needed a total parenteral and intravenous additive service (IVAS) .
When it was pointed out that this would be very labour intensive and the pharmacy did not have sufficient staff to provide it, the comment was that “nurses would be happy to run such a service”.

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Independent Pharmacist Practitioners

James Ellerson

In the region where I practice, GP’s are reluctant to comply with a patient request for a Home Medication Review.
The stock standard phrase is “I can do that for you” and so in frustration a patient will turn to me, in a professional, or quite commonly in a social setting, and asks if it is possible for me to perform a review without the doctor’s involvement.

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Disgraceful – discuss

Pat Gallagher

Disgraceful – discuss
The newspapers have been chock-a-block the past few days with dire tales but true about the black hole we are about to enter with the insane policy to re-regulate the ‘workplace’ to suit the union paymaster cliques.
While I never voted for Keating I did admire him a little bit this morning when I read a quote of his from the bad old days.
He said to some union goose: “you are carrying the jobs of (100,000) dead men around your shoulders”.
Giving a dead hand to this union unfettered power play will ensure that the nation will soon look like NSW; where the government is actually the plaything of a few loosely combined public ‘service’ union mugs.
Depending on how large your pharmacy is, in terms of overall staffing, you will soon be touched by the coming dead hand of the new/old order.

Comments: 3

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UK Dispensing Errors Under Review

Staff Writer

The recent furore in the UK over pharmacist Elizabeth Lee receiving a conviction for a criminal offence and subsequently a suspended jail sentence, has really lit a fire under the imbalances that exist when a pharmacy dispensing error is made.
The dispensing pharmacist or the supervising pharmacist under current UK legislation, has been made to bear the brunt of legal responsibility, with pharmacy owners escaping with little pain.
According to an article in PJ Online "In many cases, all that the employer needs to establish is that he had standard operating procedures in place and that the employee or locum had simply not complied with them. In these cases, the employer can walk away leaving the employee or locum to face the, often damaging, consequences".
There is now a rush in the UK to have current legislation amended to reflect a more proportionate responsibility for all parties involved.

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A New Ministery - Indigenous, Rural and Regional Health

Staff Writer

The appointment for the first time of a Minister for Indigenous, Rural and Regional Health and Regional Service Delivery is an important strategic recognition of the special needs and circumstances facing people in Australia's rural and remote communities.
People in the bush will expect this position to be part of a permanent increase in the Government's commitment to rural communities.
In welcoming Minister Warren Snowdon to the new position, Dr Jenny May, Chairperson of the National Rural Health Alliance (NRHA), said the appointment will be important both for substantive policy reasons and to boost the place of rural issues on the political agenda.

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NZ fish killed by water quality

Staff Writer

The following news item was recently published in Science Alert. It would seem that the pristine environment of New Zealand is under attack. The reasons are similar to those findings in Australia surrounding the protection of the Great Barrier Reef.

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New theory for global diabetes epidemic

Staff Writer

A new "fertility first" hypothesis published this week by a group of international experts in the American Journal of Human Biology, proposes that the global epidemic of Type 2 diabetes has its origins in the struggle, over millennia, to sustain human fertility in environments defined by famine.
A surprising and important implication for us in the modern world is that this hypothesis gives cause for optimism that the modern epidemics of diabetes and cardiovascular disease will diminish.
Source: Sydney University

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Immune system key discovered

Staff Writer

A team of Monash University researchers has discovered the importance of a protein, which could improve the way the drug interferon is used to strengthen the human immune system.
Published online in the prestigious journal Immunity, the findings show that the protein promyelocytic leukemia zinc finger (PLZF) is a key player in the body's immune response to disease, increasing our understanding of the function of the immune system.(Source: Science Alert )

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Political suspicions raised as China cracks down on bogus online health info

Staff Writer

China is notable for its authoritarian approach to the Internet and other forms of media communications.
Restrictions on Internet activity may have some long-term implications for Australia, particularly as these restrictions are intruding into the health arena.
Source: Tech.Blorge

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Senior Pharmacists - A Valuable Resource

Staff Writer

Little thought seems to have occurred in maintaining and supporting mature aged pharmacists in the workplace.
Given that this group of pharmacists is the one with the "corporate memory" of the profession, with many having started life as compounding pharmacists and counter-prescribers, there is a wealth of untapped intellectual resource that could be internally utilised in mentoring or even training pharmacists in how to sell a professional service.
This group of pharmacists is concerned with the development of retail clinics proposing to do almost exactly what they were successfully doing 30-40 years ago.
What went wrong?

Well, there is plenty of evidence to illustrate that the process of commoditising medicines is the primary reason for this loss, because if you strip everything out of a process to sell at the cheapest possible price, you get a barren professional offering
Source: Science Alert

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Terry White Makes a Move

Staff Writer

Introduction:

It is clear that the Terry White pharmacy group is on the move with the recent purchase of Pharmacy Direct and a restructure of its own management. Terry has had a distinguished pharmacy career and his stewardship will see possibly the strongest pharmacy group in Australia emerge He is opening up the opportunity for equity for senior members of his management team.
The following excerpt extracted from pharmacy media reports explains the process.

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Methadone induced long QTc and "torsade de pointe". Bittar P, Piguet V, Kondo-Oestreicher J et al. Swiss Medical Forum 2002 S4;P

Dr Andrew Byrne & Associates

articles by this author...

A Harm-Minimisation Research Perspective: Dr Byrne (and his associates) advocate for better policies which are proven to reduce risks for drug users and the general community, under a framework in parallel with Australia’s official policy of harm minimisation.

Dear Colleagues,

This instructive case history which pre-dates Krantz’s report by several months, describes a long term methadone patient aged 39 developing ‘torsade de pointes’ a few days after starting triple therapy for HIV in the context of opioid withdrawal symptoms/signs and low blood levels. The patient also had chronic hepatitis C and epilepsy. As well as valproic acid for the latter, benzodiazepines, cannabis and alcohol were also involved in this seminal case.

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The patient presented to the emergency room in opioid withdrawal. There was no electrolyte disturbance but methadone level was found to be ‘sub-therapeutic’ despite daily doses of 115mg administered by suppository (this is routinely used by some doctors in Switzerland). The QTc interval was available from a month before the episode at 480ms (n < 450ms). That cardiograph may have been ordered as part of a ‘work-up’ prior to starting anti-retroviral therapy but this is not detailed in the text.

While in hospital, 15 minutes following the daily rectal methadone dose the patient developed bradycardia, bigeminy and then torsade tachycardia. He was successfully resuscitated despite major seizures occurring simultaneously. The methadone was replaced by morphine 200mg twice daily which was associated with QTc interval reduction from 480 to 430ms.

Subsequent challenge a few days later with just 40mg methadone saw the QTc interval increase to 520ms and so the trial was abandoned due to the perceived risk. A cardiograph two weeks later showed the QTc interval to be still slightly elevated at 460ms despite the methadone having been long ceased. These observations are consistent with other evidence that methadone causes some modest prolongation of the QT interval and that this effect alone is generally of little clinical significance.

This patient took methadone, valproic acid, alcohol, cocaine and cannabis for at least 7 years without reported cardiac problems and so the onset of torsade during a period when the methadone level was low is hard to ascribe as a direct and dose-related effect. Rather, a combination of factors including possibly some myocardial ‘priming’ may be occurring.

This appears to be the very first of over 100 case reports in the literature of torsade de pointes in patients taking methadone maintenance for addiction. In nearly every case where details are available there were other drugs, extremely high dose, overdose, HIV and/or electrolyte disturbance reported. Pearson has called this a ‘threshold’ effect. Since methadone levels are sometimes in the low range it is possible that the drug is sometimes a ‘bystander’ while other drugs and/or the HIV virus itself might be responsible for the electrical instability in the heart.

Like others, these authors give some details of the management given to the patient. Even 7 years later, there still appears to be little agreement about an approach to treatment as cardiologists, intensivists and emergency physicians describe quite diverse approaches. These have included (1) efforts to maintain heart rate, (2) restoring electrolyte balance, (3) removal of triggering factors and (4) supportive measures. Magnesium and potassium infusions, administration of isoprenaline, atenalol, quinidine, lignocaine, amiodarone (!), glucoheptonate; implantable cardioverter-defibrillator (ICD); reducing methadone; continuing methadone; changing to morphine or buprenorphine. A review of such clinical manoeuvres by a cardiologist would be highly desirable in my view.

Instead of this logical step, Krantz and his panel have advised ‘discussions of risk’ (which are still largely unknown), pre-treatment ECG and continued QT interval monitoring. This is in the context of a lack of evidence for the effectiveness of such a strategy to prevent arrhythmias. Krantz’s group, in their extensive literature review of almost 100 papers left out numerous seemingly relevant articles (eg. Justo, Athanasos, Krook and Cruciani). It is hard to understand how the CSAT panel of experts could have completely overlooked these crucial papers, each of which is available on a simple internet search.

Further, despite the clear association with HIV infection (40% according to Justo), HIV is not even mentioned in the entire Annals paper from March 2009. The drugs gabapentin and ciprofloxacin come up in numerous reports, including 5 of Krantz’s original series of 9 pain management cases. Likewise, the issue of targeting strategies to those taking such medication is not emphasised by the CSAT panel report.

This early report from Switzerland contains some vital but conflicting evidence concerning causation. Like others, these authors find evidence of multifactorial causes for their patient’s torsade tachycardia. Yet there seems to be QT prolongation in relation to methadone dose levels, despite torsade occurring only very rarely in such cases. The cautious trial to reintroduce methadone caused QT prolongation but no arrhythmia. At the same time, it is questionable that a purported side effect of methadone would occur when the blood level was low and the patient was in a drug-induced withdrawal state.

Comments by Andrew Byrne ..

Clinic web page: http://www.redfernclinic.com/c/

References:

1. Justo D, Gal-Oz A, Paran Y, Goldin Y, Zeltser D. Methadone-associated Torsades de Pointes (polymorphic ventricular tachycardia) in opioid-dependent patients. Addiction. 2006 101:1333-1338

2. Krook AL, Waal H, Hansteen V. Routine ECG in methadone-assisted rehabilitation is wrong prioritization. Tidsskr Nor Laegeforen 2004 124;22:2940-1

3. Athanasos P, Farquharson AL, Compton P, Psaltis P, Hay J. Electrocardiogram characteristics of methadone and buprenorphine maintained subjects. J Addict Dis. 2008 27(3):31-5

4. Cruciani R. Methadone: To ECG or Not to ECG…That Is Still the Question. Journal of Pain and Symptom Management 2008 36;5:545-552

 

 

 

 

 

 

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