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Tuesday, July 21, 2015

Losing That Restless Feeling: Drug-Induced Akathisia Treatment Options

Akathisia

Akathisia  (from the Greek καθίζειν: inability to sit) is one of the most prevalent and distressful psychotropic-induced extrapyrimidal adverse effects. It is a neuropsychiatric syndrome characterized by both subjective (inner feeling) and objective (physical symptoms) restlessness.

Due to this inner restlessness, patients may experience fidgeting, pacing, rocking while standing or sitting, crossing and uncrossing legs while sitting, and constant movement of the feet. Patients have also described these feelings as “wanting to jump out of my skin”and as a “crawling skin sensation.” (4)

Among the drugs used to treat delirium, haloperidol, might be the antipsychotic with the highest risk for development of akathisia. (5) The risk for akathisia in patients with delirium taking antipsychotics appears to be a dose-related phenomenon. Effective and well tolerated treatment is a major unmet need in akathisia that merits a search for new remedies.

Assessment Scales

"Studies using specific scales for evaluation of akathisia in delirium are lacking. Some populations, such as patients with cancer or terminally ill patients in palliative care settings taking antipsychotics for the treatment of delirium, could be at higher risk for development of akathisia as a side effect." (5)

The Barnes Akathisia Rating Scale (BARS) is one such scale.

Treatment  

Early management of akathisia is important because it may be associated with poor treatment response and medication noncompliance, and most importantly is distressing to the patient and caregivers. Unfortunately many patients fail to respond to standard management of akathisia (typically benzodiazepines, beta blockers, anticholinergic agents). As medications used to alleviate akathisia symptoms such as anticholinergics and benzodiazepines could potentially worsen delirium, management of akathisia among delirious patients on antipsychotics should be further studied to explore the efficacy of other agents.

In addition to dopaminergic mechanisms, it has been hypothesized that serotonin may play a prominent role in the pathophysiology of akathisia. 

Trazodone  is an antidepressant agent demonstrating prominent serotonergic antagonistic properties. An open-label pilot study investigated the efficacy of trazodone in the management of akathisia. Nine female patients with a score of at least “mild akathisia” on the Barnes Akathisia Scale, and receiving a stable dose of antipsychotic medication, were administered trazodone, titrated up to a dosage of 100 mg/day over a period of 5 days. The patients demonstrated marked improvement in symptoms of akathisia. In addition, some improvement  was  noted  in  symptomatology  of  anxiety,  depression,  and  psychosis. (3)

Low-dose mirtazapine was found to be efficacious for neuroleptic-induced akathisia. (2) "The most compelling evidence indicating that 5-HT2A antagonists may represent a new class of effective anti-akathisia agent comes from the largest-to-date randomised controlled trial comparing low-dose mirtazapine with propranolol in 90 patients with FGA-induced (first-generation antipsychotics) acute akathisia. Mirtazapine is characterised by potent presynaptic alpha-2 adrenergic antagonism, which accounts for its antidepressant activity, and marked 5-HT2A blockade that seems to preponderate in a low dose and contribute to its anti-akathisia properties. Mirtazapine, given once daily (15 mg) was as effective as propranolol (80 mg twice daily) in producing a greater improvement in akathisia compared with placebo (reduction in BARS global scale: 1.10 (s.d. = 1.37) points (34%) and 0.80 (s.d. = 1.11) points (29%) v. 0.37 (s.d. = 0.72) points (11%) respectively; P = 0.036). Responder analysis (BARS global scale reduction 52) yielded a similar robust anti-akathisia effect in mirtazapine and propranolol v. placebo (43.3% and 30% v. 6.7% respectively; P = 0.005). Low numbers needed to treat (3 and 4 respectively) support high clinical efficacy of both compounds. Importantly, mirtazapine achieved an anti-akathisia effect with more convenient dosing than propranolol and better tolerability, with mild transient sedation as the only observed side-effect. The favourable mirtazapine safety profile was also supported by the absence of significant changes in vital signs." (1)

Suggested Approach

Discontinue [alternatively, dose decrease] the offending agent. If this is not possible or ease of symptoms is required, when the decision is to add an anti-akathisia agent

  • propranolol (40–80 mg/day twice daily) or 
  • low-dose mirtazapine (15 mg once daily) as first-line treatment have the most supportive evidence.
  • Mianserin (15 mg once daily) and cyproheptadine (8–16 mg/ day) are alternative options
    • however, large-scale trials are not yet available. (1)

References


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Friday, July 10, 2015

Opioids Available in Canada

The following table highlights currently available prescription opioids in Canada, including formulations and strengths. Any of the coverage notes are specific to the province of Alberta.

Click on the download icon (upper right hand corner) or the title below to view table in full screen mode.

Opioids Available in Canada:

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Thursday, June 11, 2015

Medical Marijauna: All Formulations Now Legal; Cannabis Harms Brain, Fails in Cancer Pain Study


1. You  might have heard the news by now:
- Ruling in Canada this AM:

Medical marijuana legal in all forms, Supreme Court rules (via CBC)

Excerpt:
"Medical marijuana patients will now be able to consume marijuana — and not just smoke it — as well as use other extracts and derivatives, the Supreme Court of Canada ruled today."

This is an important ruling for patients as we see more and more form - for instance, with cannabis oil  being all the buzz these days.
2. That's the "good" news for patients; now for some sobering updates:

Cannabis Harms Brain, Imaging Shows (via Medscape)

Excerpts:
" The heavy, long-term use of cannabis is associated with negative changes in parts of the brain not previously implicated, and is linked to deficits in learning and memory, new research suggests."
"Cannabis shares a negative impact on dopaminergic transmission with other drugs, only with a different regional profile," explained Dr Abi-Dargham. An exploratory analysis showed a significant association between lower dopamine release capacity in the associative striatum and decreased cognitive measures in probabilistic category learning and working memory tasks, Dr Weinstein reported.
In their study, the team compared 11 heavy cannabis users with 12 healthy control subjects, all approximately 28 years of age."

"The blunting of dopamine release that they find fits with other studies showing reduced dopamine synthesis in cannabis users. This could be linked to the addictive potential of cannabis and other problems, such as lack of motivation, seen in regular users," Dr Howes told Medscape Medical News."
3. From January, but relevant when considering prescribing Sativex (which has refractory advanced cancer pain as indication in Canada):

GW Pharma's cannabis drug [Sativex] fails in cancer pain study, shares fall (via Reuters)

Excerpts:

"An experimental cannabis drug failed to alleviate pain in cancer patients as hoped in a clinical study, sending shares in its British maker GW Pharmaceuticals as much as 21 percent lower on Thursday. GW, which is developing the drug Sativex for pain in collaboration with Japan's Otsuka, said the first of three late stage trials found no statistically significant difference between subjects using its product and those given a placebo.

GW Chief Executive Justin Gover said the findings were both disappointing and surprising, given encouraging results in earlier tests, but the company's scientists had not given up hope. Results from two further Phase III trials are due later this year and, if positive, could still allow the drug to be submitted for treating pain in patients with advanced cancer, where it is designed to be given on top of opioids.

"Although we missed the primary endpoint in this trial, based upon the positive data seen in the Phase II programme, we remain confident in the ability for Sativex to relieve cancer pain in this patient population,” Gover said."

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Tuesday, April 14, 2015

Expired Medications: Drugs past the "best before date" may lose potency, but how soon?

Medications past best before date may lose potency, but how soon? | Canadian Healthcare Network - Pharmacists



Excerpt of key points from the article:

"Suggesting it’s better to be safe than sorry, Emberley [Phil Emberley, director of pharmacy innovation at the Canadian Pharmacists Association] advises consumers to cull any out-of-date drugs from their medicine cabinets and take them to a pharmacy to be destroyed.
Dr. David Juurlink, head of clinical pharmacology and toxicology at Sunnybrook Health Sciences Centre in Toronto, said concerns about diminished potency depends on the drug and how much time has elapsed since the best-before date.
“For most drugs, the passage of a short amount of time after the expiry date is really of little clinical consequence,” he said. “In general, something that’s six to 12 months past the expiry date, with rare exceptions, is not going to be a problem at all. They’re not going to be dangerous.”

A 2012 study of a small number of drugs—some of them bottled or packaged 40 years earlier—found that active ingredients did degrade over time, but some more than others. For instance, researchers found ASA pills dropped in strength from 200 milligrams to two milligrams, while codeine barely lost any of its chemical constituents.




“It’s not like milk, and it’s not as though something magical happened on the expiry date and the drug loses all of its potency,” Juurlink said. “With most, but not all, it’s probably safe to take drugs that have expired recently. But the more time that has elapsed from the expiry date, the less advisable it becomes.”



Link to full article: click here

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Tuesday, April 7, 2015

Opioid Tapering Guidelines

McMaster University > Michael G. DeGroote National Pain Centre > Canadian Guideline for Opioid Use for Pain — Appendix B-12: Opioid Tapering:

"Rate of the Taper
The rate of the taper can vary from 10% of the total daily dose every day, to 10% of the total daily dose every 1–2 weeks.

  • Slower tapers are recommended for patients who are anxious about tapering, may be psychologically dependent on opioids, have co-morbid cardio-respiratory conditions, or express a preference for a slow taper. 
  • Once one-third of the original dose is reached, slow the taper to one-half or less of the previous rate.
  • Hold [or increase] the dose when appropriate: 
  • The dose should be held or increased if the patient experiences severe withdrawal symptoms, a significant worsening of pain or mood, or reduced function during the taper."
Click here for link to the article

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eLearning: Lancet Oncology Podcasts


Lancet Oncology produces podcasts - the frequency looks to be about every 2 to 4 weeks.

Click here for the link and learn while you're on the go.

Please share in the comments section below any oncology or palliative related podcasts that you find helpful or Tweet me @OncoPRN.

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Monday, January 19, 2015

"Palliative Care" - The Words We Use

Via Pallium Canada, who have been producing a great series of videos helping to bridge the gap with respect to some of the misconceptions surrounding palliative care.


"Supportive Care…Supportive Oncology…The Comfort Team…The Butterfly Team (as may be heard in pediatrics)…
Why is there so much resistance to the use of the “P” word – palliative? The truth is, palliative care might not be what many people think it is.
Language provides us with a tapestry of tools for communication and understanding. In palliative care, the use of poetic license is certainly no less than in any other fields of medicine. However, the words we use can be confusing."


Choose your words wisely...

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About Onco-PRN

Welcome and thanks for visiting Onco-P.R.N. - The oncology website with a focus on all things oncology pharmacy/pain/palliative care-related. It is intended to be an information resource for those pharmacist and relevant health care professionals involved in whatever fashion with cancer and palliative care. Stay tuned for the latest and greatest links and information with respect to: oncology medications, continuing education, pharmaceutical care initiatives, pain and symptom control, supportive care topics, and whatever else that might fit into the theme.

*Note: This website is not affiliated with Alberta Health Services (AHS) or CAPhO and the opinions expressed herewithin are that of the author(s).

Pharmacy History

"The earliest known compilation of medicinal substances was ARIANA the Sushruta Samhita, an Indian Ayurvedic treatise attributed to Sushruta in the 6th century BC. However, the earliest text as preserved dates to the 3rd or 4th century AD.
Many Sumerian (late 6th millennium BC - early 2nd millennium BC) cuneiform clay tablets record prescriptions for medicine.[3]

Ancient Egyptian pharmacological knowledge was recorded in various papyri such as the Ebers Papyrus of 1550 BC, and the Edwin Smith Papyrus of the 16th century BC.

The earliest known Chinese manual on materia medica is the Shennong Bencao Jing (The Divine Farmer's Herb-Root Classic), dating back to the 1st century AD. It was compiled during the Han dynasty and was attributed to the mythical Shennong. Earlier literature included lists of prescriptions for specific ailments, exemplified by a manuscript "Recipes for 52 Ailments", found in the Mawangdui tomb, sealed in 168 BC. Further details on Chinese pharmacy can be found in the Pharmacy in China article."

From Wikipedia: http://en.wikipedia.org/wiki/Pharmacy#History_of_pharmacy

Journal of Palliative Medicine - Table of Contents

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