We can now leave naloxone out of the discussion, and focus on the side effects of Suboxone that are caused by buprenorphine.
Side effects are symptoms caused by a given medication that are not part of the therapeutic benefit of that medication. Whether a symptom is a side effect depends on the reason for taking the medication. For example, decreased intestinal motility is the desired effect of opioids used to treat diarrhea, but a bothersome side effect when taking opioids for pain. The term ‘side effect’ is not on the package insert for medication, the symptoms and actions instead referred to as ‘adverse reactions.’ Package inserts also have a section entitled ‘warnings and precautions’ where the most dangerous adverse reactions are listed.
Some medications have a ‘black box warning’ for adverse reactions that are particularly common or particularly dangerous, consisting of a frightening statement at the start of the package insert (enclosed, naturally, by a black box). Black box warnings in psychiatry include the warning for increased suicidal ideation in children and adolescents treated with antidepressants, and the increased risk of death in people with dementia treated with atypical antipsychotics.
Increased risk of cancer or mutations, and effects on fertility or fetal development, are listed in yet another section entitled ‘nonclinical toxicology.’ They are listed as ‘nonclinical’ because the events do not involve the intended physiologic system or pathway targeted by the medication. For example, slowing of intestinal activity by opium …
Today I read about the stereotactic brain surgery used to treat opioid dependence in China over the past ten years. The procedure is relatively straightforward; the patient’s skull is clamped in place while small holes are drilled, guided by computerized, 3-dimensional maps of the brain. Probes are inserted deeply through brain tissue to the nucleus accumbens, where electric current destroys varying amounts of brain tissue. Patients are awake and talking during the procedure, so that surgeons know if the probes are too close to brain regions that control speech or other functions.
A large number of ablations for the treatment of addiction were performed in China about ten years ago. The rapid growth in popularity of the technique, before full knowledge of the risks and long-term effects, led to a ban on the procedures by the Chinese Ministry of Health in 2004. Still, ablations were performed as part of research studies, with over 1000 people treated by ablation since 2004.
The scientific community outside of China overwhelmingly condemns the technique, and medical journals are pressured to withhold publication of ablation studies. Human rights advocates claim that such experiments are performed on people who are not fully aware of the risks, or who are pressured to participate in the studies to avoid harsh punishments for drug offenses. The veracity of the results from ablation studies has also been challenged. Ablation treatment of opioid dependence is in the news lately because of …
People who read this blog are aware of the shortage of physicians who can prescribe buprenorphine to treat people addicted to pain pills, even as an epidemic of addiction to heroin and pain pills devastates the heartland of the country. In order to prescribe buprenorphine, physicians take a short course and obtain special certification. To obtain certification, physicians must promise to treat no more than 30 patients at one time, a number that can be increased to 100 patients after one year.
If you only have a few minutes, please take the time to go to the White House web site and add you name to a petition to allow individual doctors to treat more than 100 patients using buprenorphine. The whole process is fast and easy, and only requires your name and email address through this link: http://wh.gov/QR6K
If you have more time, need convincing, or just like hearing a 52-y-o rage against the machine, continue reading my thoughts about limiting treatment for this one health condition.
The reason for the patient cap, according to cap proponents, is to prevent pill-mill practices where patients could obtain narcotic medications without adequate care for their underlying addiction. That concern is reasonable, I suppose, but I often discover that proponents of the cap have other motives to keep the limits in place. For example, one person at a ‘linked in’ group argued that individual physicians don’t provide the all-encompassing care that he provides… to the 800+ …
Several of my patients have warned me about the world ending in a few days, on December 21, 2012. There are variations on the theme, but the basic idea is that the Mayans, who were accomplished mathematicians and astronomers, used an advanced calendar to measure planetary cycles… and that calendar ends at the end of this week. Some patients tell me that the end of the Mayan calendar coincides with predictions by the French seer Nostradamus, although the definitive authority on everything, Wikipedia, holds that Nostradamus did not make such a prediction.
I’ve browsed internet sites about this topic in order to prepare this post and found that there are about as many different versions as there are web sites about the prediction. I suspect that some versions have more adherents than others, and I have no idea which web sites are the most authoritative. I’ve read, though, that the world will end as described in the Book of Revelation in the Bible, or that instead, humanity will be erased, leaving the Earth unscathed. I’ve read that the Earth and Sun will line up in a way that eclipses the energy flowing from the center of the Milky Way Galaxy, causing humanity to die off and be replaced by aliens from outer space.
Like any good prediction, this one has plenty of wiggle-room. Comparisons between our modern calendar and the Mayan calendar require assumptions about how the Mayans determined months and years, …
Lately it seems as if I’ve been hearing more calls to change US marijuana laws. The legalization of marijuana has been a cause for some citizens for decades, and efforts to change marijuana laws have waxed and waned since I was a teenager in the 1970’s. Some people believe that this time around, attitudes are truly changing. A recent Quinnipiac University poll showed that as of November 2012, a majority of US voters favor legalization of the drug for recreational use.
The current status of marijuana laws are confusing, to say the least. Marijuana is regulated at multiple jurisdictional levels, so a person in any one location is subject to state, federal, and sometimes local statutes. These statutes are often at odds with each other, so the legality of marijuana depends largely on the employer of the agent or officer making the arrest.
There are also multiple forms of legality. In November, Colorado and Washington State legalized the possession of up to one ounce of marijuana. Another dozen-or-so states decriminalized marijuana over the past 20 years, so that possession of the drug is punishable by citation, not prison time. Another 20 or so states have laws allowing for the medical use of marijuana, including in some cases provisions to grow marijuana for personal use or for a small number of patients.
By federal law, marijuana continues to be illegal in virtually all settings. The DEA classifies marijuana as ‘Schedule I’, the same status as …
The LA Times ran a very interesting story a few days ago about deaths from overdose of narcotic pain medications. I strongly encourage readers of this blog to read the story, which discusses the issue from the perspectives of doctors, patients, and family members.
The story reports that a small number of Southern-California doctors wrote prescriptions that have killed a large number of patients. Over the past five years, 17% of the deaths related to prescription-drug overdose–298 people—were linked to only 0.1% of the area’s doctors. I was not surprised by the findings in the article, as I have read stories from other parts of the US reporting similar statistics.
There is a simple reason for the skewed numbers. Prescribing opioids for chronic pain is associated with risk of death by overdose. More and more doctors are avoiding that risk by refusing to treat chronic pain with opioid pain medication. That means that the few doctors who are willing to prescribe such medications are linked to a higher number of deaths from those medications.
Are the doctors who prescribe narcotic pain medications ‘bad doctors?’ Some doctors would claim that they are. I have described the doctors in a group called PROP, or Physicians for Responsible Opioid Prescribing, who take the position that almost all opioid treatment of chronic pain is inappropriate. I understand the point made by those physicians. Treating chronic pain using opioids carries significant risks. Complications, including death, are common. But I have met …
In my last post, I wrote about the work-up of a patient who experiences symptoms similar to opioid withdrawal that start about an hour after each dose of Suboxone. We decided that the symptoms were signs of withdrawal—i.e. reduced activity of mu-opioid pathways—and that the symptoms were triggered by taking a daily dose of Suboxone (buprenorphine/naloxone).
Note that I wrote that the symptoms seemed to be caused by reduced mu activity, i.e. not necessarily by reduced mu-receptor binding. Endogenous opioid pathways are very complex. Decreased activity in opioid pathways may arise from decreased binding of agonist at the receptor, or from changes in a number of other chemical or neuronal pathways.
This diagram shows the processes that are triggered by mu-receptor binding in humans before and after opioid tolerance. The diagram only shows the complexity of processes within the neuron with opioid receptors; realize that each neuron 1. Has receptors for many other neurotransmitters as well, and 2. Receives input from thousands of other neurons. As we sort through possible causes of our patient’s symptoms, keep in mind the complexity of neural pathways.
While we are on the subject of complexity, the web site linked above is an incredible resource for those interested in biochemistry. The site includes diagrams of a number of metabolic pathways that describe how different molecules, including neurotransmitters, are manufactured by the human body. I encourage people to browse the site. You will gain insight into why the actions …
I struggle with the length of my posts. I shoot for 1000 words—an amount of reading that most people can knock off in a typical trip to the bathroom— but I find it difficult to limit posts to that size. So as I have done in the past, I will break this post into a couple of sections. In the first, I’ll lay the groundwork for investigating symptoms of withdrawal in a patient taking buprenorphine. The second post will go into greater detail.
A patient recently contacted me to complain that he was experiencing withdrawal symptoms for several hours after each dose of Suboxone. I will describe my thought process, in case the description helps someone else experiencing similar symptoms.
My first decision point is whether or not the person is truly experiencing symptoms of withdrawal. Some people will misinterpret symptoms from excess opioid stimulation as withdrawal symptoms, for example. Nausea is a not-uncommon complaint among people taking buprenorphine, and patients often assume that nausea is the result of insufficient opioid activity, and so take higher doses of buprenorphine. But nausea is actually more common in opioid overdose than during opioid withdrawal, along with constipation, whereas withdrawal primarily causes diarrhea.
Pupil diameter is a good indicator of withdrawal vs. overdose; small or ‘pinpoint’ pupils suggest an excess of opioid activity, whereas withdrawal is associated with very large pupil diameter.
Other symptoms are also misinterpreted as withdrawal. Many opioid addicts develop a strong fear of withdrawal over …
The FDA recently released a Drug Safety Announcement regarding the use of codeine in young children after tonsillectomy/adenoidectomy surgery for obstructive sleep apnea. I was somewhat surprised to see a safety announcement on a medication that has been in use for decades, but the release underscores our improved knowledge of drug metabolism, and the broadening demographics of the United States.
Codeine has little activity at opioid receptors. The analgesic effects of codeine are actually caused by morphine, after the conversion of codeine to morphine at the liver. The conversion is catalyzed by an enzyme called CYP2D6, part of the cytochrome system of enzymes that are involved in the breakdown of a number of compounds.
I have written about the addictiveness of narcotic pain medications. People addicted to opioids often go to significant lengths to obtain prescriptions for narcotic pain relievers from healthcare practitioners. Emergency room physicians and nurses become aware of the efforts of ‘narcotic-seekers’, which range from faking pain symptoms or dental injuries to self-catheterization and instilling blood into the bladder to fake kidney stones. Distinguishing those with real pain from those who are addicted and not experiencing pain is a serious situation, but doctors roll their eyes at some of the more-typical presentations. One such situation is the patient who reports an ‘allergy’ to all of the weaker narcotics, and claims that ‘the only drug that works is (insert Dilaudid, morphine, oxycodone, or another potent opioid here).
Codeine is one drug that is …
A couple weeks ago the manufacturer of Suboxone, Reckitt-Benckiser, filed a Citizens Petition with the FDA, announcing a voluntary recall of one of the company’s signature products, Suboxone Tablets. Suboxone was sold in tablet form for almost ten years, and the patent ran out on Suboxone Tablets last year. A couple years ago the same company began making Suboxone Film; a rapidly-dissolving form of the medication that comes with each dose individually packaged.
Suboxone is used to treat opioid dependence, and the medication has been a vital, albeit expensive, tool for saving the lives of patients addicted to narcotic pain medications or heroin.
Last week I expressed anger at the company for their actions. Uninsured patients treated for opioid dependence pay a high cost for the medication that helps keep them safe, and have been looking forward to a generic form of the medication for years. It appeared to me that Reckitt Benckiser was trying to tarnish the tablets, perhaps to reduce insurance or Medicaid coverage of the tablets when they inevitably (?) hit the market.
I have carefully read through the entire Citizens Petition, and I now have a better understanding of what, exactly, was accomplished by that action by the manufacturer of Suboxone. It turn out that I underestimated the people at Reckitt-Benckiser.
The Citizens Petition explains that Reckitt-Benckiser (RB) hired an independent group, RADARS (Researched Abuse, Diversion, and Addiction-Related Surveillance), to investigate the exposure of small children to Suboxone tabs and Suboxone Film. The …