Tag Archives: opioid

What is fentanyl: the deadliest drug in America

Fentanyl is a synthetic opioid that is prescribed for severe, crippling pain — really bad pain since this drug is about 100 times stronger than morphine and 50 times stronger than heroin. Because it’s so strong and cheap to make, in recent years the opioid black market, which was typically dominated by heroin and prescription painkillers, has been flooded with fentanyl or fentanyl-cut products.

However, the line between medicine and poison is very thin with fentanyl. Imagine a dash of salt — if that were fentanyl, it would be enough to kill you. 

The low toxicity threshold makes it incredibly easy for people to overestimate the quantity of the substance they’re using and overdose. But most of the time people are not even aware that they are taking fentanyl as the drug is often cut into other substances to make them stronger.

According to researchers at the Centers for Disease Control and Prevention (CDC), as of 2018 fentanyl is officially the deadliest drug in the United States.

Both heroin and fentanyl are causing an opioid epidemic in the United States, but the number of deaths due to fentanyl has been rising in an alarming trend. Credit: CDC.

Official data from 2016 shows that nearly 63,000 people died of drug overdose in the United States that year. Fentanyl was involved in nearly 29% of those cases, while heroin came in second with 25% and methamphetamine was third at a rate of over 10%. What’s staggering is that in 2011, fentanyl was responsible for only 4% of overdoses. Between 2013 and 2016, overdoses from fentanyl rose 113% a year.

Since 2015, the U.S. has lost more than $2.5 trillion due to the opioid crisis.

How is fentanyl used?

Fentanyl was first developed in 1959 and is commonly used in multiple avenues of healthcare, most commonly for chronic pain management and in surgical settings under the guidance of an anesthesiologist. It is typically used in patients under great pain who are already tolerant to opioids, such as morphine.

Fentanyl pharmaceutical products come in many forms, including effervescent buccal tablets (Fentora), sublingual tablets (Abstral), sublingual sprays (Subsys), lollipops (Actiq), nasal sprays (Lazanda), skin patches (Duragesic), and injectable formulations.

But although fentanyl is prescribed in legitimate pharmaceutical varieties, most users procure illicit versions of the drug smuggled from China through the US postal service and Mexican drug cartels. Most often, smuggled fentanyl comes in the form of a white powder. Alternatively, the drug is dropped onto blotter paper, put in eye droppers and nasal sprays, or made into pills that look indistinguishable from other prescription opioids.

Part of the problem behind fentanyl being so difficult to control lies in its chemical composition, which makes it easy and cheap to reproduce by street chemists. Most of the fentanyl associated with recent overdoses is made in clandestine labs.

Many drug dealers mix fentanyl with other illicit street drugs, such as heroin, cocaine, methamphetamine, and MDMA. Fentanyl triggers an intense high for very little money, so there’s an economic incentive to use it to dope other drugs. However, if users are not made aware they are taking fentanyl, they may risk taking stronger opioids than their bodies are accustomed to, making an overdose more likely.

How does fentanyl affect the body?

Like any other opioid, fentanyl molecules bind to the body’s opioid receptors, which are mostly concentrated in areas of the brain responsible for controlling pain and emotions.

When the fentanyl binds to these receptors, it increases dopamine levels in the brain’s reward centers and produces an intense state of euphoria and relaxation.

Some of fentanyl’s effects include:

  • extreme happiness and euphoria
  • drowsiness
  • nausea
  • confusion
  • constipation
  • sedation
  • problems breathing
  • unconsciousness

Due to its extremely high potency, fentanyl is also highly addictive. Those who are addicted to the opioid and stop using it can experience severe withdrawal symptoms that begin as early as a few hours after the drug was last taken. These withdrawal symptoms include:

  • muscle and bone pain
  • sleep problems
  • diarrhea and vomiting
  • cold flashes with goosebumps
  • uncontrollable leg movements
  • severe cravings

What are common street names for fentanyl?

Fentanyl goes by many names, including Apache, China Girl, China Town, Dance Fever, Friend, TNT, Goodfellas, Great Bear, He-Man, Jackpot, King Ivory, Murder 8, and Tango & Cash.

What makes fentanyl so dangerous?

When used appropriately, fentanyl is a very effective pain mitigator for those who have grown a high tolerance to opioids, such as cancer patients who have been taking painkillers for years.

But fentanyl not only binds to receptors in the brain’s reward centers but also to those located in other areas of the brain, including those that control breathing. So although fentanyl produces a very potent high, it can also cause difficulties breathing that can potentially lead to death.

This is a problem that is caused by heroin too, as well as other opioids, but fentanyl is particularly dangerous because its chemical makeup allows it to enter opioid receptors much faster than heroin.

What’s more, fentanyl also adheres more tightly to the opioid receptor than other opioids. This means that only a small amount is enough to catalyze the molecular chain of events that initiates the opioid’s effects on the body.  

This explains why even less than a milligram of fentanyl can trigger an overdose in a user with no tolerance.

Credit: Twink Twice.

Naloxone is a medicine that can be given to a person to reverse a fentanyl overdose. Multiple naloxone doses might be necessary because of fentanyl’s potency.

Can fentanyl be stopped in the future?

According to the latest drug overdose death data from the National Institute of Drug Abuse (NIDA), 68,000 people in the United States were killed by prescription opioid painkillers and other drugs in 2018. That’s a kill rate higher than the peak annual deaths from car crashes, AIDS, or guns — combined.

On the bright side, 2018 was the first year since 1990 that drug overdoses have declined, a 5% reduction relative to 2017.

Experts in addiction and law enforcement say that the overall drop in deaths to overdoses can be pinned to tighter regulations of opioid prescriptions. In 2016, Massachusetts became the first state in the nation to pass a law that limits opioid prescriptions to 7 days. Since then, over half of all states have enacted laws that restrict the prescribing or dispensing of opioids for acute pain. 

However, while prescription opioid overdoses have fallen considerably since 2016, deaths attributed to synthetic narcotics, which includes fentanyl, are still on the rise.

Credit: Centers for Disease Control and Prevention, National Center for Health Statistics. Multiple Cause of Death 1999-2018.

From 2012 to 2018, the number of drug overdose deaths involved fentanyl or fentanyl analogs increased nearly 12-fold.

There’s no clear-cut solution to the rise of fentanyl or synthetic opioids in general. And as if fentanyl wasn’t scary enough, an analog called carfentanil is also creeping up in the illicit drug market. Carfentanil is 100 times stronger than fentanyl and is normally used as a sedative for large animals such as elephants. It’s so dangerous that some countries, the U.S. included, have described it as a ‘chemical weapon’ and have prepared contingency plans in the face of its potential use in war.  

In order to curb the opioid epidemic, both the Obama and Trump administrations have attempted to persuade Chinese authorities to crack down on the supply of fentanyl from China to the United States. These efforts seem to have paid off as China announced in April 2019 that the production, sale, and export of fentanyl and all its analogous products are prohibited, except for some authorized firms that have been granted special licenses.

However, it remains to be seen the degree to which these rules can be enforced. It’s believed there are hundreds of thousands of chemical and pharmaceutical facilities in China, which would make the challenge of enforcing fentanyl production laws formidable. What’s more, policy experts at Brookings claim that China has a history of downplaying narcotics problems, so it will be unlikely to mount counternarcotics cooperation with the United States unless it starts experiencing its own synthetic opioid epidemic. Strained U.S.-China relations add further uncertainty. 

Drug overdoses in the U.S. on the decline for the first time since 1990

The drug overdose epidemic in the United States is such a huge problem that it has effectively reduced life expectancy in the country. In 2018, more than 68,000 were killed by prescription opioid painkillers and other drugs, particularly heroin, fentanyl, and methamphetamine. That’s a kill rate higher than the peak annual deaths from car crashes, AIDS, or guns.

On the upside, at least there are fewer overdose fatalities than in 2017, a 5% decline that marks the first drop in three decades.

The reduction was reported by the Centers for Disease Control and Prevention — one of the rare good news in a string of depressing updates on drug abuse in the country.

Experts in addiction and law enforcement say that the overall drop in deaths to overdoses can be pinned to tighter regulations of opioid prescriptions. In 2016, Massachusetts became the first state in the nation to pass a law that limits opioid prescriptions to 7 days. Since then, over half of all states have enacted laws that restrict the prescribing or dispensing of opioids for acute pain. More cautious prescribing of opioid drugs has thus hit the supply and, consequently, the risk of overdose.

However, prescription painkillers are no longer the leading cause of overdose deaths. In the past decade, heroin — which now kills four times as many people than in 2000 — and then fentanyl, surpassed prescription opioid drugs as the main cause of overdose death. These factors are much harder to control and regulate by the federal government. To make things even more challenging, the CDC reports a 21% rise in deaths provoked by methamphetamine, 12,987 fatalities in 2018 from 10,749 in 2017. Deaths provoked by cocaine also spiked this year by nearly 5%.

The pattern of death by overdose is not uniform across the country. The hardest-hit states include Ohio, New Jersey, Delaware, and Maryland.

In order to further stave off drug overdose fatalities, local authorities and treatment facilities plan to improve access to local drug rehab and treatments. For instance, naloxone is a life-saving drug that reverses overdoses, sparing thousands thus far. Growing awareness about the dangers of opioids, particularly the synthetic variety, is also paramount. Fentanyl — the deadliest drug in America —  is a very powerful synthetic opioid that’s 50 to 100 times more concentrated than morphine. For a user with little tolerance to the drug, even less than a milligram of fentanyl can trigger an overdose. And if fentanyl wasn’t scary enough, carfentanil — a fentanyl analog that’s 10,000 times more powerful than morphine — is becoming a growing presence across the country.

There is already some good progress in treating America’s opioid epidemic. Today, it is easier than ever to gain access to methadone, buprenorphine, and naltrexone — three F.D.A.-approved medications that suppress craving and withdrawal symptoms related to opioid consumption.

Marijuana legalization helps decrease opioid consumption, research shows

Every day, 90 Americans die from opioid overdoses, according to existing research. Two new studies published in the journal JAMA Internal Medicine now show that in states where marijuana is legal, opioid prescriptions decreased significantly.

Image credits Flickr / Jeffrey Beall.

Researchers have analyzed prescription data from Medicare Part D and Medicaid from the past five years and discovered that opioid prescriptions and the average daily dose of opioids patients took were significantly lower in areas where marijuana is legal.

“In this time when we are so concerned — rightly so — about opiate misuse and abuse and the mortality that’s occurring, we need to be clear-eyed and use evidence to drive our policies,” said W. David Bradford, an economist at the University of Georgia and an author of one of the studies.

“If you’re interested in giving people options for pain management that don’t bring the particular risks that opiates do, states should contemplate turning on dispensary-based cannabis policies.”

Previous research suggests the same. A 2014 paper discovered that in states where cannabis use is legal for medical purposes, nearly 25 percent fewer deaths from opioid overdoses occurred.

One of the studies revealed that Medicare patients filled 14% fewer opioid prescriptions after medical cannabis use became legal. The other study, which monitored Medicaid opioid prescriptions, found that participants filled nearly 40 fewer opioid prescriptions per 1,000 people (4%) each year after their state passed laws that made cannabis accessible — states that legalized both medical and recreational marijuana showed greater falls in opioid prescriptions.

With the arrival of fentanyl on the black market, doctors fear we’ll see even more cases opioid overdose. This powerful opioid is up to 100 times more potent than morphine. Due to its powerful effect, fentanyl doses are very small, which is actually a problem. Overdoses usually occur when miscalculating the amount of drug administered, and it’s easier to go wrong with smaller doses. When fentanyl became a go-to drug for dealers, opioid deaths immediately spiked due to its high potency at low doses. Basically, people did not know that surpassing the dosage with only a few micrograms might be fatal.

So, the findings seem positive from a public health point of view. Marijuana is generally perceived as ‘safe’, and according to The National Center for Biotechnology Information, there is insufficient evidence to support or refute a statistical association between cannabis use and death due to cannabis overdose — in other words, there’s not enough data to say that cannabis use can or cannot be fatal, which, relative to fentanyl, makes it super-duper safe.

One recent paper even suggested that opioids didn’t provide any more relief for chronic arthritis pain than over-the-counter painkillers.

The studies also discovered differences in decline in opioid prescription between the states that legalized medical marijuana: states with dispensaries open for business saw the greatest decrease in opioid prescriptions, while states without active dispensaries saw a far less dramatic decline — about 14% and 7%, respectively

Bradford said that this made sense. The difference between picking up ready-to-use marijuana and growing your own plant with little support from the authorities is huge.

One impediment in substituting opioids with marijuana is that neither Medicaid nor Medicare will reimburse people for the money they spend on marijuana.

“I did a back-of-the-envelope calculation that suggested that a daily pain management dose of hydrocodone would be about $10 out of pocket in the U.S,” Bradford said, although Medicare Part D plans cover much of that.

Last year, a daily dose of marijuana cost around $6 — and that sum should be smaller by now, Bradford said. “It’s becoming relatively comparable in cost.”

“I know policymakers are often skeptical of cannabis. But we need to be terrified of things like fentanyl, and we need to be willing to use evidence-based approaches to help address that,” Bradford added. “Cannabis looks like it could be one,” he concluded.

Opioids no better than Tylenol for treating chronic pain

Some people swear by opioids — it’s the only thing that helps them get through the day, they’ll argue. But a new study found that opioids aren’t really justifiable for chronic pain management. Generic medications (like Tylenol or ibuprofen) are just as effective and have fewer side effects.

Image in public domain.

A new comprehensive study offers rigorous evidence against the usage of opioids. Dr. Erin Krebs, a physician and researcher with the Minneapolis Veterans Affairs Health Care System, recruited 240 patients suffering from chronic back pain or hip or knee osteoarthritis. He then split them into two groups, assigning half of them to receive opioids, and the other half to non-opioid drugs. He then followed them for up to a year.

The opioid group was prescribed morphine, oxycodone, or hydrocodone, while the non-opioid group was prescribed acetaminophen (i.e., Tylenol) or a nonsteroidal anti-inflammatory drug (i.e., Advil). If the prescription didn’t work, it would be changed, selecting from drugs that had been shortlisted. The participants were then asked to rate their pain every three months, on two scales: intensity and functionality (how easy it is to go about your day-to-day life).

Both the doctors and the patients knew their group assignment, since a patient’s expectation can influence how effective the drugs are, with a placebo-like effect.

“We found at the beginning of the study that patients who were enrolled really thought that opioids were far more effective than non-opioid medications,” she says.

Except this wasn’t the case: although patients were expecting opioids to be more effective, they weren’t. When the treatment was started, the opioid and non-opioid groups scored almost exactly the same on both intensity and functionality.

As some of the treatments were changed, both groups improved performance — but both were still equally effective in dulling the pain. Actually, opioids fared slightly worse, as they doubled the number of unpleasant side effects (dizziness, nausea, etc.).

“Opioids aren’t better than non-opioid medications,” Krebs summed up, “and we already knew from other research they are far more risky — and that the risk of death and addiction is serious.”

Researchers didn’t assess why this happens, though Krebs suspects it’s because in time, the body tends to build up a resistance to opioids.

This isn’t the first study to throw shade at long-term opioid use: just last year, a thorough research found that a cocktail of two over-the-counter drugs (ibuprofen and acetaminophen, commonly known as Advil and Tylenol) are more effective than heavy opioids in dealing with pain than heavy opioids.

The study concludes:

“Conclusions and Relevance Treatment with opioids was not superior to treatment with nonopioid medications for improving pain-related function over 12 months.

This study does not support initiation of opioid therapy for moderate to severe chronic back pain or hip or knee osteoarthritis pain.”

Journal Reference: Krebs et al. ‘Effect of Opioid vs Nonopioid Medications on Pain-Related Function in Patients With Chronic Back Pain or Hip or Knee Osteoarthritis Pain’, JAMA.

cannabis

Medical cannabis helps one third of chronic pain patients quit prescription opioid drugs

Medical marijuana is helping patients dealing with chronic pain by replacing their use of prescription drugs. These opioid drugs can be fatally dangerous when abused. They killed more people last year than guns or car accidents, causing health professionals to signal that America is deep in an opioid crisis, which is why these latest findings come as great news.

cannabis

Credit: Pixabay.

The study performed by researchers at the University of New Mexico (UNM) involved 37 patients enrolled in the New Mexico Medical Cannabis Program (MCP) and 29 participants who used opioids alone. The MCP participants used both opioids and legally supplied medical cannabis.

Ten months later, MCP participants had significantly reduced their prescription drug use. Most impressively, more than a third of the MCP patients stopped using prescription drugs altogether compared to only two percent of the non-MCP group, the authors reported in the Journal of the American Medical Directors Association. 

MCP participants also reported “improvements in pain reduction, quality of life, social life, activity levels, and concentration, and few side effects from using cannabis one year after enrollment.”

Although this wasn’t a randomized trial and the sample size was rather small, the UNM team concludes that medical cannabis is significantly associated with “opioid prescription cessation and reductions”, as well as “improved quality of life”.

Mean prescribed daily opioid dosage by month. Credit: PLOS One

Mean prescribed daily opioid dosage by month. Credit: PLOS One

The UNM researchers followed the patients for two whole years, including the six months during which opioid use was tracked before patient enrollment in the marijuana program. It wasn’t until months 16 through 24 that medical marijuana began to significantly displace opioids in the MCP group.

Previously, scientists at the University of Michigan reached a similar conclusion, also reporting that chronic pain patients saw a large reduction in opioid use and improved quality of life once they started using medical marijuana. Another study found that doctors working in states where medical marijuana is legal prescribe fewer opioids to patients than in those states where medical marijuana is illegal.

All of these findings suggest that medical marijuana might become a worthy ally in the nation’s fight against opioid drugs. Every day, more than 90 Americans die after overdosing on opioids. The Centers for Disease Control and Prevention (CDC) estimates that the total “economic burden” of prescription opioid misuse alone in the United States is $78.5 billion a year, including things like treatments and reduced productivity. Last month, President Trump “declared the opioid epidemic a national public health emergency.”

Cocktail of simple over-the-counter drugs as effective as heavy opioids in treating pain

Americans are already taking way more opioids than they should in the first place — new study shows many are not even as effective as you’d think.

Credits: j_lai / Flickr.

Since the early 1990s, the US has gone through a dramatic opioid crisis. What started as a case of national over-prescription turned into a full-blown epidemic, with approximately 80 percent of the global pharmaceutical opioid supply being consumed in the US. For a country with only 5% of the world’s population, that’s extremely concerning.

Of course, the easiest way to avoid becoming hooked on opioids is to avoid taking them in the first place. In surprisingly many cases, even a few days of prescription can lead to an addiction. However, some patients don’t have the luxury of not taking opioids — in the case of people arriving in the emergency room or with broken limbs, opioids are required to ease the excruciating pain. Or so we thought.

A new randomized, double-blind clinical trial found that a combination of ibuprofen (Advil) and acetaminophen (Tylenol) was just as effective at dealing with acute pain as three other common opioid treatments. The authors suggest that in some cases, medics could simply skip the opioid treatment, offering instead the two very common over the counter drugs.

This change could have a significant impact in tackling the opioid crisis, as well as opening new, simpler avenues for pain management. Considering that every day, opioid overdoses kill an estimated 91 Americans, it could make a big difference.

“This change in prescribing habit,” they write, “could potentially help mitigate the ongoing opioid epidemic by reducing the number of people initially exposed to opioids and the subsequent risk of addiction.”

In the study, researchers had 416 patients (ages 21 to 64 years) with moderate to severe acute extremity pain in two urban emergency departments. The patients were randomly assigned to receive:

  • 400 mg ibuprofen and 1,000 mg acetaminophen
  • 5 mg oxycodone and 325 mg acetaminophen
  • 5 mg hydrocodone and 300 mg acetaminophen; or
  • 30 mg codeine and 300 mg acetaminophen

Oxycodone (commonly sold as OxyContin and Percocet) and hydrocodone (Vicodin) are two of the most commonly used opioids.

Two hours after each treatment, researchers assessed the pain the patients were in, finding no significant difference between the four groups. In other words, whether they took opioids or a cocktail of ibuprofen and acetaminophen, the pain still dropped significantly, with minimal differences. The reason why the two work so well together is because they act in different ways, working on the brain and nervous system respectively.

Authors point out that data from the World Health Organization suggest that opioids are much more effective at dealing with pain, but this study casts a big question mark on that data.

Of course, while they pose a much lower risk than opioids, Tylenol and Advil also shouldn’t be abused.

Journal Reference: Andrew K. Chang et al. Effect of a Single Dose of Oral Opioid and Nonopioid Analgesics on Acute Extremity Pain in the Emergency Department. doi:10.1001/jama.2017.16190

 

Each 40 mg Opana pills has a street value of $150. These often end up in the wrong hands. Credit: WDRB.

FDA wants the Opana opioid painkiller off the market

The U.S. Food and Drug Administration requested a drug maker to remove a powerful opioid painkiller off the market after finding “the benefits of the drug may no longer outweigh its risks.” This is the first time the FDA has taken action to remove an opioid from the market due to consideration dealing with public health risks of abuse. As such, it may set a precedent for action against other risky opioids.

Each 40 mg Opana pills has a street value of $150. These often end up in the wrong hands. Credit: WDRB.

Each 40 mg Opana pills has a street value of $150. These often end up in the wrong hands. Credit: WDRB.

Opioids, including legal and illegal drugs like heroin, killed more than 33,000 people in 2015, more than any year on record. Nearly half of all opioid overdose deaths involve a prescription opioid.

The Centers for Diseases Control and Prevention is officially calling this an opioid epidemic given the steep rise of abuse rate and death. Since 1999, the number of overdose deaths involving opioids quadrupled and the last 15 years have seen half a million Americans die after abusing these drugs.

An increasing number of people are abusing some of the most powerful prescription opioid painkillers by any means possible, even crushing, dissolving, and then injecting the pills’ contents.

“We are facing an opioid epidemic — a public health crisis, and we must take all necessary steps to reduce the scope of opioid misuse and abuse,” says Dr. Scott Gottlieb, the FDA’s commissioner, meaning business.

“We will continue to take regulatory steps when we see situations where an opioid product’s risks outweigh its benefits, not only for its intended patient population but also in regard to its potential for misuse and abuse.”

Age-adjusted rate of drug overdose deaths and drug overdose deaths involving opioids — United States, 2000–2014. Credit: CDC.

Age-adjusted rate of drug overdose deaths and drug overdose deaths involving opioids — United States, 2000–2014. Credit: CDC.

Following an extensive investigation, the FDA found a shift in the way reformulated Opana ER (oxymorphone hydrochloride) is used from nasal to injection. Opana ER, a potent extended-release opioid, was approved by the FDA for pain management in 2006. Its widespread abuse around the country has been associated with a serious outbreak of HIV and hepatitis C, as well as cases of a serious blood disorder (thrombotic microangiopathy). Because it’s so strong, a lot of people seek it specifically for non-medical purposes to induce intoxication.

The company behind the drug, Endo, released a reformulated version that should have made the pills harder to crush, dissolve and inject. This proved futile, though. Now, the agency is taking steps to remove the reformulated Opana ER from the market.

“The abuse and manipulation of reformulated Opana ER by injection has resulted in a serious disease outbreak. When we determined that the product had dangerous unintended consequences, we made a decision to request its withdrawal from the market,” said Janet Woodcock, M.D., director of the FDA’s Center for Drug Evaluation and Research. “This action will protect the public from further potential for misuse and abuse of this product.”

Endo reacted to request stating it “feels a strong sense of responsibility to improve the care of pain for patients, while at the same time taking comprehensive steps to minimize the potential misuse of its products,” and is “reviewing the request and is evaluating the full range of potential options.”

Right now, the FDA is kindly requesting Endo to retreat its product voluntarily. Should Endo refuse, the agency stated it intends to take steps to formally require the removal of reformulated Opana ER from the market. Meanwhile, the FDA is also talking to doctors around the country to inform them about the risks associated with the abuse of this product.

“This action will protect the public from further potential for misuse and abuse of this product,” said Dr. Janet Woodcock, director of the FDA’s Center for Drug Evaluation and Research.

 

 

Scientists make new opioid painkiller, without the nasty side effects

Using brute computational power, researchers have developed a new drug that blocks out pain without sharing many of the unwanted side effects painkillers often bring.

Photo by sfxeric, via Flickr.

They started from scratch, using computational techniques to explore more than four trillion different chemical interactions. In the end, the drug seemed to do as good as morphine in terms of killing pain (on mice), while not causing addiction and not impairing breath in any way. More work is needed to confirm that these effects will carry on in humans, but if they do, then it could very well be a game changer.

Morphine itself was a game changer back in the day – and it still is. It allowed us to develop medicine in a way which would have otherwise been impossible, but there’s also a price to pay. Even in small amounts, morphine can be addictive, and especially in large doses it can be life threatening.

“Morphine transformed medicine,” said Brian Shoichet, PhD, a professor of pharmaceutical chemistry in UCSF’s School of Pharmacy and co-senior author on the new paper. “There are so many medical procedures we can do now because we know we can control the pain afterwards. But it’s obviously dangerous too. People have been searching for a safer replacement for standard opioids for decades.”

Several research groups have attempted to develop viable alternatives to morphine. The general approach is to take morphine and try to eliminate the parts of it which have the unwanted effects. This time however, the team went for a much more radical approach – they started everything from scratch.

“We didn’t want to just optimize chemistry that already existed,” Shoichet said. “We wanted to get new chemistry that would confer completely new biology.”

They did this because the very structure of morphine (your starting block) can limit the path you go on. Basically, they wanted to think outside the morphine box:

“With traditional forms of drug discovery, you’re locked into a little chemical box,” Shoichet said. “But when you start with the structure of the receptor you want to target, you can throw all those constraints away. You’re empowered to imagine all sorts of things that you couldn’t even think about before.”

There is still a lot of work that still needs to be carried out, especially on the non-addictive claims. Basically, they haven’t chemically shown that the drug doesn’t cause addiction, even though they did show that mice don’t actively seek out the drug, which would imply a lack of addiction.

As it so often happens in recent times, the work is a result of an intensive cross-disciplinary collaboration.

“This promising drug candidate was identified through an intensively cross-disciplinary, cross-continental combination of computer-based drug screening, medicinal chemistry, intuition and extensive preclinical testing,” said co-senior author and 2012 Nobel laureate Brian Kobilka, MD, a professor of molecular and cellular physiology at the Stanford University School of Medicine.

“If you took away any one of these collaborators it simply wouldn’t have worked,” Shoichet added.

Journal Reference: Structure-based discovery of opioid analgesics with reduced side effects. Nature, 2016; 1 DOI:10.1038/nature19112

Image: Ed in the Ed

9/10 of patients who overdosed on opioids and survived still get their meds

Fatal overdoses due to painkillers have reached epidemic levels, greatly exceeding those from heroin and cocaine combined and becoming the worst drug epidemic in US history. Prescriptions for painkillers in the United States have nearly tripled in the past two decades, and the results are dreadful. In 2012, enough painkillers were prescribed to keep every single citizen medicated around the clock for a month – or once every 12 days for an entire year. Even after a patient overdoses, but survives, he’s still put on prescriptions: 91% of the time, according to a paper published in the Annals of Internal Medicine.

Image: Ed in the Ed

Image: Ed in the Ed

According to a report released on Jan 1st by the Centers for Disease Control and Prevention (CDC), in 2014 “a total of 47,055 drug overdose deaths occurred in the United States, representing a 1-year increase of 6.5%, from 13.8 per 100,000 persons in 2013 to 14.7 per 100,000 persons in 2014.” In the same year, 150% more people died from drug overdoses than from car crashes. Fatal overdoses due to heroin, an illegal drug, increased by 26% from 2013 to 2014 and have more than tripled since 2010, from 1.0 per 100,000 in 2010 to 3.4 per 100,000 in 2014. Yet, most drug overdoses are due to prescribed opioid pain relievers, like oxycodone and hydrocodone. With these stark findings in mind, the CDC recommends safer prescribing of prescription opioids. Reality is a tad different, though. Opioid prescriptions have quadrupled since 1999, and it seems like even those who overdose on the meds, but survive, are given the same prescriptions.

In 2013, 16,235 people died of overdoses of opioid prescription painkillers.

The researchers from Boston, Massachusetts picked 2,834 patients from a huge database numbering 50 million people who filed insurance claims between 1999 and 2010. These patients were prescribed an opioid for chronic pain, then at some point in the 12 year-long survey had  a nonfatal overdose. In the next 299 days following the overdose, more opioids were dispensed to 91% of patients. Two years later,  17% of those who were prescribed a high dose had a repeated overdose; 15% for those receiving a moderate those and 9% for those receiving a low dose. Moreover, 70% of the patients of the overdose survivors were prescribed opioids by the same doctor.

Opioid drugs work by binding to opioid receptors in the brain, spinal cord, and other areas of the body. They reduce the sending of pain messages to the brain and reduce feelings of pain, hence they’re prescribed for alleviate the suffering of people with advanced cancer, but also for many other afflictions that cause chronic pain. Considering this huge drug epidemic sweeping the United States, it may be that many doctors are too lenient with how and in what conditions they decide to prescribe opioids and their dosage.

Some have suggested that the endemic opioid painkiller usage is driven by  small groups of prolific prescribers and “corrupt pill mills”. A study published in the journal JAMA Internal Medicine suggests this isn’t the case. The study found  a huge number of those drugs are coming from run-of-the-mill family doctors and general practitioners. “You can’t just blame a handful of pain doctors,” said Dr. Jonathan Chen, an internist at the Stanford School of Medicine, and lead author of the study published in JAMA. “All of us are part of this problem whether we want to admit it or not.”

From the study’s data, it’s hard to make out if the same dosage was prescribed to the overdose survivors. After all, these drugs were prescribed in the first place because the patients experienced severe pain, so pulling out the medication altogether is unethical. No doctor wants to see patients in pain. What they hate most, I suspect, is seeing their patients die, though. As such, these findings should serve as a wakeup call. There are too many opioids being prescribed.  Maybe, pain is better than the alternative: the risk of overdose and addiction.

 

 

Painkiller abuse

Prescription painkillers cause 67.8% of opioid overdoses. Heroin a distant second at 16.1%

An American national study that looked at hospital emergency department visits for opioid overdoses found that 67.8% of the cases involved overdosing on prescription opioid drugs, including methadone. Next in line were heroin, other unspecified opioids and multiple opioids. It’s estimated that the treatment costs for the hospitalized overdosed patients in 2010 alone was $2.3 billion.

Prescription drugs cause four times more opioid overdoses than heroin

Painkiller abuse

Credit: Corner Stone Recovery Center

Recreational use of prescription drugs is a serious problem with teens and young adults. National studies show that a teen is more likely to have abused a prescription drug than an illegal street drug. Actually, according to the  National Institute on Drug Abuse an estimated 48 million people (aged 12 and older) have used prescription drugs for nonmedical reasons in their lifetime or roughly 20% of the US population. The three most commonly abused prescription drug classes are:

  • Opioids used to treat pain
  • Central nervous system (CNS) depressants, such as benzodiazepines (Xanax, Valium, Ativan, Klonopin), used to treat anxiety and sleep disorders
  • Stimulants, such as Adderall or Ritalin, used to treat attention deficit disorder and narcolepsy (a sleep disorder)

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A recent study made by researchers at Stanford University School of Medicine yet again highlights these disheartening statistics after it found an overwhelming majority of patients hospitalized for opioid overdoses used legally prescribed drugs. The researchers crunched the numbers from the 2010 Nationwide Emergency Department Sample and identified 135,971 weighted ED visits that were coded for opioid overdose. Of these 67.8 percent involved prescription opioids, followed by 16.1 percent heroin overdoses, while  unspecified opioids and and multiple opioid types accounted for 13.4 percent and 2.7 percent of overdoses, respectively. The greatest proportion of prescription opioid overdoses happened in urban areas (84.1 percent), in the South (40.2 percent) and among women (53 percent).

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About 1.4 percent of patients who arrived in the ED eventually died of overdose and the authors suggest hospitals should ramp up their overdose emergency services. About half of the patients in the study sample who went to the ED for opioid overdoses were admitted to the hospital and costs for both inpatient and ED care totaled nearly $2.3 billion, according to the study published in JAMA Internal Medicine.

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I think it’s important to get one thing straight, though. Some readers might get the impression after reading this article that prescription drugs are more dangerous than heroin, which is true in absolute numbers, but far from being true when accounting proportions. It’s estimated 0.2% of Americans use heroin, so  heroin’s contribution to ER visits heavily outweighs painkillers.

“Opioid overdose exacts a significant financial and health care utilization burden on the U.S. health care system. Most patients in our sample overdosed on prescription opioids, suggesting that further efforts to stem the prescription opioid overdose epidemic are urgently needed,” the study concludes.