Tag Archives: opioid overdose

07/12/22

Tranq Dope and Its Consequences

© aradaphotography | 123rf.com

A church friend of mine was lamenting his recent visit to Philadelphia. He said that for a city with so many different historic sites, he thought the officials there should have done a better job keeping the sites cleaned up. One of the noticeable parts of the debris were used needles and syringes. This led to us exchanging comments on the opioid epidemic, and how fentanyl had made the situation even worse. What neither of us realized at the time was that our assessment wasn’t quite accurate. We had never heard of “tranq dope.”

Although fentanyl has been replacing the heroin in the Philadelphia drug market, increasingly a substance known as xylazine has been found combined with fentanyl. It is a non-opioid veterinary tranquilizer that is not approved for human use. A brief report by Johnson et al, published in the journal Injury Prevention, reported that xylazine was detected in merely 2% of the unintentional overdose deaths in Philadelphia between 2010 and 2015. That rose to 11% in 2016; 18% in 2018 and 31% in 2019. See the chart below taken from the brief report.

NIDA (National Institute on Drug Abuse) said most overdose deaths linked to xylazine and fentanyl also involved other substances, including cocaine, heroin, benzodiazepines, alcohol, gabapentin, methadone and prescription opioids. When xylazine is taken in combination with other central nervous system depressants, it increases the risk of overdose.

Focus groups in Philadelphia said xylazine added to fentanyl gives the ‘nod’ that heroin provided before fentanyl took over the drug market. It “makes you feel like you’re doing dope (heroin) in the old days.” STAT News reported on paper published in the journal Drug and Alcohol Dependence that said while fentanyl produces a powerful high, its euphoria is short-lived when compared to other opioids like heroin. Adding xylazine gives fentanyl “legs,” meaning it extends the high.

The newer study by Friedman et al noted xylazine use is spreading beyond the Philadelphia area. It was found increasingly present in overdose deaths in all four US Census Regions. The highest prevalence data was still in the North East, in Philadelphia (25.8% of deaths), followed by Maryland (19.3%), and Connecticut (10.2%). Disturbingly, xylazine-involved overdoses may resist naloxone since it isn’t an opioid. That’s not all. “People who used drugs with xylazine seem to be more susceptible to wounds and infections on their skin and other tissues.”

The arrival of xylazine is “when we started to see way more people coming in with necrotizing skin and soft tissue issues. The amount of medical complaints related to xylazine was pretty astounding and terrifying. Xylazine wounds are a whole other kind of … just horror.”

The term “opioid crisis” doesn’t really capture what is developing with overdoses in the U.S. over the past two years. It’s an overdose crisis of polysubstance use—opioids, stimulants, and benzodiazepines; often used in combination. Friedman was quoted by STAT News as saying xylazine was an “especially noxious contaminant that is spreading through the drug supply.” A CDC MMWR Report said during January-December of 2019, xylazine was found in the overdoses reported in 23 states. It was listed as the cause of death in 64.3% of deaths in which it was reported.

Xylazine, or “tranq dope” as it’s known on the streets in Philadelphia, is an analogue of clonidine, and is used for sedation, anesthesia, muscle relaxation and analgesia in animals. It seems to reduce sensitivity to insulin and glucose levels in humans. It can lead to diabetes mellitus and hyperglycemia. Its side effects include bradycardia (a slow, resting heart rate), respiratory depression, blurred vision, disorientation, drowsiness, fainting, slurred speech, staggering, and shallow breathing. Chronic use is associated with physical deterioration, abscesses and skin ulceration.

Since xylazine is FDA approved for veterinary use only, it is not a controlled substance by the DEA. It is available in liquid form and is structurally similar to phenothiazines (first generation antipsychotics).

Its human use in Puerto Rico was reported by Rafael Torruella in a short report for Substance Abuse Treatment, Prevention, and Policy in 2011. He said Puerto Rican injecting users had been using it since the early 2000s. There, it is called Anestesia de Caballo (Horse Anesthetic). The report contained descriptions of how xylazine was viewed from a drug user’s perspective. One individual said the following about the first time he used xylazine and his later physical dependence on both heroin and xylazine:

I shot the anestesia […] and I felt asleep face first and when I opened my eyes five hours had gone by and I was laying on the floor. […] I don’t remember anything. I don’t remember anything! I fell down and I was gone. And I said: What the hell is this?! Oh, and I woke up sick [withdrawing]!I get there and don’t cop just heroin. I cop anestesia. Because that it what is going to get me high and what is going to get me straight [and reverse withdrawal symptoms]. I am not going to waste my money in just heroin because I’m going to stay the same. Do you understand? I’m going to stay the same.

Torruella said abscesses or ulcers were a serious health concern for several reasons. First, they are very painful. This encourages further injections in the abscess site with xylazine functioning as a sedative/anesthetic. This creates a need for medical attention and treatment.

Second, these open skin ulcers ooze and emit a strong odor. In severe cases, the mobility of the extremities where they appear is limited. Sometimes, amputations have been performed on the affected limbs. Third, when xylazine users asked for help in Puerto Rico, they were denied services because of their ulcers.  The drug user quoted above said he was lucky because by the time his abscesses developed, he had relocated to the states and could access medical services:

[T]he times when the abscesses […] started to appear, I would come here, to the United States. […] [When the abscesses began to appear] I already knew. […] I had seen them [before]. […] [T]here are people that take a longer time in blowing up [with abscesses] than others. […] I am one in which it took a while. But when I saw that people were rotting I would get scared because I always have said that I am a junky with style.

Without basic healthcare needs, like medical/wound care, syringe exchanges and education, these open sores look terrible to both the medically trained and the untrained-eye. When a colleague saw the ulcers and their effects on non-users, she said: “Injecting drug users are being treated as if they were lepers.”

According to NIDA, the full scope of overdose deaths involving xylazine is unknown. But research shows they have spread westward across the U.S. NIDA-supported research is underway to illuminate emerging drug use patterns and changes to the illicit drug supply across the U.S. with xylazine, opioids and the evolving pattern of polydrug use, abuse and overdose. Stay tuned for the next sea change.

03/16/18

Overdose No-Brainers

© Robert Hyrons | 123rf.com

The governor of Pennsylvania, Tom Wolf, declared the heroin and opioid epidemic as a statewide disaster emergency. Among the enhancements of the declaration, there will be increased access to the Prescription Monitoring Program so that state officials can identify doctors who are overprescribing opioid medication, as well as patients who may be seeing more than one physician to multiply their access to prescription opioids. Several measures to expand, speed up, and improve access to treatment and will be instituted. These measures include: enabling EMS to leave naloxone behind after responding to an overdose and expanding access to medication for Narcotic Treatment Programs. Pharmacists will be permitted to partner with prisons and treatment programs to make naloxone available to individuals leaving those facilities.

The Fix reported there was bipartisan support for the governor’s action. U.S. Senators, Pat Toomey (R) and Bob Casey (D) publically praised the declaration. Senator Toomey said: “The opioid and heroin crisis has rightfully drawn bipartisan attention in Congress and all levels of government. Today’s opioid emergency declaration sends a clear message that more work remains to be done.” Senator Casey added: “This declaration will bring additional resources to bear on this horrific public health emergency that has ripped apart far too many families.”

Increased access to the Prescription Monitoring Program by state officials is not as Orwellian as it may sound. Limitations placed upon the DEA by the “Ensuring Patient Access and Effective Drug Enforcement Act of 2016” hobbled the DEA’s ability to go after drug companies suspected of enabling the widespread distribution of prescription pain medication. “Overall, the drug industry spent $102 million lobbying Congress on the bill and other legislation between 2014 and 2016, according to lobbying reports.” See “Head of a Snake” for more information on this issue.

Drug overdose data from the CDC indicated that in 2016, Pennsylvania had the fourth highest increase in drug overdose deaths with 37.9 per 100,000. West Virginia (52.0 per 100,00), Ohio (39.1 per 100,00), New Hampshire (39.0 per 100,00) and Kentucky (33.5 per 100,000) rounded out the top five states. This was a 44.1% increase from 2015 to 2016 for Pennsylvania, again placing them fourth behind the increases with the District of Columbia (108.6%), Maryland 58.9%) and Florida (46.3%). New Jersey (42.3%) rounded out the top five states with percentage increases of overdose deaths. See the following graphic from the CDC report on rates of drug overdose death by state for 2016.

Another CDC report indicated the death rate for drug overdoses for the twelve-month period ending with the 4th quarter of 2016 was 19.8 per 100,000, an increase over the same time period for the 4th quarter of 2015, 16.3 per 100,000. This was an increase of 21% from 2015. The New York Times said Dr. Andrew Kolodny, the director of opioid policy research at Brandeis University, was not surprised by the data. “We have roughly two groups of Americans that are getting addicted. . . . We have an older group that is overdosing on pain medicine, and we have a younger group that is overdosing on black market opioids.” See the following table from the CDC report.

Naloxone, as it was noted in the opening paragraph, is a crucial tool in the struggle against opioid overdoses. Yet it had a quiet, and rather unassuming life until the rise of the opioid epidemic. Jack Fishman originally synthesized naloxone for a private narcotics lab owned by Mozes Lewenstein in 1961. Harold Blumberg, a colleague of Lewenstein’s, had the idea of developing an opioid antagonist by making a small structural change to oxymorphone, a synthetic opioid. The FDA approved naloxone as an injection, Narcan, to reverse opioid intoxication in 1971. Generic versions of naloxone became available in 1985.

As the opioid crisis began to pick up steam in 2013, the FDA approved Evzio, a portable injection kit with a fixed dose of naloxone. In late 2015, they approved Narcan, now packaged as a nasally administered form of naloxone. A series of governmental initiatives were enacted to increase access to naloxone. From 2012 to 2016, the number of states with at least one law expanding access to naloxone increased from 8 to 46. A growing number of community organizations now provide naloxone kits and education programs to laypersons. But as Gupta et al. reported in The New England Medical Journal, between 2009 and 2015 the annual number of naloxone prescriptions only increased from 2.8 million to 3.2 million. While retail-prescription numbers were unchanged, the proportion attributed to clinics and EMS providers increased from 14% to 29%.

Although the slowed rate of using naloxone could be attributed to the stigma of opioid use and unfamiliarity with how to use naloxone, the rising cost and the limited number of manufacturers producing it, are more insidious reasons. While there are three manufacturers of naloxone approved by the FDA, there is only one supplier for all three formulations. Amphastar, the manufacturer of the 1-mg-per-millileter dose used off-label as a nasal spray, increased its price 95% to $39.60 in September of 2014. “Newer, easier-to-use formulations are even more expensive. Narcan costs $150 for two nasal-spray doses. A two-dose Evzio package was priced at $690 in 2014 but is $4,500 today, a price increase of more than 500% in just over 2 years.” See the following table of previous and current prices for naloxone.

The price increase for naloxone is related to the overall trend of rising prescription drugs prices across-the–board. See “Pharma’s Not Getting the Message” and “Pharma Companies Hunt in Packs” for more information on this. But unfortunately, none of the federal or state initiatives to expand the availability of naloxone address the drug’s high price. “Evzio’s price jumped significantly and without explanation the month before the CDC’s coprescription guidelines were released.” Several U.S. senators have sent letters to naloxone manufacturers asking them to explain their price increases, but this hasn’t resulted in any changes or public outrage, as happened with Mylan, the manufacturer of the EpiPen. Gupta et al. had some recommendations to address naloxone’s price increase.

First, naloxone could be purchased in bulk, which would create stable demand that might motivate additional companies to begin manufacturing the medication — a strategy that’s been used for vaccine manufacturing. Second, governments could invoke federal law 28 U.S.C. section 1498 to contract with a manufacturer to act on behalf of the United States and produce less costly versions of Evzio’s patented auto-injector in exchange for reasonable royalties — an approach that was considered for procuring ciprofloxacin during the anthrax threat in 2001. Third, in response to increases in generic drug prices, some observers have proposed allowing importation of generics from international manufacturers that have received approval from regulators with standards comparable to those of the FDA, a strategy that could be pursued for naloxone.

Gupta et al. also suggested the federal government could motivate additional companies to obtain approval to market generic versions of naloxone by prioritizing timely approval and waiving application fees. This would likely stimulate price competition. Resurrecting a discussion of the FDA switching naloxone to over-the-counter-status would benefit patient access. “The relative ease of receiving FDA authorization for over-the-counter medications would also probably attract additional manufacturers.”

 Naloxone coprescribing and expanded availability represents only one of many potential strategies for reducing the number of prescription-opioid and heroin overdose deaths in the United States. But when governments promote naloxone use, they have a responsibility to ensure the drug’s affordability. Taking action now is essential to ensuring that this lifesaving drug is available to patients and communities.

As illustrated within the actions taken by Governor Tom Wolf of Pennsylvania, naloxone is a key factor in the fight against the opioid epidemic. Given the potential influence of state and federal officials and legislators, concerted efforts to force manufacturers to decrease the cost of naloxone products or to take steps to increase their competition should be a no-brainer strategy. Otherwise—and this itself is another no-brainer—the pharmaceutical companies will continue to siphon as much profit as they can from the opioid epidemic.

01/29/16

High on Overdoses

© diego_cervo | stockfresh.com

© diego_cervo | stockfresh.com

A recent CDC Morbidity and Mortality Weekly Report indicated that in 2014 more people in the U.S. died from drug overdoses than any other year on record. There were approximately one and a half times more deaths from drug overdoses than from motor vehicle accidents. Sixty-one percent (28,647) of all drug overdose deaths were from opioids; the rate has tripled since 2000. Drug overdose deaths from heroin have more than tripled in 4 years. The overdose death rate involving synthetic opioids almost doubled between 2013 and 2014.

Drug overdose deaths are up for both men and women; in adults of nearly all age groups. The following table presents data for all overdose deaths in 2013 and 2014; by sex; and by age group. The death rates per 100,000 are given, as is the percentage increase from 2013 to 2014.

2013

2014

% change 2013-2014

#

Rate

#

Rate

All

43,982

13.8

47,055

14.7

6.5%

Male

26,799

17.0

28,812

18.3

7.6%

Female

17,183

10.6

18,243

11.1

4.7%

Age Group (yrs)

0-14

105

0.2

109

0.2

0.0%

15-24

3,664

8.3

3,798

8.6

3.6%

25-34

8,947

20.9

10,055

23.1

10.5%

35-44

9,320

23.0

10,134

25.0

8.7%

45-54

12,045

27.5

12,263

28.2

2.5%

55-64

7,551

19.2

8,122

20.3

5.7%

≥65

2,344

5.2

2,568

5.6

7.7%

The authors of the Report said these figures indicate the opioid overdose epidemic is worsening. That almost seems to be an understatement. In a CDC Press Release Tom Frieden, the Director of the CDC, said the increased number of overdose deaths was alarming. “The opioid epidemic is devastating American families and communities. To curb these trends and save lives, we must help prevent addiction and provide support and treatment to those who suffer from opioid use disorders.” He added how important it was for law enforcement to intensify its efforts to reduce the availability of heroin, illegal fentanyl and other illegal opioids.

The 2014 data on overdose deaths showed there were two interrelated trends driving the increase: “a 15-year increase in overdose deaths involving prescription opioid pain relievers and a recent surge in illicit opioid overdose deaths, driven largely by heroin.” Natural and semisynthetic opioids, which include oxycodone and hydrocodone, continued to be the most common type of opioid involved in overdose deaths.

Drug overdose deaths involving heroin continued to climb sharply, with heroin overdoses more than tripling in 4 years. This increase mirrors large increases in heroin use across the country and has been shown to be closely tied to opioid pain reliever misuse and dependence. Past misuse of prescription opioids is the strongest risk factor for heroin initiation and use, specifically among persons who report past-year dependence or abuse. The increased availability of heroin, combined with its relatively low price (compared with diverted prescription opioids) and high purity appear to be major drivers of the upward trend in heroin use and overdose.

The 2014 rates were highest in these five states: West Virginia, New Mexico, New Hampshire, Kentucky and Ohio.  There were statistically significant increases in overdose deaths for fourteen states: Alabama, Georgia, Illinois, Indiana, Maine, Maryland, Massachusetts, Michigan, New Hampshire, New Mexico, North Dakota, Ohio, Pennsylvania and Virginia. Here is an interactive CDC map with this data.

Supporting these findings by the CDC, the National Institute on Drug Abuse (NIDA) reported in “Overdose Death Rates” that there was a 3.4-fold increase in the total number of overdose deaths from opioid pain relievers and a six-fold increase in the total number of overdose deaths from heroin from 2001 to 2014. The following charts are from the NIDA report.

prescription overdoses

heroin overdosesThe CDC pointed to four ways to prevent overdose deaths:

  • Limit initiation into opioid misuse and addiction. Opioid pain reliever prescribing has quadrupled since 1999. Providing health care professionals with additional tools and information—including safer guidelines for prescribing these drugs—can help them make more informed prescribing decisions.
  • Expand access to evidence-based substance use disorder treatment—including Medication-Assisted Treatment—for people who suffer from opioid use disorder.
  • Protect people with opioid use disorder by expanding access and use of naloxone—a critical drug that can reverse the symptoms of an opioid overdose and save lives.
  • State and local public health agencies, medical examiners and coroners, and law enforcement agencies must work together to improve detection of and response to illicit opioid overdose outbreaks to address this emerging threat to public health and safety.

Overdoses are not just a U.S. problem. The World Health Organization (WHO) estimated that globally 69,000 people die from opioid overdose each year. The World Drug Report 2014 estimated thee were 183,000 drug-related deaths worldwide in 2012. The main type of drug implicated in those deaths is opioids.

International Overdose Awareness Day reported that like the U.S. both the UK and Australia have had more deaths due to overdose than road fatalities. Nearly four Australians die each day from overdoses. Ontario, Canada had a 242% increase in fatal opioid overdoses between 1991 and 2010. European Union nations reported 6,100 overdose deaths in 2012. “It is estimated that more than 70,000 lives were lost to drug overdoses in European union countries in the first decade of the 21st Century.”

The CDC recommendations, for the most part, are ones I’d endorse. But like riders attached to big spending bills that have to be passed by Congress, the little phrase in the second recommendation “including Medication-Assisted Treatment” isn’t necessary. Medications like naloxone and naltrexone have a place in the expansion of substance use disorder treatment. But the phrase “medication-assisted treatment” refers to these medications as well as two opioids—methadone and buprenorphine—used in opioid substitution therapy. There is proposed legislation to expand the availability of buprenorphine, the Recovery for Addiction Treatment Act, in committee.

My objection is simple. You don’t “treat” an opioid use disorder with another opioid. You simply substitute dependence on one opioid for another.

I’ve regularly voiced concern over the treatment of opioid dependency with methadone and buprenorphine. Stop and think for a minute. Isn’t it reasonable to find that an individual who was physically addicted to heroin or prescription opioids would improve when they substitute ingesting enough methadone (a Schedule II controlled substance) or buprenorphine (a Schedule III controlled substance) to neutralize their physical withdrawal symptoms? The positive evidence base for opioid substitution treatment is based upon medically assisting an addict to begin using another opioid.

The “evidence-based” effectiveness of opioid “maintenance” treatment involves using these acknowledged addictive substances (methadone and burprenorphine) for weeks and even years to manage or stabilize an addiction to other opioids. There is more information on this issue in other articles I’ve written: “The Seduction of Opioid Substitution,” “Another Head for the Hydra,” and “A Double-Edged Drug.”

Another one of the drug types showing an increase in overdose deaths since 2001 in NIDA’s “Overdose Death Rates” was benzodiazepines. There has been a five-fold increase in the total number of deaths related to benzodiazepines. “Benzos” combined with opioids like methadone and buprenorphine have a synergistic effect and will give the person a heroin-like euphoria with the right drug cocktail. They also contribute to the higher rates of accidental overdose deaths. Expect the opioid overdose death rates to continue to rise even if the expansion of opioid substitution curtails overdose deaths from heroin.