05/16/17

Trouble with Tramadol

© Vitaliy Vodolazskyy | 123rf.com

Regularly in the U.S. we hear news about the opioid epidemic. There is an ever-growing use of powerful opioids such as fentanyl, which is 50 to 100 times the strength of morphine; and carfentanyl (used as a sedative for large land animals) whose strength is 10,000 times that of morphine. Recent CDC data released on December 30, 2016 indicated that 60.9% of the overdose deaths in 2014 involved an opioid. Between 2014 and 2015 drug overdose deaths increased by: 11.4%.  The CDC suggested this increase was largely driven by synthetic opioids, most likely fentanyl, and heroin. While the opioid epidemic is not uniquely a US problem, it has a different face in other countries, such as Egypt, where the opioid of choice for abusers is tramadol. Yes tramadol, which is one-tenth the potency of morphine.

The Economist said tramadol use in Egypt was everywhere. Taxi drivers used them to stay awake. Wedding guests receive them as token gifts. Petty government officials even accept them as bribes. “Tramadol has become Egypt’s favourite recreational drug, supplanting heroin and cannabis.” Taha, a bank teller, said the drug helps him work. “It just makes you feel relaxed. Even if there are two men fighting to the death beside you, you wouldn’t care.”

There is no social stigma attached to tramadol use. It’s seemingly more religiously acceptable than alcohol or marijuana. Ibrahim began using half a tablet of tramadol because he felt socially awkward at the age of seven. “I found myself feeling unusually outgoing and positive.” Ten years later, he was using ten tablets daily.

Until recently, tramadol sold for the equivalent of 15 to 30 cents per pill. Tramadol use accelerated after the 2011 uprising in Egypt, partly because of the weakened state controls. Ehab El-Kharrat, an Egyptian doctor, said the tramadol came largely from India or China. Customs inspections began to tighten and the price rose sharply. At one point the price reached $1 to $3 a pill. “Since then we have seen a flood of people seeking help.”  The head of a Cairo rehabilitation center said at least 40% of those attending his clinic are addicted to tramadol.

Yet enforcement is poor. Court cases are thrown out because of shoddy police work. Officers are often in cahoots with the drug dealers, or are themselves drug-users. And even if the government succeeds in restricting the supply of tramadol, there may be unintended consequences. If the pills become more expensive, users may switch to stronger heroin. Some worry that the worst of Egypt’s drug problem is yet to come.

The Daily Beast also reported on the tramadol problem in Egypt. A taxi driver threw up the first time he tried tramadol. But now he takes for or five doses daily. He justified his use by saying its one of the few ways to dull the pain of Egypt’s weak economy and trying political circumstances. “Food, gas, everything is so expensive. People are exhausted and take things like tramadol just to keep going.” Young cash strapped males form the core of its users.

A UNODC (United Nations Office on Drug and Crime) official estimated that 90% of the illicit tramadol in Egypt is produced in India, and then smuggled into the country. One supplier said it’s never been easier to keep stocked up on tramadol. Because of its ready availability, its use has begun to spread from younger working class males into the more affluent areas of Cairo, which doesn’t make drug dealers very happy. “It’s not good when [those] people buy tramadol, because it means they won’t buy more expensive things. . . But with the economy and everything, this seems to be what Egyptians want right now.”

The Expert Committee on Drug Dependence of the World Health Organization (WHO) gave an Updated Review Report on tramadol at its thirty-sixth meeting in June of 2014. The report noted how Egypt had up-scheduled tramadol in 2009 because of its increasing rate of abuse. There was also growing evidence of tramadol abuse in other African and West Asian countries, including: Egypt, Gaza, Jordan, Lebanon, Libya, Mauritius, Saudi Arabia and Togo. In most countries it is a prescription-only medicine.

Marketing authorizations for tramadol are held by dozens of companies. The WHO Report listed around thirty-five companies as examples. Corresponding to this, it also goes by dozens of trade names, literally from A (i.e., Acerna, Amanda, or Astradol) to Z (i.e., Zamadol, Zentra, or Zodol). The common formulas in the US are: ConZip, Ryzolt and Ultram.

Overall, tramadol has been seen as having a low potential for drug dependence. However, in the last few years, new data suggests that dependence may occur when it is used daily for more than a few weeks or months. The WHO finding here is consistent with the above reported abuse of Tramadol in Egypt. It is listed as a controlled or scheduled substance in several countries, including: Australia, Iran, Sweden, Venezuela, Ukraine, China, the United Kingdom, Jordan, Saudi Arabia, and Egypt. Since the WHO Report was published, tramadol has become a Schedule IV controlled substance in the U.S.

In summary, the data on the dependence potential of tramadol show that tramadol has a relatively low dependence potential and that dependence is associated with the use of tramadol over an extended period of time (more than a few weeks to months). The data also show a higher risk profile in former drug abusers and in medical staff personnel than in pain patients. Several studies indicate that the incidence of tramadol dependence may differ between countries and within different regions of countries, which may be associated with the availability and prescription practice for tramadol, and with the availability of alternative psychoactive substances for drug abusers.

DrugAbuse.com described tramadol as a fully synthetic opioid originally synthesized by a German company in 1962. It was finally brought to market as Tramal in 1977. It was not until 1995 that it became available in the U.S. as “Ultram.” Initially it was not a controlled substance. By 1996 the FDA revised the product label to require warnings about the potential for abuse. In 2009, the FDA again changed the product warning, now the alert of the possibility of a life-threatening condition, serotonin syndrome.

Between 2005 and 2011, emergency department visits related to non-medical tramadol use rose over 250%. Between 2008 and 2013, prescriptions for tramadol increased by 20 million. In 2014 another increase of 44 million prescriptions of tramadol occurred, possibly a reaction to the rescheduling of Vicodin from Schedule III to Schedule II. Also in 2014, tramadol was made a Schedule IV controlled substances by the DEA.

In 2009, Sansone and Sansone gave a good summary of some of the health risks with tramadol, including a description of serotonin syndrome (SS), and the risk of seizures if it was used concurrently with antidepressants, both tricyclics and SSRIs. There was a “Dear Healthcare Professional” letter distributed by the manufacturer warning of the potential adverse drug event of seizures when using tramadol and antidepressants. A follow up study noted a small and insignificant change in the prescribing habits after the release of the warning letter.

Serotonin syndrome was more common with excessive use/overdose of tramadol or coadministration with other medications, particularly antidepressants among the elderly. SS has been reported with combinations of tramadol and the following: fluoxetine (Prozac),sertraline (Zoloft), paroxetine (Paxil), citalopram (Celexa),  fluvoxamine (Luvox),venlafaxine (Effexor),and TCAs (tricyclics). Rimeron was implicated in one case study of tramadol use with elderly residents in a long-term care facility. They summarized their conclusions as follows:

In primary care settings, tramadol is a commonly prescribed synthetic analgesic. Two potential adverse reactions of tramadol are seizures and SS. Either of these reactions may occur with tramadol monotherapy, but both appear to be much more common with either abuse/overdose or in combination with other drugs, particularly antidepressants. These adverse reactions appear to be more common in the elderly. The majority of commonly prescribed antidepressants have been implicated in both of these adverse reactions. Clinicians are advised to be mindful of these potential adverse sequelae when prescribing antidepressants to patients on tramadol, particularly in the elderly and/or those who might be at a heightened risk (i.e., individuals with epilepsy, head injuries, neurological dysfunction). If coadministration is undertaken, we advise careful monitoring for these two particular hazards. Tramadol is a remarkable drug, but like all drugs, effective use entails balancing the benefits versus the risks.

Then on April 20, 2017, the FDA restricted the use of tramadol (and codeine) in children. They also recommended against the use of these medicines in breastfeeding mothers. Tramadol is contraindicated (the FDA’s strongest warning) to treat pain in children younger than 12 years old and for pain in children younger than 18 after surgery to remove tonsils and/or adenoids. “These medicines carry serious risks, including slowed or difficult breathing and death, which appear to be a greater risk in children younger than 12 years, and should not be used in these children.”

01/26/15

Meth is Coming to YOUR House

Congratulations, Walter White. Methamphetamine production (meth, speed, crank crystal meth, “ice” and others) has gone international … big time.  There has been a seizure of 2.8 tons of drugs, worth more than $1.5 billion dollars in Australia. There were 1,917 kilograms of MDMA and 849 kilograms of methamphetamine. This made it the largest seizure of meth in Australia and the second largest seizure of MDMA. The previous record for meth seizures was 580 kilograms.

To put this in context, the entire amount of all drugs seized last year by Customs and Border Protection in Australia, was about 5 tons. The Commissioner of the Australian Federal Police, Andrew Colvin, said: “By any measure this is an enormous seizure of illicit narcotics that have been removed from distribution on our streets.” The investigation is ongoing and they expect to arrest more than the initial six Australians currently in custody. “This obviously has linkages overseas that will take us, I’m sure, into Europe and parts of Asia.” They expect to have a number of people and a number of organized crime groups involved.

The drugs were concealed with furniture and other belongings within a sea cargo container that came from Hamburg Germany. The Australian authorities are working closely with the German federal police and Interpol. The message the authorities wanted to send to the “Breaking Bad” individuals involved in this operation was: “Go somewhere else, go to another country. Don’t bring your evil poison here to Australia.”

The UNODC (the United Nations Office on Drugs and Crime) Global SMART Update, Vol. 12, said that in North America, meth production has been primarily within the U.S. and Mexico. The movement in the U.S. to control the precursors for cooking meth, such as pseudoephedrine and ephedrine, led the Mexican drug cartels to begin manufacturing it in large quantities. In February of 2012 Mexican soldiers overran an abandoned ranch south of Guadalajara and found 15 tons of methamphetamine. There was, of course, a laboratory and another seven tons of the precursor chemicals used to manufacture meth. “The cheap and potent meth they supply now provides some three quarters of the drug consumed in America.”

East and South East Asia has been another center for the manufacture and distribution of meth. In 2011 and 2012, eleven countries in the region reported methamphetamine laboratories, “with China (46 percent) and New Zealand (39 percent) accounting for the largest share.” Although Myanmar has reported finding only small-scale meth labs, it is one of the main destinations for trafficked preparations containing ephedrine and pseudoephedrine. This suggests that industrial-scale meth production is going on within that country.

In Africa, the illicit manufacture of meth had been confined to South Africa. But since 2010, laboratories have been reported in Egypt, Nigeria and Kenya. In 2011 and 2012, five large-scale labs were discovered and dismantled in Nigeria. In May of 2012, Nigerian drug enforcement agents raided a building on the outskirts of Lagos and discovered a factory capable of producing 25 kg of crystal meth every few hours. Four large-scale labs have been found in Nigeria. In 2013, Kenya reported that it had dismantled its first meth lab.

In 2008, meth or sheesheh/shishe (Farsi for “glass”) was introduced to Iran. By 2010, Iranian meth manufacturing operations expanded their reach into Japan, Malaysia and Thailand. In 2011 and 2012 Iran reported seizing bulk amounts of ephedrine. By 2012, Iran was the world’s fourth largest importer of pseudoephedrine (used to manufacture meth). Iran spends around 1 billion dollars per year on anti-drug operations. Since 1979, almost 4,000 Iranian law officers have been killed in the country’s fight against the drug trade. In part, this results from severe punishments given out. “Nearly 80% of prosecuted traffickers are given the death penalty.”

One of the primary reasons the use of meth has spread so quickly in Iran is the lack of information. Azarzksh Mokri, a psychiatrist who teaches at Tehran University of Medical Sciences, said: “We really had a hard time convincing people that this is addiction.” Drug use and addiction in Iran is now the second highest cause of death after traffic accidents.

The Global SMART Update Vol. 12 said that illicit methamphetamine manufacture in Europe seems to be concentrated in Central Europe (the Czech Republic, Germany and Slovakia) and the Baltic States, mostly in Lithuania. The Czech Republic typically has small-to medium scale operations that sell their product locally, as well as in Austria and Germany. Conversely, Lithuania has medium-to large-scale laboratories that supply the demand for meth in the Nordic countries and the United Kingdom.

There is a series of twenty segments, or brief reports on global meth operations in the 2014 Global Smart Report. Here is a sampling of three of them. London Police have found a suspected meth lab in a residential area of West London in February. Again in February, a joint operation by U.S. agencies and the Australian Federal Police prevented 60kg of “black ice” methamphetamine from being shipped to Australia. In May, Guatemalan authorities dismantled a lab estimated to manufacture nearly 3 tons of drugs per month.

“Imagine this:
Ice is coming to YOUR house.
Can you HEAR it knocking?
Are you ready?
What will YOU do?”
Cornelia Connie D. DeDona