Monday, November 22, 2010

Ice, Ice, Baby or How Not To Treat an Opiate Overdose

James Mann's friend became unresponsive after consuming approximately 120mg of Oxycontin along with alcohol and marijuana.  Mann, a 20-year old Norcross, Georgia man, decided he would awaken him  Alas, while his heart was in the right place his judgment was fogged by 160 mg of oxycodone.  Thankfully, he was coherent enough to realize that he was in over his head after his efforts to rouse his friend failed.

When paramedics arrived on the scene, they discovered Mann's friend was indeed unconscious. He was also bleeding profusely as the result of injuries sustained when Mann had forced ice cubes into his rectum.  The victim was transported to Gwinnet Medical Center: Mann was charged with misdemeanor reckless conduct after police determined that his actions constituted "a gross deviation of standard care."

Mann's efforts to awaken his friend with Frosty the Enema may elicit some chuckles.  But many other opiate users labor under similar mistaken ideas.  It is quite common for users to throw ice water on an unresponsive friend, put them under a cold shower or throw them in an icewater bath.  But these methods will not bring a comatose user out of an overdose.  While the initial jolt of ice may cause gasping, it will not dislodge the opiates from their receptors.  Should the "treatment" persist it may cause hypothermia and shock, further complicating the situation.  Perhaps most important is the time which is wasted: when someone stops breathing a few minutes may be the difference between recovery and permanent brain injury or death.

If you are in the vicinity of an overdose, the best thing you can do is seek medical attention.  Unfortunately, many users do not receive aid - or receive it too late - because of heavy-handed law enforcement attacks on overdose victims and their companions.  One answer to this problem is "Good Samaritan" laws which protect those who seek medical treatment for themselves or their friends. Another would be ready availability of Naloxone, a powerful opiate antagonist which can reverse an opiate OD within seconds. But while these ideas have gained traction in a few areas, they still face resistance from those who equate harm reduction with encouraging drug abuse.

Monday, November 8, 2010

The Schneider Pain Clinic and the Pain Relief Network (Part II)

On June 10, 2008, when a lawyer representing Linda Schneider failed to return his phone call promptly, District Judge Monti Belot wrote a terse letter threatening to have lawyers who did not return his phone calls on the same day brought to court in handcuffs by U.S. Marshalls. In November 2008 he refused the still-jailed Linda Schneider's request for a bond.  In December 2008 he dismissed a request by Schneider's counsel challenging the prosecution's expert witnesses.

But on January 28, 2009 Belot ruled in favor of the defense, stating that prosecutors could present evidence to the jury on only four of the 59 deaths they claimed were connected to the Schneider Clinic. The prosecution immediately filed an appeal with the 10th Circuit Court of Appeals: on February 8, 2010 that court reversed Belot's decision, ruling that "A trial court's case management may not interfere with the government's ability to prosecute criminal activity any more than it can intrude upon a defendant's opportunity to defend."

Throughout these proceedings, Siobhan Reynolds and the Pain Relief Network continued to assist the Schneiders in their defense.  Reynolds, PRN's founder, is the widow of chronic pain patient Sean Greenwood.  Greenwood suffered from Ehlers-Danlos Syndrome, a rare and painful disorder of the connective tissues. After years of misery, he finally found relief when he came under the care of Dr. William Hurwitz, a pain management doctor and outspoken critic of the DEA's war on physicians. After Hurwitz received a controversial 25-year sentence for "drug trafficking"  (a sentence later reduced to 5 years on appeal), Greenwood was unable once again to receive adequate medication: later he died of a brain hemorrhage which Reynolds blamed on his long agony.

Reynolds saw the Schneider Pain Clinic case as a parallel to the attacks on Dr. Hurwitz and brought all the PRN's resources to bear in the case.  The PRN assisted in the Schneider defense, rented a billboard proclaiming "Dr. Schneider Never Killed Anyone," and regularly contributed to the media coverage of the trial.  Irritated by continual PRN criticism, the prosecutor's office sought a gag order forbidding the Schneiders, their family members and the Pain Relief Network from publicly commenting on the case. But once again Belot ruled for the defendants and denied the prosecution's request. 

Tuesday, November 2, 2010

The Schneider Pain Clinic and the Pain Relief Network (Part I)

In December of 2007 a Topeka grand jury returned a 34-count indictment against Dr. Stephen J. Schneider and his wife, nurse Linda K. Schneider. The indictment charged that 56 of the doctor's patients had died from accidental prescription drug overdoses between 2002 and 2007. While it admitted that only four of the deaths were found to be directly caused by drugs prescribed by Schneider's Haysville, Kansas clinic, it claimed that the doctor was known among addicts as "the candy man," "the pill man" and "Schneider the [prescription] Writer."

From the start, the government pursued its case against the Schneiders and their clinic aggressively. They sought to revoke court-appointed counsel to the defendants, while seizing assets belonging to the couple and even to their family members. Local jail officials barred them from visitation with their daughters when they tried to assist in a petition drive and media coverage of their case.

On February 1, 2008 thirty of Dr. Schneider's patients protested his indictment, calling his arrest "a great injustice." Standing outside his shuttered clinic, they carried signs including "Decriminalize Compassion," "Where Can I be Euthanized?" and "Our Blood Will Be On Your Hands." Many of his suffering former patients talked about how they had been "blackballed" for pain treatment at local hospitals and emergency rooms. 43-year old Anthony Trask, disabled from a  gunshot wound to the spine, tearfully described his life with untreated pain:
You start to get very emotional and unstable to the point you are no longer in control. You begin to hit things, kick things. You are restless, hopeless and have suicidal thoughts.
On February 12 these patients took their fight to court with the help of the Pain Relief Network, a New Mexico nonprofit corporation. Their lawsuit against Attorney General Michael Mukasey, U.S. Attorney Eric Melgren, the state of Kansas and the Kansas Board of Healing Arts, claimed suspending Dr. Schneider's license endangered the lives of over 1,000 patients of the Schneider Clinic and deprived them of necessary medical care for their pain. Taking over the Schneiders' defense in the criminal case as well, the Pain Relief Network sought to make the Schneider Clinic case a national issue and challenge the constitutionality of federal drug laws when applied to doctor-patient relationships.

On March 1, their request for a restraining order against Schneider's license suspension was denied. Despite repeated reports that they were unable to find appropriate medical care, U.S. District Judge Wesley Brown told Schneider's former patients that if they needed care they should go to the emergency room, not the court. They also claimed that the Pain Relief Network, who had brought the suit on behalf of the Schneider Clinic's patient, had no standing to participate in the suit.  "Strangers don't get to enforce the constitutional rights of others, and the PRN is a stranger here," said Kansas deputy attorney general Mike Leitch. Meanwhile, Dr. Schneider and his wife remained jailed without bond as federal prosecutors linked three more overdoses to patients of the Schneider Clinic.

Monday, November 1, 2010

Intranasal Availability of Opana

There was recently some discussion on Opiophile concerning the amount of bioavailable oxymorphone in crushed and insufflated tablets of the popular painkiller Opana ER.  (The most common method by which they are used for recreational purposes). Given oxymorphone's potentially lethal strength, it is important for users to keep tabs on how much they have consumed in a sitting.  Alas, a quick look at the available research reveals this may be a daunting task.

Our first exhibit would be Hussain, M. A. and Aungst, B. J. (1997), Intranasal absorption of oxymorphone. Journal of Pharmaceutical Sciences, 86: 975–976. doi: 10.1021/js960513x.  From the abstract:
The nasal bioavailability of oxymorphone HCl was determined. Rats were surgically prepared to isolate the nasal cavity, into which a solution of oxymorphone was administered. A reference group of rats was administered oxymorphone HCl intravenously. Plasma oxymorphone concentrations were determined by HPLC. Nasal absorption was rapid, nasal bioavailability was 43%, and the iv and nasal elimination profiles were similar. Oxymorphone HCl appears to have the solubility, potency, and absorption properties required for efficient nasal delivery, which is an alternative to injections.
I wonder how applicable information about surgically prepared rat nostrils is to the nostrils of a human user, or how the absorption of oxymorphone dissolved in saline solution compares to oxymorphone contained within ground-up pill powder. I suspect sniffing pills is less efficient than using saline, especially depending on how well the pills are crushed. The sniffer's technique introduces yet another variable: someone who is railing enormous lines will lose more to drip than someone who sniffs several small lines over a few minutes. Does the sniffer have a clear nose (at least at the start of the evening?)

Some of the pill will invariably be lost to the nose's natural immune systems: it will get covered in mucus and blown out just like other small foreign particles. The rest will either be absorbed into the bloodstream in the sinuses or carried via post-nasal drip to the stomach where we would see oral absorption rates. I do not know the percentage of any given pill which will fall into each category.

And then there's a factsheet on Opana ER on the National Institute of Health website.

Food Effect
After oral dosing with 40 mg of OPANA in healthy volunteers under fasting conditions or with a high-fat meal, the Cmax and AUC were increased by approximately 38% in fed subjects relative to fasted subjects. As a result, OPANA should be dosed at least one hour prior to or two hours after eating (see DOSAGE AND ADMINISTRATION).

Ethanol Effect
The effect of co-ingestion of alcohol with OPANA has not been evaluated. However, an in vivo study was performed to evaluate the effect of alcohol (40%, 20%, 4% and 0%) on the bioavailability of a single dose of 40 mg of OPANA ER (an extended-release formulation of oxymorphone) in healthy, fasted volunteers. Following concomitant administration of 240 mL of 40% ethanol the Cmax increased on average by 70% and up to 270% in individual subjects. Following the concomitant administration of 240 mL of 20% ethanol, the Cmax increased on average by 31% and up to 260% in individual subjects. In some individuals there was also a decrease in oxymorphone peak plasma concentrations. No effect on the release of oxymorphone from OPANA ER was noted in an in vitro alcohol interaction study. The mechanism of the in vivo interaction is unknown. Therefore, co-administration of oxymorphone and ethanol must be avoided.
While I'm not clear on how much fats or alcohol would influence the absorption of sniffed vs. oral Opana, I think it is reasonable to assume they might have at least some effect. Given all these variables, it would seem to me like 35% bioavailability would be a generous but not unreasonable estimate for intranasal Opana: higher levels might well be achieved under certain circumstances. I would also caution that this may vary a good bit based on any number of factors, and urge users to dose conservatively.

Sunday, October 31, 2010

Yunnan Province: Life in China's Heroin Zone

Despite its abundant natural resources, Yunnan is one of China's poorest and most underdeveloped provinces. While Yunnan's GNP tripled between 1991 and 1996, the number of its people living in poverty increased. Those belonging to "minority groups" - some 38% of Yunnan's 43 million people - have gained little from China's capitalist experiment.  Han Chinese leaders in Beijing are more likely to greet Yunnan's disempowered with suspicion than concern: among them are Muslims with ethnic and cultural ties to the Uighurs of restive Xinjiang Province and Tibetans fleeing that region's long separatist conflict.

In the days of the Silk Road, this poor and remote area was a major stop for merchants selling silk, spices and the region's still-famous Pu-erh tea. Today it has become a major stopping place for a more shadowy trade. Located at the base of the Burmese/Laotian Golden Triangle, much of the heroin which makes its way to Southeast Asia passes through Yunnan - and a fair bit of it stays there.

In the late 1980s Dongxiang merchants, descendents of nomadic Mongolian converts to Sunni Islam, began trading with the Miao - a Hmong people related to tribesmen in nearby Laos and Vietnam - and the Dai, whose language and history connected them to Thailand.  These hill tribes passed at will over the porous border between China and Myanmar, bringing back opium and heroin which the Dongxiang could sell to traffickers in Hong Kong.  

At first Chinese law enforcement, wary of stirring up trouble amongst minorities, turned a blind eye to this trade.  So long as the heroin was being exported - and the proper palms were being greased - the flow to the outside world could continue unabated.  But then local youths began spending their newly-found wealth on heroin: more than a few became addicted.  As one Dongxiang heroin seller said:
Yes, drugs are illegal. But our people don't usually get hooked. It is only the Han who are weak, and we don't care so much about them because they have never cared about us.
And with the drug came a new disease. In 1991 397 of China's 410 confirmed AIDS cases were in Yunnan Province: by 2006 Yunnan had 30,000 recorded HIV-positive residents, with experts speculating the actual number could be as 200,000.   Many of these cases were contracted through sharing needles: others could be traced to the sex trade which rose up alongside the heroin industry.  Meanwhile, the province's drug problem was now spreading throughout the country, as smugglers catered to an increasingly prosperous market.  Some enterprising farmers in Yunnan and other southern provinces even returned to old family traditions: today as much as 15% of China's heroin is made from locally grown poppies.

Faced with these threats, Chinese leaders have taken the expected forceful response against traffickers. Those caught with over 50 grams of heroin face a death sentence. (British subject Akmal Shaikh was recently executed after being caught with four kilograms of heroin, despite strong diplomatic pressure from Great Britain).  Those caught using drugs are often sent to Orwellian compulsory drug rehabilitation centres where forced labor and beatings are commonplace.  Still, heroin use continues to increase along with disposable income, while widespread police and judicial corruption helps ensure the biggest players in the drug game can buy their way out of sentencing.

Despite these problems, Beijing has made comparatively little effort to shut down the Golden Triangle's heroin industry.  They may see the major opium producing groups in Myanmar as a counterbalance against the ethnic Burmese military junta, since most have direct ties to China. The Kokang are descendants of Chinese who moved to the area in the 17th century. The Wa once were most famous for their habit of ritual decapitation. But during the 1960s many of the Wa gave up headhunting for Maoism, becoming part of a well-armed (by Beijing) Communist insurgency.

Friday, October 22, 2010

Anti-Abuse Mechanisms: TIMERx and OxyContin OP

In James Fogle's classic autobigraphical novel Drugstore Cowboy "blues" - Numorphan tablets containing 10mg of oxymorphone - are the Holy Grail of drugstore heists.  Containing few binders, these little azure beauties dissolved easily in water and made for the greatest (and not infrequently the last) rush of a junkie's shooting career.  In 1972 Numorphan tablets were pulled off pharmacy shelves, thanks to a rash of abuse-related deaths.

When Endo Pharmaceuticals decided to re-introduce oxymorphone to the market as Opana ER (Extended Release)®, they employed TIMERx®, a drug delivery system created by Penwest.  TIMERx tablets contain xanthan and locust bean gum. When swallowed, these components become a tight, thick gel which slowly releases oxymorphone into the patient's system.  This allows for steady, gradual dosing. It also makes it nearly impossible to use Opana ER intravenously.  When water is added to the powdered tablet, it becomes a needle-clogging gel which cannot be drawn up into a syringe or injected into a vein.  

Alas, an Opana ER tablet can be insufflated if it is powdered and kept dry: while there will be some gelling in the nose, plenty of oxymorphone will still reach the bloodstream through the sinuses.  And as the gel goes into the stomach via post-nasal drip, it will continue to have an effect.   While oxymorphone has a low oral bioavailability - roughly 90% is digested via "first pass" metabolism before entering the system - it is still twice as powerful milligram for milligram as a comparable dose of oxycodone. Snorted Opana has become very popular amongst many opiate afficionados for its long-lasting and euphoric high: quite a few of said afficionados have found themselves facing a harsh withdrawal when their Opana supply ran out. 

Purdue Pharma is still stinging from the debacle surrounding their "abuse-proof" oxycodone formulation, OxyContin®.  Soon after its release users discovered that one could gain instant access to the active ingredient merely by crushing the pill.  Many took to shooting them up as a supposedly "safer" alternative to street heroin.  (In fact, IV usage of pills is extremely dangerous: talcosis, abscesses and other damage can result). Others snorted them to gain a slightly quicker rate of onset, despite the risks associated with that mode of usage.

The newest formulation of OxyContin, OxyContin OP, is a plastic matrix shot through with oxycodone.  The tablets are nearly impossible to crush and can only be shaved into flakes through hard work with a hose clamp, file or similar object.  They also gel when exposed to water: people who have tried snorting them report near-suffocation as their nose became clogged by a gluey substance with the texture of hot mozzarella cheese. As a result, OPs are not favored by those who use OxyContins recreationally. After their release the price of the original formulation rose to as much as $120 for an OC 80, while OP 80s could be had for $15 to $20. 

Unfortunately, OxyContin OPs have fallen out of favor with many chronic pain patients as well.  Many report the undigestible pills cause serious stomach upset.  Others claim they are considerably less effective for pain management. Many recreational users have put their minds to breaking the polymer matrix by microwaving and freezing, soaking it in Coca Cola,  using chemicals like acetone and MEK, placing them in epsom salts, or other equally ingenious methods. So far the results have been mixed: some users have injured themselves trying to IV the results of their home chemistry experiments, while others have turned to heroin as a cheaper, easily available substitute.

Coaxil and the Crocodile: Post-Soviet Heroin Substitutes

Thanks to Bugsy of Opiophile and Dankycodone of Bluelight for pointing me toward some primary sources!

*This link contains graphic imagery: discretion in clicking is advised.

The former Soviet Republics have seen better days - and even those weren't particularly good.  Between the Berlin Wall's collapse and 2001, the average ex-comrade's buying power decreased nearly 25% in Russia, approximately 60% in Georgia, and over 80% in Tajikistan.  The social services provided by the Party (such as they were) got swept aside in the new rush to economic freedom: the entrenched culture of corruption and oppression remained firmly in place.  A few plutocrats became richer while most of the populace got a whole lot poorer.

Seeking solace or anesthesia, many turned to drugs. Today much of the region is awash in cheap Afghan heroin, imported through Uzbekistan, Kyrgyzstan, Tajikistan and Kazakhstan.  But many users who lack the means to support a heroin habit - or who would rather avoid harsh penalties and legal harassment - have discovered new ways to abuse drugs which are readily available at their local pharmacies.

Antidepressants like Prozac and Paxil act as SSRIs, selective serotonin reuptake inhibitors.  They interfere with the brain's uptake of serotonin, thereby leaving more available at the synapses to stimulate the receptors.  Tianeptine, the active ingredient in the Russian antidepressent Coaxil, has the opposite effect: it encourages uptake and decreases extracellular serotonin levels. Nobody is sure why this also alleviates depression, or indeed, how tianeptine works within the human brain.  But some experimentally-minded addicts have discovered that it also has a pronounced effect on the opiate receptors.  Users compare intravenous Coaxil to a slightly speedier heroin shot, with a euphoric if somewhat short-lasting rush. 

Alas, these effects only appear at a comparatively high dosage.  A Coaxil tablet contains 12.5 milligrams of tianeptine: to get high, users shoot dozens of pills. The resulting solution is filled with insoluble particulates. Most Coaxil abusers use large needles to avoid clogging: this causes damage upon the first venipuncture and results in greater quantities of thrombosis-causing gunk pouring into the circulatory system. Abscesses and gangrene* are common: amputations are frequently required.

Other addicts start with codeine tablets, which are widely available in most pharmacies.  After crushing the pills, they engage in a multi-step chemical process akin to the making of "bathtub meth." Iodine and red phosphorous are added to solvents in an effort to transform the codeine into desomorphine, a powerful analog 10 times stronger than morphine and 5 times more powerful than heroin.

The end result of this process contains some desomorphine: it also contains codeine and large amounts of iodine, phosphorous, acids and other toxic chemicals. Russians call it "Crocodile" because users soon develop open sores, peeling and ulcers on their skin*.  The liquid is highly corrosive and acidic, causing enormous damage to the circulatory system.  Excessive iodine poisons the kidneys, thyroid and liver*: excessive phosphorous can cause bone loss and necrosis of the jawbone, known among 19th century matchmakers as "phossy jaw." Intravenous codeine can cause pulmonary edema and histaminic shock. And because desomorphine is a relatively fast-acting opiate, users tend to inject repeatedly, thereby magnifying the consequences of each dose.