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.