Substance abuse: July 2009 Archives

Not sure which is more shocking: The report that at least 20 non-OTC drugs were recovered from Michael Jackson's home or the fact that ABC News is sourcing The Sun on this one. Maybe ABC's reporters were impressed by alleged autopsy information printed last week by the tabloid—namely that Jackson's arms were riddled with needle marks. Yesterday ABC reported the same ("Jackson's arms were scarred with track marks"), citing "investigators."

On the basis of reportage from ABC and The Sun, the partial, cobbled-together list of drugs (save propofol [Diprivan]) found in Jackson's home includes the following (in alphabetical order):

1. Demerol: Generic names, meperidine and pethidine. A fast-acting opioid available in injectable and oral formulations. Legitimate use has become unpopular during the last 2 decades, owing to the drug's potential neurotoxicity and abuse potential. Jackson allegedly took Demerol daily and possibly several times a day.
2. Dilaudid: Generic name, hydromorphone. A morphine derivative available in injectable and oral formulations. Typically used for pain management.
3. Fentanyl: A highly potent synthetic opioid available in injectable, transdermal patch, and "lollipop" formulations. Typically used in anesthesia induction and pain management.
4. Lidocaine: Presumably in the form of low-concentration vials to produce local anesthesia. Possibly used in conjunction with propofol to reduce injection-associated pain.
5. Methadone: A synthetic oral opioid. Most commonly used as a maintenance medication when kicking opioid addiction.
6. OxyContin: Generic name, oxycodone. A wildly popular, semi-synthetic oral opioid. Jackson allegedly took the medication daily.
7. Paxil: Generic name, paroxetine. An orally administered, selective serotonin-reuptake inhibitor (SSRI). Indicated for the treatment of depression, OCD, panic disorder, anxiety disorders, and PTSD.
8. Percocet: Generic ingredients, oxycodone (same as OxyContin) and acetaminophen (eg, Tylenol). Typically prescribed short term for pain relief.
9. Soma: Generic name, carisoprodol (a metabolite of meprobamate, aka Miltown). An orally administered, centrally acting muscle relaxant that potentiates opioid-induced analgesia.
10. Versed: Generic name, midazolam. A very-short-acting benzodiazepine in oral and injectable formulations. Typically used as a premedication before surgical or medical procedures.
11. Vicodin: Generic ingredients, hydrocodone and acetaminophen. Orally administered and should be prescribed short term for pain relief. (N.B.—I've witnessed physicians dispense this drug like Pez candy.)
12. Xanax: Generic name, alprazolam. An orally administered, short-acting benzodiazepine. Prescribed for anxiety and/or sedation.
13. Zoloft: Generic name, sertraline. An orally administered SSRI. Indicated for the treatment of depression, OCD, panic disorder, anxiety disorder, PTSD, and premenstrual dysphoric disorder (which Jackson presumably did not have).

There are a number of permutations for lethal combinations of these drugs, some of which can kill all by themselves. Perhaps more surprising than Jackson's death is his survival—given the duration of his alleged polypharmacy use and dependence.

OCD = obsessive-compulsive disorder; OTC = over the counter; PTSD = posttraumatic stress disorder.

Props must be given to TMZ. Multiple news sources have been citing the entertainment news-gossip web site in the widespread coverage of Michael Jackson's suspect death.

The latest: Edward Chernoff, criminal defense lawyer for Conrad Murray (Michael Jackson's doctor), won't confirm or deny that Murray gave Jackson propofol (trade name, Diprivan). In a phone interview last night, Chernoff reportedly told TMZ, "I have no statement on whether the Dr. prescribed or administered Propofol." Although the lawyer was apparently willing to repeat that Murray did not administer Demerol or OxyContin to Jackson.

In its update, TMZ implies that Chernoff is now backtracking somewhat on last night's statements and "can't speak for anything that was in the [Jackson] home."

Image of Diprivan formulations from APP.

Sources are now implicating propofol (Diprivan; sanofi-aventis) in Michael Jackson's death. TMZ reports that police recovered the anesthesia inducer at Jackson's rented home. And ABC News interviewed Jackson's nutritionist, Cherilyn Lee, who stated that the singer asked her for Diprivan, by trade name, 3 months ago. Jackson's alleged intention, bizarre as it may sound, was to be put to sleep at home under the guidance of an anesthesiologist.

In use for more than 2 decades, Diprivan is a rapidly acting (within 40 seconds) IV sedative-hypnotic that is FDA approved for the induction and maintenance of anesthesia and for sedation in an intensive care unit (in both cases, patients are mechanically ventilated). According to the prescribing information, the induction dosage for ICU sedation begins at 5 microg/kg/min and should be titrated (by increments of 5-10 microg/kg/min) to the desired clinical effect. Maintenance rates are generally 5-50 microg/kg/min or higher for adults.*

For anesthesia induction, the typical dosage is 40 mg every 10 seconds in healthy adults younger than 55 years of age; maintenance of anesthesia can be achieved by intermittent boluses of 20-50 mg. However, slow infusion or injection techniques are recommended to avoid apnea and hypotension. Diprivan dosages should be reduced in patients who have received large doses of narcotics.

Common adverse events with Diprivan use include bradycardia or other arrhythmias, hypotension, and apnea. Burning pain or stinging at the injection site, which is also common, may be reduced by preinjecting the vein with a 1% lidocaine solution (1 mL).

Subanesthetic doses of Diprivan may have the potential for abuse by inducing euphoria. Diprivan's abuse potential is particularly high among physicians who have access to the drug—namely, anesthesiologists. An e-mail survey in 2007 indicated that Diprivan abuse has increased substantially in academic anesthesia departments during the last 10 years. Among the 25 reported abusers in the survey, 16 (64%) were resident physicians. Seven (28%) abusers died; 6 of the deceased were resident physicians. In academic centers where abuse occurred, none had established pharmacy protocols to account for the drug (as is done routinely with opiate medications).

In 2008, an anesthesia nurse was convicted of killing a University of Florida student, with whom he was infatuated, by injecting her with propofol in her home. The victim's propofol blood level was 4.3 microg/mL. The expected propofol concentration after a bolus induction dose of 2.5 mg/kg (175 mg for a 70-kg man) is 1.3-6.8 microg/mL.

If a vial or vials of Diprivan were indeed recovered from Jackson's home, it seems almost certain that the medication was palmed by someone who had access, rather than formally prescribed.

Addendum: It also appears that Diprivan can be purchased through online pharmacies. For instance, drugdelivery.ca offers a 50-mL prefilled syringe for $122.99 USD. The completion of a patient questionnaire is necessary (along with payment); it is not clear that a valid prescription is required.

* So for a 70-kg man (~154 lbs), 0.35 mg/min would be administered for induction, and the maintenance dosage ranges from 0.35 to 3.5 mg/min. Vials of Diprivan contain 10 mg/mL and come in 20-, 50-, and 100-mL vials.

Image of Diprivan formulations from APP.

07/04/09 update: Yesterday the AP, citing an anonymous law enforcement official, confirmed that Diprivan was found in Jackson's rented home. CNN also reported that Neil Ratner, an anesthesiologist, traveled with Jackson during his HIStory tour in the mid-90s. Ratner's NY medical license was suspended in 2002 after being convicted of insurance fraud.