New drug of abuse comes to America – Enter krokodil

Reports developed in the media last month identifying suspected cases of ‘krokodil’ use in Utah, Arizona, and Illinois.  While the drug’s presence has not officially been confirmed there is a significant health concern when considering this new drug’s properties and what the results of its use are.

Background

‘Krokodil’ is the street name given to a substance whose active ingredient is likely to be desomorphine.  Easily made at home from codeine, this drug’s presence has increased in Russian in recent years where more than 100,000 people are thought to be addicted and where 65 million doses were seized in the first quarter of 2011.  ‘Krokodil’ seems to be a fitting name as it refers to both a codeine derivative step in its production (chlorocodide) and the adverse effects it causes, namely the scale-like green-black skin of its users.

Pharmacokinetic/pharmacodynamic properties

While ‘krokodil’ is relatively new, desomorphine is not.  It was first synthesized and patented in 1932 in the United States in an attempt to find an alternative analgesic for morphine with a more favorable side effect profile.  Pharmacokinetically, desomorphine differs from morphine in that it is a ten times more potent analgesic, three times as toxic, and has a much shorter half life.  Its quick onset and short half life contribute to its increased addictive potential versus morphine.  Users are left with little time for anything other than the loop of acquiring, synthesizing, and administering the drug in order to avoid withdrawal.

Production

‘Krokodil’ is produced via various recipes with the most common being a reduction process to desomorphine.  It can be produced in as quickly as 10 minutes with minimal laboratory equipment and easily available chemicals.  A strong alkali (household cleaner), organic solvents (gasoline, paint thinner), iodine, red phosphorus (heads of matches), and hydrochloric acid are combined with codeine in a way to produce either dried desomorphine or a solution which can be intravenously injected directly. Essentially there are two steps; first, extraction of codeine from the starting medication form (in Russia, codeine is cheap and was not restricted to pharmacies until mid-2012) and second, reduction of codeine to desomorphine.  Due to variations in production and substrates used, the resultant product is likely a composition that varies between users and probably contains desomorphine.

Risk

The adverse effects of ‘krokodil’ are those of opioids and opioid withdrawal in addition to devastating systemic and injection-related injury.  Localized damage includes serious venous damage and skin and soft tissue damage which quickly advances to gangrene and necrosis.  This includes skin and soft tissue infection, bone infection, open ulcers, large eschars, and veins that rot from the inside requiring surgical removal.  Other systemic damage may include: kidney and liver problems; pneumonia; sores and ulcers on the head, ears, nose, and lips; meningitis; rotting gums, jaw, and facial bones; and thyroid disorders.  These systemic effects are not at traditional inject sites so they may be the consequence of the chemicals and heavy metals used in the production in ‘krokodil’.  The final product is a suspension that is highly impure and likely not pH neutral, isotonic, or even filtered prior to injection.

Management

Outcomes for users of ‘krokodil’ are very grim and have been sensationalized in the media.  Abstinence of ‘krokodil’ use and minimizing barriers of care is essential.  A coordinated surgical management plan (which often includes amputation) along with infectious disease management is also recommended.

References:

1.  Grund JP, Latypov A, Harris M.  Breaking worse: The emergence of krokodil and excessive injuries among people who inject drugs in Eurasia.  Int J Drug Policy 2013;24:265-74.

2.  Gahr M, Freudenmann RW, Hiemke C, et al. Desomorphine goes “Crocodile”.  J Addict Dis  2012;31:407-12.

3.  Micromedex.  Available at www.micromedexsolutions.com