Medpedia

My previous post examined the epidemiology of rise in opioid abuse and opioid overdose deaths in the U.S.  The number of these deaths has increased fourfold in the last decade and appears to be higher in states with higher rates of prescriptions for the opioid drug class.

Members of the prescribed opioid compounds includes the following generic (Trade name) drugs in the U.S.:

• Methadone
• Oxycodone (Oxycontin/Percodan)
• Hydromorphone (Vicodin/Lortab)
• Meperidine (Demerol)
• Hydromorphone (Dilaudid)
• Codeine

Drug overdoses of the opioid drug classes produce somnolence, CNS depression and in severe cases the central drive to breath is suppressed to the point of respiratory failure, hypoxia and death.  Cardiac arrhythmias due to direct drug toxicity or to the effects of hypoxia.

One feature of the toxicity of the opioid compounds is the relatively narrow therapeutic window.  This means the dose for therapeutic indication is close to the lowest potential fatal dose or blood level.  For example, the adult drug therapeutic dose for oxycodone is listed as 10 mg every 12 hours.  However, a single dose of only 40 mg in a drug intolerant individual is potentially lethal.  Individuals with chronic pain often develop tolerance to opioids and may be prescribed 60 mg (or more) per day of oxycodone.

So the daily dose that opioid-tolerant grandma requires for cancer pain may be sufficient to kill her grandchild who decides to "try one".

The toxicity of opioids appears to increase in the context of other drug use.  Most forensic studies of opioid-related deaths find the presence of other drugs that can reduce respiratory drive.  In fact, death due to a overdose of a single opioid prescription drug appears to make up a small minority of opioid-related deaths.  In one study of 172 deaths with a positive blood oxycodone level in Palm Beach County, Florida found only 18 where oxycodone toxicity was the sole cause of death.  One hundred seventeen were judged to be due to combined toxicity with another drug.

In a recent study of deaths due to oxycodone overdose in Australia, multiple drug classes were identified. The most frequent drug classes (and specific drug in that class) in this study were:

• Sedatives (diazepam) 69%
• Other opioids (codeine) 54%
• Antidepressants (tricyclics) 41%
• Alcohol 33%
• Antipsychotics (olanzapine) 19%

So the key clinical facts to consider in prescription opioid toxicity and risk for overdose death are the narrow therapeutic window and the risk of toxicity with other CNS depressants.  Prescription opioids drugs are effective short-term analgesic agents but are dangerous when used outside the therapeutic range and in combination with other drugs and alcohol.

In upcoming posts, I will examine some of the factors that make some individuals more vulnerable to development of prescription opioid abuse.

Molecular model of the opioid drug oxycodone from the Wikipedia Commons file authored by subdural12.

Wolf BC, Lavezzi WA, Sullivan LM, & Flannagan LM (2005). One hundred seventy two deaths involving the use of oxycodone in Palm Beach County. Journal of forensic sciences, 50 (1), 192-5 PMID: 15831018

Darke S, Duflou J, & Torok M (2011). Toxicology and characteristics of fatal oxycodone toxicity cases in New South Wales, Australia 1999-2008. Journal of forensic sciences, 56 (3), 690-3 PMID: 21361931