Commentary on Painkillers

Today's NYT contains an article on painkillers.  The author is referring to opiate derivatives used to control pain.  The article got my attention, paradoxically, not because it is news; rather, because it is not news.  Why print something in a newspaper that is not news?  Ironically, the author completely misses the one really newsworthy aspect of the story.

Drug Makers Hope to Kill the Kick in Pain Relief
By SANDRA BLAKESLEE

Published: April 20, 2004
(From NYT)

orried that millions of Americans are using prescription opiate painkillers to get high rather than to ease severe chronic pain, drug makers are working on ways to prevent abuse.

Cooperating closely with government officials and pain specialists, the companies are educating doctors, rewriting warning labels and tracking pills as they move from pharmacy to patient.

They are also reformulating pills with added ingredients. One combination blocks euphoria. Another produces a nasty burning sensation.

"The problem of prescription painkiller abuse is much bigger than people realize," said Dr. Clifford Woolf, director of the neural plasticity group and professor of anesthesia research at Massachusetts General Hospital in Boston and Harvard Medical School.

"No other drug type in the last 20 years had been so abused in such a short period of time," he said. "It's an epidemic."

It has been known for a long time that there is a problem with abuse of prescription opiates.  Ms. Blakeslee provides the obligatory other side of the story:

Fear of addiction led to the undertreatment of pain and to untold suffering, said Dr. Russ Portenoy, chairman of the department of pain medicine and palliative care at Beth Israel Medical Center in New York.

She goes on to report that two strategies are being researched, with the intent of reformulating slow-release opiates so that they are less appealing to drug abusers.  Opiates such as Oxycontin are formulated so that the active ingredient is released slowly.  This prevents the person taking the drug from getting a sudden euphoria when the drug hits their brain all at once.  Of course, people have tried to find ways to get around this:

Unfortunately, addicts quickly found that they could grind the pills, swallow or snort the powder and get a high dose of opiates delivered directly into their bloodstreams. They also liked the fact that the drugs were pure and the exact dosage was known.

To counter abuse, drug makers are developing ways to reformulate prescription painkillers. Purdue Pharma in Stamford, Conn., which makes OxyContin, is thinking of adding a second drug, called an opiate antagonist, that neutralizes the effects of the opiate.

[...]

A second approach is to mix in a chemical irritant like capsaicin, the main ingredient of hot chili peppers, said Dr. Woolf, who has a patent on the idea.

Because the esophagus and stomach do not have many receptors for hot peppers, patients could take the pills as prescribed and find relief, he said. But the lining of the nose and cheeks are loaded with pepper receptors, and anyone who ground up such a pill would get a burning feeling in the chest, face, rectum and extremities, as well as paroxysmal coughing.

Does this make sense?  At first glance, it may seem that it does.  Persons who abuse prescription opiates not only screw up their own lives, they contribute to crime (organized and disorganized) and they make it harder for people who really need the medications to get them.  But let us look at the pharmacology of these proposed products to see if they really are sensible. 

Opiate medication works by stimulating a class of receptors, the opiate receptors.  The effect can be blocked by administering a second drug, one that blocks these receptors.  The strategy would be to mix in with the opiate some little beads that contain an opiate blocker.  If someone tampers with the pill in an effort to circumvent the slow-release property, the opiate blocker is released.  That would be fine if it merely canceled out the euphoric effect of the drug.  If the dosage of the blocker is just right, nothing good and nothing bad would happen.  It would be as if the person had taken nothing at all. 

The problem is that people's brains are not all alike.  If a person happens to be extraordinarily sensitive to the effect of the blocker, and if that person is physically dependent upon opiates, he or she could go into withdrawal.  For most people, this is uncomfortable, but not dangerous.  For some people, though, it could be extremely dangerous.  Persons with heart disease or epilepsy could die from sudden opiate withdrawal. 

What about the second strategy?  Mixing capsaicin into the opiate would provide a strong disincentive to tampering with the drug.  Grinding it up and snorting it would be extremely unpleasant.  However, a person with asthma could stop breathing.  Also, some people no doubt will try to inject the medication in order to produce euphoria.  I don't know what happens if capsaicin is injected, but I'm sure it is bad. 

The real news in this story is not, as the headline suggests "Drug Makers Hope to Kill the Kick in Pain Relief."  The real story is this: drug makers are willing to expose people to really dangerous stuff in order to sell more pills.

Now, I don't have anything against people making money.  And I agree that abuse of prescription opiate medication is a big problem.  I even agree that the drug abuse problem is so bad, that in some cases a little risk could be justified.  But why take any risk at all, if it can be avoided?

The nutty thing about this, is that the article is about people who are essentially re-inventing the wheel.  And the new wheel is not as good as the old one. 

Opiates are not the only prescription drugs that are abused.  Stimulants, such as methylphenidate (Ritalin ®), are abused fairly often.  ALZA Corporation addressed this by producing Concerta ®.  Concerta is a slow-release capsule that so far has defied efforts to circumvent the slow-release mechanism.  A good chemist could extract the active ingredient and abuse it, but it would be too much trouble for this to be feasible.  Likewise, Novartis produces Ritalin ® LA .  This has turned out to have a much lower potential for abuse than regular Ritalin.   The technologies in Concerta and Ritalin LA are available already, have proven their worth, and do not pose any hazards. 

I am not claiming that this would solve the problem.  Some people will abuse anything.  There are people who abuse Haldol, for example.  But there is no point in replacing a round wheel with an octagonal one, even if the octagon gives a safer ride than the hexagon.  Putting an opiate antagonist (such as naltrexone), or an irritant, (such as capsaicin) into Oxycontin might work, but it might kill a few people too.