Posts Tagged ‘opioids’

Pain Part two: Physiology & pharmacology

Sunday, December 23rd, 2012

some drugs are legal and some aren't

In my last post I went through the history of medications used to treat pain and  how one of those, originally a trademarked drug, became the terribly addictive, unfortunately popular, street drug, Heroin. Before I discuss controversies in the use of legal pain medicine we need to review some basic pharmacology and physiology.

The term opiate refers to chemicals extracted naturally from the opium plant with the most familiar being morphine and codeine. Opioids, on the other hand, are semi-synthetic derivatives of opium such as oxycodone and hydrocodone. These are controlled drugs, supposedly available only by a doctor's prescription.

In 2004 the FDA issued a statement on an extended release form of oxycodone called OxyContin approving its usage, but cautioning its potential for abuse. In 2009 an FDA panel voted (in a fairly close vote) that two combination pain pills be taken off the market. They were only the tip of the iceberg; there's a host of such mixes of an opioid with standard non-narcotic pain medicine such as acetaminophen (Tylenol) or acetylsalicylic acid (AKA aspirin) or even ibuprofen (Motrin). Oxycodone + acetaminophen is called Percocet and hydocodone  + acetaminophen is marketed as Vicodin. A 2012 363-page summary (sic) report  from HHS's FDA Center for Drug Evaluation and Research makes it clear that many of the earlier recommendations have still not been implemented.

The International Association for the Study of Pain has a shorter summary of the physiology of pain. I suppose it's intuitively true, but it certainly wasn't my first thought that pain is a protective mechanism. When I burned my hand on a hot stove as a child, I learned to avoid repeating the process (although I confess that hasn't been 100% successful). These days if I turn on a burner on my gas range, I also turn on its built-in light as a warning signal.

There's a  part of our nervous system that warns us of pain (Med-speak for this is nociception from the Latin word nocere, to hurt). It's a separate section from the part that tells our brain of a pleasant smell, or a nice taste or other sensations that won't harm us. Some of our nerves end in nociceptors, unspecialized fibers that convert a number of unpleasant, potentially harmful stimuli into signals to our brain that shout (not literally), "Careful there; that's dangerous!"  Nerve cell receptors, in simplest terms, are spots for chemicals to latch on to give signals.

In the 1960s and 70s, receptors for opiods were found in parts of the human nervous system. Some endogenous (produced in our bodies) chemicals can also bind there: two kinds of those are dopamine and endorphins.

Endorphins come in 20 or so types, are most commonly released in response to stress or pain and act to reduce our pain perception much as morphine does. In general they are not felt to lead to addiction or dependence (my only quibble with this statement is the "runner's high" as I vividly remember my Nephrology Fellow who ran 10 miles at a time, twice a day; when he got married his wife persuaded him to cut down to ten miles once a day). Eating chocolate, hot chili peppers and having sex can can cause endorphin release and acupuncture, message therapy and meditation are felt to also stimulate the levels of these beneficial chemicals.

pain comes in many different shapes

When our cells are damaged, as in a bad sunburn, our peripheral nociceptors are activated by a variety of chemical substances that the injury produces or releases. At the same time other chemicals are released that dilate blood vessels in the affected area leading to swelling, redness, and a localized warmth. The resultant increase in local blood flow and inflammation itself promote healing and help protect the injured area against infection.

I think that's enough background; next I'll write of problems with pain pills.

 

 

Pain Pills and their ugly cousin: Part 1

Thursday, December 20th, 2012

I had a total knee replacement nearly twelve years ago. On the Orthopedic ward I was told I could have one or two strong pain pills every 4 to 12 hours depending on how much pain I was experiencing. Since I have a fairly high pain threshold I decided to take the minimum dose, one every twelve hours. I took the first pill, felt considerable relief from the pain, but also felt strange, so I stayed at that dose.

One way to flex & extend after a total knee replacement

Then I ran into a snag. My release from the hospital depended on the degree of flexion I could achieve in the leg with the new knee. Several times a day I was hooked up to a device that gradually bent my leg. It really hurt, but I toughed it out. The nurses and the physical therapists (PT) didn't seem to communicate with each other and I was a bit slow to catch on.

"You're not making enough progress," my surgeon said. "I think we'll have to extend your stay."

Something finally clicked in my mind. I was hurting enough so the ward staff hadn't set the machines degree of flexion higher. I decided to take two of the pain pills an hour or so before the PT appeared to check my ability to have the leg bent passively.

This time I was in no pain, although I did feel weird.

"You're doing much better today," she said. "I'll tell your doc you can go home tomorrow."

I had been given a strong pain pill, probably oxycodone and they were going to give me a prescription for several weeks worth to take at home. I asked, "Can I have extra strength Tylenol instead?" I repeated that request when I had low back surgery six months later.

Since that time there's been considerable controversy about strong pain medications. The initial question was whether physicians were under-prescribing for patients with severe pain, usually cancer-related, in fear of getting them "hooked" on the drug. Subsequently there have been at least two tidal shifts in how pain medicines are viewed, one urging more treatment of pain including giving the most potent meds for chronic non-malignant pain (CNMP) as well as for cancer patents (who clearly needed to have adequate pain control and weren't always getting it).

Very recently there's been a re-evaluation of the trend. I want to go back to the basics and then follow the timeline of expert opinion that's been expressed on the subject in the last two hundred years. But I'll begin much further back than that.

A 2008 article now available online and authored by staff from the National Development and Research Institutes and from the Department of Pain Medicine and Palliative Care at New York City's Beth Israel Hospital explored the treatment of chronic pain in depth. A few comments from that article surprised me.

a field of opium poppies

In Mesopotamia, nearly 5,500 years ago, Sumerian farmers cultivated a plant called Hul Gil which translates as the "joy plant." We call it the opium poppy. An August 2002 PBS special titled "Bitter Harvest" walks through how this plant is processed into the highly potent street drug, heroin, with at that time 13 million addicts worldwide The United Nations Office on Drugs and Crimes (UNODC) has a 2009 paper online estimating similar numbers. The major alklaloid (a usually colorless, complex and bitter organic chemical) in opium  was isolated in 1903 and named morphine (the Greek god of dreams was Morpheus). Then the Bayer company made a chemical from morphine and gave it the brand name Heroin.

Nowadays much of the world's crop of opium poppies is grown in Afghanistan. The 2009 estimate from UNODC was for $60 billion of the worldwide total of $68 billion.

But I've strayed away from my theme, which isn't street drugs, but prescription medications, so I'll stop here and get back to the synthetic opiods in my next post..