live, love, hurt

In March, I was told by my pain management physician that he’d be leaving the office and indeed Hopkins all together. Long story short, Hopkins wanted him to do a bunch of things to patients purely for the sake of bringing in revenue, and he refused to do so and instead quit, taking several other physicians with him. I was told, at the time, that he’d be there until May and in May I’d get several post-dated prescriptions to cover me until he had his private practice set up in June. That plan–like so many plans–didn’t quite turn out that way.

In May I met–for the last time–with my pain management physician. He refilled all my medications and told me which physician I’d be seeing until he gets set up somewhere. This was now not a certainty as I’d been led to believe before. Now he may or may not continue his practice elsewhere, and I’m somewhat concerned. I take the scripts and bid him farewell.

Thirty days later it’s time for a refill. I don’t have a treating physician anymore. I call the office and they arrange for a one-time 30 day refill of my medications in exchange for a urine sample. Apparently it was horrible of my previous physician to simply trust me and not require urine analyses (UAs) in the past, and some more stuff about why he’s a bad doctor and I should stay there. I’m told to make an appointment with the new physician. The appointment was 52 days away, and I had scripts for 30 days.

Thirty days later it’s time for a refill. I call up and this time I’m told that I’m not allowed a refill. Why not? Apparently it was “made clear to me” that the previous script was a “one-time thing” (which it wasn’t [made clear to me]). I was supposed to get an appointment before those scripts ran out! Wait, I did make an appointment. It was 52 days away. How am I supposed to get one 30 day script when my appointment was more than 30 days away? Well, according to “the system” my appointment was “just created” (likely because someone modified it or something and it changed the date it was edited) and that means I didn’t make an appointment and it’s my fault. I go in and they decide that, for yet another urine sample, I may obtain 14 days worth of my medication. Except that you can’t fill 14 days of fentanyl patches because they come in boxes of 5 and 14 days would be 7 patches and they can only fill them per box, so they only give me 5. I tell the office this. When my urine comes back “clean” they give me another 30 days.

Not quite thirty days later is finally time for my appointment. I come in for my new physician, the one that’s been writing these scripts, and the first words out of his mouth consist of some FUD about my current treatment being all wrong, and it’s very wrong for someone as young as me to be on “two hardcore narcotics” (he specifically and repeatedly used the word “narcotic” over “opiate” or “opioid”–both of which are more appropriate for medical professionals–because “narcotic” is a scary-sounding word) and instead I should look into permanent back surgery. I argue that I have no surgical options given my condition and that I’ve already had every interventional procedure that I could have. He tells me of an orthopedic surgeon I should immediately go see for a second opinion. As it turns out I know this orthopedic surgeon. He referred me to pain management–to the very office I am currently sitting in. When I tell him this I’m still instructed to “go back” to get new radiographs and with new radiographs, a new opinion on surgery. The surgeon had before told me the only thing he could offer me were spinal fusions. I turned him down given my age, which he agreed with, and he sent me to pain management which he deemed, in his own words, “the only reasonable next step.” Two years later my only reasonable next step is backwards, it seems. The new physician continues to try to alarm me about my current treatment, telling me that my medications are “dangerous and addictive.” I tell him I’ve been on them off and on for four or five years and have yet to have any issues with abuse or addiction, and that every UA he’s ordered on me has come back pristine. He tells me that narcotics build up in the body and always eventually cause addiction and that they’ll make me sleepy and surely I must be intolerably constipated and throws in every other classic opioid side effect, trying to get me to admit that there’s a reason to discontinue the therapy. I tell him no, the only side effect I even notice is constipation and I simply have a fiber bar or two every day and don’t even notice the difference. He’s angry, realizing that I’m actually educated about my condition and the treatment and ties up the appointment by telling me I have until August to find “other options” before he discontinues my medications.

One of the best parts of this whole thing is that when I first got there a resident finishing up her fellowship came in and talked to me first. After she went through everything she agreed with my current treatment and, after asking how it was working, thought I should increase my fentanyl dose (which I’ve been wanting to do for months). When the attending came in and shot down all that with his bullshit, she looked rather put off and disappointed. I don’t know if she was disappointed because he didn’t agree with her and thus she must be wrong, or because he was being so obviously obtuse about my treatment and there was nothing she could do to help me. The best part of this was that his own Fellow disagreed with him and thought my current treatment should stand. I liked her. She was a very nice lady. I’m sad I’ll never see her again.

Currently I’m waiting for some results from various tests I had with my rheumatologist. He’s a very smart physician. While he doesn’t know exactly what’s wrong with me (he suspects an extremely mild non-specific “type” of Ehlers-Danlos Syndrome, but it’s a wild shot) he told me he was positive it wasn’t progressive osteoarthritis, which is what my pain clinic has been telling me for two years. They also tell me it “just happens,” even to males in their early 20s. I’m also expected to see the orthopedic surgeon that originally referred me to the pain clinic in the first place. I’m not totally sure I’m going to do this, because I don’t see the point. I’m not going to have surgery, and the last time I saw him my options were “surgery or pain management.” Guess which one I chose.

Monday I’m going to talk to my primary care physician about what she could do for me if I lose my medications. The Monday after that I’m going to get the results of all my rheumatology tests, and maybe have an answer and even treatment. If all of this fails, come August I’ll have no answers and no pain management. I will have to quit my job, move home to St. Louis, and try desperately not to curl up into a miserable ball of existence, wondering why I should continue to bother to live.

For interested fans of hydrocodone (Vicodin®, Lortab®, Norco®, etc.), a private pharmaceutical company called Zogenix, Inc. is in Phase III trials of a controlled-release version of hydrocodone. In comparison, controlled-release oxycodone (OxyContin®) has been on the market since 1996. A similar formulation with hydrocodone instead of oxycodone could do wonders for patients that can’t tolerant oxycodone or other opioid drugs. Hydrocodone is sometimes known for producing less constipation than other opioids; however, it’s also known for producing more euphoria than some other opioids which could lead to the same abuse patterns we saw with OxyContin®.

When OxyContin® was released, abusers quickly found that crushing the tablet easily defeated the time-release mechanism, causing all of the oxycodone–meant for slow release over 8-12 hours–to be released into the body at once. This caused a surge in abuse of the drug in the late ’90s and well into later decades as well. Zogenix has announced that the release mechanism for its new hydrocodone formulation is the same currently used by Avinza®, a brand-name of controlled-release morphine. Other drugs using the same release mechanism include Ritalin® LA, Focalin® XR and Luvox® CR. The release mechanism is called Spheroidal Oral Drug Absorption System, or SODAS® and is licensed from Elan Drug Technologies. The SODAS® capsules contain tiny extended-release beads that release too much medication if crushed, chewed, snorted, dissolved, or injected, which will likely lead to a sharp increase in abuse of the drug much in the same manner as OxyContin®. However, for those in pain taking their medication as prescribed, it will be a welcomed addition to the pain pharmacopeia.

Under the US Controlled Substances Act, products containing “no more than 15mg of hydrocodone compounded with an NSAID or APAP” are allowed to be treated as Schedule III drugs, but hydrocodone on its own or in amounts more than 15mg are Schedule II, along with morphine, oxycodone, fentanyl, and most other opioids. Due to an additional law, there are currently no hydrocodone-only drugs on the US market today. This drug would change that.

While only in Phase III trials, the drug remains 3-5 years away.

• Zogenix Press Release
• Elan Drug Technologies Press Release

Today, I commented on an old friend’s Wall post on Facebook. This friend was from grade school in a tiny (pop. 1,800) farming town that I spent a good portion of my childhood in. It was about the recent healthcare bill and he was saying inaccurate things about it, so I tried to correct him. Unfortunately, he wouldn’t have any of it. I’m not going to start a Democrats vs. Republicans debate, because both sides are pretty stupid, but during the raging comment thread that followed, a ton of his friends (and people that used to know me from childhood) started commenting on me being a “drug user,” because I have information about my chronic pain condition on my Facebook profile. The thread is long and filled with ignorance, so I’ll do my best to summarize while still making this a worthwhile story to tell.

These people are from a secluded farming town in rural Illinois, near the St. Louis Metro East area. They don’t know anything about anything remotely medical. If their back hurts, they take Benedryl and go to sleep (or become alcoholics). These people only see narcotic analgesics when someone’s passing around some Vicodin along with the joint of marijuana. It only exists for people to take and feel good on. As far as these people are concerned, it might as well be beer for all they care. The first couple of guys told me “we all have aches and pains” and another mocked my “poor little back pain.” I gave them the benefit of the doubt and carefully explained what degenerative facet disease (or “facet syndrome”) is and what it does to you, and what foraminal narrowing (or “foraminal stenosis”) is and what it does to you. I explained it to them calmly, and with no anger. What do you suppose I received in response?

You need to see a doctor. You need help. It’s okay to admit you have a drug problem. Someone will help you. The pain can’t be that bad! The pain is from the withdrawal!

That was a summary of a couple of them… well, the nicer ones, and;

You’re just a junkie that doesn’t want to admit it. No pain can be that bad that you have to go and trick these doctors into giving you drugs all the time. You’re probably crushing them and snorting them or shooting them up. Show us some pictures of your arms, you dirty junkie.

that’s a summary of the vast majority of them. Why is this? Why are people more likely to believe you have a massive drug problem than a simple medical condition? In the world of the chronic pain patients we are used to being looked at with suspicion because of the narcotic analgesics we use every day to control our pain. Most of us are used to this prejudice; however, today I discovered another prejudice that I realized I’ve often been the victim of: not believing the intensity of the pain. I mean, it’s a no-brainer, it happens all the time–sometimes almost every day–but you explain it’s a serious medical condition that employs an entire field of study for specialist physicians and other medical professionals and the seriousness of the matter can usually–at that point–be somewhat understood by the general population. However, there’s always that group of people out there that will never believe you. No matter what’s medically wrong with you, there’s no possible way on earth that you could ever have pain that you can’t just get used to, or grin and bear. Like I said: these are tough farm boys, after all. The only time they’ve seen opioids is when someone’s passing around some Vicodin along with the joint of marijuana. It only exists for people to take and feel good on. As far as these people are concerned, it might as well be beer for all they care. They have no idea that heroin–a drug that has been demonized as to be the worst possible thing anyone can take because they’ll end up on the streets as a junkie–is an opioid, just like that Vicodin they use to relax from time to time. In small rural farm towns like this the drugs of choice tend to be alcohol and tobacco. When it comes to illicit drugs things like cocaine and even (or sometimes especially) meth are soft drugs, go ahead and have fun with them. For the most part, these people would never consider doing heroin–despite the fact they’ve all had a narcotic at some time or another.

The only extremely sad part about this particular conversation is that I went to school with most of these people from ages five through fourteen. Some of us were close friends. These people should know me. These people should be able to be entrusted with the knowledge of my medical condition. A few years out of town, and you’re a dirty junkie. This is why we, as a minority group, tend to not tell most people about our medical problems. It’s not a big deal to tell someone you can’t eat that because you’re diabetic and have to shoot insulin after every meal, but it’s a big horrible thing to tell someone you can’t do something because your pain limits your abilities and you have to take narcotic analgesics after every activity. Suddenly it’s no longer just a medical condition, but you’re a drug addict that’s totally faking it. When no one’s watching, you run and dance and play and do backflips, but when someone’s watching you break out the cane just so people will feel sorry for you.

If only.

I’ve written about some pharmacology topics before, and usually they’re coherent, but this one is being written when I am rather, well, pissed off.

There’s a group of drugs called opioids, which, simply put, are drugs that behave like morphine. A lot of the general public may have taken these drugs are one point or another, such as after dental surgery. Common examples are Tylenol #3, Vicodin, Lortab, and Percocet. These drugs are all controlled under the Controlled Substances Act. There are different levels of control status, called “schedules.” Schedule I are the most tightly controlled, and Schedule V are the least controlled. What schedule a drug is placed on depends on

1. How medically beneficial it is;
2. How likely it is to be abused;
3. How likely it is to cause physical dependence;
4. How likely it is to cause psychological dependence, or addiction.

(For more information on this topic, see my rather technical piece here)

Drugs that are Schedule I are completely illegal. They’re not recognized as having any medical purpose, and they’re very likely to cause abuse, dependence, and addiction. Examples are heroin, marijuana, etc. Schedule II drugs are very tightly controlled, but can be prescribed. These drugs include highly potent opioids like morphine, methadone, oxycodone, and hydrocodone (unless combined with a non-opioid); amphetamines (used for ADD drugs), and others. Surprisingly, some drugs like methamphetamine and cocaine are Schedule II, because they have some recognized medical use. However, they’re rarely used or prescribed. Schedule III drugs are where drugs like Tylenol #3 and Vicodin fall (Percocet is still Schedule II even though it has a non-opioid). They contain a Schedule II substance, but they’re combined with a non-opioid, usually acetaminophen/APAP (Tylenol) or aspirin. Schedule III drugs are a lot easier for doctors to prescribe, because they’re not as controlled. Schedule II drugs are required by law to be locked in a separate drawer in pharmacies that stock them, and are hand delivered and tracked heavily to reduce diversion to the black market.

These Schedule III opioids like Vicodin are only Schedule III because of the combined ingredient. Well, why does that matter? Drug companies claim the acetaminophen (APAP) enhances the effects of the opioid, and so makes it so you require a lower dose of the narcotic. This has never really been proven clinically, but it is possible. But, if APAP made the opioid stronger, why is it in a schedule that has fewer controls? The real reason these drugs are combined is to deter abuse. Acetaminophen is highly toxic to the liver in overdose. So, if someone pops a dozen Vicodin to get high, the APAP that’s in those pills is going to make them really sick, by causing permanent liver damage. If someone takes a WHOLE lot, it will destroy their liver, and they will die, very, very painfully.

The thing is, people abusing these medications don’t care. They’re going to take them to get high even if it makes them sick, because they just don’t care. So now people are turning up with liver failure from abusing drugs like Vicodin. Now the FDA is considering banning all prescription drugs containing acetaminophen. Their official reasoning is that people are dumb, and they come home from the dentist with some Vicodin and pop those and then think “hey I’ll take some extra strength Tylenol too!” and that exceeds the maximum safe APAP dosage. The FDA max APAP dose per day is 4,000mg. In Europe, it’s 6,000mg. It’s never been proven what’s safe and what isn’t. It also depends on the specific users metabolism. My doctor insists I don’t take more than 2,000mg per day, which is half the legal maximum.

The thing that really gets me is that the FDA put APAP into these drugs specifically to prevent abuse by damaging the liver. Now that it’s working, they’ve decided they should ban these drugs. Who is running this shit? They’re mad at themselves. So if they ban these drugs, how will people that depend on them continue to have pain relief? For example, if a chronic pain patient taking something like Vicodin suddenly can’t get Vicodin because it’s now illegal, what are they to do? They can’t get JUST the hydrocodone component because that’s illegal in the United States. They can’t get Percocet because it would have been banned too. Their only options are to move to morphine, oxycodone, or any number of Schedule II drugs which are a lot harder to get doctors to give you (it’s hard enough to get them to give you Schedule IIIs). An interesting exception is Percodan, which is oxycodone + aspirin instead of APAP. Aspirin has its own overdose risks, including total loss of hearing.

So in summary, the FDA demanded drug companies put APAP into drugs to avoid abuse, and now they’re scolding them for causing liver failure. They’re blaming everyone else for their mistakes, including the patients. Sure, your average person that gets Vicodin three times their entire life isn’t going to lose out on this so much, but what about chronic pain patients that depend on these types of medication in order to lead a normal life. People like me.

Acetaminophen is over-the-counter. Anyone can grab a bottle and overdose, but we need to worry about the APAP content in controlled drugs?

The mind boggles.

This post is mostly to clarify, to journalists, what the difference between drug tolerance, drug dependence, and drug addiction is. Why does some loser like me on a tiny corner of the internet need to clarify this? Apparently, no journalists can be bothered to do any actual research.

I have read time and time again in several prominent publications that all pain medications lead to addiction. No ifs ands or buts, always. Therefore, they are dangerous and evil, we should hate them, and doctors shouldn’t prescribe them.

But who really cares? If these medicines are so widely regarded as dangerous, no one must need or use them, right? This stuff is only used by hard core junkies on the street to get high. These are the narcotics they’re always going after on COPS.

These are all excellent points. It’s too bad none of them are true.

First of all, no one uses the term “narcotic” correctly. In fact, it is so widely misused that the medical profession has completely given up. Now, “narcotic” is referred to as a legal term, and medical professionals use terms like opioids. So, what is a narcotic, really? A narcotic refers to opium, opium derivatives, and their semi-synthetic or fully synthetic substitutes. This means cocaine, meth, LSD, steroids, DXM, and yes, even marijuana are ruled out. None of these are narcotics, no matter how much the police insist upon calling them that. Why does law enforcement do this? I don’t know. Probably because “narcotic” is a scary sounding word. Opium is a milky substance produced by certain species of poppy flowers, and it contains a great many chemicals, called opiates. An opioid is any substance that binds to opioid receptors in the central nervous system (or “any substance which behaves pharmacologically like morphine”). The terms opioids and narcotics are, in essence, synonymous.

So, what are opioid receptors?

The brain works by sending messages between cells to tell those cells what to do. These messages are sent by chemicals known as neurotransmitters. Examples of neurotransmitters include melatonin, dopamine, serotonin, epinephrine (adrenaline), endorphins, and so on. Neurotransmitters that are produced directly by our bodies are referred to as endogenous ligands. These transmitters are made to fit into certain spots on the outsides of cells, like a key into a lock. These spots are called receptors. The ligand for 5HT receptors is serotonin. The ligands for (parts of) NMDA receptors include glutamate and aspartate (specifically, N-methyl D-aspartate). It is thought that all receptors have corresponding ligands, but there are several receptors we know of that we have yet to discover natural ligands for (such as the sigma receptors). A ligand for the various opioid receptors is endorphin.

(Update: A few people emailed me to let me know the ligand for sigma receptors is angeldustin. This isn’t entirely correct. The theorized ligand used to be called angeldustin, but is currently referred to as endopsychosin (never say neuroscientists don’t have a sense of humor). The reason it was called this is because PCP appears to exhibit effects on the sigma receptors, and PCP tends to make you a bit of a nut. The argument goes along the lines of “why would the brain have a natural ability to mimic the effects of PCP on the brain, and in effect make itself nutso.” Some theories of schizophrenia point at the sigma receptors. The antipsychotic drug haloperidol appears to have effects on sigma receptors. We really have absolutely no idea what they do.)

Drugs that act on the brain do so by manipulating neurotransmitters or receptors in one way or another. Some drugs prevent neurotransmitters from being produced, some prevent them from being reabsorbed, and others mimic the transmitters themselves.

In general, there are three ways that a transmitter works on a receptor. In one way, the transmitter binds to the receptor and activates it, causing changes within the cell. These transmitters are called agonists. In the second way, a transmitter binds to the receptor but doesn’t activate it, and these transmitters are called antagonists. In the third way, a transmitter binds to the receptor and partially activates it, and these are appropriately named partial agonists. One interesting property of partial agonists is that they tend to “normalize” receptor activity levels. In the presence of a low amount of neurotransmitter, the partial agonist will increase receptor function. In the presence of a high amount of neurotransmitter, however, the partial agonist will limit receptor activity. This is a type of negative feedback. The best example I can think of negative feedback is a thermostat: when it’s hot, it turns the heat off; when it’s cold, it turns the heat on.

When you take a narcotic painkiller, the drug binds to and activates various opioid receptors in the brain, spinal cord, and gastrointestinal tract. Drugs like this are opioid agonists. The opioid receptors influence many things, most notably pain and mood. Wait, the gastrointestinal tract? Yes, actually, one of their most noted side-effects is constipation, which can be severe. Opioids reduce gut motility, which means it slows down your bowels, which gives your body more time to absorb water from the bowels, which solidifies the stool. If you’ve ever taken Immodium for diarrhea, you’ve taken a very potent opioid (although, one which does not cross the blood-brain barrier and thus it is only active in the gastrointestinal tract, so it does not cause analgesia or euphoria). The effects and side-effects are enourmous and complicated, and if you’re interested in how exactly these things happen, see the Wikipedia article on opioid receptors. We’ll sum it up by saying that opioids invoke pain relief, or analgesia, feeling nice, or euphoria, and, over time, the need to increase the dosage to achieve the same effects, or drug tolerance.

The one we’re mostly concerned about is tolerance. Tolerance occurs because your brain is an amazing thing. When there are larger than normal amounts of opioids in your system for an extended period of time, the brain compensates by down-regulating the receptors. That is, it starts creating less of these receptors, so that the opioids have a lesser effect at the same dose. In order to achieve the original effects (be it analgesia or, in the case of an abuser, euphoria), the dosage must be increased so that more receptors are reached. Other than needing increasing dosages, this is not necessarily a bad thing. This is simply how the brain compensates. This is simply reality. Anyone who takes opioids for an extended period of time will experience tolerance.

So, what does this all entail? Tolerance usually implies dependence. Is this a bad thing? Maybe. Drug dependence means that your brain has become tolerant to this drug to one degree or another, and if you suddenly stop taking it, your brain chemistry is suddenly messed up. This manifests as withdrawal symptoms, which can be severe.

So wait, the journalists are right? Anyone that takes opioids for a while will go into withdrawal? Well, yes, but that doesn’t mean that you’re addicted to the drugs. This just means that, as your brain readjusts itself to the way it was before the drugs were introduced, you won’t be having a great time. This can be avoided by slowly and carefully stepping down your dosage over a period of time. By doing this, the brain adjusts slowly to each new dosage, and withdrawal is minimal or nonexistent. This means that people can take opioids for a week, a month, or even years and, so long as their dose is slowly reduced, they’ll return to their pre-opioid state just fine, and (assuming the reason for taking the drugs in the first place is gone) will be perfectly normal.

Okay, then, what is addiction? Well, many people hold somewhat personal views about this, but I’ll discuss how medical professionals view it. Addiction is defined as a psychological dependence on something. The key difference is that one is “all in their heads,” and one is physical. Whether it’s drugs, sex, food, gambling, whatever. In the case of drug addiction, someone thinks they need a particular drug in order to be normal. You can see the confusion. People who are drug dependent actually do need the drug to be normal. Drug addicts only think they do. They crave the drug. They’ll do anything to get more of it, including selling everything they own, including their bodies. Addicts will continue to do the activity despite harmful consequences to the individual’s health, mental state or social life. Addicts are usually dependent on their drug of choice, and usually experience withdrawal fairly often because of their inability to obtain their drug. This has absolutely nothing to do with addiction. There are several drugs which people may become addicted to, like marijuana, but which do not invoke drug dependence.

(Update: It is worth noting that there is a behavior that is noted as pseudo-addiction, and is defined as exhibiting addiction-like behaviors toward a drug. That is, a patient is obsessed with getting more of a drug, but not because they’re addicted. This is seen often in pain patients whose pain is not being adequately treated. Trust me, if you were in severe pain your entire life, you’d probably be pretty obsessed with obtaining pain relief. This can appear to be addiction, and, very unfortunately, many pain patients which exhibit this behavior will be marked as drug seeking and are doomed to suffer.)

So what makes people become addicted to something? No one really knows. As it is a psychological disorder, it’s hard to pin it down. Anyone can become addicted to anything at any point. The unfortunate thing is that most drugs that people are interested in developing an addiction to tend to be either controlled or illegal. This means they have to turn to the black market, and become criminals in the process. So how many people become addicts? Clinically, for people who are taking prescribed medication as it was prescribed, less than 1% of all patients become addicted. This means that, out of 1,000 pain patients, around 0-10 of those patients will experience addiction. Some people think this is unacceptable, and that it’s better to let those 990-1000 patients simply suffer.

For those of you who aren’t in pain, good for you, that’s a reasonable position to take. Pain is transient, you can tough it out, right? Except when it isn’t transient. Millions of people, including me, are in chronic pain. That means we’re in pain every minute of every day. There are many treatments for many conditions that cause this, but for millions of people the only answer to their pain is to be on opioids long-term. People have a stigma about this because they only time they hear about opioids is when someone ODs on heroin. Because of the <1% of patients, the other >90% have to suffer more. Doctors are terrified to prescribe opioids because of their psychological effects, so they’d rather not treat anyone at all. I think this is stupid, and I don’t understand how, as someone who has promised to “limit suffering,” they can do this. Sure, opioids make you feel good, and in our society that is a Bad Thing™, but for the rest of us who need them to live, please, I implore you, pull your heads out of your asses.