Pain Management: The tl;dr Pharmacy Guide
Sam here. In a not so previous life, I had the opportunity to spend some time working with the neurology team at the hospital I was working at. This was the result of an APPE rotation, followed by a residency rotation, and a genuine interest in the field. Particularly pain management.
While I am no longer practicing in that setting, I felt compelled by Brandon (and by many requests from our readers) to write this post.
Before I start, I want to set the scope for this guide.
Opioid abuse comes in many forms; and it's not just the stereotypical junkie that's doctor shopping and trying to refill their Norco 2 weeks early "because the cops stole them." Opioid abuse can also show up in more insidious ways. It can be the secretary at your physician’s office...
The cashier at your local grocery store...
Your Madden buddy...
The mother of two next door…
For the purposes of this post, we'll cover basic pathophysiology and the foundations of pain management.
This is not going to be a soapbox post where we issue some blanket recommendation to avoid filling all opioids. Or to deny patients access to medication because of fear of abuse (whether rational or irrational).
This is an educational post. The newsworthy, headline-grabbing stuff is best left for another time.
So with that being said, let’s take a little dive into the world of nociception.
What is ‘pain’?
Not to sound textbook-y or cliché, but the Merriam-Webster definition of pain is:
“usu. localized physical suffering associated with bodily disorder (as a disease or an injury); also: a basic bodily sensation induced by a noxious stimulus, received by naked nerve endings, characterized by physical discomfort (as pricking, throbbing, or aching), and typically leading to evasive action.”
Or, as Urban Dictionary’s top definition states:
“What happens when you reach into the blender to dislodge a stuck icecube without unplugging it first.”
I don’t… well. Yes. That’s probably pain.
No, that definitely is pain.
If you’re cringing just like I am, this song will soothe you. I promise.
Now, let’s get back to it.
While our bodies are intricate, beautiful machines comprising billions of cells working together, we’ve generally simplified our communication system. A handful of neurotransmitters, a few modulators (mmm, modulation), and you’ve got our nervous system.
Pain, or rather, the sensation of pain, is basically a signal from some part of your body to your brain saying “I don’t like this.” So, are vegetables painful to children? Maybe.
There are a million-and-one diagrams showing how pain signaling works and what chemicals/etc "cause" the pain. While each step is important (#snore), the details are probably good to know. For visual learners, here is a pretty video to look at for the basic ideas behind the neuronal pathways and signaling.
But to break it down to simpler words:
- Inflammation – tnf alpha/arachidonic acid/interleukins -> cox -> prostaglandins -> neuronal firing
- Neuropathy – inappropriate neuronal firing, out-of-whack neurotransmitters
Okay! Now we know how pain works, let’s throw some drugs at it!
Slow down there, Jimmy. Let’s take it one step at a time.
Like when you played with those blocks as a kid, you need to start by knowing what "shape" (i.e. pain) you’re looking for.
You can’t be that one kid who tries to brute force the freakin’ square into EVERY hole.
That's not how this works. THAT’S NOT HOW ANYTHING WORKS!
Start by identifying the type of pain.
Essentially, you can boil down pain into two major groups:
Nociceptive (from the Latin word nocēre, or to injure, and “receptive”) is basically pain caused by some injury.
Neuropathic (from the Greek neuron, or nerve, and pathos, or suffering/sensation) is essentially pain that is neurologic in origin.
Or in simple-man terms, pain caused by neurons. Yes, those things that are essential for your body to communicate with itself. When one goes rogue, it really lets you know.
There are a few telltale signs when it comes to identifying the type of pain you are treating. Think of them like the blacklight in a crime scene or residual powder on someone’s finger (yay, CSI). By listening to a patient describe their pain, you'll get clues as to what is causing it.
Nociceptive pain is often directly associated with some type of injury, so the pain can be described as throbbing, aching, or sharp.
Au contraire, neuropathic pain is often described as needle-like, tingling, ice-like or burning. There generally isn’t an identifiable cause or injury associated with this.
Unless it’s diabeetus.
Or you’re playing with needles.
Then you know. You know.
Now that you have identified the type of pain, you need to figure out what would work best. And no, the answer is most likely not “Percocet”.
The answer should almost never be “Percocet”. Unless the question is: "Why is some guy showing up at 4 AM in your pharmacy from three states over?"
In a very general sense, you can approach pain management the same way you would approach managing type 2 diabetes (T2DM) in the inpatient setting with insulin. With T2DM, you start by giving the patient a sort of 'prn' short acting prandial insulin. This is to cover the meal they are about to eat.
With pain management, you start with something short acting to cover the breakthrough pain. In a perfect world, whatever the patient just took will cover them until they are due for their next prn dose.
Eventually with T2DM, you may also need to provide 'basal' insulin support. This is like having a low level of "background" insulin available for use. We accomplish it with long acting insulin formulations such as Lantus or Levemir. Even when using basal insulin, you'd still have a short acting formulation on board for as needed use.
Update: A super smart reader pointed out to me that this insulin management analogy primarily applies to inpatients. In the outpatient setting, you usually start with basal insulin and then add bolus. Thanks for the clarification!
Similarly with pain, for patients that need a step up from prn management, you can include a "basal" analgesia with long-acting formulations of pain meds. These should be taken on a scheduled basis, as their goal is to prevent pain in the first place. Then you would still have short acting formulations on board for breakthrough pain.
So the basic idea for patients with extreme pain is:
- Provide scheduled, "basal" pain relief with long acting formulations
- Use short acting formulations for as needed (prn) breakthrough pain
This stepwise approach is also nearly identical to how we manage Asthma or COPD (using scheduled long-acting steroids and beta 2 agonists with the prn short acting albuterol rescue inhaler).
Anyway, based on feedback from the patient, a pain regimen can be tweaked. If they are requiring every single dose of their prn for breakthrough pain, you may need to increase the basal long acting dose.
The general goal is to keep the patient comfortable, but not sedated and drugged up.
And as a final point, chronic disease states such as anxiety, depression, and stress can all contribute to physical pain and associated limitations. Be sure to fully evaluate your patient to ensure that there isn't a psychological "root cause" of the chronic pain he/she is experiencing. If so, this can often be treated with counseling or antidepressants.
Let's look at our options for treating pain, shall we?
The Magnificent Seven: Analgesic Classes Used in Pain Management
Your professor might say this is an NSAID, or that it works on COX-1 and COX-2. They are wrong. Yes.
The correct answer lies behind door number 3: COX-3. While not very well understood, COX-3 is found mostly in the CNS. When you inhibit it, you don’t get as much anti-inflammatory effect as you do general pain relief. Read: headaches, general aches and pains.
There's a whole group of other agents that we usually call “centrally acting.” We'll cover those below, but I wanted to give special mention to our friend acetaminophen because he usually gets lumped into the rest of the centrally acting agents incorrectly.
Kind of like that one kid in your class that you keep calling Chinese, but he’s really Taiwanese. There is a difference.
Nancy Sells Antidepressants In Dozens?
Nope. Non-Steroidal Anti-Inflammatory Drugs. And, well, that’s basically what they are.
More specifically, they target a set of receptors, COX-1 and COX-2 (Cyclooxygenase 1 and Cyclooxygenase 2, not Courtney 1 and Courtney 2).
Some NSAIDs equally inhibit both, while others seem to prefer COX-2.
So what exactly does COX (both 1 and 2) do?
To give you a hint, COX is also known as Prostaglandin-Endoperoxide Synthase. However, COX is way easier to say, and funnier too #morejuvenilehumor.
Essentially, these little buddies will act directly on the inflammation pathway to decrease prostaglandin production.
Now, you may have heard of a concept, “COX-2 specificity”. Basically, COX-1 is involved in prostaglandin production in the GI tract (hence the GI side effects of many NSAIDs), while COX-2 is involved in the inflammatory process.
So theoretically, if you could focus all your activity on the COX-2 side, you could treat pain without causing GI side effects. However, in practice this leads to other problems.
Remember that COX also has a role in platelet function. COX-1 is especially prominent here. It turns out that if you inhibit COX-2 too strongly, you create a sort of "imbalance." That imbalance can lead to an increased risk of heart attacks and strokes.
It's exactly what got Vioxx and Bextra (COX-2 inhibitors) removed from the market.
Currently, the only available COX-2 specific inhibitor in the US is celecoxib [Celebrex]. While the warning of MI and stroke is still there, it turns out that Celebrex doesn't inhibit COX-2 quite as strongly or preferentially as Vioxx and Bextra.
That's why it won The Hunger Games and is still on the market. In practice, we try to avoid it if the patient is at risk of MI or stroke.
Anyway, back to COX-1 inhibition...
How bad are the GI effects? Well, there is a measurable, dose-dependent effect of aspirin on GI bleed. Really.
So if you can avoid that, you can reduce the risk of ulcers and bleeding and the such.
So then, how do you decide which NSAID to use?
Simple. There are handy-dandy charts on the interwebs.
An interesting thing to note here is that while celecoxib is marketed as a COX-2 selective NSAID, meloxicam and diclofenac seem to show much more specificity on this graph. You can also see that aforementioned super COX-2 specificity of rofecoxib [Vioxx] that got it pulled from the market.
Reading a little further will show you that the specificity of meloxicam and diclofenac tends to fall off as dosages increase. But if you’re looking to recommend something relatively cheap at lower doses, these two agents are pretty great.
Gotta use that #Pharmacoeconomics knowledge, ya know.
Remember that from pharmacology you learned about how antidepressants work on neurotransmitters? The "language" of our nerves?
By modulating the activity of the different neurotransmitters you get changes in nerve activity. Which, if your pain is neuropathic in origin, may be a world of difference.
In general, you’ll see TCAs as a standard go-to here (remembering that they can modulate the activity of NE, 5HT, and maybe even a little Dopamine).
To tell a little story, I once had a patient who had been dealing with pain for years, and he’d been on a wide range of treatments from NSAIDs to opioids. After asking about the presentation and location of the pain, and what medications he had tried, it seemed to me like his pain was neuropathic.
I suggested a short trial of nortriptyline, and after conferring with his provider he went home with a prescription. About a month later, he came in so ecstatic that he was no longer suffering pain, but he was now having problems ‘getting it up’.
A slight decrease in dosage and after another visit I never saw him again. Still, this sticks with me to this day. It helps to actually listen to your patients and to do a little digging.
Beyond TCAs, SNRIs are pretty common here, also. Again, note that they have activity primarily on NE and 5HT (you should be noticing a trend). Duloxetine is often used, and venlafaxine by extension.
One thing to note, however. With antidepressants (and with anticonvulsants, for that matter), keep in mind that relief isn’t overnight. It can take a few weeks to really kick in, so hold your horses before adjusting wildly.
Much like antidepressants, the anticonvulsants focus on neural activity. So you'll also see these used for neuropathic pain. Particularly conditions like trigeminal neuralgia.
For neuropathic pain like diabetic neuropathy, you'll commonly see gabapentin. Followed closely by pregabalin (great television marketing can do wonders). These both work by modulating the inhibitory neurotransmitter GABA, which can decrease the firing of neurons.
For trigeminal neuralgia our drug(s) of choice are carbamazepine or oxcarbazepine.
For some people, nothing quite does the trick like a 21-tablet pack of sheer happiness. The boost in energy, decrease in inflammation, and overall “strength” is phenomenal, and it really does the trick when the pain is skeletomuscular or inflammatory in origin.
Steroids, of course, should be used judiciously. They have a full metric shit-ton of side effects. They work on the molecular level, literally upregulating or downregulating the proteins that your DNA is synthesizing. The down stream effects can include osteoporosis, susceptibility to infections, leukocytosis, stomach ulcers, lipodystrophy, and general 'craziness' just to name a few.
One of the ways steroids help alleviate pain and inflammation is by inhibiting Phospholipase A2. This particular phospholipase converts phospholipids into Arachidonic acid (which is then broken down to the inflammatory prostaglandins via COX-1 and COX-2).
So steroids sort of work in the same pathway, but at more of a 'precursor' step than NSAIDs.
Incidentally, arachidonic acid can also be broken down via the lipoxygenase pathway to leukotrienes, which can cause mast cell degranulization and neutrophil activation. You've heard of leukotriene inhibitors (think monteleukast, a.k.a. Singulair) being used for allergic rhinitis and asthma. This is why steroids are also effective in treating these conditions.
And as a final clinical pearl here, you've probably also heard of the 'paradoxical' reaction of aspirin and other COX inhibitors exacerbating asthma attacks. Well now you know the nature of it...and it isn't paradoxical.
By inhibiting COX-1 and COX-2, aspirin and other NSAIDs effectively shunt arachidonic acid metabolism to the lipoxygenase pathway. This can cause bronchospasm and exacerbate an asthma attack in some sensitive individuals.
Other (including, but not limited to, "Opioid-like")
This section is a general catch-all for other therapies, but there are two in particular that I would like to review.
Tramadol is like duct tape. It’s not quite scotch tape, but it’s not quite nails. It’s somewhere in between. In drugs, tramadol has some TCA-like activity (antidepressant!), but also some opioid-like activity (Percocets!).
Basically, its parent molecule has the NE and 5HT activity (meaning you need to watch out for it on test questions about serotonin syndrome). But its active metabolite has the mu-1 activity, which is right in the opioid wheel house. This is why it was re-scheduled a few years ago and is now a controlled substance.
Capsaicin is another interesting agent. You can take it orally in the form of hot peppers, but that's probably not the best for treating pain. At the very least, it definitely causes pain on the way in and on the way out.
In actual real life medicine, we apply capsaicin topically via creams/gels or patches. It creates a mild burning sensation, which is actually the release of substance P. This causes inflammation, vasodilation, and pain.
While that sounds counter intuitive, the idea behind capsaicin is that it depletes the substance P from your nerves, "crowding out" the much worse pain that you're treating.
In effect, this means: Some pain, some gain.
There are many naturally occurring substances that have made their way into modern medicine in one form or another.
- Willow bark: aspirin
- Tobacco: nicotine (well, not sure about the ‘medicine’ part, since it really only treats its own addiction #meta)
- Ouabain: digoxin
- Botulinum: botulinum (#science!)
- Sweet clover silage: warfarin
- Pacific yew: paclitaxel
- Horny goat weed (heh-heh #juvenilehumor?)
So, naturally, we took one look at opium and decided: Market it.
Purify it, modify it, package it and sell it.
And it worked.
When opioids were first marketed, they were primarily reserved for severe pain and end-of-life care. It wasn’t until the advent of the modern opioids that we saw a marked increase in opioid use.
They were obviously very effective at treating pain, but we didn’t have a lot of data on the long term effects.
Well, now we’re starting to get some.
To take a quick step back, let’s talk about endogenous opioids – endorphins. Produced in the pituitary, endorphins are neuropeptides that are "morphine-like." They are produced in response to pain signals and various activities (laughter, aerobic exercise – runner’s high).
Endorphins agonize the opioid receptors (primarily mu-1) to block pain and cause euphoria.
We've said this before, but basically every treatment we use in medicine either mimics or blocks some natural process. Opioids are not an exception.
They bind to and agonize the same mu and kappa receptors that endorphins do.
What is unique about opioids compared to the other pain meds we've talked about is that they don't do anything to the actual source of the pain. They just stop your brain from "feeling" it.
For example, NSAIDs actually decrease inflammation...which will reduce the excessive neuronal activity leading to pain in the first place.
Opioids, by contrast, just stop the neuronal activity before it hits your brain. It's kind of like when a child plugs their ears and says "La La La" to avoid hearing you tell them that it's time for bed. You're still telling them it's bed time, they just aren't hearing you.
The side effects of opioids are also pretty well documented. While they are useful analgesics, they also can cause profound CNS and respiratory depression. Almost all of the opioid-related deaths that you hear about in the news are due to this effect. Particularly if patients combine opioids with other CNS depressants (such as alcohol, benzos, and sleeping pills).
It turns out that opioid receptors are found in the digestive tract. And that when you agonize these receptors, you bring peristalsis to an all out halt. The result? Crippling constipation. It's so bad that we have drugs designed specifically to treat opioid-induced constipation (such as methylnaltrexone [Relistor]).
In fact, the over the counter anti-diarrhea medication loperamide [Immodium] is chemically related to morphine. It works by agonizing opioid receptors to "induce" constipation.
It's designed to not cross into the CNS, but some enterprising individuals have recently proven that if you take enough of it, it will...leading to a few unfortunate and untimely deaths.
Anyway, let's dig into a few opioids worth noting.
When we’re talking about the specific agents, they are generally separated by “potency” or “duration.”
Potency is measured against morphine, the prototypical opioid. So for example, we might say how "strong" a given opioid is by saying that it is 'X morphine equivalents.'
Where would this discussion be without mentioning good old fashioned morphine? It's got both immediate release and sustained release formulations available. Making it useful for both basal and breakthrough pain.
It's got a few clinical pearls worth noting. For starters, it is the lone opioid that can claim usefulness in Acute Coronary Syndrome (ACS). It seems to have some vasoactive properties in addition to analgesia. You'll see the acronym "MONA" thrown around a lot in this setting. It stands for Morphine, Oxygen, Nitrates, and Aspirin.
Another thing is that it can induce itching or a rash in some patients. This is histamine mediated---morphine somehow causes the release of histamine in sensitive patients. If symptoms show up in your patient, it's best to switch them to another opioid. Often, the synthetic opioids (oxymorphone / hydromorphone, and fentanyl) are useful here, with the caveat that the synthetics are more potent than morphine.
As a final clinical pearl for morphine, it has active metabolites. And those metabolites accumulate in renal failure. So morphine is usually NOT the best choice for patients with renal disease or for the elderly. The half life of morphine is extended a good bit in these cases, and over-sedation can be a real problem.
Hydrocodone and Oxycodone
Your standard, run-of-the-pill-mill drugs are hydrocodone and oxycodone, which can more or less be considered equivalent or close-to-equivalent with morphine. It's not exact, of course, but for general discussion it's close enough. Hydrocodone and oxycodone are commonly co-formulated with acetaminophen, and there are a million-and-one variations of a common theme (the theme being ratios of acetaminophen to opioid). Think Haydn.
Hydromorphone and Oxymorphone
A few steps up you’ll find hydromorphone and oxymorphone, with somewhere between 5-10x the potency of morphine by general consensus. You’ll see this often for patients with tolerance and severe pain, and in PCAs for hydromorphone.
Fentanyl and Remifentanil
Fentanyl is a helluva drug.
Seriously though, with potency marked at about 200 times that of morphine, it’s got Chuck Norris knock-out power. Whether you’re sucking on lollipops, injecting it, or slapping a 3-day patch on, it can really do a number on you.
Generally reserved for anesthesia or severe pain (think cancer pain), you really shouldn’t be seeing fentanyl on a regular basis outside of specialty clinics or surgery.
One of the benefits of fentanyl is that it is short acting. This is why surgeons love it. It's potent and the effects wear off quickly. Perfect for a procedure. As mentioned above, it's also a synthetic opioid...meaning that it should have a relatively low risk of histamine related rash.
It's important to note that the fentanyl patch is contraindicated in opioid-naive patients. The IV formulation is not. Remember, it's short acting (hence why you even need a patch formulation). So even if you dose a patient too high with the IV formulation, the effects will be short lived.
However, if a patient hasn't used opioids before, the patch is a risky proposition. And one that has led to fatalities in patients. Make sure you remember this fact for the NAPLEX and life after.
Another interesting tidbit on fentayl patches is regarding disposal. It turns out that even after 72 hours, there is still a good amount of fentanyl left in the patches. And that remaining fentanyl is enough to kill children and small animals. There are, unfortunately, multiple reports of this.
The fentanyl patch is one of only a few drugs the DEA and ISMP actually recommend flushing down a toilet after removed. This is after folding the sides together so that the "fentanyl" side is safely trapped in the middle.
Remifentanil is used primarily for surgery and for anesthesia. It's similar to fentanyl, but it's even more potent. Unless you spend a good amount of time in the OR, you probably won't come across this as much.
This one’s a little weird. You’ve got drug interaction issues, neurotoxicity, and possible seizures. It's main area of usage comes in treating rigors, which often show up during infusion reactions. You may see it from time to time in these settings. Before we had better options that didn't give patients seizures, meperidine used to be used in L&D or diverticulitis.
Methadone is fascinating. It’s listed as an essential medicine by WHO, and it’s mostly used for treatment of opioid and heroin addiction. Why use an opioid to treat opioid addiction? It has to do primarily with the pharmacokinetics. Methadone has an incredibly long half-life.
This means (for those of you who remember warfarin’s PK/PD) that it takes time for it to build up, and time for it to flush out. So, conventional wisdom decided that a slow, gradual process is the best way to quit the highly addictive opioids.
That concept is not unlike developing a cigarette that burns slower and longer. The idea is that you eventually smoke fewer cigarettes, and at some point it’s easier to quit one cigarette a week than it is a pack a day.
However, methadone treatment is inconvenient. It turns out that this is one of the most abused medications by healthcare professionals. And again, it's a CII meaning that it is highly addictive itself. Methadone clinics usually involve requiring the patient to show up every day to get their dose. This makes it tough to keep a regular 9-5 job.
It can also be costly: methadone clinics have equipment needs, staffing needs, overhead, and a lot of other expenses.
For pain management, methadone is potent and lasts a long time. And it's pretty cheap. For patients on high doses of opioids multiple times a day, methadone may be a good option.
Just keep in mind that there are legal issues with treatment vs addiction doses. Many states require an Act of God to dispense methadone to hospital patients if it's for addiction.
These laws exist to prevent addicted patients from coming to the ED to get their methadone fix. They often require verification of the dose from the patient's methadone clinic, and a lot of documentation. If the methadone clinic cannot be reached, the laws indicate that methadone should only be dispensed to prevent withdrawal symptoms (and only for a limited number of days).
There isn't a hard and fast rule here, but in general, you can tell the difference of pain management vs addiction by the dose. Pain management doses are usually lower (around 10 - 15 mg), while addiction doses may be in the 90 - 120 mg range.
When switching between opioids, the most important "rule" is that you do NOT do a 1:1 switch based on potency. There's a concept called cross tolerance in the opioid world. The gist of it is that the tolerance you develop to one opioid is likely to (at least partially) transfer to another opioid. This affects how we transition patients from one opioid to another.
The general idea is to:
- Add up the total daily dose of all opioids the patient is taking
- The key here to keep in mind is that this is based on what the patient is actually taking, not what they were prescribed
- Convert that data into the total daily morphine equivalents
- Reduce that number by 30 - 50% (this is to account for cross tolerance)
- While 50% is a drastic drop, it's much easier to adjust up than it is to scramble for that naloxone when the patient overdoses
- Convert to the total daily dose of your new desired opioid
- Divide the daily dose to a reasonable 24-hour regimen
- Adjust based on patient need
Opioid Conversion Charts
There are plenty of calculators on the dot com to help you with this. GlobalRPh.com has a good one that we like. Just be careful with your units. Fentanyl patches are in micrograms per hour, but most opioid calculators are looking for a total of milligrams per day. If you get a crazy dose when you use the calculator, check your units.
So converting opioids isn't that bad, right? Just remember that the "currency" of our switching is morphine. That's the Rosetta Stone that we use to translate one opioid to another.
To point out some other charts to check out:
The key is that there is a general consensus on the relative potencies (more/less), but the exact numbers are somewhat subject. It's important to keep in mind that pain is highly subjective and it's important to keep your patient's experience in mind.
Other Opioid Clinical Pearls
While everyone talks about the deadly effects of opioids (it’s deadlier for Hollywood celebrities than a Chuck Norris roundhouse), there are a few other things to consider. Remember that I mentioned that we have more data now on long-term opioid therapy?
For starters, you should know that naloxone [Narcan] is an opioid antagonist (it's technically an inverse-agonist...meaning that it shuts down already activated receptors) that can be used to reverse opioid overdoses. It out-competes the opioid for the mu receptor and quickly reverses the effects of the opioid.
It should go without saying, but naloxone can also precipitate symptomatic opioid withdrawal.
If you've ever seen someone reversed with naloxone, you won't forget it. As a resident, I once went to a Code Blue where a patient crashed during dialysis. She had been receiving high doses of opioids so the team gave her naloxone to try to wake her up. Almost immediately, she perked up (in fact she nearly stood up in her dialysis chair). She then proceeded to say some things that I don't feel comfortable typing out on a semi-professional website.
There is increasing data (and several advocacy groups) recommending that naloxone be co-prescribed to patients taking high dose opioids. The thought is to educate patients (and providers) on the symptoms of opioid overdose and to help prevent yet another opioid-induced death.
Going back to our earlier insulin analogy, you could consider this the equivalent of giving a diabetic patient a prescription for a glucagon syringe. As a caveat, the exact definition of "high dose opioid" is not fully agreed on by everyone, and there will always be patient-to-patient variations.
But, to give you a reference point, a wonderful group in Texas, Operation Naloxone, recommends that any patient receiving 50 mg of morphine equivalent per day or greater should have a prescription for naloxone.
The paradox to end all paradoxes. Simply put, opioid therapy can eventually cause increased sensitivity to pain. The idea is pretty intuitive if you think about it. When your body repeatedly does something, it adapts and gets better at it.
If you haven't ever exercised before, and you try to run a 10K, you're probably going to fail, hurt yourself, or both. But if you keep running every week, your body will develop new neural connections and muscles to deal with the new strain that's become it's normal. You'll also notice this in your first two weeks of P90x or a similar program. It's absolute hell when you start, but soon the soreness goes away as your body gets used to the new workload.
In a similar manner, the more you aid the body in dealing with pain, the less your body is capable of dealing with it. Whether it’s decreased endorphins, decreased receptors or decreased receptor sensitivity, you end up needing more and more opioids, and the drugs work less and less. This is exactly how physical addiction works.
Opioid-Induced Hormonal Imbalance
Long-term opioid therapy can also lead to hormonal imbalance. The effect seems particularly pronounced in men, as it's usually testosterone levels that plummet. This means feeling less “manly”, potential depression, and even worse wound healing. When you’re already dealing with pain, this is probably the last thing you need.
Psychological Effects of Long-Term Opioid Use
Aside from the obvious (addiction), depression is a real adverse effect of opioid therapy. The dependency, the loss of hope for a pain-free life, and the general CNS effects and hormonal imbalance are a lot to deal with.
Add the very real possibility of an insatiable need for more drugs, and you’ve got a winning problem. This part is often glazed over, but it's worth paying attention to. Patients with chronic pain should have access to psychological support and a holistic approach to therapy. Not holistic like those little strip-mall shops that promise virility and long life. A multidisciplinary approach.
Pain is a terrible thing. There's a lot more to it than just a general sensation that says “Hey, something’s wrong!”
It's a natural response, but we human-types have a sort of instinct to avoid pain. Whether we’re talking about a run-of-the-mill headache, a stubbed toe, or falling on a sword.
The most important thing that we can do as pharmacists is to be and advocate for the patient, educate patients on the perils of long-term opioid therapy, and be a knowledgeable partner in the healthcare team.