The concept of tolerance. Why medicines quit working and opioids kill.

Peaceful command is not a constant, and will be eliminated by tolerance.

HH.

A painful disease state is inconsistent, often elusive, and takes on a life of its own. Rule five. Do not chase pain.

Particularly evident with muscle aches, or myalgias, is their transient and regional variation. Today may be a good day, next week you're exhausted from pain that started by the shoulders, now in the low back, and you can't sleep. Don't they (who is they) make a pill for this. Most assuredly "they" do. And they don't. They can be pharma, a boutique pharmacy, internet quick care, and a miracle cure. Remember, you can't cure a syndrome. That's off the list.

 So, where's the help. Where are you going with this.

Rule four. The risk reward ratio. Know thy meds. Let's go down the classes. Not all but relevant drug classes to the fibro five. Gabapentinoids.

Gabapentin is an older drug first used in Europe. Introduced in the US and found to be useful for its unintended purpose. This gabapentinoid is an anti-convulsive, with then unknown mechanism of action, and took on a life of its own in the early 90s. A letter to the editor, suggested this drug helpful for pain disorders, particularly nerve type pain (neuropathic) and had few undesirable side effects. The opiod load could be decreased, and people slept better. Not a good seizure drug, but a good "adjunct agent" to treat pain. Gabapentin was labeled Neurontin brand name, and it took off. A windfall for Parke-Davis, which owned the rights, it rapidly replaced the other drugs used for neuropathy. Choices up to this point were awful, requiring careful monitoring, and gabapentin did not. It wasn't habit forming, and could be used on a number of diagnoses in the behavioral health arena to the neurology world. Off label of course. And that's where the trouble started.

Without going down the rabbit hole, the FDA requires labeling for a drug and limits promotion off label. Another company acquired this drug, which was the precursor to the labeled fibromyalgia sibling, pregabalin, or Lyrica labeled. The mechanism of action was eventually worked out, but it is an adjunct to widespread pain, or better put, used with another drug to improve fibromyalgia symptoms and function. Gabapentin is widely used today generically and in a new timed release formulation that significantly improves absorption, and therefore action. There is more to the gabapentin story, and another class.

Opioids.

Pain management came into its own in the mid 90s. Certification processes developed, and societies grew. New order thinking evolved, and sparred a deadly crisis that we deal with today. Misguided recommendations from a small handful of physicians resulted in a relaxed philosophy about opioid use. Drop the stigma and apply aggressive prescriptive habitary to treat pain. Federation Of State Medical Boards, and others, assured providers that no actions would be initiated, even with high doses of prescribed drug, if rules were followed. Providers of care became comfortable, in a short period of time, treating even mild pain with opioids. The consequences were felt to be minimal, maybe except for constipation. Pain clinics started popping up like Starbucks registered, and pain clinics in certain parts of the country proliferated. Then the added problem of pain physicians everywhere with no training, pharmacy suckers, same day appointments, out-of-state patients welcome, chartered buses, special flights, and a new term "Pill mill".

 Risk Versus Reward.

Dependence is not addiction. Addiction usually reveals dependency. Some people are dependent by their second opiod prescription. Dependency then devalues into the same as addiction, others not, and many factors are at work to manage a course. Risk is a process of loss, and addiction can take your soul. When opioids are an important part of an individual's life, neurobiological events cascade in that primitive part of the brain to incite craving. Remember behind the ear. The desire to contain the craving is driven by dopamine. Dopamine is a molecule, structurally similar to a stimulant, but does not act like one. Dopamine fuels the reward system, and when depleted, results in a let down, a low, a feeling of funk. Tolerance is developing, and the brain wants more of something to feel better. Hedonic tone, the brain seeks relief, and a drug is taken, often an opioid, to avoid withdrawal.

 Bugs Are All Over Me ...

Withdrawal is a spectrum, as mild as the flue, or as dangerous as a seizure, the drug does matter. Opioid withdrawal can be miserable, abrupt benzodiazepine and alcohol abstinence can be fatal. Rule four, know your drugs. Know your five classes. Fibromyalgia knows these most commonly. Benzodiazepine, opioid, gabapentinoids, muscle relaxants, and anti-inflammatories. Which has risk, and where is the reward.

Opioids rarely add a positive relief cycling to fibromyalgia, or many pain states. These drugs add a new layer of complexity to the care model. Taken, an effect is evident, and a sense of wellbeing is reinforced by dopamine in the reward circuitry. Those hurting from the symptoms of fibromyalgia relate a desire to repeat this feeling that is mistaken as a positive result. Realistically, function is rarely enhanced, and persistent difficulties with sleep and fog are a dominant part of the symptom cascade. Pain rarely improves, and is sometimes worse as the dose escalates. This process of opioid induced hyperalgesia is a real problem. (Will talk glial cells later) this paradoxical expectation of opioids is common. Increasing the opioid dose can result in more sensitivity and pain. This is not addiction, just one more problem with opioids.

Opioids really are a dead end. The risk reward benefit is really not in your favor. This class deserves more attention, but the next class is even tougher.

Benzodiazepines.

This class of drug is most misunderstood and misprescribed drug in America. There is very little upside in fibromyalgia. Common reports in the exam room - I need them for sleep, I've been on them for years, they help me relax, I have anxiety, PTSD, fear of people and places, I can't think without them, I have depression - this list won't stop. So what's the problem with a little pill? Wildly habit forming, much worst than opioids in some cases. It is potentially life-threatening to abruptly discontinue. Winning can take months. They don't help with sleep, they interrupt sleep architecture. Fibromyalgia imposes enough problems that are hard to control.

This is one we can. This allows stage four sleep. This sleep is critical for mood, memory, learning, and just plain thinking. Those with fibromyalgia have alterations in deep stage sleep (stage four). This is called alpha 2 intrusion, no wonder fibro fog is so prevalent in fibromyalgia. Forgetfulness, tired all the time, heightened anxiety, situational depression is a person where fibromyalgia has entered into their life. The rational response is to seek better sleep, less anxiety, peace. Benzodiazepines are your pariah. These drugs suppress serotonin, which further exaggerates anxiety and depression.

They disrupt the trip to stage four sleep, further aggravating memory disturbances and peace. These drugs are purposely used to promote amnesia in the operating room and the procedure area, ICU, and necessary, to diminish activity in the brain. The exact opposite of our restorative desire is to improve function and quality of life. They do not reduce pain or muscle spasms. At an AMERICAN SOCIETY OF ADDICTION MEDICINE board preparation meeting, a presenter at the podium declared "there is no place in medicine for benzodiazepines to be routinely prescribed." The room exploded with applause. We have better choices.

Benzodiazepines are not recommended for anxiety by the American Psychiatric Association, the Canadian Psychiatric Society, or the British system called NICE. Benzodiazepines are often associated with fatal overdoses. A recent CDC guideline singled out and discouraged their use with opioids. Don't stop these drugs without qualified medical guidance.

Pick Number 5. Let's talk NSAIDS, Non-Steroidal Anti-Inflammatory Drugs, and a Rant.

This class of drugs is everywhere-prescription, non-prescription, generic, labeled non-generic. Famous, notorious, used from the cradle to the grave, these drugs are not benign. They have a history.

A millennial ago, we sucked willow bark for salicylic acid (like aspirin). A storied history name Bayer developed aspirin for a company. The rest is history. Actually, like so many other drugs (Morphine, Heroin, Barbiturates, to Benzo's) there is a pre-story. Ketamine was developed as an "ideal" anesthetic. When its predecessor, PCP, better known as "angel dust," failed. The same prior to aspirin, acetal-salicylic acid ... A more contemporary evolution of NSAID (aspirin is an NSAID, acetaminophen as well) we eventually produced ibuprofen. Not the first iteration, but it stook and it would for decades, but the dreaded side effects evolved (read ignored). These type of agents gave the impression of profound safety. No worries. All comers, babies to the elderly, alcoholics to the cardiac cripples, we all manage to consume. Enter Rofecoxib (Vioxx-brand) in Celecoxib (Celebrex-brand). NSAID wars. These two drugs, better known as the names above, Vioxx and Celebrex, were a "new" class of COX 2 inhibitors. Cyclooxygenase 2 inhibitors were reported to be an ideal agent. By selectively avoiding COX 1, COX 2 drugs were at the time, inherently safely. COX 1 and COX 2 effect different biological activities. COX 1 is constitutive, 2 inducible. Number 1 is always on, 2 when an inflammation or pain is present. 1 is associated with GI problems, 2 is selective for only stuff we take these agents for granted. What followed was the calamity called The Fallacy of False Generalization. People were having issues not seen, or duly alarm winning in the trials. Hypertension, heart attacks, bleeding, renal disease and others, but the bell was rung. Without relieving a turbulent time in pharmaceutical without reliving a turbulent time in pharmaceutical history, Vioxx-brand name was taken off the market, as was Bextra. This was another COX 2 drug, and the lawsuits began.

 

How these remarkable drugs work is by diminishing or blocking the inflammatory cascade. They are not steroids, they are anti-inflammatory in a way, but they share certain characteristics of steroids. Use these drugs with care, as in the case of any drug, monitor blood pressure, know the cardiovascular renal and GI risk, and talk it over with your healthcare provider. They are not benign, despite the over the counter availability.

Fibromyalgia deserves a brood acceptance. Very few diagnosis that we face in contemporary medicine is resisted by so many practitioners. Despite evidence of its existence, and under utilized treatments to improve quality of life of a sufferer, there is a lack of enthusiasm to treat aggressively. Advice to anybody that is diagnosed - resist a label. You are a real patient, deserving any tool and therapy available to get to a better place. Maybe those with fibromyalgia will lead a new consumer driven healthcare model. This will contain costs. Avoid disabling symptoms, prove the concept of disease management where we are proactive, not reactive. Be that patient. Win.

Fibro...I can't think, I can't sleep, I forget, I hurt. Wassup?

We touched on neurobiology, and all agree, we aren't interested in becoming a citizen scientist. People do not want to know why this thing is eating at their quality of life. Is there a common denominator? A link? Cure? Most just want to sleep. Fibro is a complex problem and deserves careful evaluation and management. There are three types of fibromyalgia. The fibro that exist, the fibro that controls you, and the fibro that you control. Back to the brain.

Once again we all win when we avoid over thinking a problem. Ocums Razer sort of says it best: all things considered the simplest answer is usually the correct one. And in fibro, the least complicated explanation and treatment is usually the best. The brain is a beast it is your best friend and your most evil enemy. It is both close and far and again, you. Remember that most chronic pains issues are inside out, not outside in. The brain that learns its symptoms stays there. A brain that controls its way is healthy, learns, sleeps, and is free of situational anxiety and depression. Undertreated and ignored, fibro exists. A person that ignores healthy behaviors and allows the brain to reduce neuronal health, spine formation, and diminish brain derived neurotrophic factor (BDNF). These sick neurons can be seen in many disease states such as heart disease, diabetes, obesity, Alzheimers, and yes, fibro. The brain actually shrinks a bit in a disease state. BDNF rises when symptoms are controlled. Depression and anxiety improve, as does sleep and learning (memory). So pick the modifiable features in healthcare that you can control. Avoid alcohol and quit smoking. Exercise raises BDNF, eat right, condition, lose weight. This is the fibro you control. Simple common sense. It's not a drug, or a whimsical treatment, and not a cure. There is no cure, but we can get better. Keep it simple. When you commit to this inside out strategy and not outside in, you will improve. Quit obsessing about "knots" you feel, the "swelling", surface anatomy is not important. Believing that fibro is inside out eliminates complex treatment algorithms. Trying to massage otherwise perfectly normal muscles is a flawed concept devoid of science. Most agree a massage feels good for a while, but the return pain is worse. That's the outside in approach and aggravating a peripheral manifestation of a central nervous system problem. This nociceptor or "trigger point" is centrally mediated and is responding to an agitation. Quit trigger point injections as well. Avoid steroids unless absolutely necessary (per a qualified provider). Muscle relaxers are useless. Keep it simple, stay focused, and you will win. Socialize with health focused (read not neurotic self-focused obsessors). You are the average of the five people you hang with. Love the ones you should love, and say it often, in words and otherwise. Keep your brain healthy and you will be rewarded.