Thursday, October 3, 2013

PossibleTramadol Connection to Myasthenia Gravis by Increasing Norepinephrine?

By George Barron
In my search to discover what may have happened that caused my immune system to against my body, I investigated the medications that I was taking before the onset of Myasthenia Gravis. One of those drugs was particularily interesting to me -Tramadol. It had been part of my daily intake for about four years before I developed MG in my early 60's. I have a strong suspicion that it contributed to my MG by pushing my adrenal system over the edge with it's norepinephrine-re-uptake action.

It is no secret that several drugs have been associated with either the
onset or the exacerbation of myasthenia gravis. Tramadol has many unique properties, two of which might be a reason to add it to the list of culprits: It's affects on nicotinic acetylcholine receptors and the pushing of the adrenal glands by increasing the availability of norepinephrine. My thinking is that the use of Tramadol alone may not necessarily lead to myasthenia gravis but when its use is combined with other factors - such as a high stress environment - it could be a contributor. Ironically Tramadol, prescribed for pain, is also used (off label) to help relive stress by mood enhancement as does specific norepinephrine-re-uptake inhibitor medications do. That being the case, and if there is some truth to my little theory, there would be a host of other drugs that may have the same effect on the adrenal glands.

For the few that may be interested, the following notes were taken from a physical fitness blog during a discussing Tramadol and its effects during and after a workout. Apparently the person posting the information did a little homework. And here's a link to a study that may also be of interest:

Tramadol has several effects and several ramifications of its effects.

Tramadol is a serotonin-reuptake inhibitor - increasing serotonin levels

Tramadol is a norepinephrine-reuptake inhibitor - increasing norepinephrine levels

Tramadol is a partial opiate-receptor agonist - acting partially like opiates (e.g. morphine, Vicodin). It can possibly be addicting to heroin abusers.

Tramadol has possibly an antiinflammatory agent by reducing inflammatory cytokine production (a common antidepressant mechanism of action - which is not commonly known).

Increasing Serotonin helps block the perception of stress. It has a calming effect on mood.

Increasing Norepinephrine drives the adrenal glands harder so that one does not feel so exhausted after the stress of working out. It has an uplifting effect on mood - so long as the adrenal glands are not fatigued.

Activity at the opioid receptor reduces pain - though generally it doesn't have a euphoric component like other opiate agonists. But reduction of pain may have helped give one a better sensation of well-being by masking the damage done during a work-out. Opiate agonists can in some people reduce adrenal function - which can worsen one's sense of well-being

The combination of Serotonin and Norepinephrine increases can increase one's tolerance of pain - reducing the perception of pain.

Increasing Serotonin and Norepinephrine (with Norepinephrine doing its primary work through driving adrenal function) may also reduce inflammatory cytokines which are released by the brain in response to stress (such as of a workout or other stress). The inflammatory cytokines would have slowed down recovery from a workout or illness - impairing one's immune system and healing. Thus Tramadol may have an antiinflammatory effect.

Tramadol's effects can wear out over time because it is dependent on good adrenal function.

The increase in norepinephrine resulting from Tramadol works the adrenal glands harder.

Norepinephrine is the primary signal for stress in the brain.

Over time, the higher chronic levels of norepinephrine can cause adrenal fatigue.

Workouts are a stress to the neuroendocrine and immune systems of the body - of which the adrenal glands are one of the most important organs.

The adrenal glands need to recover from a workout just as the muscles have to recover from a workout.

Muscles may recover in 1 week. But the adrenal glands may take much longer to fully recover - depending on the workload and stress they had to handle.

Progressively more intense workouts stress the adrenal glands out.

If one is masking oneself from the stress of a workout by taking Tramadol, then one may not realize that one has not fully recovered their adrenal glands from the workout because of the sense of well-being that Tramadol gives one.

As the adrenal glands fatigue, Tramadol becomes less effective a medication. The weakened adrenal glands do not respond as well to the higher norepinephrine levels that the stress of workouts and Tramadol create.

One then develops the return of fatigue and lack of motivation - as well as other problems associated with adrenal fatigue if the depletion of adrenal function is severe enough.

There is no single substance that can substitute for Tramadol. It is a unique medication.

It is most like Effexor - if one removes the opiate-agonist property of Tramadol.

However, the limiting factor in both medications is the increase in norepinephrine level as one mechanism of action.

Increasing norepinephrine - a stimulant effect - is a double-edged sword. It may keep one alert, more focused, drive the adrenals to at least temporarily drive adrenal function to a higher level - which then can improve mood and reduce stress levels.

Initially the adrenal glands may respond by increasing in size and productive capacity - generating the good sense of well-being (if they become excessively large, one can become psychotic or manic or agitated).

But over time, the adrenal glands can become depleted or fatigued when driven constantly to high levels of activity - rather than being used intermittently, particularly when there is no adequate period of rest for recovery.

In bodybuilding, one of the most important factors for growth is adequate rest to build muscle. The recovery of adrenal glands are an important component of that rest period.

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