Mechanisms by Which Pharmacologic Agents May Contribute to Fatigue, and Drug-induced change in transmitter identity is a shared mechanism

[Sly Saint]

I'm sure there is a lot more research out there on how different meds cause 'fatigue'.

Has anyone looked at any of these mechanisms to see if they are evident in ME patients?
ie caused by ME, not by any particular medication. or if any of the mechanisms might be applied to the concept of PEM, either as a possible immediate or cumulative trigger.


Abstract
Fatigue is a common side effect of medications. This review summarizes some of the mechanisms by which drugs may cause fatigue. One major mechanism by which medications can cause fatigue is by central nervous system (CNS) depression. CNS depression can result from decreased excitatory activity, as is commonly seen with some anticholinergic agents, centrally acting α-agonists, and anticonvulsants. CNS depression can also result from increased inhibitory activity within the CNS, as is seen with benzodiazepines and barbiturates, which augment the effects of the inhibitory neurotransmitter, gamma-aminobutyric acid. Opioids also increase inhibitory CNS activity through their interactions with the various subtypes of opioid receptors. Acting outside of the CNS, medications may cause fatigue as a result of either a true or a functional anemia by a number of mechanisms. Bone marrow toxicity, which results in decreased hematopoiesis, is such a mechanism. This is commonly seen with antineoplastics agents, but can also be observed in association with a wide variety of medication classes, including anticonvulsants, antidepressants, and antimicrobial agents. Another way that medications can cause anemia is by increased red blood cell destruction, as is seen with immune hemolytic anemia. Additionally, medications may cause a functional anemia through alteration of the heme group within the hemoglobin molecule, as is seen in methemoglobinemia. Finally, many drugs, including placebos, cause fatigue by unknown mechanisms. In addition to causing fatigue, some medications may be used to help relieve fatigue, although this drug class is limited in number at this point in time.

Mechanisms by Which Pharmacologic Agents May Contribute to Fatigue - ScienceDirect

I'm sure there is a lot more research out there on how different meds cause 'fatigue'.

Has anyone looked at any of these mechanisms to see if they are evident in ME patients?
ie caused by ME, not by any particular medication. or if any of the mechanisms might be applied to the concept of PEM, either as a possible immediate or cumulative trigger.

similarly for cognitive problems
Drug-induced change in transmitter identity is a shared mechanism generating cognitive deficits

Brain impairments are often characterized by constellations of symptoms and behavioral alterations, some of which are shared across disorders. Cognitive deficits are found in mood and neuropsychiatric disorders such as drug misuse, schizophrenia and depression, raising the possibility that shared mechanisms could produce the same impairments in response to different stimuli. While studies have focused on the actions of single drugs, less attention has been given to investigating the mechanisms of action that different drugs of abuse have in common. We investigated the effect of sub-chronic treatment with phencyclidine (PCP) or methamphetamine (METH), two drugs belonging to different classes of chemicals. PCP affects glutamatergic transmission by acting as an NMDA antagonist1, while METH affects signaling by dopamine and other monoamines2. Although differing in their molecular targets in the brain and in some behavioral effects3,4,5,6, PCP and METH have been extensively studied for their ability to cause long-lasting cognitive deficits and mimic symptoms of schizophrenia7,8,9. However, the process by which they generate similar behavioral impairments has been unknown. Understanding shared neuronal mechanisms underlying drug-induced cognitive deficits could foster development of effective treatments and be beneficial for a spectrum of disorders10,11.

Drug-induced change in transmitter identity is a shared mechanism generating cognitive deficits | Nature Communications

eta:
an article on this paper
Neuroscientists identify a reversible biological mechanism behind drug-induced cognitive deficits

Researchers from the University of California, San Diego, have identified a shared mechanism in the brain that explains how different drugs, such as methamphetamine and PCP (commonly known as “angel dust”), result in similar cognitive impairments, including memory loss. The study, published in Nature Communications, reveals that these drugs cause neurons in the medial prefrontal cortex to alter the way they communicate through a process called neurotransmitter switching.

Neuroscientists identify a reversible biological mechanism behind drug-induced cognitive deficits

 

[Creekside]

I expect there are "fatigue"-causing mechanisms in addition to the ones known to be caused by pharmaceuticals. There are probably others that are still undiscovered. On top of that, "fatigue" is so undefined that we don't know which type of "fatigue" is being considered in a given study and what that might have to do with "fatigue" in a different study.

 

[Snow Leopard]

Has anyone looked at any of these mechanisms to see if they are evident in ME patients?

I spent years, looking at all sorts of possibilities. The problem is that it is too non-specific, numerous metabolic disruptions can increase fatigue.

I took a special interest in post-cancer fatigue since that can persist even after the medication ceases. I was trying to look at common receptors.

But the truth is that the side-effect symptoms are not characterised well enough in studies - it is hard to say what the actual impact is and the severity, whether it causes cognitive fatigue as well, or something like PEM.