Pharmacotherapy of autonomic failure - after meals - postprandial

[aspergerian13]

An excellent review:

Pharmacotherapy of autonomic failure.

Cyndya Shibao, Luis Okamoto, and Italo Biaggioni.

Pharmacol Ther. 2012 Jun; 134(3): 279–286.

ncbi.nlm.nih.gov/pmc/articl...

The clinical picture of autonomic failure is characterized by severe and disabling orthostatic hypotension. These disorders can develop as a result of damage of central neural pathways or peripheral autonomic nerves, caused either by a primary autonomic neurodegenerative disorder or secondary to systemic illness.

Treatment should be focused on decreasing presyncopal symptoms instead of achieving blood pressure goals.

Non-pharmacologic strategies such as physical counter-maneuvers, dietary changes (i.e. high salt diet, rapid water drinking or compression garments) are the first line therapy.

Affected patients should be screened for co-morbid conditions such as post-prandial hypotension and supine hypertension that can worsen orthostatic hypotension if not treated.

If symptoms are not controlled with these conservative measures the next step is to start pharmacological agents; these interventions should be aimed at increasing intravascular volume either by promoting water and salt retention (fludrocortisone) or by increasing red blood cell mass when anemia is present (recombinant erythropoietin).

When pressor agents are needed, direct pressor agents (midodrine) or agents that potentiate sympathetic activity (atomoxetine, yohimbine, pyridostigmine) can be used. It is preferable to use short-acting pressor agents that can be taken on as needed basis in preparation for upright activities.

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[Comment] Physicians, nurses, and PWPs ought no longer pretend tha PD is only or even primarily about Substantia nigra and dopamine.]

[Rhyothemis]

Erythropoietin is interesting - it has been used to treat orthostatic hypotension in MSA patients. Patients with autonomic nervous system disorders are often anemic and it is thought that the autonomic nervous system is involved in regulation of erythropoiesis . Red blood cells regulate blood flow to tissues through binding of nitric oxide to hemoglobin.

Since glycine is required for heme synthesis, I expect that EPO also increases expression of glycine transporters. Patients with MSA have increased levels of glycine in the CSF and I think that is probably due to lower glycine transporter function such that glycine accumulates in the CSF since it cannot be transported into cells and utilized. If that is the case, then EPO may help MSA patients with excess glycine levels in CSF. Excess glycine can lead to excitotoxicity and increased neurodegeneration and perhaps is a factor in disease progression in MSA. Lots of speculation and I hope someday these ideas will be investigated.

Treatment with recombinant EPO is not without risks; 'aggressive use' is associated with increased rates of cardiovascular morbidity and mortality. Subcutaneous injection is associated with a lower risk of developing hypertension than IV administration.

Someday I hope to write a blog pots on this and include references.

[aspergerian13 in reply to Rhyothemis]

A grand speculation. My hunch: a much needed synthesis.