Document Detail

Paradoxical strategy for treating chronic diseases where the therapeutic effect is derived from compensatory response rather than drug effect.
MedLine Citation:
PMID:  15780510     Owner:  NLM     Status:  MEDLINE    
Reversing chronic conditions remains an elusive goal of medicine. The modern medical paradigm based on blocking overactive pathways or augmenting deficient pathways offers symptomatic benefit, but tolerance to therapy can develop and treatment cessation can produce rebound symptoms due to compensatory mechanisms. We propose a paradoxical strategy for treating chronic conditions based on harnessing compensatory mechanisms for therapeutic benefit. Many current drugs may be repurposed for a paradoxical indication where the therapeutic effect is derived from compensatory response, rather than drug effect. For example, although exercise is associated with acute adrenergia, paradoxical downregulation of baseline sympathovagal ratio occurs as a remodeling response. For conditions that manifest chronic sympathetic bias such as cardiovascular diseases, judicious administration of adrenergic agonists may induce compensatory downregulation of baseline sympathovagal ratio. The concept may generalize to many other diseases, especially those involving pathways which exhibit strong homeostatic tendencies such as the neurologic, immune, and endocrine systems. Careful consideration of chronobiologic features is necessary to optimize dosing strategies for modulating compensatory responses, and eccentric dosing schedules, shorter-acting formulations, or pulsatile delivery may be desirable in some cases. To what extent the effect of desensitization to current therapy is mistaken for disease progression in conditions such as diabetes, myopia, depression, and hypertension warrants investigation. The merits of combining behavioral and drug therapies such as diet-insulin therapy for diabetes and exercise-beta-blockade for cardiovascular disease should be revisited since there is a risk for exacerbating the underlying dysfunction. The reduced dynamic range of various environmental experiences and the tendency to revert to the mean through medical intervention, thermoregulation, and other modern lifestyle changes may play under-recognized roles in human diseases. Perhaps alternating agonists and antagonist may exercise the entire dynamic range of pathways and improve health.
Anthony J Yun; Patrick Y Lee; Kimberly A Bazar
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Medical hypotheses     Volume:  64     ISSN:  0306-9877     ISO Abbreviation:  Med. Hypotheses     Publication Date:  2005  
Date Detail:
Created Date:  2005-03-22     Completed Date:  2005-07-28     Revised Date:  2006-01-04    
Medline Journal Info:
Nlm Unique ID:  7505668     Medline TA:  Med Hypotheses     Country:  Scotland    
Other Details:
Languages:  eng     Pagination:  1050-9     Citation Subset:  IM    
Department of Radiology, Stanford University, 470 University Avenue, Palo Alto, CA 94301, USA.
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MeSH Terms
Adrenergic Agonists / therapeutic use
Chronic Disease / drug therapy*
Reg. No./Substance:
0/Adrenergic Agonists
Comment In:
Homeopathy. 2005 Oct;94(4):265-6   [PMID:  16226210 ]

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