Treatment of conditions through pharmacological modulation of the autonomic nervous system

Abstract

Methods are provided for treating a subject for a condition caused by an abnormality in the subject's autonomic nervous system. In accordance with the subject methods, at least a portion of a subject's autonomic nervous system is pharmacologically modulated with at least one beta-blocker in a manner that is effective to treat the subject for the condition. The subject methods find use in the treatment of a variety of different conditions, where such conditions include various disease conditions. Also provided are systems and kits for use in practicing the subject methods.

1 . A method of treating a subject for a condition caused by an autonomic nervous system abnormality comprising modulating at least a portion of said subject's autonomic nervous system by administering an effective amount of at least one beta-blocker to said subject to treat said subject for at least one of: neurodegenerative conditions; neuroinflammatory conditions; orthopedic inflammatory conditions; lymphoproliferative conditions; autoimmune conditions; inflammatory conditions; infectious diseases, pulmonary conditions; transplant-related conditions, gastrointestinal conditions; endocrine conditions; genitourinary conditions selected from the group of renal failure, hyperreninemia, hepatorenal syndrome and pulmonary renal syndrome; aging associated conditions; neurologic conditions; Th-2 dominant conditions; conditions that cause hypoxia; conditions that cause hypercarbia; conditions that cause hypercapnia; conditions that cause acidosis; conditions that cause academia, pediatric-related conditions; OB-GYN conditions, sudden death syndromes, fibrosis; post-operative recovery conditions; post-procedural recovery conditions; chronic pain; disorders of thermoregulation, cyclic vomiting syndrome and trauma.  
     
     
         2 . The method according to  claim 1 , wherein said modulation results in a sympathetic bias in at least a portion of said autonomic nervous system.  
     
     
         3 . The method of  claim 2 , wherein said abnormality is characterized by a sympathetic bias.  
     
     
         4 . The method of  claim 2 , wherein said abnormality is characterized by a parasympathetic bias.  
     
     
         5 . The method according to  claim 1 , wherein said modulation results in a parasympathetic bias in at least a portion of said autonomic nervous system.  
     
     
         6 . The method of  claim 5 , wherein said abnormality is characterized by a sympathetic bias.  
     
     
         7 . The method of  claim 5 , wherein said abnormality is characterized by a parasympathetic bias.  
     
     
         8 . The method according to  claim 1 , wherein said modulating results in a substantially equal parasympathetic and sympathetic functions in at least a portion of said autonomic nervous system.  
     
     
         9 . The method of  claim 8 , wherein said abnormality is characterized by a sympathetic bias.  
     
     
         10 . The method of  claim 8 , wherein said abnormality is characterized by a parasympathetic bias.  
     
     
         11 . The method of  claim 1 , wherein said abnormality is characterized by an abnormally high parasympathetic activity.  
     
     
         12 . The method of  claim 11 , wherein said abnormality is characterized by an abnormally low sympathetic activity.  
     
     
         13 . The method of  claim 11 , wherein said abnormality is characterized by normal sympathetic activity.  
     
     
         14 . The method of  claim 11 , wherein said abnormality is characterized by an abnormally high sympathetic activity.  
     
     
         15 . The method of  claim 11 , further comprising decreasing said abnormally high parasympathetic activity.  
     
     
         16 . The method of  claim 1 , wherein said abnormality comprises an abnormally low parasympathetic activity.  
     
     
         17 . The method of  claim 16 , wherein said abnormality comprises an abnormally low sympathetic activity.  
     
     
         18 . The method of  claim 16 , wherein said abnormality comprises normal sympathetic activity.  
     
     
         19 . The method of  claim 16 , wherein said abnormality comprises an abnormally high sympathetic activity.  
     
     
         20 . The method of  claim 10 , further comprising increasing said parasympathetic activity.  
     
     
         21 . The method of  claim 1 , wherein said at least one beta-blocker is chosen from atenolol, betaxolol, bisoprolol, carvedilol, esmolol, labetalol, metoprolol, nadolol, pindolol, propranolol, sotalol, timolol, acebutalol, oxprenolol, carvedilol, and entbutolol.  
     
     
         22 . The method of  claim 1 , wherein said method comprises increasing the parasympathetic activity/sympathetic activity ratio in at least a portion of said subject's autonomic nervous system.  
     
     
         23 . The method of  claim 1 , further comprising administering an effective amount of at least one non-beta-blocker agent.  
     
     
         24 . The method of  claim 23 , wherein said at least one non-beta-blocker agent is chosen from aldosterone antagonists; angiotensin II receptor blockades; angiotensin converting enzyme inhibitors; statins; triglycerides lowering drugs; niacin; anti-diabetes agents; immunomodulators; nicotine; sympathomimetics; cholinergics; acetylcholinesterase inhibitors; magnesium and magnesium sulfates, calcium channel blockers; muscarinics; sodium channel blockers; glucocorticoid receptor blockers; peripheral andrenergic inhibitors; blood vessel dilators; central agonists; combined alpha and beta-blockers; alpha blockers; combination diuretics; potassium sparing diuretics; nitrates; cyclic nucleotide monophosphodiesterase inhibitors; alcohols; catecholamines inhibitors; analgesics; neurotoxins; vasopressin inhibitors; oxytocin inhibitors; alcohol; relaxin hormone; renin inhibitors; estrogen; estrogen analogues; estrogen metabolites; progesterone inhibitors; testosterone inhibitors; gonadotropin-releasing hormone analogues; gonadotropin-releasing hormone inhibitors; vesicular monoamine transport inhibitors; dipeptidyl peptidase IV inhibitors; antihistamines and melatonin.  
     
     
         25 . The method of  claim 23 , wherein said at least one beta-blocker and at least one non-beta-blocker are concomitantly administered in unit dosage form.  
     
     
         26 . The method of  claim 1 , further comprising stimulating at least a portion of said subject's autonomic nervous system.  
     
     
         27 . The method of  claim 26 , wherein said stimulating comprises contacting at least a portion of said subject's autonomic nervous system with at least one electrode and applying electrical energy to at least a portion of said subject's autonomic nervous system.  
     
     
         28 . The method of  claim 1  wherein said at least one beta-blocker is administered orally at least once a day to said subject.  
     
     
         29 . The method of  claim 1 , wherein said condition is a neurodegenerative condition chosen from the group of: Alzheimer's disease, Pick's disease, dementia, delirium and amyotrophic lateral sclerosis.  
     
     
         30 . The method of  claim 1 , wherein said condition is a neuroinflammatory condition chosen from the group of: viral meningitis, viral encephalitis, fungal meningitis, fungal encephalitis, multiple sclerosis, charcot joint and myasthenia gravis.  
     
     
         31 . The method of  claim 1 , wherein said condition is an orthopedic inflammatory condition chosen from the group of: osteoarthritis, inflammatory arthritis, regional idiopathic osteoporosis, reflex sympathetic dystrophy, Paget's disease and osteoporosis.  
     
     
         32 . The method of  claim 1 , wherein said condition is a lymphoproliferative condition chosen from the group of: lymphoma, lymphoproliferative disease, Hodgkin's disease and inflammatory pseudomotor of the liver.  
     
     
         33 . The method of  claim 1 , wherein said condition is an autoimmune condition chosen from the group of: Graves disease, hashimoto's, takayasu's disease, kawasaki's diseases, arteritis, scleroderma, CREST syndrome, allergies, dermatitis, Henoch-schlonlein purpura, goodpasture syndrome, autoimmune thyroiditis, myasthenia gravis, Reiter's disease, raynaud's, and lupus.  
     
     
         34 . The method of  claim 1 , wherein said condition is an inflammatory condition chosen from the group of: acute respiratory distress syndrome, multiple sclerosis, juvenile rheumatoid arthritis, juvenile chronic arthritis and rheumatoid arthritis.  
     
     
         35 . The method of  claim 1 , wherein said condition is an infectious disease chosen from the group: sepsis, viral and fungal infections, diseases of wound healing, wound healing, tuberculosis, infection, acquired immune deficiency syndrome and human immunodeficiency virus.  
     
     
         36 . The method of  claim 1 , wherein said condition is a pulmonary condition chosen from the group of: tachypnea, fibrotic lung diseases such as cystic fibrosis and the like, interstitial lung disease, desquamative interstitial pneumonitis, non-specific interstitial pneumonitis, lymphocytic interstitial pneumonitis, usual interstitial pneumonitis, idiopathic pulmonary fibrosis, pulmonary edema, aspiration, asphyxiation, pneumothorax, right-to-left shunts, left-to-right shunts and respiratory failure.  
     
     
         37 . The method of  claim 1 , wherein said condition is a transplant-related condition chosen from the group of: transplant rejection, transplant-related tachycardia, transplant related renal failure, transplant related bowel dysmotility and transplant-related hyperreninemia.  
     
     
         38 . The method of  claim 1 , wherein said condition is a gastrointestinal condition chosen from the group of: hepatitis, xerostomia, bowel mobility, peptic ulcer disease, constipation, ileus, irritable bowel syndrome, post-operative bowel dysmotility, inflammatory bowel disease and typhilitis.  
     
     
         39 . The method of  claim 1 , wherein said condition is an endocrine condition chosen from the group of: hypothyroidism, hyperglycemia, diabetes, obesity, syndrome X, insulin resistance and polycycstic ovarian syndrome.  
     
     
         40 . The method of  claim 1 , wherein said condition is a skin condition chosen from the group of: wrinkles, cutaneous vasculitis and psoriasis.  
     
     
         41 . The method of  claim 1 , wherein said condition is an aging associated condition chosen from the group of: shy dragers, multi-system atrophy, age related inflammation conditions, and cancer.  
     
     
         42 . The method of  claim 1 , wherein said condition is a neurologic condition chosen from the group of: epilepsy, seizures, stroke, insomnia, cerebral vascular accident, transient ischemic attacks, stress, bipolar disorder, concussions, post-concussive syndrome, cerebral vascular vasospasm, depression, schizophrenia, central sleep apnea and obstructive sleep apnea.  
     
     
         43 . The method of  claim 1 , wherein said condition is aTh-2 dominant condition chosen from the group of: typhilitis, osteoporosis, lymphoma, myasthenia gravis and lupus.  
     
     
         44 . The method of  claim 1 , wherein said condition is a condition that causes at least one of: hypoxia, hypercarbia, hypercapnia, acidosis and acidemia.  
     
     
         45 . The method of  claim 44 , wherein said conditions is chosen from the group of: acute pulmonary embolism, sudden infant death syndrome, sudden adult death syndrome, chronic pulmonary embolism, pleural effusion, cardiogenic pulmonary edema, non-cardiogenic pulmonary edema, acute respiratory distress syndrome, neurogenic edema, hypercapnia, academia, renal tubular acidosis and lung diseases that cause acidosis.  
     
     
         46 . The method of  claim 1 , wherein said condition is a pediatric-related condition chosen from the group of: respiratory distress syndrome, sudden infant death syndrome, hirschsprung disease, bronchopulmonary dysplasia, congenital megacolon and aganglionosis.  
     
     
         47 . The method of  claim 1 , wherein said condition is an OB-GYN condition chosen from the group of: amniotic fluid embolism, pregnancy-related arrhythmias, fetal stress syndrome, fetal hypoxia, menopausal mood disorders, premenstrual mood disorders, and amniotic fluid embolism.  
     
     
         48 . The method of  claim 1 , wherein said condition is a sudden death syndrome chosen from the group of: sudden infant death syndrome and sudden adult death syndrome.  
     
     
         49 . The method of  claim 1 , wherein said condition is fibrosis.  
     
     
         50 . The method of  claim 1 , wherein said condition is a post-operative recovery condition chosen from the group of: post-operative pain, post operative ileus, post-operative fever and post-operative nausea.  
     
     
         51 . The method of  claim 1 , wherein said condition is a post-procedural recovery condition chosen from the group of: post-procedural pain, post procedural ileus, post-procedural fever and post-procedural nausea.  
     
     
         52 . The method of  claim 1 , wherein said condition is chronic pain.  
     
     
         53 . The method of  claim 1 , wherein said condition is trauma.  
     
     
         54 . The method of  claim 1 , wherein said condition is a disorder of thermoregulation.  
     
     
         55 . The method of  claim 1 , wherein said condition is cyclic vomiting syndrome.  
     
     
         56 . An algorithm for administering said at least one beta-blocker to said subject in accordance with method of  claim 1  recorded on a computer-readable medium.  
     
     
         57 . A system comprising: 
 (a) an algorithm for administering said at least one beta-blocker to said subject in accordance with method of  claim 1  recorded on a computer-readable medium    (b) a pharmaceutically effective amount of at least one beta-blocker, and    (c) a drug delivery device.    
     
     
         58 . The system of  claim 57 , wherein said at least one beta-blocker is chosen from atenolol, betaxolol, bisoprolol, carvedilol, esmolol, labetalol, metoprolol, nadolol, pindolol, propranolol, sotalol, timolol, acebutalol, oxprenolol, carvedilol, and entbutolol.  
     
     
         59 . The system of  claim 57 , wherein said drug delivery device is an implantable drug delivery device.  
     
     
         60 . The system of  claim 57 , further comprising a pharmaceutically acceptable amount of at least one non-beta-blocker agent.  
     
     
         61 . A kit comprising: 
 (a) a pharmaceutically effective amount of at least one beta-blocker; and    (b) instructions for practicing the method of  claim 1.