Diabetes neuropathy

Used in treatment of diabetic neuropathy and retinopathy ponalrestat [72702-95-5] C2yH22BrFN202... 

Tolrestat (28) is a long-acang aldose reductase inhibitor useful in the prophylaxis of diabetic neuropathy, retinopathy, and cataracts [24 25] Lastly, the intro-ducuon of fluorine into steroids probably ushered in the modem era of fluonnated drugs Many commercial products were introduced [2] Typical of the products are the anti inflammatory glucocorticoids dexamethasone (29 X = F, Y = H), para-methasone (29, X = H, Y = F), and flumethasone (29, X = H, Y = F)... 

In diabetic rats, TRPVl is enhanced on myelinated fibres and is hyperphos-phorylated by PKC [127]. In accordance with these findings, anti-TRPVl antiserum was shown to ameliorate pain in a murine model of diabetic neuropathy [128]. In humans, the density of TRPVl-positive nerve fibres is increased in women with chronic breast pain [129] and with vulvodynia [19]. Disruption of TRPV 1 gene causes attenuation of bone cancer pain in mice [130]. Pharmacological blockade of TRPVl by agonists relieved pain in AIDS patients [131]. 

Owing to the lag time between initiation and effect, capsaicin is not used for treatment of acute pain from injury. Instead, topical capsaicin is used for chronic pain from musculoskeletal and neuropathic disorders. Capsaicin preparations have been studied in the treatment of pain from diabetic neuropathy, osteoarthritis, rheumatoid arthritis, postherpetic neuralgia, and other disorders.48 It is often used as an adjuvant to systemic analgesics in these chronic pain conditions. 

Other diseases with disruptions in neurofilament organization include diabetic neuropathy and Charcot-Marie-Tooth disease. For these diseases, the disruption of neuro filaments may be a secondary effect as in the case of trembler axons or a direct effect. For example, some forms of Charcot-Marie-Tooth peripheral neuropathy result from mutations in a neurofilament subunit [22, 43]. In most cases, neuronal degeneration is an eventual consequence, but neuronal function may be impaired prior to substantial loss of neurons. Generally, disruptions of neurofilaments have the most severe consequences in large motor neurons, which is consistent with the fact that the largest neurons have the highest levels of neurofilament expression. 

Calcutt, N. A., Allendoerfer, K. L., Mizisin, A. P. et al. Therapeutic efficacy of sonic hedgehog protein in experimental diabetic neuropathy. /. Clin. Invest. Ill 507-514,2003. 

Said, G., Lacroix, C., Lozeron, P., Ropert, A., Plante, V. and Adams, D. Inflammatory vasculopathy in multifocal diabetic neuropathy. Brain 126 376-385, 2003. 

Neuropathic and functional pain is often described in terms of chronic pain. Neuropathic pain (e.g., postherpetic neuralgia, diabetic neuropathy) is a result of nerve damage, but functional pain (e.g., fibromyalgia, irritable bowel syndrome, tension-type headache) refers to abnormal operation of the nervous system. Pain circuits may rewire themselves and produce spontaneous nerve stimulation. 

Duloxetine, a dual inhibitor of serotonin and norepinephrine reuptake indicated for depression and painful diabetic neuropathy, is expected to become first-line therapy for SUI. Duloxetine is thought to facilitate the bladder-to-sympathetic reflex pathway, increasing urethral and external urethral sphincter muscle tone during the storage phase. 

In addition to treating MDD [51-53], duloxetine was approved as the first agent for the treatment of painful diabetic neuropathy in the U.S. [54-56]. It also has been used for stress urinary incontinence in women in Europe [57,58]. In 2007, duloxetine was approved for the treatment of generalized anxiety disorder in the U.S. 

The recent approval of the SNRI duloxetine for the treatment of diabetic neuropathy reinforces the utility of this drug class in the treatment of neuropathic pain. Other largely untapped areas which remain to be exploited with this drug class include sexual dysfunction, such as premature ejaculation, irritable bowel syndrome, obesity, neurodegenerative diseases such as Parkinson s disease, restless leg syndrome, and substance abuse and addiction. It is apparent that considerable opportunities for drug discovery will exist in this area for some time to come. 

Neuroanatomically both the locus coeruleus and the raphe nuclei project to the spinal cord where they gate sensory pathways from the skeletomuscular areas. As there is evidence that both noradrenaline and 5-HT are dysfunctional in depression, it is perhaps not surprising to find that the pain threshold is often reduced in patients with depression. Conversely, different types of antidepressants have been shown to have an antinociceptive effect in both rodent models of neuropathic pain, and clinically in fibromyalgia, chronic fatigue syndrome, postherpetic neuralgia and diabetic neuropathy. In general, it would appear that the dual action antidepressants (such as the TCAs and SNRIs) are more effective than the SSRIs. 

Temporary relief of pain from rheumatoid arthritis, osteoarthritis, and relief of neuralgias such as the pain following shingles (herpes zoster) or painful diabetic neuropathy. 

Another complication of diabetes is the loss of peripheral neuronal function. It has recently been shown that camosine and its zinc complex can ameliorated progressive diabetic neuropathy in mice (Kamel et al.,... 

K /Na exchange in distal tubule Dose Adults. 5-10 mg PO daily Peds. 0.625 mg/kg/d X in renal impair Caution [B, ] Contra T K, SCr >1.5 mg/dL, BUN >30 mg/dL, diabetic neuropathy Disp Tabs SE T K HA, dizziness, dehydration, impotence Interactions T Risk of hyperkalemia W/ ACEI, K-sparing diuretics, NSAIDs, K salt substitutes T effects OF Li, digoxin, antihypertensives, amantadine T risk of hypokalemia W/ licorice EMS Monitor ECG for signs of hyperkalemia (peaked T waves) T effects of digoxin OD May cause bradycardia, light-headedness, and syncope symptomatic and supportive... 

Antiepileptic drugs as a class have been widely smdied and prescribed for the relief of acute and chronic pain. In general, there is the greatest support for the efficacy of antiepileptics in the treatment of trigeminal neuralgia and diabetic neuropathy and for migraine prophylaxis. 

Unlabeled Uses Relief of neuropathic pain, such as that experienced by patients with diabetic neuropathy or postherpetic neuralgia treatment of anxiety, bulimia nervosa, migraine, nocturnal enuresis, panic disorder, peptic ulcer, phantom limb pain... 

Trigeminal neuralgia, diabetic neuropathy PO Initially 100 mg 1-2 times a day. May increase by 100 mg/day at weekly intervals. Usual dose 400-1000 mg/day. 

Unlabeled Uses Treatment of alcohol abuse, dementia, diabetic neuropathy, obsessive-compulsive disorder, panic disorder, smoking cessation... 

Geriatric Considerations - Summary Compared to placebo, duloxetine is effective for the treatent of depression and painful diabetic neuropathy Few head-to-head studies are available comparing duloxetine to other agents in the treatment of depression or painful neuropathy. Because this agent may increase urethral sphincter activity, it is now being assessed as an agent for the treatment of stress urinary incontinence. This same property may increase the risk of urinary retention, although this has not been well documented. Duloxetine has not been well studied with respect to falls. 

Goldstein DJ, Lu Y, Detke MJ, et al. Duloxetine vs. placebo in patients with painful diabetic neuropathy. Pain 2005 16 109-118. 

Neuropathy Amitriptyline 0.1 mg/kg/day 1-2 h before bedtime. Titrate to 0.5-2 mg/kg/day over 2-3 weeks Diabetic neuropathy Shannon and Berde, 1989 (G)... 

Diabetic neuropathy Oral administration of methylcobalamin (500 meg three times daily for four months) resulted in subjective improvement in burning sensation, numbness, loss of sensation and muscle cramps. 

Mexiletine has also shown significant efficacy in relieving chronic pain, especially pain due to diabetic neuropathy and nerve injury. The usual dosage is 450-750 mg/d orally. This application is off label. 

Bujalska M, Tatarkiewicz J, Gumulka SW Effect of bradykinin receptor antagonists on vincristine- and streptozotocin-induced hyperalgesia in a rat model of chemotherapy-induced and diabetic neuropathy. Pharmacology 2008 81 158. [PMID 17989505]... 

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