Issue No. 4
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July 2013
Diabetic neuropathies Update on definitions, diagnostic criteria, estimation of severity, and treatments
Source: Tesfaye S, Boulton AJM, Dyck PJ, et al. Diabetic neuropathies: update on definitions, diagnostic criteria, estimation of severity, and treatments. Diabetes Care 2010;33:22852293.
"Treatment of painful DPN almost exclusively consists of symptomatic therapies, which improve the symptoms without affecting underlying causes or natural history"
"An abnormality of nerve conduction tests, which is frequently subclinical, appears to be the first objective quantitative indication of diabetic sensorimotor polyneuropathy"
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Article 1
Issue No. 4
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July 2013
Diabetic sensorimotor polyneuropathy (DSPN) Thought to be the most common variety; this typical DPN is a chronic, symmetrical, length-dependent sensorimotor polyneuropathy attributable to metabolic and microvessel alterations because of chronic hyperglycemia exposure and cardiovascular risk covariates Total hyperglycemic exposure is perhaps the most important risk covariate, and, hence, the variety has been shown to be stabilized, perhaps even improved, by rigorous glycemic control Autonomic dysfunction and neuropathic pain may develop eventually Atypical DPNs Atypical DPNs differ from DSPN in several important features, for instance, onset, course, manifestations, associations, and maybe putative mechanisms. These intercurrent varieties, developing at any time during the course of a patients diabetes, may exhibit be acute, subacute, or chronic onset of symptoms; though the course is usually monophasic or fluctuating over time. The typical features are pain and autonomic symptoms; whilst altered immunity has also been suggested.
Estimating severity
A reliable objective and quantitative measure (i.e., nerve conduction abnormality) is suggested as the minimal criteria for the diagnosis of DSPN The sum scores of various measures of neurologic signs, symptoms, neurophysiologic test abnormalities, or scores of function of activities of daily living may provide an indication of the severity of DSPN.
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Article 1
Issue No. 4
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July 2013
Probable DSPN Presence of a combination of symptoms and signs of neuropathy include any two or more of the following: Neuropathic symptoms; Decreased distal sensation, or ; Clearly decreased or absent ankle reflexes Confirmed DSPN Presence of an abnormality of nerve conduction and a symptom(s) or a sign(s) of neuropathy confirm DSPN. In case nerve conduction is normal, a validated measure of small fiber neuropathy may be used
Painful DPN
Peripheral neuropathic pain in diabetes is defined as pain arising as a direct consequence of abnormalities in the peripheral somatosensory system in patients with diabetes The diagnosis of painful DPN in practice is a clinical one, relying on the patients description of pain Symptoms of painful DPN are distal, symmetrical, often associated with nocturnal exacerbations, and commonly described as prickling, deep aching, sharp, like an electric shock, and burning with hyperalgesia and frequently allodynia upon examination Symptoms are usually associated with the clinical signs of peripheral neuropathy The severity of pain can be reliably assessed by the visual analog scale (VAS), the oldest and best validated measure, or the numerical rating scale, such as, the 11-point Likert scale (0 = no pain, 10 = worst possible pain).
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Article 2
Issue No. 4
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July 2013
Prevalence and characteristics of painful diabetic neuropathy in a large community-based diabetic population
Source: Abbott CA, Malik RA, Van ross ERE, et al. Prevalence and Characteristics of Painful Diabetic Neuropathy in a Large Community-Based Diabetic Population in the U.K. Diabetes Care 2011;34:22202224.
"One-third of all patients with diabetes in the community have painful neuropathic symptomatology, irrespective of whether they have clinical neuropathy"
"Greater neuropathic pain levels are observed in type 2 diabetes, in women, and in people of South Asian origin"
Objective
To assess, in the general diabetic population The prevalence of painful neuropathic symptoms The relationship between symptoms and clinical severity of neuropathy The role of diabetes type, sex, and ethnicity in painful neuropathy.
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Article 2
Issue No. 4
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July 2013
Results
The prevalence of painful symptoms (NSS 5) and PDN (NSS 5 and NDS 3) was 34 and 21%, respectively Painful symptoms were found to occur in 26% of patients without neuropathy (NDS 2) and 60% of patients with severe neuropathy (NDS > 8) Adjusted risk of painful neuropathic symptoms in type 2 diabetes was double that of type 1 diabetes [odds ratio (OR) = 2.1, P < 0.001), which remained unaffected by severity of neuropathy, insulin use, foot deformities, smoking, or alcohol Compared with men, women exhibited 50% increased adjusted risk of painful symptoms (OR = 1.5, P < 0.0001) Interestingly; despite less neuropathy in South Asians (14%) than Europeans (22%) and African Caribbeans (21%) (P < 0.0001), painful symptoms were greater in South Asians (38 vs. 34 vs. 32%, P < 0.0001) In addition, compared with other ethnic groups, South Asians without neuropathy maintained a 50% increased risk of painful neuropathy symptoms (P < 0.0001).
Conclusions
Regardless of the neuropathic deficit, one-third of all community-based diabetic patients have painful neuropathy symptoms The prevalence of PDN was found to be higher in patients with type 2 diabetes, women, and people of South Asian origin The study, accordingly, highlights a significant morbidity attributable to painful neuropathy, identifying key groups for screening for PDN.
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Article 3
Issue No. 4
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July 2013
The KORA F4 Study Older subjects with diabetes and prediabetes are frequently unaware of having distal sensorimotor polyneuropathy
Source: Bongaerts BWC, Rathmann W, Heier M, et al. Older subjects with diabetes and prediabetes are frequently unaware of having distal sensorimotor polyneuropathy. Diabetes Care 2013;36:11411146.
"Adequate attention should be given to professional foot examinations in diabetic foot prevention practice"
"Older subjects with diabetes, and prediabetes, are frequently unaware of their distal sensorimotor polyneuropathy (DSPN) status"
Objective
To assess the prevalence of unawareness of distal sensorimotor polyneuropathy (DSPN), a severe complication of type 2 diabetes, in prediabetes and diabetes in a sample of the older population.
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Article 3
Issue No. 4
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July 2013
Methods
The investigators determined glucose tolerance status amongst 61- to 82-year-old participants of the population-based KORA F4 Study (n = 1100) The presence of bilaterally impaired foot-vibration perception and/or bilaterally impaired foot-pressure sensation was identified to define clinical DSPN Answering no to the question, Has a physician ever told you that you are suffering from nerve damage, neuropathy, polyneuropathy, or diabetic foot?, let DSPN case subjects to be considered unaware of their condition.
Results
Clinical DSPN was found to be prevalent in 154 (14%) participants, 140 (91%) of whom were unaware of their disorder With a prevalence of 23.9%; participants with combined impaired fasting glucose and impaired glucose tolerance had the highest prevalence of DSPN - of these, 10/11 (91%) were unaware of having clinical DSPN Participants with known diabetes exhibited an equally high prevalence of DSPN (22.0%), with 30/39 (77%) DSPN case subjects being unaware of having the disorder Among subjects with known diabetes who reported having had their feet examined by a physician, 18/25 (72%) clinical DSPN case subjects were unaware of having DSPN.
Conclusions
The findings of the study highlights a high prevalence of unawareness of having clinical DSPN among the prediabetic and diabetic groups Besides, an insufficient frequency of professional foot examinations suggests inadequate attention to diabetic foot prevention practice.
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Article 4
Issue No. 4
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July 2013
Lancet 2010
An analysis of the ACCORD randomised trial Effect of intensive treatment of hyperglycemia on microvascular outcomes in type 2 diabetes
Source: Ismail-Beigi F, Craven T, Banerji MA, et al. Effect of intensive treatment of hyperglycaemia on microvascular outcomes in type 2 diabetes: an analysis of the ACCORD randomised trial. Lancet 2010; 376:41930.
"Microvascular benefi ts of intensive therapy should weigh against the increased total and cardiovascular diseaserelated mortality, increased weight gain, and high risk for severe hypoglycaemia"
"Significant reductions in the development of peripheral neuropathy, if further sustained, suggest that intensive glycemia therapy could decrease the risk of ulcers and number of future leg amputation"
Objective
To investigate whether reduction of blood glucose concentration reduces the rate of microvascular complications in patients with type 2 diabetes.
Methods
In the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, a parallel group, randomised trial, patients with diabetes, high HbA1c concentrations (>75%), and cardiovascular disease (CVD) (or 2 cardiovascular risk factors) were randomly assigned to intensive [target hemoglobin A1c (HbA1c) of <60%) or standard (7079%) glycemic therapy
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Article 4
Issue No. 4
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July 2013
In the current analysis, the pre-specified composite outcomes were: dialysis or renal transplantation, high serum creatinine (>2917 mol/L), or retinal photocoagulation or vitrectomy (first composite outcome); or peripheral neuropathy plus the first composite outcome (second composite outcome) In addition, 13 prespecified secondary measures of kidney, eye, and peripheral nerve function were also assessed Both the investigators and participants were aware of treatment group assignment The authors did analysis for all patients who were assessed for microvascular outcomes, based on treatment assignment, regardless of treatments received or therapeutic compliance.
Results
A total of 10251 patients were randomized to the intensive glycemia control group (n=5128) and to the standard group (n=5123). Intensive therapy was stopped earlier than study end due to higher mortality in that group, and patients were transitioned to the standard therapy At this transition, the first composite outcome was recorded in 443/5107 (8.7%) patients in the intensive group vs. 444/5108 (8.7%) in the standard group (p=100), and the second composite outcome was noted in 1591/5107 (31.2%) vs. 1659/5108 (325%) (p=019) Results were similar at the study end [first composite outcome, 556/5119 (109%) vs. 586/5115 (115%) (p=042); and second 1956/5119 (382%) vs. 2046/5115 (400%), respectively (p=012)] Though intensive therapy did not reduce the risk of advanced measures of microvascular outcomes, it delayed the onset of albuminuria and some measures of neuropathy and eye complications Six secondary measures at study end appeared to favour the intensive therapy (p<005) Peripheral neuropathy, as established by a Michigan neuropathy screening instrument score of 20 or more, was less common in the intensive group than in the standard therapy group at study end.
Conclusion
This analysis of the ACCORD trial suggests that microvascular benefits of intensive therapy needs to be weighed against the increase in total and CVD-related mortality, increased weight gain, and high risk for severe hypoglycemia.
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Article 5
Issue No. 4
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July 2013
The only effective treatments for patients with distal symmetrical polyneuropathy are glucose control and pain management The prevalence of diabetic neuropathic pain may be higher than reported. "Increasing evidence supports an association between components of the metabolic syndrome, including prediabetes, and neuropathy."
Diabetic neuropathy
Diabetes is by far the most common cause of neuropathy Distal symmetrical polyneuropathy (DSP) represents the most common manifestation of diabetic peripheral neuropathy (DPN), a prevalent, disabling disorder; though many patterns of nerve injury patterns like small-fibre predominant neuropathy, radiculoplexopathy, and autonomic neuropathy, can also occur
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Article 5
Issue No. 4
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July 2013
Patients with DSP typically have one or more of the following symptoms: numbness, tingling, pain, or weakness Symptoms follow the so-called stocking-and-glove distribution they begin in the feet and spread proximally in a lengthdependent fashion Symptoms are symmetrical, and sensory symptoms are more prominent than motor involvement The likelihood of which symptom predominates varies substantially from patient to patient Neuropathy is one of the main risk factors for falls in patients with diabetes; others being retinopathy and vestibular dysfunction In addition, patients with severe DSP are at risk of ulcerations and lower-extremity amputations Neuropathic pain is one of the most disabling symptoms in patients with DSP that is difficult to treat and therefore causes substantial suffering and burden Glucose control considerably decreases the development of neuropathy in patents with type 1 diabetes; however, the effect is probably much smaller in those with type 2 diabetes Whilst use of specific anticonvulsants and antidepressants is suggested for pain management in patients with DPN, a lack of other disease-modifying therapies, save for glucose control, for diabetic DSP makes identification of new modifiable risk factors essential Components of the metabolic syndrome, including prediabetes, are potential risk factors for neuropathy; however, studies are needed to establish the causality related to neuropathy.
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Article 6
Issue No. 4
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July 2013
"Pain resolution in an individual is complex, and need a holistic approach to medicine, employing empathy, compassion, and understanding to succeed in alleviating pain" Pain syndromes in diabetes may be focal or diffuse, proximal or distal, acute or chronic Neuropathic pain must be distinguished from nociceptive pain, which is a consequence of trauma, injury, or inflammation.
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Article 7
Issue No. 4
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July 2013
BMJ 2007
"In the clinical setting, management of diabetic neuropathy focuses on two aspects: disease modifying treatment such as glycaemic control and the use of various kinds of analgesics to reduce the intensity of the pain"
"Compared with newer generation anticonvulsants, oral tricyclic antidepressants and traditional anticonvulsants are better for short term pain relief"
Objective
To evaluate the effects of treatments for the symptoms of diabetic painful neuropathy.
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Article 7
Issue No. 4
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July 2013
Method
A systematic review of double blind randomised trials Primary outcome was dichotomous information for 50% or moderate reduction of pain Secondary outcomes were 30% reduction of pain and withdrawals related to adverse events.
Results
Odds ratios (ORs) were calculated for achievement of 30%, 50%, or moderate pain relief and for withdrawals related to adverse effects Twenty five reports were included, which compared anticonvulsants (n=1270), antidepressants (94), opioids (329), ion channel blockers (173), N-methyl-D-aspartate antagonist (14), duloxetine (805), capsaicin (277), and isosorbide dinitrate spray (22) with placebo ORs in terms of 50% pain relief were 5.33 for traditional anticonvulsants, 3.25 for newer generation anticonvulsants, and 22.24 for tricylic antidepressants ORs in terms of withdrawals related to adverse events were 1.51 for traditional anticonvulsants, 2.98 for newer generation anticonvulsants, and 2.32 for tricylic antidepressants ORs for ion channel blockers could not be calculated because of insufficient dichotomous data.
Conclusion
The most commonly used options to manage diabetic neuropathy include anticonvulsants and antidepressants Evidence of the long term effects of oral antidepressants and anticonvulsants is still lacking.
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Article 8
Issue No. 4
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July 2013
The Canadian Diabetes Association 2013 Clinical Practice Guidelines for the Prevention and Management of Diabetes are intended to guide practice, to enhance diabetes prevention efforts, and to reduce the burden of diabetes complications in people living with this disease. This presentation highlights pertinent principles related to the complication of neuropathy.
Patients with diabetes should be offered timely diabetes education tailored to enhance self-care practices and behaviours Optimal glycemic control is the key to the management of diabetes Treatment in most patients with type 1 or type 2 diabetes should be targeted to achieve an A1C 7.0% so as to reduce the risk of microvascular complications and, if implemented early in the course of disease, macrovascular complications of diabetes. Screening for peripheral neuropathy should begin at diagnosis of diabetes in patients with type 2 diabetes, and occur annually thereafter. However, in patients with type 1 diabetes, annual screening should commence after 5 years postpubertal duration of diabetes.
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Article 8
Issue No. 4
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July 2013
Individualize glycemic targets based on age, duration of diabetes, risk of severe hypoglycemia, presence or absence of cardiovascular disease, and life expectancy Antihyperglycemic pharmacotherapy is indicated if glycemic targets are not achieved within 2 to 3 months of lifestyle management To screen for peripheral neuropathy, assess loss of sensitivity to the 10-g monofilament or loss of sensitivity to vibration at the dorsum of the great toe.
Diabetic neuropathy
The chronic hyperglycemia seen in patients with diabetes is associated with significant long-term microvascular and macrovascular complications Detectable sensorimotor polyneuropathy develops in about 40% to 50% of people with type 1 or type 2 diabetes within 10 years of the onset of diabetes The timing of diagnosis may be important given that whilst clinical neuropathy is uncommon in people with type 1 diabetes within the first 5 years after the onset of diabetes, in contrast, people with type 2 diabetes may have neuropathy at the time of diagnosis Risk factors for neuropathy include: elevated blood glucose levels, elevated triglycerides, high body mass index (BMI), smoking and hypertension
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Article 8
Issue No. 4
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July 2013
Foot ulceration, dependent on the degree of foot insensitivity, and amputation are two important and costly sequelae of diabetic neuropathy Mononeuropathy, especially the carpal tunnel syndrome, is common in patients with diabetes and can be difficult to diagnose Intensive glycemic control is effective both for the primary and secondary intervention of neuropathy in patients with type 1 diabetes Lower levels of blood glucose are associated with a reduced frequency of neuropathy in patients with type 2 diabetes It has been noted that simple physical examination screening tests, for instance the monofilament and vibration perception tests for neuropathy, perform reasonably well for identification of neuropathy, and predicting its future onset The following agents may be used alone or in combination for relief of painful peripheral neuropathy. Anticonvulsants (pregabalin, gabapentin, valproate) Antidepressants (amitriptyline, duloxetine, venlafaxine) Opioid analgesics (tapentadol ER, oxycodone ER, tramadol) Topical nitrate spray Generally, few patients have complete relief of painful symptoms with any treatment for neuropathic pain. A 30% to 50% reduction in baseline pain is considered to be clinically meaningful response.
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Article 9
Issue No. 4
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July 2013
Neurology 2011
"The guidelines give a scientifically sound and clinically relevant evidence-based method for the treatment of painful diabetic neuropathy"
Effective treatments for painful diabetic neuropathy are available, but many have side effects that limit their usefulness. Few studies have sufficient information on treatment effects on function and quality of life Pregabalin is effective and should be offered for relief of painful diabetic neuropathy Venlafaxine, duloxetine, amitriptyline, valproate, gabapentin, opioids, and capsaicin are probably effective and should be considered for treatment of painful diabetic neuropathy.
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Article 9
Issue No. 4
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July 2013
Objective
To develop evidence-based guidelines for the treatment of painful diabetic neuropathy.
Methods
A systematic literature review was performed, with studies classified according to the American Academy of Neurology (AAN) classification of evidence scheme for a therapeutic article, and recommendations were linked to the strength of the evidence The research question: What is the efficacy of a given treatment to reduce pain and improve physical function and quality of life in patients with painful diabetic neuropathy?
Results/recommendations Anticonvulsants
If clinically apt, pregabalin should be offered for the treatment of painful diabetic neuropathy Sodium valproate and gabapentin and should be considered for the treatment of painful diabetic neuropathy. However, sodium valproate is potentially teratogenic and should be avoided in diabetic women of childbearing age There exists insufficient evidence to support or refute the use of topiramate for the treatment of painful diabetic neuropathy Oxcarbazepine, lacosamide, and lamotrigine should probably not be considered for the treatment of painful diabetic neuropathy.
Antidepressants
Amitriptyline, duloxetine, and venlafaxine should be considered for the treatment of painful diabetic neuropathy. Venlafaxine may be added to gabapentin for a better response There exists insufficient evidence to support or refute the use of desipramine, fluoxetine, imipramine, or the combination of fluphenazine and nortriptyline in the treatment of painful diabetic neuropathy.
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Article 9
Issue No. 4
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July 2013
Opioids
Dextromethorphan, tramadol, morphine sulfate, and oxycodone controlled-release should be considered for the treatment of painful diabetic neuropathy Chronic use of opioids can lead to tolerance and frequent dose escalation.
Non-pharmacologic modalities
Percutaneous electrical nerve stimulation should be considered for the treatment of painful diabetic neuropathy Electromagnetic field treatment, low-intensity laser treatment, and Reiki therapy should probably not be considered for the treatment of painful diabetic neuropathy There exists insufficient evidence to support or refute the use of amitriptyline plus electrotherapy for treatment of painful diabetic neuropathy.
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Article 10
Issue No. 4
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July 2013
NICE clinical guidelines The pharmacological management of neuropathic pain in adults in non-specialist settings
Source: Neuropathic pain. The pharmacological management of neuropathic pain in adults in non-specialist settings. NICE clinical guideline 96; 2010.
Regular clinical reviews, which include assessment of pain reduction, adverse effects, daily activities and participation, mood, quality of sleep and overall improvement as reported by the person, should be performed to assess and monitor the effectiveness of the chosen treatment.
experience, and can have a significant impact on a person's quality of life the adverse effects associated with effective medications; neuropathic pain is often difficult to treat including antidepressants, anticonvulsants, opioids and topical treatments such as capsaicin and lidocaine, but the correct choice of drugs, and the optimal sequence for their use, remains largely indistinct.
"Treatment and care should consider patients' needs and preferences, whilst giving them the opportunity to make informed decisions"
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This continuing medical education program is intended only to enhance knowledge of the diseases and improve management skills of doctors. The usage of all knowledge/information acquired/derived during or on account of this activity will be at their sole discretion/judgment, USV will not be accountable for any liability arising out of the use and for any other act of commission/omission. If you wish to unsubscribe to these mailers, please send a mail to us informing about your decision at: unsubscribe@diabetespearls.com
Article 10
Issue No. 4
HOME PRODUCT BASKET FEEDBACK
July 2013
Second-line treatment
Offer treatment with another alternative drug, rather than or in combination with the original drug, if satisfactory pain reduction is not achieved with first-line treatment at the maximum tolerated dose. Such decision should be based on informed discussion with the patient Consider switching to, or combine with, oral pregabalin, if the first-line treatment was with amitriptyline (or nortriptyline or imipramine)
Download PPT
Previous
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Article 1 | Article 2 | Article 3 | Article 4 | Article 5 | Article 6 | Article 7 | Article 8 | Article 9 | Article 10
This continuing medical education program is intended only to enhance knowledge of the diseases and improve management skills of doctors. The usage of all knowledge/information acquired/derived during or on account of this activity will be at their sole discretion/judgment, USV will not be accountable for any liability arising out of the use and for any other act of commission/omission. If you wish to unsubscribe to these mailers, please send a mail to us informing about your decision at: unsubscribe@diabetespearls.com
Article 10
Issue No. 4
HOME PRODUCT BASKET FEEDBACK
July 2013
Consider switching to, or combine with, oral amitriptyline if first-line treatment was with pregabalin (consider imipramine or nortriptyline as an alternative if the patent cannot tolerate the adverse effects of amitriptyline) For people with painful diabetic neuropathy: Consider switching to amitriptyline or pregabalin, or combine with pregabalin, if first-line treatment was with duloxetine Consider switching to, or combine with, pregabalin, if first-line treatment was with amitriptyline
Third-line treatment
Refer the patient to a specialist pain service and/or a condition-specific service if satisfactory pain reduction is not achieved with second-line treatment Whilst waiting for referral: Consider oral tramadol, instead of, or in combination with, the second-line treatment For patients unable to take oral medication because of medical conditions and/or disability, consider topical lidocaine for localised pain Tramadol monotherapy start at 50 to 100 mg not more often than every 4 hours; if required, titrate upwards to an effective dose or the person's maximum tolerated dose of no higher than 400 mg/day. More conservative titration may be required when tramadol is used as combination therapy.
Other treatments
It is recommended not to start treatment with opioids (such as oxycodone or morphine) other than tramadol without an assessment by a specialist pain service or a condition-specific service.
Download PPT
Previous
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Article 1 | Article 2 | Article 3 | Article 4 | Article 5 | Article 6 | Article 7 | Article 8 | Article 9 | Article 10
This continuing medical education program is intended only to enhance knowledge of the diseases and improve management skills of doctors. The usage of all knowledge/information acquired/derived during or on account of this activity will be at their sole discretion/judgment, USV will not be accountable for any liability arising out of the use and for any other act of commission/omission. If you wish to unsubscribe to these mailers, please send a mail to us informing about your decision at: unsubscribe@diabetespearls.com
Product Basket
Issue No. 4
HOME PRODUCT BASKET FEEDBACK
July 2013
PRODUCT BASKET
This continuing medical education program is intended only to enhance knowledge of the diseases and improve management skills of doctors. The usage of all knowledge/information acquired/derived during or on account of this activity will be at their sole discretion/judgment, USV will not be accountable for any liability arising out of the use and for any other act of commission/omission. If you wish to unsubscribe to these mailers, please send a mail to us informing about your decision at: unsubscribe@diabetespearls.com