Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0012833 (dizziness)
 9,689 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chronic pain requires chronic treatment. Dihydrocodeine retard (DHC) complies with the requirements for treatment of chronic pain: its sustained release formula provides pain relief for up to 12 h. Thus, taking two tablets of this preparation daily is sufficient to ensure continuous pain relief. Patients and methods The 309 physicians participating in the study treated a total of 1502 patients and provided more than 5000 reports containing data on pain relief and side effects. Treatment was performed according to the WHO principles for the analgesic treatment of cancer pain patients, i.e., doctors and patients were taught that two tablets are taken per day, one in the morning and one in the evening, irrespective of whether pain was present or not. Most of the data were derived from the first 4 weeks of treatment. Patients were selected at random. All had chronic pain, but the diagnosis was not a selection criterion. The patients had had prior treatment with various analgesic regimens, and in most cases drugs were administered at irregular intervals, i.e., on demand. About half of the patients (54%) suffered from pain related to the musculoskeletal system such as back pain, joint pain, polyarthritis. Twenty-four percent had cancer pain and 22% had pain caused by other sources, mostly neuropathic pain, including cases of severe postherpetic neuralgia. Most of the patients were older than 50 years; the average age in the patient population was 62 years. There were 816 women and 686 men. Patients assessment of analgesic treatment was performed before starting therapy with DHC (thus conferring to prior therapy) and after 1 and 2 weeks of treatment with the new drug. While only about 10% of the patients found their prior pain treatment excellent or good, nearly 80% rated the treatment with DHC as excellent or good and only 2% as bad.Severity of pain was assessed by the patients on a four-step verbal rating scale ranging from "no or little pain" to "extremely strong pain". At the time of admission to this post-marketing surveillance 51.5% of the patients suffered from very strong pain and 41% reported strong pain. Five percent had extremely strong pain and only 2.1% reported no or little pain. After 2 weeks of treatment with DHC, 54.5% had little or no pain, 29% suffered from strong pain, 7% from very strong, and 0.4% from extremely strong pain.Sleeping problems are known to be reported by patients with chronic pain. They often cannot sleep continuously for more than a few hours. Thus, the effect of DHC on sleep was evaluated. Before starting the new treatment only 8% of the patients were having uninterrupted sleep for 6 h or more, and more than 50% of the patients slept less than 3 h. During treatment with DHC 48% of the patients had more than 6 h of uninterrupted sleep and about 82% slept continuously for more than 3 h per night. Side effects About 20% of patients reported nausea at baseline (during previous treatment); vomiting was reported in 7.6%. These percentages did not change during the first week of treatment with sustained-release DHC and even decreased slowly during the next 3 weeks. The frequency of constipation increased from 14% at baseline to about 29.5% at the end of the second week of treatment with DHC with no change during the next four weeks. A total of 312 side effects were mentioned in 5308 reports delivered by the 1502 patients during the treatment with DHC (including multiple reports). The most frequent side effects were gastrointestinal (n=106), followed by symptoms related to the central nervous system such as dizziness, sedation, etc. (n=50), and non-specific symptoms such as indisposition (n=29). Other specific symptoms were rare and distributed over many different organ systems. Insummary, the findings of this post marketing surveillance study suggest that sustained-release dihydrocodeine is an effective and safe analgesic drug for the treatment of chronic pain of various causes.
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PMID:[Pain treatment with dihydrocodeine slow release. Results of a post marketing surveillance study.]. 1841 87

Medications which bind to opioid receptors are increasingly being prescribed for the treatment of multiple and diverse chronic painful conditions. Their use for acute pain or terminal pain is well accepted. Their role in the long-term treatment of chronic noncancer pain is, however, controversial for many reasons. One of the primary reasons is the well-known phenomenon of psychological addiction that can occur with the use of these medications. Abuse and diversion of these medications is a growing problem as the availability of these medications increases and this public health issue confounds their clinical utility. Also, the extent of their efficacy in the treatment of pain when utilized on a chronic basis has not been definitively proven. Lastly, the role of opioids in the treatment of chronic pain is also influenced by the fact that these potent analgesics are associated with a significant number of side effects and complications. It is these phenomena that are the focus of this review. Common side effects of opioid administration include sedation, dizziness, nausea, vomiting, constipation, physical dependence, tolerance, and respiratory depression. Physical dependence and addiction are clinical concerns that may prevent proper prescribing and in turn inadequate pain management. Less common side effects may include delayed gastric emptying, hyperalgesia, immunologic and hormonal dysfunction, muscle rigidity, and myoclonus. The most common side effects of opioid usage are constipation (which has a very high incidence) and nausea. These 2 side effects can be difficult to manage and frequently tolerance to them does not develop; this is especially true for constipation. They may be severe enough to require opioid discontinuation, and contribute to under-dosing and inadequate analgesia. Several clinical trials are underway to identify adjunct therapies that may mitigate these side effects. Switching opioids and/or routes of administration may also provide benefits for patients. Proper patient screening, education, and preemptive treatment of potential side effects may aid in maximizing effectiveness while reducing the severity of side effects and adverse events. Opioids can be considered broad spectrum analgesic agents, affecting a wide number of organ systems and influencing a large number of body functions.
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PMID:Opioid complications and side effects. 1844 35

Gabapentin is an antiepileptic drug (AED) by design expected to mimic the action of the neurotransmitter gamma-aminobutyric acid (GABA). However, its principal proposed mechanism of action is the interaction with the alpha 2-delta subunit of L-type voltage-regulated calcium channels. Gabapentin possesses several desirable pharmacokinetic properties, along with few drug interactions, particularly with other AEDs. These properties make it a well-tolerated drug, with the most commonly reported adverse events being somnolence and dizziness. Gabapentin is one of the new first-generation AEDs that expanded its use into a broad range of neurologic and psychiatric disorders shortly after it was licensed in 1993 for use in drug-resistant partial epilepsy with or without secondary generalization. Nowadays, most worldwide prescriptions for gabapentin are for conditions other than epilepsy, especially the treatment of chronic pain of different etiologies. This article will review the pharmacology, mechanism of action, drug interactions and adverse effects of gabapentin. In addition, the clinical trial data, cost analysis and recommended schedule of administration, are also reviewed.
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PMID:Gabapentin: a Ca2+ channel alpha 2-delta ligand far beyond epilepsy therapy. 1854 37

This open-label multicenter study evaluated the long-term safety and efficacy of intrathecal ziconotide and included 78 patients with chronic pain who had completed one of two previous ziconotide clinical trials. Each patient's initial ziconotide dose was based on his or her dose from the study of origin and was adjusted as necessary on the basis of adverse events and analgesic effect. The median ziconotide dose was 6.48 mcg/day (range, 0.00-120.00 mcg/day) at the Initial Visit and ranged from 5.52 to 7.20 mcg/day across all study visits. The most commonly reported new adverse events that were considered ziconotide related were memory impairment (11.3%); dizziness, nystagmus, and speech disorder (8.5% each); nervousness and somnolence (7.0% each); and abnormal gait (5.6%). There was no evidence of increased adverse event incidence at higher cumulative ziconotide doses. Elevations in creatine kinase were noted, but the proportion of patients with creatine kinase elevations did not change from the Initial Visit to the Termination Visit (4.1% each). Stable mean Visual Analog Scale of Pain Intensity scores during the three years of the study suggested no evidence of increased pain intensity with increased duration of ziconotide exposure. Long-term treatment with ziconotide appeared to be well tolerated and effective in patients whose response to ziconotide and ability to tolerate the drug had been previously demonstrated.
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PMID:Long-term intrathecal ziconotide for chronic pain: an open-label study. 1871 48

Opioid analgesics are known to impact on the central nervous system (CNS). These CNS side effects, such as dizziness and confusion, have been shown to lead to an increased risk of falling with subsequent fractures in elderly patients being treated with opioids. The risk of experiencing fractures has been shown to be dependent on the substance administered. Therefore, a health economic model was developed to investigate the cost-effectiveness of the most commonly used strong opioids in Germany, focussing on opioid-related fractures. By means of a Markov model, the consequences of hip, spine and forearm fractures due to the prior administration of transdermal (TD) buprenorphine, TD fentanyl, oral oxycodone as well as oral morphine were assessed from the perspectives of the German statutory health insurance (SHI) and the German social security (GSS) system over a time horizon of 6 years. The most frequently prescribed strength/package-size combinations of these opioids were taken into consideration, including generics where available. The results of the present analysis predict that TD buprenorphine is dominant compared to TD fentanyl and oxycodone by showing better effects [life years gained/quality adjusted life years (QALY) gained] at lower cost. From the SHI perspective, the incremental cost-effectiveness ratio (ICER) compared to morphine is <euro> 6,801.61 per life year gained, and <euro> 7,766.11 per QALY gained. From the GSS perspective, the ICER is <euro> 2,496.77 per life year gained and <euro> 2,850.83 per QALY gained. The model is robust regarding probabilistic variations of all parameters in the sensitivity analyses. Focussing on fractures due to the prior administration of strong opioids, TD buprenorphine is less costly and more effective than TD fentanyl and oxycodone and represents a cost-effective treatment option versus morphine in patients with chronic pain from both the SHI and GSS perspective in Germany.
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PMID:Cost-effectiveness of strong opioids focussing on the long-term effects of opioid-related fractures: a model approach. 1910 43

Treatment for chronic tension-type headache (CTTH) is unsatisfactory. Our aim was to investigate the efficacy of the N-methyl D-aspartate (NMDA) antagonist memantine in the prophylactic treatment of CTTH. We included 40 patients in a randomized, double-blind, placebo-controlled, crossover trial. Memantine 20-40 mg/day or placebo was each given for 10 weeks separated by a 2-week wash-out period; 29 patients completed the study. The primary efficacy variable, area-under-the-headache curve (duration x intensity), did not differ between memantine (1352 +/- 927) and placebo (1449 +/- 976; P = 0.10). Headache intensity in both sexes was significantly lower on a 0-10 verbal rating scale with memantine (3.8) than with placebo (4.1; P = 0.03). In women, area-under-the-headache curve was significantly lower with memantine (1343 +/- 919) than with placebo (1555 +/- 1019; P = 0.01). The most common side-effects were dizziness and nausea. In conclusion, although no statistically significant effect was seen in the primary end-point, some beneficial effects of memantine were observed in women. Memantine was shown to reduce pain intensity in CTTH patients, albeit to a limited extent. Future NMDA antagonists with higher efficacy could be of major interest as regards the pathophysiology and future treatment of CTTH and other chronic pain disorders.
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PMID:Memantine for prophylaxis of chronic tension-type headache--a double-blind, randomized, crossover clinical trial. 1922 Mar 13

(1) When oral morphine does not relieve severe pain and when there is no specific treatment for the underlying cause, the first option is to try subcutaneous or intravenous administration. If this standard treatment fails or is poorly tolerated, intrathecal injection is usually preferred as the direct route to the central nervous system. However, one-quarter to one-half of patients still do not achieve adequate pain relief, and adverse effects are relatively frequent; (2) Ziconotide is not an opiate and is not related to the usual classes of drugs that interfere with nervous transmission in the posterior horn of the spinal cord. Marketing authorization has been granted for "severe, chronic pain in patients who require intrathecal analgesia". The Summary of Product Characteristics (SPC) recommends continuous infusion via an intrathecal catheter connected to a pump; (3) Clinical evaluation of ziconotide does not include any trials versus morphine in patients with nociceptive pain, or any trials versus tricyclic or antiepileptic drugs in patients with neurogenic pain; (4) In a trial in 220 patients in whom systemic morphine had failed, the mean pain score on a 100-mm visual analogue scale was 69.8 mm after three weeks on ziconotide, compared to 75.8 mm with placebo. This difference, although statistically significant, is clinically irrelevant. The proportion of "responders" (reduction of at least 30% in the initial pain score) was respectively 16.1% and 12.0% (no statistically significant difference); (5) The two other placebo-controlled trials included 112 patients with pain linked to cancer or HIV infection, and 257 patients with non-cancer pain. After a titration phase lasting 5 to 6 days, a combined analysis of the two trials showed that the mean pain score was 48.8 mm with ziconotide and 68.4 mm with placebo (statistically significant difference). However, many patients did not complete the titration phase. Efficacy also appeared to differ according to the type of pain; ziconotide was more effective on cancer pain than on neurogenic pain; (6) The main adverse effects of ziconotide in clinical trials were cerebellovestibular disorders such as ataxia, dizziness, and gait disorders, as well as confusion, hallucinations (increased in cases of overdose), nausea, vomiting, postural hypotension, and urine retention. About 40% of patients had an elevation in muscle creatine kinase activity, through an unknown mechanism; (7) Intrathecal administration carries a risk of infection (especially meningitis). Some patients might experience a paradoxical increase in pain with ziconotide; (8) In practice, the efficacy of ziconotide in relieving neurogenic pain remains to be established. In cancer pain, the available evidence showing that ziconotide is effective after opiate failure is too weak in view of the potential risks. It is better to re-examine and, if possible, correct the reasons for opiate treatment failure rather than prescribe ziconotide.
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PMID:Ziconotide: new drug. Limited analgesic efficacy, too many adverse effects. 1953 Mar 73

Ziconotide is a conopeptide intrathecal (IT) analgesic which is approved by the US Food and Drug Administration (FDA) for the management of severe chronic pain. It is a synthetic equivalent of a naturally occurring conopeptide found in the venom of the fish-eating marine cone snail and provides analgesia via binding to N-type voltage-sensitive calcium channels in the spinal cord. As ziconotide is a peptide, it is expected to be completely degraded by endopeptidases and exopeptidases (Phase I hydrolytic enzymes) widely located throughout the body, and not by other Phase I biotransformation processes (including the cytochrome P450 system) or by Phase II conjugation reactions. Thus, IT administration, low plasma ziconotide concentrations, and metabolism by ubiquitous peptidases make metabolic interactions of other drugs with ziconotide unlikely. Side effects of ziconotide which tend to occur more commonly at higher doses may include: nausea, vomiting, confusion, postural hypotension, abnormal gait, urinary retention, nystagmus/amblyopia, drowsiness/somnolence (reduced level of consciousness), dizziness or lightheadedness, weakness, visual problems (eg, double vision), elevation of serum creatine kinase, or vestibular side effects. Initially, when ziconotide was first administered to human subjects, titration schedules were overly aggressive and led to an abundance of adverse effects. Subsequently, clinicians have gained appreciation for ziconotide's relatively narrow therapeutic window. With appropriate usage multiple studies have shown ziconotide to be a safe and effective intrathecal analgesic alone or in combination with other intrathecal analgesics.
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PMID:Safety and efficacy of intrathecal ziconotide in the management of severe chronic pain. 1970 62

This systematic review summarizes existing evidence regarding the efficacy, safety, and abuse and misuse potential of opioids as treatment for chronic noncancer pain in older adults. Multiple databases were searched to identify relevant studies published in English (1/1/80-7/1/09) with a mean study population age of 60 and older. Forty-three articles were identified and retained for review (40 reported safety and efficacy data, the remaining 3 reported misuse or abuse outcome data). The weighted mean subject age was 64.1 (mean age range 60-73). Studies enrolled patients with osteoarthritis (70%), neuropathic pain (13%), and other pain-producing disorders (17%). The mean duration of treatment studies was 4 weeks (range 1.5-156 weeks), and only five (12%) lasted longer than 12 weeks. In meta-analyses, effect sizes were -0.557 (P<.001) for pain reduction, -0.432 (P<.001) for physical disability reduction, and 0.859 (P=.31) for improved sleep. The effect size for the Medical Outcomes Study 36-item Health Survey was 0.191 (P=.17) for the physical component score and -0.220 (P=.04) for the mental component score. Adults aged 65 and older were as likely as those younger than 65 to benefit from treatment. Common adverse events included constipation (median frequency of occurrence 30%), nausea (28%), and dizziness (22%) and prompted opioid discontinuation in 25% of cases. Abuse and misuse behaviors were negatively associated with older age. In older adults with chronic pain and no significant comorbidity, short-term use of opioids is associated with reduction in pain intensity and better physical functioning but poorer mental health functioning. The long-term safety, efficacy, and abuse potential of this treatment practice in diverse populations of older persons remain to be determined.
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PMID:Outcomes associated with opioid use in the treatment of chronic noncancer pain in older adults: a systematic review and meta-analysis. 2168 2

Flupirtine is a centrally acting, non-opioid analgesic that is available in a number of European countries for the treatment of a variety of pain states. The therapeutic benefits seen with flupirtine relate to its unique pharmacological properties. Flupirtine displays indirect NDMA receptor antagonism via activation of potassium channels and is the first representative of a pharmacological class denoted the 'selective neuronal potassium channel openers'. The generation of the M-current is facilitated by flupirtine via the opening of neuronal Kv7 potassium channels. The opening of these channels inhibits exaggerated neuronal action potential generation and controls neuronal excitability. Neuronal hyperexcitability is a physiological component of many pain states such as chronic pain, migraine and neurogenic pain. Although large-scale clinical trials are lacking, the clinical trial database available to date from smaller-scale studies, together with extensive clinical experience, indicate that flupirtine effectively reduces chronic musculoskeletal pain, migraine and neuralgias, amongst other types of pain. In addition, flupirtine produces, at recommended clinical doses, muscle-relaxing effects in the presence of abnormally increased muscle tension. Its analgesic and muscle-relaxant properties were comparable to tramadol and chlormezanone, respectively, in two prospective trials in patients with lower back pain. Cytoprotective, anti-apoptotic and antioxidant properties have also been associated with flupirtine use in a small number of studies to date. When provided as combination therapy with morphine, flupirtine increases the antinociceptive activity of morphine 4-fold. Flupirtine displays superior tolerability when compared with tramadol and pentazocine. The most common adverse effects associated with flupirtine use are drowsiness, dizziness, heartburn, dry mouth, fatigue and nausea. With respect to its molecular structure, mechanism of action and adverse event profile, flupirtine is a unique drug. Flupirtine is an analgesic with many potential therapeutic benefits that may prove useful in the treatment of many disease states.
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PMID:Flupirtine in pain management: pharmacological properties and clinical use. 2083 97


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