Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This paper documents the frequency of alcohol consumption and concurrent use of alcohol and medications in a random sample of elderly community dwellers. Further, a profile of older persons who are likely to be drinking alcohol is developed and the extent to which they are at potential clinical risk due to their concurrent use of alcohol with prescription and over-the-counter medications is explored. While approximately 43 percent are abstainers, the majority of older respondents reported using alcohol. Older drinkers who take one or more drugs which place them at potential risk for negative drug-alcohol interactions represent one-quarter of this sample but are often overlooked in estimating the extent of alcohol problems in the elderly. By far, the most common risk was from the use of OTC pain medications and alcohol (19 percent). The multivariate analyses revealed that sex, educational attainment, and religious affiliation are important factors to consider in developing a profile of older people who are at risk for alcohol-related ADRs. Implications for health care and social service professionals who work with elderly community-dwellers are discussed.
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PMID:Alcohol use and potential risk for alcohol-related adverse drug reactions among community-based elderly. 840 52

The accuracy of the economic analysis of the selected adverse events evaluated by McGoldrick and Bailie is questionable. The quantitative perspective on the economics of the adverse events associated with nonnarcotic analgesic use proposed by these authors is limited by the fact that they have combined data on over 30 different NSAIDs into a single value for comparison with two single-entity agents: acetaminophen and aspirin. The relative prevalence of major organ system toxicities varies markedly among the NSAIDs, and this variance invalidates the use of a class conclusion approach. Their conservative incidence estimates, the lack of data in some areas (i.e., hepatic injury), and the exclusion of combination analgesics further limit the utility of their conclusions. However, it is difficult to argue authoritatively that the relative costs of toxicities associated with the three analgesic classes they reviewed are not representative. The ultimate question is, "What is the optimal analgesic for a given patient?" This question can be addressed only if one considers the underlying cause of pain, its chronicity/acuity, the patient's concurrent disease states, if any, and the potential for drug interactions with the patient's concomitant medications. McGoldrick and Bailie concluded on an economic basis that acetaminophen is the analgesic of choice for most patients, including those with impaired renal function. This recommendation is in agreement with those of the Analgesics and the Kidney Ad Hoc Committee of the National Kidney Foundation. It also would seem prudent to use acetaminophen as the first-line agent for those patients in whom aspirin and NSAID use should be avoided or used only with caution along with frequent monitoring of renal function, blood pressure, electrolytes, and/or coagulation status. Thus, there is little to no controversy in their recommendation to initiate treatment with acetaminophen. The authors, however, also suggested that switching patients from an NSAID to acetaminophen would result in significantly decreased costs and morbidity. These authors, however, did not address one key issue that impacts their economic analysis: the relative efficacy of acetaminophen and NSAIDs. If efficacy is similar, then the risk/benefit ratio and economic consequences would favor the use of acetaminophen. However, if many patients are receiving NSAIDs because they did not obtain pain relief with the use of acetaminophen, there would be neither rationale or likely benefit with a change in therapy to acetaminophen. Finally, McGoldrick and Bailie did not evaluate an issue that has perhaps the most far-reaching consequence. Many OTC analgesics are currently marketed as combinations of aspirin, acetaminophen, salicylamide, or caffeine (Table 2). Although the intent of these combinations was [Table: see text] to enhance efficacy while minimizing adverse events, it is now apparent that at least concerning adverse events, the goal was not achieved. Therefore, in light of the markedly higher risk for renal injury with combination analgesics, these agents should be withdrawn from the marketplace. While some might argue that patient education is the key and that addition of an explicit warning on the label of OTC combination products should be an adequate intervention, this agreement is not supported by the Belgium experience. The removal of combination analgesics from the OTC marketplace could be accomplished by governmental action, such as the ban on phenacetin over 10 years ago. Alternatively, pharmacists could no longer sell these products and counsel patients on the rational use of OTC analgesics. The choice among single-entity agents could then be individualized on the basis of patient's current medical status and the adverse event profile of the available agents.
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PMID:Clinical consequences of nonnarcotic analgesic use. 903 24

Nonsteroidal anti-inflammatory drugs (NSAIDs) are one of the most widely used classes of drug worldwide, with as many as 8% of the global adult population taking prescription NSAIDs at any given time. It is well documented that NSAID-related gastrointestinal (GI) effects are a significant cause of morbidity and mortality. Data from Australia alone suggest that each year there may be as many as 2300 serious GI complications and 300 deaths. Risk factors for NSAID-related GI complications have been established and can be broadly divided into two groups: uncontrollable factors, which include elements such as age, gender, comorbidity, and a history of GI conditions, and controllable factors, such as the dose, type, and duration of NSAID treatment and cotherapy and possibly Helicobacter pylori infection. The increasing trend toward self-medication raises questions about the potential for GI complications with OTC doses of NSAIDs. Although there is some evidence that the frequency of GI complications with OTC doses may be less than that seen with prescription doses, it still exists. At present, there is insufficient evidence to determine the population attributable risk associated with their widespread use. Emerging data and factors that confound their interpretation are discussed. Given that the data are limited, a clear picture of the true extent of GI complications with OTC NSAIDs is not yet available. In light of our current understanding and because paracetamol continues to demonstrate a favorable side-effect profile, it remains a first-line analgesic for everyday pain.
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PMID:Exploring the link between gastrointestinal complications and over-the-counter analgesics: current issues and considerations. 1131 77

The aim of this blinded, randomised, multicentre study was to compare the tolerability of aspirin, paracetamol and ibuprofen in common pain resulting from musculoskeletal conditions (MSC) in general practice with patients with other non-MSC pain conditions. Patients took aspirin, paracetamol (both up to 3g daily) or ibuprofen (up to 1.2g daily) for up to 7 days. The main outcome was the rate of significant adverse events (SGAE). Four thousand two hundred and ninety one patients with MSC were evaluable (1436 aspirin, 1423 paracetamol, 1432 ibuprofen) and 4101 (95.5%) were per-protocol. A group of 4342 patients included for other (non-MSC) mild to moderate pain conditions was used for comparison. In the MSC group, SGAE were reported by 20.5% of patients with aspirin, 17.0% with paracetamol and 15.0% with ibuprofen. Ibuprofen was statistically equivalent to paracetamol and better tolerated than aspirin (p <0.0001). Ibuprofen was associated with fewer digestive system AE (4.4%) than aspirin (8.6%, p<0.0001) and paracetamol (6.5%, p <0.02). The non-MSC group showed similar intertreatment differences, but experienced fewer SGAE. No serious digestive events were observed with any of the three treatments in either group. These results show that in patients with mild to moderate pain resulting from MSC, ibuprofen given in OTC doses for 6 days is as well tolerated as paracetamol and better tolerated than aspirin.
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PMID:Comparative tolerability of paracetamol, aspirin and ibuprofen for short-term analgesia in patients with musculoskeletal conditions: results in 4291 patients. 1195 80

Adolor is developing various local and topical formulations of the antidiarrheal compound loperamide (ADL-2-1294), which acts as an opiate receptor agonist in the peripheral nervous system, for the potential treatment of pruritus and pain associated with burns, wounds, eye diseases and inflammation. Both the topical formulation and ophthalmic formulation are in phase II clinical trials. TOPICAL FORMULATION: A topical formulation is being developed for pain associated with cutaneous inflammatory lesions and other indications associated with inflammatory pain. Phase I trials were completed in spring 1997. The trials assessed the safety, tolerance, pharmacokinetics, and topical sensitivity of ADL-2-1294 in 35 burn patient volunteers. Following positive results, Adolor began two dose-ranging phase II trials in patients with minor burns, abrasions and sunburn in the first half of 1997. In July 1997, Adolor was to initiate the preclinical development of ADL-2-1294 for the potential treatment of hyperalgesia associated with surgical wounds. OPHTHALMIC FORMULATION: By July 1999, phase II clinical trials of ADL-2-1294 for the potential treatment of inflammatory corneal pain were underway. In June 1998, the FDA accepted an IND for ADL-2-1294 for the treatment of inflammatory pain associated with corneal abrasions, surgical and laser keratectomies and keratoconjunctivitis. By this time, a phase I study had been initiated to assess safety and efficacy parameters. By July 1997, an ophthalmic formulation was in preclinical development for the treatment of corneal hyperalgesia. In preclinical studies with the compound, efficacy was demonstrated in animal models of inflammatory pain. OTHER FORMULATIONS: By 1999, Adolor was also investigating mucosal, post-surgical and intra-articular indications for the compound. By 1996, Adolor had plans to carry out clinical development alone, up to and including phase II trials. Then, the company were to seek a corporate partner, probably from Japan, and hold on to US and European rights. Beyond phase III trials, Adolor had expected to sell the compound to a major US or European company. In 1997, Adolor licensed ADL-2-1294 to the South Korean OTC topically-administered epidermal analgesic. In July 1999, Adolor licensed worldwide (excluding Korea) prescription and OTC development and commercial rights to topical dermal ADL-2-1294, for use in the treatment of inflammatory pain, itching and other undisclosed indications, to SmithKline Beecham. The company was issued US-05849761 and US-05849762 in January 1999 covering the use of antidiarrheal opioid compounds for the treatment of inflammatory pain and the treatment of pruritus.
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PMID:ADL-2-1294 (Adolor). 1604 59

Non-prescription (over-the-counter [OTC]) analgesics are used for the short-term treatment of acute painful conditions of mild to moderate intensity in everyday life. Well documented safety and efficacy, a rapid onset of action and a flexible daily dosing regimen are essential in this context. Film-coated, immediate-release, low-dose diclofenac potassium, developed for OTC use, offers a flexible daily dosing regimen with an initial dose of two tablets (2 x 12.5mg) followed by one or two tablets up to a maximum daily dose of six tablets (75 mg/day). The maximum plasma drug concentration is reached 30 minutes after administration, and the mean terminal half-life is 1-2 hours, allowing a 4- to 6-hour duration of activity, depending on the condition. Thirteen randomised, double-blind trials with both placebo and active controls have demonstrated the efficacy of diclofenac potassium 12.5mg tablets in conditions suitable for treatment with OTC medication, for example, acute lower back pain, headache, acute pain after dental extraction, symptoms of cold and influenza (including fever), and dysmenorrhoea. A single dose of diclofenac potassium 12.5mg is the lowest recommended effective dose. A two-tablet single dose of 25mg is at least as effective as ibuprofen 400mg. A flexible dosing regimen of an initial two tablets followed by one or two tablets up to a total daily dose of 75 mg is as effective as ibuprofen used in comparable fashion up to a total daily dose of 1200 mg. The incidence of adverse events in patients taking single or multiple doses of diclofenac potassium is similar to that of ibuprofen and placebo. In a safety study conducted to compare diclofenac potassium with ibuprofen for up to 3 months in patients with osteoarthritis of the knee, no differences in the pattern of adverse events were noted. There was no evidence of either hepatic injury or cardiovascular safety-related issues at any time during the study. Patients are generally capable of taking diclofenac potassium appropriately. A maximum OTC treatment duration of 5 days for pain and 3 days for fever is recommended.
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PMID:Diclofenac potassium 12.5mg tablets for mild to moderate pain and fever: a review of its pharmacology, clinical efficacy and safety. 1730 13

This overview looks at some of the issues involved with the ever-increasing availability of marketed non-prescription products, specifically claiming to treat the pain and inflammation of arthritis and other musculoskeletal problems.The question of whether the buyer is getting (any) value for their money cannot be answered without considering several key issues. These include: (a) reliability of claims; (b) placebo effect (but for how long?); (c) reliability of composition, and reproducibility (especially of natural products); (d) general safety; (e) interactions with other medications; (f) honest labelling (in the absence of stricter guidelines).A particularly difficult problem is to know how to recognise a 'drug of choice', particularly for such a multi-faceted disease as chronic arthritis, when there is so little information about the actual pharmacology/potential toxicity of these OTC products in the standard drug compendia and other readily available reference texts.This grey area can only be illuminated by (i) further introduction (and enforcement) of adequate standards/quality controls for products offered OTC; (ii) earliest prosecution of clinical trials to supercede unverified testimonial claims; (iii) appropriate funding to research/establish basic pharmacology of the active principles.In summary, more research, more regulation, and more realistic investment will be required to dispel present uncertainty about which non-NSAID drugs/nutriceuticals are indeed effective against arthritis/other forms of inflammation, and which are not.
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PMID:Non-NSAID over-the-counter (OTC) remedies for arthritis: good, bad or indifferent? 1763 94

Cough is an important defensive pulmonary reflex that removes irritants, fluids, or foreign materials from the airways. However, when cough is exceptionally intense or when it is chronic and/or nonproductive it may require pharmacologic suppression. For many patients, antitussive therapies consist of OTC products with inconsequential efficacies. On the other hand, the prescription antitussive market is dominated by older opioid drugs such as codeine. Unfortunately, "codeine-like" drugs suppress cough at equivalent doses that also often produce significant ancillary liabilities such as GI constipation, sedation, and respiratory depression. Thus, the discovery of a novel and effective antitussive drug with an improved side effect profile relative to codeine would fulfill an unmet clinical need in the treatment of cough. Afferent pulmonary nerves are endowed with a multitude of potential receptor targets, including TRPV1, that could act to attenuate cough. The evidence linking TRPV1 to cough is convincing. TRPV1 receptors are found on sensory respiratory nerves that are important in the generation of the cough reflex. Isolated pulmonary vagal afferent nerves are responsive to TRPV1 stimulation. In vivo, TRPV1 agonists such as capsaicin elicit cough when aerosolized and delivered to the lungs. Pertinent to the debate on the potential use of TRPV1 antagonist as antitussive agents are the observations that airway afferent nerves become hypersensitive in diseased and inflamed lungs. For example, the sensitivity of capsaicin-induced cough responses following upper respiratory tract infection and in airway inflammatory diseases such as asthma and COPD is increased relative to that of control responses. Indeed, we have demonstrated that TRPV1 antagonism can attenuate antigen-induced cough in the allergic guinea pig. However, it remains to be determined if the emerging pharmacologic profile of TRPV1 antagonists will translate into a novel human antitussive drug. Current efforts in clinical validation of TRPV1 antagonists revolve around various pain indications; therefore, clinical evaluation of TRPV1 antagonists as antitussive agents will have to await those outcomes.
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PMID:TRPV1 antagonists as potential antitussive agents. 1792 96

Acetaminophen is an OTC medication and amongst the most used pain relievers. It is the analgesic of first choice in pregnancy. Because of its low therapeutic index, accidental and suicidal acetaminophen intoxication is one of the most common causes of acute liver failure. Thus, face-to-face counselling of patients on the proper use of acetaminophen is essential for drug safety.
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PMID:[Accidental acetaminophen overdose]. 1866 13

As escalating health-care costs continue to be a focus of public discourse, the populace has become increasingly attentive to its own health and lifestyle choices. Nonprescription (over-the-counter, OTC) medicines represent an important option in this evolving environment and, through novel "Rx-to-OTC" switch efforts, could expand beyond their traditional role in symptomatic relief of common conditions such as minor pain, coughs, colds, heartburn, and allergy. This is certainly not a new concept. In fact, the self-care movement has roots reaching into the past century. Pharmaceutical companies and their consumer-product subsidiaries or partners have long considered and, when feasible, invested in difficult OTC switch development programs.
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PMID:Increasing access to nonprescription medicines: a global public health challenge and opportunity. 2016 Jul 46


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