Effective Analgesic Agent Research Articles

Evaluation of the side-effects and thermal antinociceptive effects of intravenous hydromorphone in cats

Hydromorphone (H) may be an effective analgesic agent in cats, but fear of negative behavioral side-effects associated with opioids is cited as a reason for avoiding this class of analgesics in cats. This study was designed to assess onset and duration of antinociception using an established feline thermal threshold model in cats, given an accepted clinical dose of 0.1 mg kg−1 of H.

Anti-inflammatory and Analgesic Effects of Drypemolundein A, a Sesquiterpene Lactone from Drypetes molunduana

Previous pharmacological screening in our laboratory showed analgesic and anti-inflammatory effects of a crude stem bark extract of Drypetes molunduana. Phytochemical studies of this plant led to the isolation an structural elucidation of seven pentacylic triterpenes and one lignan, which were already known compounds, and a new furanosesquiterpene lactone, Drypemolundein A. The purpose of this study was to examine the anti-inflammatory and analgesic activities of drypemolundein A. The compound was studied against carrageenan-induced acute edema. At doses of 10 and 20 mg/kg, orally administered, it significantly reduced (57.57 and 66.66% inhibition at 1 h intervals, respectively) paw edema. At the same doses, this sesquiterpene lactone also exhibited significant analgesic action in force-induced pain in rat paw. These results indicate that drypemolundein A functions as an effective anti-inflammatory and analgesic agent.

Inhibition of prostaglandin H2 synthases by salicylate is dependent on the oxidative state of the enzymes.

Salicylic acid (SA) is an effective antipyretic and analgesic agent, yet at therapeutic concentrations exerting these effects SA lacks antiinflammatory action, distinguishing it from non-steroidal antiinflammatory drugs (NSAIDs) and selective inhibitors of prostaglandin H synthase-2 (PGHS-2). Only at concentrations much greater than are required for antipyresis does SA demonstrate antiinflammatory effects. In contrast to acetylsalicylic acid (aspirin), which irreversibly inhibits platelet PGHS-1 by acetylating a serine in the cyclooxygenase active site, SA is a weak inhibitor of platelet PGHS. The distinctive pharmacologic behavior of SA suggests that the molecular basis for its action differs from that of NSAIDs and PGHS-2 inhibitors.KeywordsSalicylic AcidLipid HydroperoxideInhibitory PotencySodium SalicylateSalicylic Acid LevelThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Prospects for cannabinoids as anti-inflammatory agents.

The marijuana plant (Cannabis sativa) and preparations derived from it have been used for medicinal purposes for thousands of years. It is likely that the therapeutic benefits of smoked marijuana are due to some combination of its more than 60 cannabinoids and 200-250 non-cannabinoid constituents. Several marijuana constituents, the carboxylic acid metabolites of tetrahydrocannabinol, and synthetic analogs are free of cannabimimetic central nervous system activity, do not produce behavioral changes in humans, and are effective antiinflammatory and analgesic agents. One cannabinoid acid in particular, ajulemic acid, has been studied extensively in in vitro systems and animal models of inflammation and immune responses. This commentary reviews a portion of the work done by investigators interested in separating the medicinal properties of marijuana from its psychoactive effects. Understanding the mechanisms of the therapeutic effects of nonpsychoactive cannabinoids should lead to development of safe effective treatment for several diseases, and may render moot the debate about "medical marijuana".

Rofecoxib: clinical pharmacology and clinical experience

Background: Rofecoxib is a member of a subgroup of nonsteroidal anti-inflammatory drugs (NSAIDs) known as cyclooxygenase-2 (COX-2)—selective inhibitors. It has been studied in adult and elderly patients in a number of painful conditions (primary dysmenorrhea, acute pain after dental and orthopedic surgery, osteoarthritis [OA], and rheumatoid arthritis). Objective: This review discusses the clinical pharmacology of and clinical experience with rofecoxib, and the role of COX-2—selective inhibitors in clinical practice. Methods: Pertinent studies were identified through searches of MEDLINE and EMBASE, as well as the Web sites and proceedings of relevant scientific meetings. Results: Although the published literature is limited, the data indicate that rofecoxib is an effective analgesic agent for the painful conditions in which it has been studied. As a COX-2—selective inhibitor, rofecoxib offers safety advantages over traditional NSAIDs. In clinical trials, gastrointestinal (GI) toxicity, including mucosal damage, perforation, ulcers, and bleeding, occurred significantly less often in healthy volunteers and patients treated with rofecoxib than in those who received NSAIDs such as ibuprofen, naproxen, or diclofenac (all comparisons, P < 0.001). In terms of renal toxicity, rofecoxib does not appear to offer a safety advantage over traditional NSAIDs. Rofecoxib has not been shown to affect platelets (bleeding time and platelet aggregation), unlike traditional NSAIDs. Conclusions: Rofecoxib is an appropriate choice for patients who do not obtain adequate analgesia with acetaminophen and those who have not obtained adequate analgesia from, cannot tolerate, or are at risk for GI toxicity with traditional NSAIDs. Patients who require chronic analgesic medication (ie, those with OA), including those who take other medications daily for comorbid conditions, may also benefit from the once-daily dosing regimen of rofecoxib.

Analgesic efficacy of ketorolac and morphine in neonatal rats

Ketorolac is a potent nonsteroidal antiinflammatory drug (NSAID). In adult humans and animals, its analgesic efficacy can be comparable to opiates. However, it has not been studied in neonatal animals. We conducted a blinded, controlled study comparing the effects of ketorolac and morphine in neonatal rats using the formalin model. Animals were given intraperitoneal (ip) injections of ketorolac or morphine at 3 or 21 days of age. Ketorolac had an analgesic and antiinflammatory effect in 21-day-old pups, but not in the 3-day-olds. Morphine had a significant analgesic, but no antiinflammatory effect at both ages. These results indicate that ketorolac is an effective analgesic agent in preweaning, but not neonatal rats. Opiates may be more appropriate analgesics in neonates.

Tol??rance gastro-intestinale des anti-inflammatoires non-st??ro??diens

Gastrointestinal Tolerability of Nonsteroidal Anti-Inflammatory Drugs Nonsteroidal anti-inflammatory drugs (NSAIDs) are effective antipyretic, analgesic and anti-inflammatory agents. One of the major concerns regarding the use of these compounds is the incidence of gastrointestinal (GI) adverse effects, ranging from dyspepsia to the serious and potentially life threatening complications of ulcers, haemorrhages, and perforations. Thus, the prevention and/or treatment of upper GI damage is estimated to increase the overall cost of NSAID therapy by at least 40%. The pathogenesis of NSAID-induced gastroduodenal mucosal injury appears to involve both topical and systemic mechanisms. The former is related to the acidic nature of most NSAIDs, which promotes the accumulation of ionised molecules (ion trapping) within the mucosal cells. Topical mucosal injury may also occur as a result of biliary excretion of active NSAID metabolites. The systemic effect has, however, the predominant role. It is mediated through cyclo-oxygenase (COX) inhibition and a subsequent decrease in gastroprotective prostaglandins. Fortunately, 2 forms of COX enzymes, designated COX-1 and COX-2, have been recognised. COX-1 appears to function as a house-keeping enzyme, whereas COX-2 is primarily induced by inflammatory stimuli and mitogens in various cells, including macrophages and synovial cells. Accordingly, the inhibition of COX-2 would result in anti-inflammatory effects, whereas gastroduodenal ulceration is thought to be related to the inhibition of COX-1. Animal data have suggested that nabumetone has a low ulcerogenic potential in comparison with other available NSAIDs. This feature was further supported by controlled clinical trials as well as epidemiological studies. The relative GI safety of nabumetone may be attributed to its lack of direct and indirect topical effects because of its nonacidic nature and absence of enterohepatic recirculation. Furthermore, the active metabolite [6-methoxy-2-naphthylacetic acid (6-MNA)] may be gastro-sparing as a result of its property of COX-2 preferential inhibition. La toxicite digestive des anti-inflammatoires non-steroidiens (AINS) est la principale responsable de la morbidite, de la mortalite et du surcout lies a l'emploi de ces medicaments. Elle resulte d'une agression locale de la muqueuse par les AINS et, surtout, d'une action systemique, consecutive a l'inhibition de la synthese des prostaglandines cytoprotectrices dans le tractus gastro-duodenal. Tous les AINS disponibles exposent certes aux complications ulcereuses, hemorragiques et aux perforations mais les donnees experimentales, cliniques et epidemiologiques montrent que le risque varie selon les molecules. A ce titre, un faisceau convergent d'arguments plaide en faveur du faible potentiel ulcerogene de la nabumetone. Ce profil avantageux serait la consequence des caracteristiques physicochimiques (AINS prodrogue non-acide) et cinetiques (absence d'elimination biliaire) du produit, des lors denue de toxicite muqueuse directe. De plus, d'apres differents travaux, son metabolite actif, l'acide 6-methoxy-2-naphtylacetique (6-MNA), apparait comme un inhibiteur preferentiel de COX-2 de sorte qu'il epargnerait relativement COX-1, iso-enzyme impliquee dans la formation des prostaglandines dans l'estomac.

The multisystem adverse effects of NSAID therapy.

The clinical utility of nonsteroidal anti-inflammatory drugs (NSAlDs) to manage pain and inflammation is limited by adverse side effects. Although effective analgesic and anti-inflammatory agents, NSAlDs are associated with side effects that are a consequence of nonspecific inhibition of both cyclooxygenase-1 (COX-1) and 1 cyclooxygenase-2 (COX-2).The primary adverse events associated with NSAID therapy are upper gastrointestinal (GI) ulceration, perforation, or bleeding, all of which involve mucosal damage of varying severity and can be asymptomatic and I occur with little warning. Clinicians who prescribe NSAIDs should be able to identify patients who are at risk of an NSAID-induced GI adverse event and to detect and manage the event should one occur. The use of COX-2-specific inhibitors to manage pain and inflammation may minimize the risks of NSAID-associated toxicities.

Analgesics in ophthalmic practice: a review of the oral non-narcotic agent tramadol.

This report reviews the causes of ocular pain and discusses the pharmacology, pharmacokinetics, efficacy, adverse effects, and dosage of tramadol, a novel non-narcotic oral analgesic. Tramadol is a synthetic analog of codeine with a dual mechanism of action that involves agonist activity at the mu opioid receptor, as well as inhibition of monoaminergic (norepinephrine and serotonin) re-uptake. Unlike opiate analgesics, tramadol has very low propensity toward physical dependence. Common dose-related adverse effects of tramadol include dizziness, nausea, vomiting, dry mouth, and/or drowsiness. Clinically, tramadol has been shown to be equivalent to acetaminophen (325 mg)-codeine (30 mg) combinations for the treatment of moderate or severe nonocular pain. Tramadol appears to be an effective analgesic agent for pain control due to postoperative surgical trauma, as well as in various chronic malignant and nonmalignant disease states. Tramadol has shown variable effectiveness in the control of pain related to dental procedures. The usefulness of tramadol in pain states from ophthalmic origin has yet to be clinically established.

The involvement of opioidergic and noradrenergic mechanisms in nefopam antinociception

Nefopam is a clinically effective analgesic agent used to control mild to moderate pain, whose mechanism of action is unknown. We have investigated the antinociceptive activity of nefopam in the mouse abdominal constriction assay and tail immersion test (48°C). Nefopam was found to possess a high degree of potency against acetic acid-induced visceral nociception (ED 50 2.5 mg kg −1). In the presence of the opioid receptor antagonists, naloxone or naltrindole, the resulting nefopam dose–response relationships were shifted to the right. Naloxone or naltrindole had no effect upon aspirin (ED 50 32.1 mg kg −1) or clonidine (ED 50 0.061 mg kg −1) induced antinociception. Acetorphan (10 mg kg −1; s.c.), an inhibitor of neutral endopeptidase (EC 3.4.24.11) was able to potentiate nefopam's antinociceptive activity (ED 50 1.5 mg kg −1). The α 2-adrenoceptor antagonist, 2-[2-(2-methoxy-1,4-benzodioxanyl)]imidazoline hydrochloride (RX821002; 1 mg kg −1; s.c.), shifted the dose–response curves for clonidine (ED 50 7.1 mg kg −1) and nefopam (ED 50 5.3 mg kg −1) to the right in this assay. Additionally, centrally administered RX821002 (1 μg/5 μl/animal; i.c.v.) reduced both clonidine (ED 50 7.2 mg kg −1) and nefopam's (ED 50 15.5 mg kg −1) efficacy in the abdominal constriction assay. Nefopam (3 and 7.5 mg kg −1; s.c.) produced significant antinociceptive effect in the thermal assay. Aspirin and RX821002 were devoid of any significant activity in the tail immersion test. Nefopam was shown to possess RX821002-reversible antinociceptive activity in both the tail immersion test and the abdominal constriction assay. These data suggest the involvement of an opioidergic and noradrenergic component to nefopam's antinociceptive activity in the mouse abdominal constriction assay and tail immersion test. However, the present results are unable to determine if the opioidergic component of nefopam antinociception is through a direct and/or indirect activation of opioid receptors.

NSAIDs revisited

PREVIEWAlthough nonsteroidal anti-inflammatory drugs (NSAIDs) are effective analgesic and anti-inflammatory agents, they may have adverse effects on the gastrointestinal, hepatic, renal, pulmonary, and platelet aggregation systems in susceptible patients. Careful consideration of the risks and benefits, judicious dosing, and careful monitoring by the primary care physician are therefore essential. The authors of this article review both the therapeutic and adverse effects of NSAIDs and provide suggestions for safe clinical use.

Nonsteroidal anti-inflammatory drug-induced gastrointestinal injury

Nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin, are the most commonly used medications worldwide. They are effective analgesic and anti-inflammatory agents. A major drawback to their use is a high frequency of adverse gastrointestinal (GI) effects that cause significant morbidity, occasional mortality, and substantial increases in cost of therapy. In this review, mechanisms of NSAID-induced GI injury are presented, and a clinical approach to diagnosis, treatment, and prevention of these adverse GI effects is provided.

Efficacy of intra‐muscular analgesics for acute pain in sheep

The analgesic action of intramuscularly injected buprenorphine, methadone, flunixin meglumine and xylazine was examined in sheep, using algesimetry based on a leg withdrawal response to an electrical stimulus. No analgesic response was detected for buprenorphine, methadone or flunixin meglumine. Only the alpha 2-adrenoceptor agonist, xylazine, produced an analgesic response. The current required to elicit a response increased by 170% (4.5 +/- 0.43 mA to 12.23 +/- 1.14 mA; mean +/- SE) after a dose of 0.05 mg/kg xylazine; by 180% (4.73 +/- 0.3 mA to 13.28 +/- 2.35 mA) after 0.1 mg/kg and by 510% (4.52 +/- 0.29 mA to 27.63 +/- 3.89 mA) after 0.2 mg/kg. Intramuscular xylazine appears to be an effective analgesic agent for acute pain in the sheep and further investigation into ideal administration regimens and dosage may provide more detailed information on relationships between dose, analgesic and sedative effects. The findings also suggest that some common analgesic agents, and opioids in particular, may be ineffective for the management of acute pain in sheep and that any analgesic should be administered only on the basis of its proven efficacy in that species.

Tenidap, a structurally novel drug for the treatment of arthritis: antiinflammatory and analgesic properties.

Tenidap is a new anti-rheumatic agent which has clinical properties characteristic of a disease modifying drug combined with acute antiinflammatory and analgesic activity. This paper details tenidap's cyclooxygenase (COX) inhibitory activity and the resulting pharmacological properties in experimental animals. Tenidap inhibited calcium ionophore-stimulated prostaglandin D2 synthesis by rat basophilic leukemia cells (COX-1) with an IC50 of 20 nM. In two different in vitro human test systems, tenidap inhibited COX-1 activity more potently than COX-2, although the relative potency ratio (COX-1/COX-2) differed markedly between the two systems. Tenidap inhibited the COX pathway when added to human blood in vitro (IC50, 7.8 mu M) and when administered orally to monkeys, rats and dogs (at 5, 2.5 and 10 mg/kg p.o., respectively) and COX activity measured ex vivo in blood collected 2 to 4 hours post dose. After oral administration to rats, tenidap inhibited carrageenan-induced paw edema with an ED50 of 14 mg/kg and inhibited the glucocorticoid-resistant UV erythema in guinea pigs with an ED50 of 1.4 mg/kg. It retained antiinflammatory activity in adrenalectomized rats indicating that this property is independent of adrenal stimulation. Oral administration of tenidap inhibited the development of adjuvant-induced polyarthritis in the rat and exhibited antinociceptive activity in the murine phenylbenzoquinone and rat acetic acid abdominal constriction tests. These data indicate that tenidap is an effective antiinflammatory and analgesic agent in animal models. These cyclooxygenase-dependent pharmacologic activities do not explain tenidap's disease modifying anti-arthritic properties but add a useful symptom modifying component to its clinical profile.

Comparison of the Efficacy and Tolerability of Tramadol, Pethidine and Nalbuphine in Children with Postoperative Pain

The analgesic efficacy and tolerability of tramadol, pethidine and nalbuphine were compared in this randomised study. 75 children aged 2 to 12 years with moderate or severe pain after mainly lower abdominal surgery received either tramadol 2 mg/kg (n = 25), pethidine 1 mg/kg (n = 25) or nalbuphine 0.1 mg/kg (n = 25) by intramuscular injection as soon as pain was expressed. An additional bolus of half the initial dose was administered 30 to 60 minutes later if analgesia was inadequate. Further doses equal to the initial bolus were given if pain requiring retreatment reappeared, up to a maximum daily dose of tramadol 12 mg/kg, pethidine 5 mg/kg and nalbuphine 1 mg/kg. Drug dosages were recorded in the patient records; the study was therefore regarded as an open trial. 60 minutes after the initial dose, children in all 3 treatment groups had either no or only slight pain. This level of efficacy was present at 30 minutes postdose in patients in the tramadol and pethidine groups and was maintained for 24 hours. In the nalbuphine group, pain of moderate intensity reappeared in 1 (4%) child 30 minutes after administration of the initial dose and in 2 (8%) children 6 hours after the initial dose. The number of repeat doses required to control pain was lowest with tramadol and highest with nalbuphine; 40% of patients receiving nalbuphine required 2 or more doses of medication compared with 28% of pethidine-treated patients and 4% of tramadol-treated patients. Overall pain relief was rated by investigators as ‘excellent’ in 40% of patients receiving tramadol, in 32% of patients receiving pethidine and in 24% of patients receiving nalbuphine, and as ‘very good’ in 48, 44 and 52% of patients, respectively. Reductions in blood pressure, respiratory rate and heart rate, and increases in arterial oxygen saturation, were minimal and were similar in all 3 treatment groups. Vomiting was the only adverse event reported, and this occurred in 1 patient treated with tramadol. Tramadol 2 mg/kg appears to be an effective and well-tolerated analgesic agent in children with postoperative pain.

Camphor Revisited: Focus on Toxicity

This Policy Statement was retired April 2013. This commentary updates a previous AAP statement developed by the Committee on Drugs concerning camphor.1 The original commentary reflected the level of concern among pediatric practitioners and poison centers about the toxicity of camphor. Since the original statement, the Food and Drug Administration (FDA) has recognized camphor as a safe and effective topical antitussive, analgesic, anesthetic, and antipruritic agent.2 Following the approval process in 1983, the FDA required that the concentration of camphor in products not exceed 11%.2 Higher concentrations were not more effective and could cause more serious adverse reactions if accidentally ingested. Most reported camphor-related fatalities involved agents containing a concentration greater than 11%. Ingestion of potentially toxic substances by children is related to the availability of a product in their environment. Camphor remains widely available (Table). The toxicity of camphor when inappropriately used is well documented.3-6 Ingestion is the most common route of potentially toxic exposure, with rapid onset of toxic effects. The risk of toxicity relates to both the concentration of camphor in the ingested product and the rate of absorption of camphor into the body. From 1985 through 1989, 32 362 human exposures to camphor were reported to the American Association of Poison Control Centers.7-11 From 1985 through 1989, life-threatening toxicity occurred in 33 children as the result of camphor ingestion. During this period, there were no Childhood deaths as the result of camphor ingestion. In 5 cases, the products ingested contained more than 11% camphor even though they had been discontinued in 1983. In 14 cases, the products contained between 10% and 11% camphor.

The use of intravenous ketorolac for the treatment of renal colic in the emergency department

The objective of this study was to report the authors' experience using intravenous ketorolac (Syntex Laboratories, Palo Alto, CA) as an analgesic in the treatment of renal colic in a convenience sample at three suburban community hospital emergency departments. Twenty-five patients with renal colic were participants. Pregnant women, patients with a history of renal or hepatic impairment, bleeding diathesis, active peptic ulcer disease, or hypersensitivity to aspirin or nonsteroidal antiinflammatory drugs (NSAID) were excluded. Ketorolac 30 mg administered intravenously during a 1-minute period, and the following parameters were monitored at times 0, 5, 10, 20, 30, and 60 minutes: pain on a scale of 0 to 10, pulse rate, blood pressure, and adverse side effects. A total of 25 patients were included in our series. Initially, they had a median pain score of 9 with an interquartile range of 1. Thereafter, the median pain scores and (interquartile ranges) were 8 (three) at 5 minutes, 5 (four) at 10 minutes, 2 (four) at 20 minutes, 1 (three) at 30 minutes, and 0 (one) at 60 minutes. There were no adverse side effects observed in any patients. Therefore, it can be concluded that intravenous ketorolac is an effective analgesic agent for the control of pain in patients with renal colic.

Analgesic Oral Efficacy of Tramadol Hydrochloride in Postoperative Pain

Tramadol hydrochloride is a synthetic opiate agonist with a plasma elimination half-life of 5 to 6 hours and peak plasma levels at about 1½ hours. It derives its activity from attachment to the μ-receptor and blockage of norepinephrine reuptake. The purpose of this single-dose, double-blind, placebo-controlled study was to determine the analgesic effectiveness of an oral administration of two dose levels of tramadol hydrochloride (75 or 150 mg) compared with the combination of 650 mg acetaminophen plus 100 mg propoxyphene napsylate in 161 patients with severe postoperative pain after cesarean section. Analgesia was assessed over a 6-hour period. Treatments were compared on the basis of standard scales for pain intensity and relief and a number of derived variables based on these data. A global rating of the study medication was also used to compare treatments. The three active treatments were effective analgesics, statistically superior to placebo for many hourly and summary measures. A dose response was seen between the two tramadol doses, with the 150 mg dose providing significantly greater analgesia over the lower dose. The 75 mg dose of tramadol was generally more effective than the acetaminophen-propoxyphene combination after hour 2, and significantly so for some hourly time points, as well as for the global rating of the medication. The 150 mg dose of tramadol was significantly more effective than the acetaminophen-propoxyphene combination from hour 2 through hour 6 for the sum of pain intensity differences and total pain relief scores, as well as for the global rating of the medication. Tramadol hydrochloride at both dose levels is an effective analgesic agent and at 150 mg is statistically superior to the acetaminophen-propoxyphene combination. No serious adverse effects were observed; however, dizziness was more frequently reported with 150 mg tramadol. Clinical Pharmacology and Therapeutics (1992) 51, 740–746; doi:10.1038/clpt.1992.86

Diminished reactivity of postmature human infants to sucrose compared with term infants.

Sucrose is an effective calming and analgesic agent in infant humans, and characteristics of this calming effect suggest it may occur through an opioid pathway. Implications of this would be that infants who have experienced chronic prenatal stress and concomitantly elevated levels of endogenous opioids resulting in tolerance should therefore be less responsive to sucrose than nonstressed infants. To test this, we compared healthy term infants (M = 39 weeks 3 days) and chronically stressed, postmature infants (M = 42 weeks) with respect to the sucrose-mediated calming effect at 5-91 hr of age

Salicylate intoxication in the elderly. Recognition and recommendations on how to prevent it.

Aspirin (acetylsalicylic acid) and its salicylate derivatives are effective antipyretic, analgesic, and anti-inflammatory agents that are still very widely used by the elderly despite the advent of newer, potentially safer nonsteroidal anti-inflammatory drugs (NSAIDs). However, none of the new NSAIDs have been proven to be more effective than aspirin or salicylic acid. Chronic salicylate intoxication which is most common in the elderly, may occur with therapeutic doses. Increased toxicity in older patients often appears due to inadvertent overdosage. Dual prescribing or additional use of nonprescription salicylates are some causes of unwitting long term toxicity. According to some studies, systemic clearance of salicylate (mainly by hepatic metabolism) is reduced with age, as is renal elimination. These changes are of increased importance in the elderly using high therapeutic doses of salicylates when metabolism is saturated and more unchanged drug is available for renal excretion. In the face of renal impairment, the risk of toxicity is increased. The diagnosis of acute salicylate intoxication generally does not pose diagnostic problems. Patients often present with a history of intentional overdose, with hyperventilation, fever, and nausea. The diagnosis can be confirmed by measuring serum salicylate concentrations. Chronic intoxication often poses a diagnostic dilemma with atypical presentations mimicking other disease states such as diabetic ketoacidosis, delirium, cerebrovascular accident, myocardial infarction or cardiac failure. The diagnosis of salicylate intoxication should be borne in mind when an older patient presents with recent deterioration in activities of daily living with no known cause. Plasma salicylate concentrations should be measured if salicylate intoxication is suspected, even if there is no documented history of salicylate ingestion. The risk of salicylate nephrotoxicity is also increased with age, and upper gastrointestinal haemorrhage is associated with increased mortality in older age groups. Treatment of acute toxicity consists of prompt recognition of salicylate intoxication, use of activated charcoal, correction of acid-base abnormalities, general supportive measures, and if concentrations are extremely high, dialysis can be effectively used. Chronic toxicity, which can occur even with marginally high salicylate concentrations, is treated with drug withdrawal and supportive therapy. Chronic salicylate toxicity can be averted by prescription of conservative doses of drug, avoidance of concomitant use of different salicylate preparations, and therapeutic monitoring to guide dosage. Renal function should be monitored to detect nephrotoxicity from chronic salicylate therapy. Patients should be regularly screened for evidence of gastrointestinal bleeding.(ABSTRACT TRUNCATED AT 400 WORDS)