Lithium Intoxication as a Result of an Interaction with Rofecoxib

Bravo, Alexandra E. Rätz; Egger, Sabin S.; Crespo, S; Probst, Willi L; Krähenbühl, Stephan

doi:10.1345/aph.1e034

Cited by 12 publications

(8 citation statements)

References 21 publications

(40 reference statements)

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“…Finally, the long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs), such as indomethacin, and COX-2-specific inhibitors (celecoxib or rofecoxib), which suppress PGE 2 production by directly inhibiting cyclooxygenases, is known to cause permanent renal toxicity and damage and/or elevated serum Li to toxic levels (6,16,39,41). Hence replacement of the current side effect-prone drugs with new drugs based on improved understanding of the molecular pathophysiology of Li-induced NDI should result in improved efficacy and fewer side effects in the clinic.…”

Section: Discussionmentioning

confidence: 99%

Potential role of purinergic signaling in lithium-induced nephrogenic diabetes insipidus

Zhang

Nelson²,

Carlson³

et al. 2009

American Journal of Physiology-Renal Physiology

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Zhang Y, Nelson RD, Carlson NG, Kamerath CD, Kohan DE, Kishore BK. Potential role of purinergic signaling in lithiuminduced nephrogenic diabetes insipidus. Am J Physiol Renal Physiol 296: F1194 -F1201, 2009. First published February 25, 2009 doi:10.1152/ajprenal.90774.2008.-Lithium (Li)-induced nephrogenic diabetes insipidus (NDI) has been attributed to the increased production of renal prostaglandin (PG)E2. Previously we reported that extracellular nucleotides (ATP/UTP), acting through P 2y2 receptor in rat medullary collecting duct (mCD), produce and release PGE2. Hence we hypothesized that increased production of PGE 2 in Li-induced NDI may be mediated by enhanced purinergic signaling in the mCD. Sprague-Dawley rats were fed either control or Li-added diet for 14 or 21 days. Li feeding resulted in marked polyuria and polydipsia associated with a decrease in aquaporin (AQP)2 protein abundance in inner medulla (ϳ20% of controls) and a twofold increase in urinary PGE2. When acutely challenged ex vivo with adenosine 5Ј-O-(3-thiotriphosphate) (ATP␥S), UTP, or ADP, mCD of Li-fed rats showed significantly higher increases (50 -130% over control diet-fed rats) in PGE 2 production, indicating that more than one subtype of P 2y receptor is involved. This was associated with a 3.4-fold increase in P2y4, but not P2y2, receptor mRNA expression in the inner medulla of Li-fed rats compared with control diet-fed rats. Confocal laser immunofluorescence microscopy revealed predominant localization of both P2y2 and P2y4 receptors in the mCD of control or Li diet-fed rats. Together, these data indicate that in Li-induced NDI 1) purinergic signaling in the mCD is sensitized with increased production of PGE2 and 2) P2y2 and/or P2y4 receptors may be involved in the enhanced purinergic signaling. Our study also reveals the potential beneficial effects of P 2y receptor antagonists in the treatment and/or prevention of Li-induced NDI. collecting duct; P 2 receptors; extracellular nucleotides; prostaglandin E 2; cyclooxygenases; bipolar disorder; neurodegeneration; rat LITHIUM (Li) has been in clinical use for about half a century, mostly for the treatment of bipolar disorder, which affects up to 2% of the US population (33), with double the incidence in veterans. Mental depression and substance abuse, which are often encountered in posttraumatic stress disorder patients, such as war veterans, are known to predispose them to bipolar disorders. Despite the advent of newer drugs for bipolar disorders, Li is still an important medication in the psychiatric treatment regimen by virtue of the significantly lower suicidal risk in Li-treated patients (3). In addition, the advances in the pharmacotherapeutics of bipolar disorder over the past 10 -15 yr have been predominantly in terms of tolerability and safety, with no new treatments being demonstrated to be more effective than Li (38). Furthermore, recent studies unraveled the neuroprotective effect of Li, thus making it a potential drug for the treatment of acute brain injury (e.g., stroke...

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Section: Discussionmentioning

confidence: 99%

Potential role of purinergic signaling in lithium-induced nephrogenic diabetes insipidus

Zhang

Nelson²,

Carlson³

et al. 2009

American Journal of Physiology-Renal Physiology

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“…Several documented drug‐drug interactions were mechanistically attributed to possible cytochrome P450 (CYP)/P‐glycoprotein (P‐gp) origins: colchicines with clarithromycin (P‐gp), 31 fluoxetine with cyclobenzaprine (CYP2D6), 32 celecoxib plus clopidogrel (CYP2C9), 33 lansoprazole plus tacrolimus (CYP2C19), 34 and simvastatin with amiodarone (CYP3A4) 35 . Other interactions were believed to be of possible pharmacodynamic origins: pseudoephedrine and tramadol, 36 lisinopril with tizanidine, 37 lithium plus rofecoxib, 38 warfarin plus orlistat, 39 and warfarin with smokeless tobacco 40 …”

Section: Traditional Methods Of Evaluating Drug‐drug Interactionsmentioning

confidence: 99%

Population‐Based Assessments of Clinical Drug‐Drug Interactions: Qualitative Indices or Quantitative Measures?

Zhou¹

2006

The Journal of Clinical Pharma

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Population-based assessments of drug-drug interactions have become more common since the introduction and acceptance of the population pharmacokinetic approach. Unlike traditional methods, population-based studies provide clinically relevant results that can be applied directly to a target patient population. Furthermore, population-based studies do not demand the traditional requirements of intensive pharmacokinetic sampling, rigorous inpatient stays, or stringent assessment schedules. As such, the population-based approach can effectively be used to confirm known drug-drug interactions and further characterize anticipated interactions. A prospectively designed analysis can also reveal drug-drug interactions that might otherwise have gone undetected with traditional methods. Ultimately, these results could help to alleviate clinicians' concerns about using widely marketed drugs in combination therapies and also reduce patients' risk of experiencing unacceptable side effects. This article intends to provide a balanced overview of the population-based approach and its merits, drawbacks, and potential utility in the assessment of drug-drug interactions during clinical drug development.

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“…Thiazide diuretics should be used with caution in lithium-induced NDI, as they reduce the renal excretion of lithium, potentially resulting in lithium intoxication; while indomethacin, a non-steroidal anti-inflammatory drug (NSAID), increases the risk of gastrointestinal disorders and bleeding. In addition, recent reports indicate that the use of NSAIDs, especially COX-2-specific inhibitors (celecoxib and rofecoxib), in patients on lithium therapy is associated with increased serum lithium concentrations [58,59]. Currently, the safety of long-term use of COX-2 inhibitors with their cardiovascular complications is in question and their future is uncertain.…”

Section: Future Perspectivesmentioning

confidence: 99%

P2Y2 receptors and water transport in the kidney

Kishore

Nelson

Miller

et al. 2009

Purinergic Signalling

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The kidneys play a critical role in the maintenance of water homeostasis. This is achieved by the inherent architecture of the nephron along with the expression of various membrane transporters and channels that are responsible for the vectorial transport of salt and water. The collecting duct has become a focus of attention by virtue of its ability to transport water independent of solutes (free-water transport), and its apparent involvement in various water balance disorders. It was originally believed that the water transport capability of the collecting duct was solely under the influence of the circulating hormone, arginine vasopressin (AVP). However, during the past decade, locally produced autocrine and/or paracrine factors have emerged as potent modulators of transport of water by the collecting duct. Recently, much attention has been focused on the purinergic regulation of renal water transport. This review focuses on the role of the P2Y 2 receptor, the predominant purinergic receptor expressed in the collecting duct, in the modulation of water transport in physiological and pathophysiological conditions, and its therapeutic potential as a drug target to treat water balance disorders in the clinic. Studies carried out by us and other investigators are unravelling potent interactions among AVP, prostanoid and purinergic systems in the medullary collecting duct, and the perturbations of these interactions in water balance disorders such as acquired nephrogenic diabetes insipidus. Future studies should address the potential therapeutic benefits of modulators of P2Y 2 receptor signalling in water balance disorders, which are extremely prevalent in hospitalised patients irrespective of the underlying pathology.

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Lithium Intoxication as a Result of an Interaction with Rofecoxib

Abstract: Coadministration of rofecoxib and lithium may result in life-threatening lithium intoxication, especially in patients with a preexisting decrease in renal function and/or decreased intravascular volume.

Cited by 12 publications

References 21 publications

Potential role of purinergic signaling in lithium-induced nephrogenic diabetes insipidus

Potential role of purinergic signaling in lithium-induced nephrogenic diabetes insipidus

Population‐Based Assessments of Clinical Drug‐Drug Interactions: Qualitative Indices or Quantitative Measures?

P2Y2 receptors and water transport in the kidney

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