Renal toxicity of non-steroidal anti-inflammatory drugs.
Abstract: Non-steroidal anti-inflammatory drugs represent the most heavily prescribed and used class of drugs in human medicine. Most are derivatives of either salicylates, propionic acid, indoleacetic acid, anthranilic acid, pyrazolone, or oxicams. They depress the synthesis of prostaglandins from arachidonic acid by reversible inhibition of the enzyme cyclooxygenase. In the kidney, prostaglandins PGE2 and PGI2 modulate the vasoconstrictor effects of angiotensin II, norepinephrine, and vasopressin. In the presence of volume contraction, anesthesia, or disease states associated with high levels of these hormones, prostaglandins regulate glomerular filtration, vascular resistance, and renin secretion. They additionally influence urine volume and sodium content. In man, a syndrome of analgesic abuse that has been identified worldwide occurs more frequently in females than males and can result in severe renal damage, most notably renal papillary necrosis. Most common laboratory animals are relatively resistant to developing the renal lesion associated with NSAIDs unless high doses are given over long periods of time and some withholding of water is introduced into the protocol. Diuresis with 5% dextrose and water is protective. Studies of paracetamol and salicylate have demonstrated that these compounds concentrate in the papillary tip of the kidney at concentrations of 4 to 13 times the plasma levels in dogs and rabbits, respectively. Renal papillary necrosis has been described in horses on maintenance doses of phenylbutazone where dehydration or reduced water consumption has occurred. The lesion can be reproduced experimentally if water is withheld during a portion of the dosing interval. An increased incidence of uroepithelial tumors have been reported in patients with a history of analgesic abuse.(ABSTRACT TRUNCATED AT 250 WORDS)
Publication Date: 1986-01-01 PubMed ID: 3487106DOI: 10.1177/019262338601400110Google Scholar: Lookup
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- Journal Article
Summary
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The research article focuses on the potential kidney damage caused by the overuse of non-steroidal anti-inflammatory drugs (NSAIDs) which are commonly prescribed and used medicines. The main concern is a condition known as renal papillary necrosis that is prevalent in people, particularly women, who repeatedly misuse these drugs.
Overview of NSAIDs and their Connection to Renal Toxicity
- The article starts by identifying NSAIDs as commonly prescribed drugs in human medicine.
- Different types of NSAIDs are mentioned, including salicylates, propionic acid, indoleacetic acid, anthranilic acid, pyrazolone, and oxicams.
- The way NSAIDs function is by inhibiting the enzyme cyclooxygenase, which lowers the production of prostaglandins from arachidonic acid.
- In the kidneys, prostaglandins play a critical part in regulating various processes, including glomerular filtration, vascular resistance, renin secretion, as well as influencing urine volume and sodium levels.
Effects of NSAIDs on Kidney Function
- The article underlines the role of certain circumstances such as disease states with high hormone levels, anesthesia, and volume contraction, where prostaglandins keep kidney functions in check. In these conditions, overuse of NSAIDs could disturb the balance, leading to kidney issues.
- A condition termed ‘analgesic abuse syndrome’ is discussed that is identified worldwide and seen more often in females than males. This syndrome leads to serious kidney damage, particularly renal papillary necrosis.
Studies on Animals and NSAIDs
- The article reveals that most laboratory animals do not easily develop kidney damage associated with NSAIDs, unless they are given high doses over extended periods and if their water availability is controlled.
- Findings showed that a regimen of diuresis with 5% dextrose and water can offer some protection against these effects.
- Research on paracetamol and salicylate showed that these substances concentrate in the kidney’s papillary tip at levels much higher than in plasma. This was seen in both dogs and rabbits.
Conclusion and Implications
- Reports of horses developing renal papillary necrosis due to prolonged use of phenylbutazone (an NSAID), particularly when dehydrated or consuming less water, were discussed. This damage can be replicated experimentally by controlling water intake during dosing.
- Finally, the paper states that there is an increased incidence of uroepithelial tumors among patients with a history of analgesic abuse.
Cite This Article
APA
Black HE.
(1986).
Renal toxicity of non-steroidal anti-inflammatory drugs.
Toxicol Pathol, 14(1), 83-90.
https://doi.org/10.1177/019262338601400110 Publication
Researcher Affiliations
MeSH Terms
- Animals
- Anti-Inflammatory Agents / adverse effects
- Anti-Inflammatory Agents, Non-Steroidal / adverse effects
- Female
- Humans
- Kidney / metabolism
- Kidney / pathology
- Kidney / physiology
- Kidney Diseases / chemically induced
- Kidney Diseases / pathology
- Kidney Neoplasms / chemically induced
- Male
- Prostaglandins / biosynthesis
- Prostaglandins / physiology
- Substance-Related Disorders / complications
Citations
This article has been cited 3 times.- Coetzee JF, Sidhu PK, Seagen J, Schieber T, Kleinhenz K, Kleinhenz MD, Wulf LW, Cooper VL, Mazloom R, Jaberi-Douraki M, Lechtenberg K. Transmammary delivery of firocoxib to piglets reduces stress and improves average daily gain after castration, tail docking, and teeth clipping1. J Anim Sci 2019 Jul 2;97(7):2750-2768.
- Shimokaze T, Akaba K, Saito E. Heparin-induced hyperkalemia in an extremely-low-birth-weight infant: a case report. J Clin Res Pediatr Endocrinol 2014;6(2):125-8.
- Ettlin RA, Kuroda J, Plassmann S, Prentice DE. Successful drug development despite adverse preclinical findings part 1: processes to address issues and most important findings. J Toxicol Pathol 2010 Dec;23(4):189-211.
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