Effects of non-steroidal anti-inflammatory drug treatment on the kidney

Ludovic Pelligand; Jonathan Elliott

doi:10.22233/9781910443354.20

British Small Animal Veterinary Association , 232 (2017); https://doi.org/10.22233/9781910443354.20

/content/chapter/10.22233/9781910443354.chap20

Effects of non-steroidal anti-inflammatory drug treatment on the kidney

GBP

BSAVA Library Pass Buy a pass

Authors: Ludovic Pelligand and Jonathan Elliott
From: BSAVA Manual of Canine and Feline Nephrology and Urology
Item: Chapter 20, pp 232 - 245
DOI: 10.22233/9781910443354.20
Copyright: © 2017 British Small Animal Veterinary Association
Publication Date: January 2017

Abstract

The population of animals that develop kidney disease are often elderly with multiple problems. It is not uncommon to have a clinical need to provide pain relief, often on a chronic basis, for dogs and cats with chronic kidney disease. This chapter provides information on pharmacology of NSAIDs; the role of COX enzyme products in normal kidney physiology; renal toxicity of NSAIDs; and benefit/harm assessment of the use of NSAIDs in patients with kidney disease.

Preview this chapter:

Full text loading...

/content/chapter/10.22233/9781910443354.chap20

Figures

/content/figure/10.22233/9781910443354.chap20.ch20fig1

20.1

Arachidonic acid cascade from membrane phospholipids to intracellular effects of its metabolites (with particular focus on prostaglandin E2). Enzyme actions are represented by a curved green arrow. The actions of enzyme inhibitors or receptor blockers are represented along the cascade by red arrows with flat ends. COX = cyclooxygenase; COXIB = COX-2 inhibitor; EP = G protein-coupled eicosanoid receptor; Gs, Gi, Gq = alpha-subunits of the G protein-coupled receptor; NSAIDs = non-steroidal anti-inflammatory drugs; PG = prostaglandin; PLC = phospholipase C; TX = thromboxane. (Reproduced from Nasrallah et al. 2014 with permission from the American Journal of Physiology) © 2017 British Small Animal Veterinary Association

10.22233/9781910443354/fig20_1_thumb.gif

10.22233/9781910443354/fig20_1.png

20.1 Arachidonic acid cascade from membrane phospholipids to intracellular effects of its metabolites (with particular focus on prostaglandin E2). Enzyme actions are represented by a curved green arrow. The actions of enzyme inhibitors or receptor blockers are represented along the cascade by red arrows with flat ends. COX = cyclooxygenase; COXIB = COX-2 inhibitor; EP = G protein-coupled eicosanoid receptor; Gs, Gi, Gq = alpha-subunits of the G protein-coupled receptor; NSAIDs = non-steroidal anti-inflammatory drugs; PG = prostaglandin; PLC = phospholipase C; TX = thromboxane. (Reproduced from Nasrallah et al. 2014 with permission from the American Journal of Physiology)

/content/figure/10.22233/9781910443354.chap20.ch20fig4

20.4

Chemical formulae of non-steroidal anti-inflammatory drugs (NSAIDs) authorized for use in the UK. (a) Chemical formulae for arachidonic acid and traditional NSAIDs: aspirin (salicylate), ketoprofen/carprofen (aryl propionic acid family; (*) denotes the presence of an asymmetrical carbon), tolfenamic acid (fenamate family) and meloxicam (oxicam family). (b) Chemical formulae for COX-2 inhibitors (COXIBs) authorized for use in companion animals: firocoxib (methylsulphone family), mavacoxib/cimicoxib (sulphonamide family) and robenacoxib (carboxylic acid family). © 2017 British Small Animal Veterinary Association

10.22233/9781910443354/fig20_4_thumb.gif

10.22233/9781910443354/fig20_4.png

20.4 Chemical formulae of non-steroidal anti-inflammatory drugs (NSAIDs) authorized for use in the UK. (a) Chemical formulae for arachidonic acid and traditional NSAIDs: aspirin (salicylate), ketoprofen/carprofen (aryl propionic acid family; (*) denotes the presence of an asymmetrical carbon), tolfenamic acid (fenamate family) and meloxicam (oxicam family). (b) Chemical formulae for COX-2 inhibitors (COXIBs) authorized for use in companion animals: firocoxib (methylsulphone family), mavacoxib/cimicoxib (sulphonamide family) and robenacoxib (carboxylic acid family).

/content/figure/10.22233/9781910443354.chap20.ch20fig5

20.5

Integration of pharmacokinetic (PK) and pharmacodynamic (PD) data applied to the administration of an original dose of 0.3 mg/kg of meloxicam subcutaneously in the cat. (a) In vitro feline whole blood assays for meloxicam ( Giraudel et al., 2005 ). Cyclooxygenase inhibition potencies were 4.1 μM for IC50 COX-1 (1440 ng/ml) and 1.35 μM for IC50 COX-2 (474 ng/ml). From the graph, one can extrapolate to the IC20 COX-1 and IC80 COX-2. (b) Spectrum of NSAID selectivity based on the IC50 COX-1:COX-2 potency ratio. COX-1 selective compounds are on the left and COX-2 selective COXIBs are on the right. (c) Plasma concentration–time curve of meloxicam (0.3 mg/kg s.c.) in the cat ( Giraudel et al., 2005 ). The time during which plasma meloxicam remains above IC20 COX-1 and IC80 COX-2 can be visualized directly on the figure. IC50 = 50% inhibitory concentration; Tx = thromboxane. © 2017 British Small Animal Veterinary Association

10.22233/9781910443354/fig20_5_thumb.gif

10.22233/9781910443354/fig20_5.png

20.5 Integration of pharmacokinetic (PK) and pharmacodynamic (PD) data applied to the administration of an original dose of 0.3 mg/kg of meloxicam subcutaneously in the cat. (a) In vitro feline whole blood assays for meloxicam ( Giraudel et al., 2005 ). Cyclooxygenase inhibition potencies were 4.1 μM for IC50 COX-1 (1440 ng/ml) and 1.35 μM for IC50 COX-2 (474 ng/ml). From the graph, one can extrapolate to the IC20 COX-1 and IC80 COX-2. (b) Spectrum of NSAID selectivity based on the IC50 COX-1:COX-2 potency ratio. COX-1 selective compounds are on the left and COX-2 selective COXIBs are on the right. (c) Plasma concentration–time curve of meloxicam (0.3 mg/kg s.c.) in the cat ( Giraudel et al., 2005 ). The time during which plasma meloxicam remains above IC20 COX-1 and IC80 COX-2 can be visualized directly on the figure. IC50 = 50% inhibitory concentration; Tx = thromboxane.

/content/figure/10.22233/9781910443354.chap20.ch20fig8

20.8

Flowchart summarizing the relationship between hypotension, renin–angiotensin–aldosterone system (RAAS) activation, cyclooxygenase (COX) dependency and renal injury mechanisms. GFR = glomerular filtration rate; MD = macula densa. © 2017 British Small Animal Veterinary Association

10.22233/9781910443354/fig20_8_thumb.gif

10.22233/9781910443354/fig20_8.png

20.8 Flowchart summarizing the relationship between hypotension, renin–angiotensin–aldosterone system (RAAS) activation, cyclooxygenase (COX) dependency and renal injury mechanisms. GFR = glomerular filtration rate; MD = macula densa.

/content/figure/10.22233/9781910443354.chap20.ch20fig9

20.9

Gross pathology of naproxen-mediated renal papillary necrosis in a dog. (Reproduced from Radi et al., 2009 with permission from Toxicologic Pathology) © 2017 British Small Animal Veterinary Association

10.22233/9781910443354/fig20_9_thumb.gif

10.22233/9781910443354/fig20_9.png

20.9 Gross pathology of naproxen-mediated renal papillary necrosis in a dog. (Reproduced from Radi et al., 2009 with permission from Toxicologic Pathology)