How Does Cocaine Cause Renal Injury

How Does Cocaine Cause Renal Injury - How Does Cocaine...

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How Does Cocaine Abuse Cause Renal Failure? David Shure May 26, 2009
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Differential Diagnosis Cocaine induced malignant HTN/ TMA ATN GN Worsening Creat 4/10 = rapid lowering BP
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Background Est: 23 mil Americans have used cocaine Subst abuse cost to US economy: ~144 bil/ year Cocaine-related hospitalizations ~ 80mil/year Well estab assoc with CVD, accelerated ASHD, CVA, accident-related deaths connection with renal failure not well established other than 2/2 rhabdomyolysis
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Metabolism QuickTimeª and a decompressor are needed to see this picture.
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Cocaine: Potent Vasoconstrictor Inhibits presynaptic nerve terminal catechol reuptake Blocks reuptake norepinephrine Stimulates release norepi/ epi from adrenal medulla Incr Ca influx in vascular smooth muscle
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Other Vasoconstrictive Pathways ET-1 RAAS
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Endothelins ET-1 = major ET isoform involved in renal dysfunction High density ET-1 receptors in vascular smoth muscle of all renal vessels Activation causes decr renal blood flow and GFR ,constricts both afferent and efferent arterioles, arcuate and interlobular arterioles. Peptide found upregulated in pregnant pt’s with cocaine use Levels of ET-1 in cocaine similar to preeclampsia, however in cocaine using pt’s, levels persist well past post-partum period attributed to cocaine metabolites
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RAAS Hendricks et al: Cocaine-stimulated Endothelin- 1 release is decreased by ACE-I in cultured endothelial cells. Cardivasc Res, 1996 Endothelial cells produce endogenous ACE,
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How Does Cocaine Cause Renal Injury - How Does Cocaine...

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