Hepatotoxicity due to cocaine has been well described in animal models. There are few reports on cocaine-induced hepatic injury in humans; however, its link to rhabdomyolysis and renal failure is better known. We report a case of reversible acute hepatonephrotoxicity associated with recreational cocaine use. The proposed mechanisms responsible for its hepatic and renal toxicity are reviewed

Alapati, Ravindra S.

Batra, Surinder K.

Gubbins, Guillermo P.

Schiffman, Rhett M.

English

Henry Ford Health System Scholarly Commons

Henry Ford Hospital Medical Journal Volume 38 Number 1 Article 15 3-1990 Cocaine-Induced Hepatonephrotoxicity: A Case Report Guillermo P. Gubbins Rhett M. Schiffman Ravindra S. Alapati Surinder K. Batra Follow this and additional works at: https://scholarlycommons.henryford.com/hfhmedjournal  Part of the Life Sciences Commons, Medical Specialties Commons, and the Public Health Commons Recommended Citation Gubbins, Guillermo P.; Schiffman, Rhett M.; Alapati, Ravindra S.; and Batra, Surinder K. (1990) "Cocaine-Induced Hepatonephrotoxicity: A Case Report," Henry Ford Hospital Medical Journal : Vol. 38 : No. 1 , 55-56. Available at: https://scholarlycommons.henryford.com/hfhmedjournal/vol38/iss1/15 This Article is brought to you for free and open access by Henry Ford Health System Scholarly Commons. It has been accepted for inclusion in Henry Ford Hospital Medical Journal by an authorized editor of Henry Ford Health System Scholarly Commons. Cocaine-Induced Hepatonephrotoxicity: A Case Report GuiUermo P. Gubbins, MD,* Rhett M. Schiffman, MD,* Ravindra S. Alapati, MD,* and Surinder K. Batra, MD* Hepatotoxiciry due to cocaine has been weU described in animal models. There are few reports on cocaine-induced hepatic injury in humans; however, its link to rhabdomyolysis and renal failure is better known. We report a case of reversible acute hepatonephrotoxicity associated with recreational cocaine use. The proposed mechanisms responsible for its hepatic and renal toxicity are reviewed. (Henry Ford Hosp MedJ 1990;38:55-6) Cocaine, an alkaloid prepared from the leaves of Erythroxyton coca, is recognized as one of the most dangerous if i ici t dmgs in common use today. As cocaine abuse has escalated, co-caine-related emergency room visits, hospital admissions, car-diovascular events, and deaths due to overdosage have increased throughout the nation (1). Cocaine-mediated hepatotoxicity in humans has been suspected since 1967 (2). Since then, numer-ous studies in mice have defined several possibte mechanisms of liver injury (3,4). Cases of probable cocaine-induced liver disor-ders in humans have been reported only recentiy (4,5), and co-caine-induced nephrotoxicity has been reported with increasing frequency during the last two years (6-11). We report a case of acute, reversible hepatonephrotoxicity associated with recre-ational cocaine use. Case Report A previously healthy 35-year-old woman came to the emergency room complaining of myalgias, fever, chills, diffuse abdominal pain, diarthea, and vomiting. The symptoms had begun four days after drink-ing alcohol and smoking "crack" cocaine. She also related passing dark urine two days prior to admission. The patient denied intravenous dmg use, had no history of hepatitis, and had one sexual partner who did not use drugs intravenously. She worked as a janitor in a nursing home, but was not aware of recent exposure to organic solvents. She did admit to drinking one-half pint of vodka or whiskey two to three times a week. On admission the patient's blood pressure was normal but her pulse was 120 beats/min and her temperature was 37.6°C (99.7°F). Jaundice was present along with mild hepatomegaly and tenderness in the right upper quadrant. The complete blood count was normal, but the creatinine was 468 ixmol/L (5.3 mg/dL), and blood urea nifi-ogen 8.6 mmol/L (24 mg/dL). The prothrombin time was 20.5 seconds (control 10.5 seconds) and the partial thromboplastin time was 38 seconds (nor-mal 22 to 36 seconds). The bilirubin was 51 |xmol/L (3.0 mg/dL [2.5 mg/dL direct]), SGOT 1,711 lU/L (normal < 33 lU/L), SGPT 9,295 IU/ L (normal < 40 lU/L), alkaline phosphatase 131 lU/L (normal 0 to 100 lU/L), and creatine phosphokinase 258 lU/L (normal 0 to 190 lU/L). Ethanol was not detected in the serum. Urinalysis revealed 14-"blood," 24- bilirubin, and 3 4- albumin. Eight red blood cells, 4 to 6 renal tubular cells in clumps, 0 to 1 hyaline casts, and 3 to 4 granular casts were seen per high power field. Urinary myoglobin was not as-sayed, but urinary sodium was 38 mEq/L and the fractional sodium ex-cretion was 1.6%. The urine drug screen was positive for cocaine me-tabolites, morphine, codeine, and amphetamines. Serologic tests for hepatitis A and B were negative. The patient was given supportive care. The SGOT peaked at 2,482 lU/L on the second day but administration of vitamin K quickly cor-rected her coagulopathy. The serum creatinine peaked at 1,547 ixmol/L (17.5 g/dL) on the eighth day; however, she maintained a urine output ranging from 1,600 to 2,400 mL/24 hrs. The patient did not require di-alysis and was discharged after 15 days with a seram creatinine of 371 |i.mol/L (4.2 mg/dL) and an SGOT of 28 lU/L. Discussion tn the mouse, cocaine is largely detoxified by plasma and liver chotinesterases to the water-soluble, nontoxic metabolites benzoyl ecgonine and ecgonine methyl ester which are excreted in the urine. However, a minor oxidative pathway, centered around the tropane nitrogen, is believed to be responsible for the generation of hepatotoxic metabolites (1,3,4). Two mechanisms have been proposed to account for the production of these hepa-totoxic metabolites in man. The first of these involves a futile, enzymatically catalyzed cycling between N-hydroxy norco-caine and norcocaine nitroxide, which depletes intracellular NADPH, thereby reducing intrahepatic glutathione. As a conse-quence, cellular concentrations of hydrogen peroxide and super-oxide radicals, which are generated by normal cellular metabo-fism, reach toxic levels resulting in lipid peroxidation ofthe cellular membranes and cell wall dismption (3). The second pro-posed mechanism is based on the further oxidation of norco-caine nitroxide to the extremely reactive nitrosonium ion which also depletes glutathione. Catecholamines, whose circulating Submitted for publication: December?. 1989. Accepled for publication: January 23, 1990. 'Division of Gastroenterology, Henry Ford Hospital. tBone and Mineral Division, Henry Ford Hospilal. tFormeriy Division of Gastroenterology, Henry Ford Hospilal. Curtently Anaheim Fam-ily Practice, Anaheim, CA. Address cortespondence to Dr Batra. Division of Gastroenterology. Henry Ford Hospi-tal. 2799 W Grand Blvd, Detroit, Ml 48202. Henry Ford Hosp Med J—Vol 38, No I , 1990 Cocaine-induced Hepatonephrotoxicity—Gubbins et al 55 levels are elevated as a consequence of cocaine use, may con-tribute by causing liver damage directly or by serving as cofac-tors for the oxidation of norcocaine nitroxide to the nitrosonium ion (4). It has been suggested that individuals with low plasma pseudocholinesterase activity could be especially susceptible to the hepatotoxicity of cocaine because more cocaine may be shunted through the oxidative bioactivation pathway. Similarly, individuals deficient in gIucose-6-phosphate dehydrogenase would have an increased risk for cocaine-induced hepatotoxicity because they generate fewer reducing equivalents (NADPH) than do normal individuals (3). Finally, cytochrome P^ o^ oxidase system inducers, such as ethanol and phenobarbital, which po-tentiate cocaine-induced hepatotoxicity in mice, could play a similar predisposing role in human subjects. The only report of subclinical cocaine hepatotoxicity ap-peared in 1967 (2). Of the 89 heroin users evaluated at a psychi-atric institution, most of whom were also users of cocaine, six were jaundiced and 80% of the patients had serum enzyme ab-normalities which returned to normal after abstinence. How-ever, the contribution of cocaine to hepatotoxicity could not be dissociated from that of heroin; and viral hepatitis, which is prevalent among intravenous drug users, was not excluded serologically. Considering the large number of people who abuse cocaine, it is surprising that cases of overt hepatotoxicity are so rare (4-6); however, the susceptibility to liver damage from cocaine is influenced by so many different factors that frank hepatotoxicity may not become a common feature of co-caine addiction (4). It is possible that ethanol, by inducing cytochrome P45„, predisposed our patient to cocaine hepatotox-icity. Glucose-6-phosphate dehydrogenase and plasma pseudocholinesterase levels were not measured. Cocaine abuse has been linked recently to rhabdomyolysis and acute renal failure (6-11), The mechanisms for this are not completely understood; however, the dmg is known to cause hy-perpyrexia by affecting the temperature-regulating center in the hypothalamus (1) and can also induce seizures and hyperac-tivity. Each of these factors may contribute to cocaine-induced rhabdomyolysis (1). The renal failure associated with cocaine abuse and rhabdomyolysis is usually nonoliguric, self-limited, and seldom requires dialysis (6). Factors other than myoglobin, however, may contribute to the development of acute renal failure in cocaine intoxication and may alter the course of the kidney failure. These include hypotension, hypovolemia, and disseminated intravascular coagulation (6). In addition, cocaine may have a direct vasoconstrictive effect on the renal vas-culature, and a case of renal infarction associated with intra-venous cocaine use has been reported (12). Our patient's urinalysis, fractional sodium excretion, and clinical course were most consistent with nonoliguric acute tu-bular necrosis. Consequently, although we cannot mie out a di-rect tubular cocaine toxicity, we feel that our patient's renal failure was probably due to rhabdomyolysis, in view ofthe his-tory of passing dark urine (possibly myoglobin) two days before admission. White hepatonephrotoxicity is probably a rare complication of cocaine abuse, it should be considered in the differential diag-nosis of patients with simultaneous hepatic and renal failure, es-pecially in the presence of potentially predisposing factors such as ethanol and barbiturate abuse or gIucose-6-phosphate de-hydrogenase and p.seudochoIinesterase deficiencies. References 1. Cregler LL, Mark H. Medical complications of cocaine abuse. N Engl J Med 1986:315:1495-500. 2. Marks V, Chappie PAL. Hepatic dysfunction in heroin and cocaine users. BrJ Addict 1967:62:189-95. 3. Kloss MW. Rosen GM, Rauckman EJ. Cocaine-mediated hepatotoxicity: A critical review. Biochem Pharmacol 1984:33:169-73. 4. Shuster L, Garharl CA, Powers J, Gmnfeld Y, Kanel G, Hepatotoxicity of cocaine. NIDA Res Monogr 1988;88:250-75. 5. Perino LE. Warten GH, Levine JS, Cocaine-induced hepatotoxicity in hu-mans. Gastroenterology 1987:93:176-80. 6. Roth D, Alarcon FJ, Femandez JA, Preston RA, Bourgoignie JJ. Acute rhabdomyolysis associated with cocaine intoxication. N Engl J Med 1988; 319:673-7. 7. Merigian KS, Roberts JR, Cocaine intoxication: Hyperpyrexia, rhab-domyolysis and acute renal failure. Clin Toxicol 1987:25:135-48. 8. Lombard J, Wong B, Young JH. Acute renal failure due to rhabdomyolysis associated with cocaine toxicity. West J Med 1988;148:466-8. 9. Menashe PI, Gottlieb JE. Hyperthermia, rhabdomyolysis and myo-globinuric renal failure after recreational use of cocaine. South Med J 1988:81:379-80. 10. Anand V, Ghodratollah S, Stone WJ. Cocaine-associated rhabdomyolysis and acute renal failure. South Med J 1989;82:67-8. 11. Herzlich BC, Arsura EL, Pagala M, Grob D. Rhabdomyolysis related to cocaine abuse. Ann Intem Med 1988;109:335-6. 12. Sharff JA. Renal infarction associated with intravenous cocaine use. Ann Emerg Med 1984;13:1145-7. 56 Henry Ford Hosp Med J—Vol 38. No 1, 1990 CtKaine-induced Hepatonephrotoxicity—Gubbins et al 

Cocaine-Induced Hepatonephrotoxicity: A Case Report

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Cocaine-Induced Hepatonephrotoxicity: A Case Report

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