OVERVIEW

CASE REPORT

PRODUCT INFORMATION

CHEMICAL FORMULA AND STRUCTURE

View in own window

DRUG	CAS REGISTRY NUMBER	MOLECULAR FORMULA	STRUCTURE
Cocaine	50-36-2	C17-H21-N-O4

ANNOTATED BIBLIOGRAPHY

References updated: 26 October 2017

• Zimmerman HJ. Cocaine. Miscellaneous drugs and diagnostic chemicals. In, Zimmerman, HJ. Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver. 2nd ed. Philadelphia: Lippincott, 1999, pp. 712-4.

  (Expert review of hepatotoxicity published in 1999 mentions that cocaine is known to cause hepatic injury, although this is often eclipsed by cardiac, neurological or muscular damage; it is a dose dependent hepatotoxin in experimental animals).
• Larrey D, Ripault MP. Illegal and recreational compounds. Hepatotoxicity of psychotropic drugs and drugs of abuse. In, Kaplowitz N, DeLeve LD, eds. Drug-induced liver disease. 3rd ed. Amsterdam: Elsevier, 2013, pp. 456-7.

  (Review of hepatotoxicity of drugs of abuse mentions that cocaine can cause a severe hepatitis, usually arising within 2 days and associated with marked aminotransferase elevations and other organ failure).
• O’Brien CP. Drug addiction. In, Brunton LL, Chabner BA, Knollman BC, eds. Goodman & Gilman’s the pharmacological basis of therapeutics. 12th ed. New York: McGraw-Hill, 2011, pp. 649-59.

  (Textbook of pharmacology and therapeutics).
• Ehrlich P. [Studies on the effects of cocaine]. Dtsh Med Wochenschr 1890; 16: 716. Not indexed in PubMed.

  (Early report on effects of cocaine, largely as an anesthetic).
• Marks V, Chapple PA. Hepatic dysfunction in heroin and cocaine users. Br J Addict Alcohol Other Drugs 1967; 62: 189-95. [PubMed: 5231851]

  (Among 89 heroin and cocaine users, 6 were jaundiced and 69% had ALT elevations and marked elevations occurred with relapse in cocaine and heroin use).
• Rubel LR, Ishak KG. The liver in fatal exertional heatstroke. Liver 1983; 3: 249-60. [PubMed: 6672506]

  (Liver histology of 50 cases of fatal heatstroke arising during military training in 17-36 year olds; initially fatty change, vacuolization and congestion, followed by zone 3 coagulative necrosis, cholestasis and microvacuolar fatty change).
• Kloss MW, Rosen GM, Rauckman EJ. Cocaine-mediated hepatotoxicity. A critical review. Biochem Pharmacol 1984; 33: 169-73. [PubMed: 6367747]

  (Discussion of the mechanism of hepatic injury by cocaine in animal model systems).
• Armen R, Kanel GC, Reynolds T. Phencyclidine-induced malignant hyperthermia causing submassive liver necrosis. Am J Med 1984; 7: 167-72. [PubMed: 6741977]

  (3 patients developed agitation, combative behavior and hyperthermia [107-108 oF] shortly after phencyclidine abuse with rise in CPK, ALT and bilirubin [peak levels 15.7-22.5 mg/dL] by day 2; one patient died and 2 recovered with rapid fall of enzymes to normal, liver histology on autopsy showing centrolobular necrosis suggestive of hyperthermia injury).
• Cregler LL, Mark H. Medical complications of cocaine abuse. N Engl J Med 1986; 315: 1495-500. [PubMed: 3537786]

  (Review of the severe medical complications of cocaine abuse including coronary artery spasm, myocardial infarction, rupture of aorta, subarachnoid bleed, stroke, seizures, intestinal and renal infarction; hepatotoxicity not discussed).
• Bates CK. Medical risks of cocaine use. West J Med 1988; 148: 440-4. [PMC free article: PMC1026136] [PubMed: 3291396]

  (Clinical description of cocaine reactions; early, mild effects are behavioral changes and teeth grinding with tachycardia, hypertension and hyperthermia; more severe reactions are then followed by excited delirium, stupor, ventricular arrhythmias and sudden death usually from myocardial infarction or respiratory arrest).
• Perino LE, Warren GH, Levine JS. Cocaine-induced hepatotoxicity in humans. Gastroenterology 1987; 93: 176-80. [PubMed: 3582904]

  (32 year old man developed bizarre behavior and respiratory arrest after snorting cocaine, with AST rising from 620 to 10,700 U/L and bilirubin 0.3 to 4.5 mg/dL and with progressive bradycardia and cardiac arrest within 2 days of admission; autopsy showed mild fatty change and periportal and midzonal necrosis).
• Porter JM, Sussman MS, Rosen GM. Cocaine-induced hepatotoxicity. Hepatology 1988; 8: 1713. [PubMed: 3192186]

  (Commentary on Perino et al [1987]).
• Roth D, Alarcón FJ, Fernandez JA, Preston RA, Bourgoignie JJ. Acute rhabdomyolysis associated with cocaine intoxication. N Engl J Med 1988; 319: 673-7. [PubMed: 3412385]

  (39 patients with acute rhabdomyolysis after cocaine use; 35 were agitated or combative, 4 comatose; CPK levels >10 times ULN in all, muscle tenderness in 20, hyperthermia in 13, acute renal failure in 13, 8 requiring dialysis, disseminated intravascular coagulation in 7, severe liver dysfunction in 13 [ALT mean 5558 U/L, AST 4415 U/L, direct bilirubin 8.7 mg/dL]; 2 died of cardiac arrhythmias and 4 of multiorgan failure).
• Campbell BG. Cocaine abuse with hyperthermia, seizures and fatal complications. Med J Aust 1988; 149: 387-9. [PubMed: 3173196]

  (23 year old woman developed agitation and seizures shortly after cocaine use with fever to 42 ^oC and subsequent disseminated intravascular coagulation, rhabdomyolysis, acute renal failure, and jaundice [bilirubin initially normal rising to 2.6 mg/dL, AST 99 to 3415 U/L, CK 152 to 10,000 U/L], dying 45 hours after admission).
• Jandreski MA, Bermes EW, Leischner R, Kahn SE. Rhabdomyolysis in a case of free-base cocaine ("crack") overdose. Clin Chem 1989; 35: 1547-9. [PubMed: 2758612]

  (27 year old man developed bizarre behavior followed by combativeness after smoking crack cocaine, with CPK 30 times ULN, ALT and AST >40 times ULN the following day and rise in creatinine, but spontaneous recovery and resolution within one week).
• Bauwens JE, Boggs JM, Hartwell PS. Fatal hyperthermia associated with cocaine use. West J Med 1989; 150; 210-2. [PMC free article: PMC1026353] [PubMed: 2728444]

  (2 men, aged 30 and 38 years old, developed seizures and agitation after cocaine use with temperature of 41.1 and 43 ^oC with rapid appearance of rhabdomyolysis, renal failure, disseminated intravascular coagulation, liver failure within 1 day and death at 7 days).
• Kanel GC, Cassidy W, Shuster L, Reynolds TB. Cocaine-induced liver cell injury: comparison of morphological features in man and in experimental models. Hepatology 1990; 11: 646-51. [PubMed: 2328957]

  (24 year old man developed bizarre behavior after cocaine use with rhabdomyolysis and subsequent jaundice [bilirubin rising from 1.9 to 8.7 mg/dL, ALT 135 to >10,000 U/L, CPK 617 to 46,480], renal failure, seizures, multiorgan failure and death; autopsy showed zone 2 and 3 hepatic necrosis, periportal fat and minimal inflammation: Case 1).
• Wanless IR, Dore S, Gopinath N, Tan J, Cameron R, Heathcote EJ, Blendis LM, et al. Histopathology of cocaine hepatotoxicity. Report of four patients. Gastroenterology 1990; 98: 497-501. [PubMed: 2153087]

  (Liver histology in 3 women and 1 man with cocaine hepatotoxicity including one fatality; ages 24-28 years, 2 presenting acutely with bizarre behavior followed by rhabdomyolysis and renal and liver failure [bilirubin 3.7 and 4.9 mg/dL, ALT 7300 and 10,200 U/L, Alk P 71 and 123 U/L], one dying on day 6 and one recovering by day 12; two patients had a more subacute presentation several days after exposure [bilirubin normal, ALT 1940 and 435, CPK 6720 and 27,000 U/L], resolving in 7-10 days; histology showed variable amounts of zone 3 coagulative necrosis sometimes extending to zone 2 with fat in remaining hepatocytes, minimal inflammation).
• Gubbins GP, Schiffman RM, Alapati RS, Batra SK. Cocaine-induced hepatonephrotoxicity: a case report. Henry Ford Hosp Med J 1990; 38: 55-6. [PubMed: 2228713]

  (35 year old woman developed dark urine 2 days after smoking crack cocaine [bilirubin 3.0 mg/dL, ALT 9295 U/L, Alk P 131 U/L, CPK 258 U/L, creatinine 5.3 mg/dL], resolving over next two weeks).
• Tabasco-Minguillan J, Novick DM, Kreek MJ. Liver function tests in non-parenteral cocaine users. Drug Alcohol Depend 1990; 26: 169-74. [PubMed: 2242718]

  (56 users of cocaine, but not injection drugs, only 3 had elevated ALT levels [peak 111 U/L] and two of them had hepatitis B suggesting that cocaine use, by itself, does not cause chronic hepatitis or persistent ALT elevations).
• Silva MO, Roth D, Reddy KR, Fernandez JA, Albores-Saavedra J, Schiff ER. Hepatic dysfunction accompanying acute cocaine intoxication. J Hepatol 1991; 12: 312-5. [PubMed: 1940259]

  (Retrospective analysis of 39 patients with cocaine intoxication and rhabdomyolysis; 23 had ALT elevations, 16 were severe; liver injury occurred in all 13 patients with renal failure and in 7 of 8 who died; autopsy showed centrolobular necrosis, compatible with shock or hyperthermia).
• Mallat A, Dhumeaux D. Cocaine and the liver. J Hepatol 1991; 12: 275-8. [PubMed: 1940255]

  (Editorial accompanying article by Silva [1991]).
• Saltzman JR, Johnston DE. Sickle cell crisis and cocaine hepatotoxicity. Am J Gastroenterol. 1992; 87: 1661-4. [PubMed: 1442696]

  (33 year old man with sickle cell anemia and multiple crises, presented with rise in bilirubin [6.2 at baseline to 37.5 mg/dL], ALT [24 to 726 U/L] and Alk P [152 to 370 U/L] after cocaine use; also taking amoxicillin/clavulanate).
• Peyrière H, Mauboussin JM. Cocaine-induced acute cytologic hepatitis in HIV-infected patients with nonactive viral hepatitis. Ann Intern Med 2000; 132: 1010-1. [PubMed: 10858171]

  (3 patients with HIV/HBV or HCV coinfection who had rises in ALT levels [baseline of 7-30 rising to 340-1669 U/L], without jaundice or rise in Alk P a few days after intranasal cocaine use ).
• Campos Franco J, Martínez Rey C, Pérez Becerra E, González Quintela A. [Cocaine related fulminant liver failure]. An Med Interna 2002; 19: 365-7. [PubMed: 12224146]

  (23 year old woman presented with confusion 10 hours after cocaine use [bilirubin 1.2 mg/dL, ALT 1031 U/L, Alk P 103 U/L], worsening for 6 days and then resolving rapidly over next 10 days; biopsy showed centrolobular coagulative necrosis with minimal inflammation).
• Hurtova M, Duclos-Vallée JC, Saliba F, Emile JF, Bemelmans M, Castaing D, Samuel D. Liver transplantation for fulminant hepatic failure due to cocaine intoxication in an alcoholic hepatitis C virus-infected patient. Transplantation 2002; 73: 157-8. [PubMed: 11792999]

  (33 year old man with chronic hepatitis C presented with acute liver failure shortly after iv cocaine use [ALT 30 times ULN, CPK 27,000 U/L, prothrombin index 9%], undergoing liver transplantation; explant showing centrolobular coagulative necrosis and marked steatosis).
• Kramer L, Bauer E, Schenk P, Steininger R, Vigl M, Mallek R. Successful treatment of refractory cerebral oedema in ecstasy/cocaine-induced fulminant hepatic failure using a new high-efficacy liver detoxification device (FPSA-Prometheus). Wien Klin Wochenschr 2003; 115: 599-603. [PubMed: 14531175]

  (27 year old man developed coma within hours of injecting heroin and cocaine and taking 300 mg of MDMA with evidence of multiorgan failure and rhabdomyolysis [bilirubin 1.1 rising to 9.5 mg/dL, ALT 5870 U/L, LDH 11,030 U/L, INR 1.6 rising to 3.2] and was treated with a fractionated plasma separation and adsorption device, with ultimate resolution within 3 weeks).
• Balaguer F, Fernández J, Lozano M, Miquel R, Mas A. Cocaine-induced acute hepatitis and thrombotic microangiopathy. JAMA 2005; 293: 797-8. [PubMed: 15713768]

  (22 year old woman developed jaundice a few days after cocaine use [bilirubin 12.0 rising to 71.4 mg/dL, ALT 1305 U/L, Alk P 308 U/L], with respiratory and renal failure and hemolytic anemia but eventual resolution).
• Abd El-Rahman AM, Ammar H. Cocaine-induced acute hepatitis and thrombotic microangiopathy. JAMA 2005; 293: 2715; author reply 2715-6. [PubMed: 15941798]

  (Letter in response to Balaguer [2005] discussing use of fresh frozen plasma exchange rather than albumin).
• Jiménez Pérez M, Marín García D, Santaella Leiva I, Olmedo García R. [Cocaine-induced hepatotoxicity]. Med Clin (Barc) 2008; 130: 279. Spanish. [PubMed: 18355433]

  (42 year old man became semicomatose 10 hours after inhaling cocaine [bilirubin 1.9 mg/dL, ALT 2673 U/L, GGT 244 U/L, creatinine 5 mg/dL], with rhabdomyolysis and renal failure requiring dialysis, but ultimate recovery and near normal liver enzymes 8 days after admission).
• Chalasani N, Fontana RJ, Bonkovsky HL, Watkins PB, Davern T, Serrano J, Yang H, Rochon J; Drug Induced Liver Injury Network (DILIN). Causes, clinical features, and outcomes from a prospective study of drug-induced liver injury in the United States. Gastroenterology 2008; 135: 1924-34. PubMed Citation . [PMC free article: PMC3654244] [PubMed: 18955056]

  (Among 300 cases of drug induced liver disease in the US collected between 2004 and 2008, 3 cases were attributed to atomoxetine and one to methylphenidate, but none to cocaine or ecstasy).
• Reuben A, Koch DG, Lee WM; Acute Liver Failure Study Group. Drug-induced acute liver failure: results of a U.S. multicenter, prospective study. Hepatology 2010; 52: 2065-76. PubMed Citation . [PMC free article: PMC3992250] [PubMed: 20949552]

  (Among 1198 patients with acute liver failure enrolled in a US prospective study between 1998 and 2007, 133 were attributed to drug induced liver injury, including one attributed to cocaine and one to ecstasy).
• Björnsson ES, Bergmann OM, Björnsson HK, Kvaran RB, Olafsson S. Incidence, Presentation and outcomes in patients with drug-induced liver injury in the general population of Iceland. Gastroenterology 2013; 144: 1419-25. [PubMed: 23419359]

  (In a population based study of drug induced liver injury from Iceland, 96 cases were identified over a 2 year period, but none were attributed to cocaine or amphetamine use).
• Giuliani E, Albertini G, Vaccari C, Manenti A, Barbieri A. Multi-organ failure following severe cocaine-tetramisole intoxication in a body-packer. Anaesth Intensive Care. 2012; 40: 562-4. [PubMed: 22577932]

  (51 year old woman, who had swallowed sealed packets of cocaine to smuggle them into Italy, had sudden onset of seizures followed by coma and cardiac arrest; after resuscitation, ALT levels rose starting on day 2 to a peak of 6000 U/L on day 4 and rapid recovery and discharge on day 7).
• Zimmerman JL. Cocaine intoxication. Crit Care Clin 2012; 28: 517-26. [PubMed: 22998988]

  (Review of the major complications of cocaine overdose including cardiac, neurologic, respiratory and renal; no discussion of hepatotoxicity).
• Trabulo D, Marques S, Pedroso E. Cocaine capsules in the colon: the internal concealment of illicit drugs. J Gastrointestin Liver Dis 2015; 24: 9. [PubMed: 25822426]

  (26 year old man was arrested and jailed for drug smuggling and developed fever and abdominal pain 2 days later, X-rays showing "nodules" in colon which were successfully removed by enemas; no follow up provided).
• Guollo F, Narciso-Schiavon JL, Barotto AM, Zannin M, Schiavon LL. Significance of alanine aminotransferase levels in patients admitted for cocaine intoxication. J Clin Gastroenterol 2015; 49: 250-5. [PubMed: 24518798]

  (Retrospective analysis of 93 patients wtih cocaine intoxication, 5 of whom had marked ALT elevations [>20 times ULN], all were critically ill and had rhabdomyolysis, two had renal failure and one died).
• Chalasani N, Bonkovsky HL, Fontana R, Lee W, Stolz A, Talwalkar J, Reddy KR, et al.; United States Drug Induced Liver Injury Network. Features and outcomes of 899 patients with drug-induced liver injury: The DILIN Prospective Study. Gastroenterology 2015; 148: 1340-52.e7. [PMC free article: PMC4446235] [PubMed: 25754159]

  (Among 899 cases of drug induced liver injury enrolled in a US prospective study between 2004 and 2013, no cases were attributed to cocaine or other illicit drugs).