J Med Cases
Journal of Medical Cases, ISSN 1923-4155 print, 1923-4163 online, Open Access
Article copyright, the authors; Journal compilation copyright, J Med Cases and Elmer Press Inc
Journal website https://www.journalmc.org

Case Report

Volume 12, Number 2, February 2021, pages 54-56


Use of N-Acetylcysteine in Amphetamine-Induced Acute Liver Failure

Saif Affasa, c, Mohamad Fekredeen Ayasa, c, d, Ihab A. Kassabb

aDepartment of Internal Medicine, Ascension St. John Hospital, Detroit, MI, USA
bDivision of Hospital Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA
cThese authors contributed equally to this work.
dCorresponding Author: Mohamad Fekredeen Ayas, Department of Internal Medicine, Ascension St. John Hospital, 22101 Moross Rd, Detroit, MI 48236, USA

Manuscript submitted October 23, 2020, accepted November 14, 2020, published online December 30, 2020
Short title: NAC Role in Amphetamine-Induced ALF
doi: https://doi.org/10.14740/jmc3611

Abstract▴Top 

Acute liver failure (ALF) is a serious complication of many drugs. Amongst recreational drugs, cocaine, amphetamines and ecstasy (methylenedioxymethamphetamine) have been known to cause ALF as a complication. However, the true effects and management on the liver of such cases have not been well reported and treatment of such conditions needs prompt action. N-acetylcysteine (NAC) is a known hepatoprotective agent but remains controversial in the use of recreational drug-induced acute liver injury. We present a case of ALF secondary to amphetamine ingestion, with a rapid recovery after administration of intravenous NAC.

Keywords: Acute liver failure; NAC; Amphetamine

Introduction▴Top 

Amphetamine is a popular recreational drug in the western world, as it induces euphoria and boosts self-confidence. Excessive doses can cause a wide variety of symptoms including, but not limited to increased state of arousal, euphoria, increased energy, talkativeness, agitation, visual hallucinations, cardiovascular manifestations and hyperthermia [1, 2]. Moreover, hepatotoxicity has been reported in the literature with no clear treatment recommendations [3].

N-acetylcysteine (NAC) is a known medication used in the treatment of acetaminophen-induced hepatitis as well as other conditions, such as acute respiratory distress syndrome, and the use in influenza as well as other viral diseases such as COVID-19-induced hepatitis, and its use in cocaine-related liver injury; however, all still remains controversial [4-7]. NAC works as a hepatoprotective agent via multiple mechanisms, including restoring hepatic glutathione (GSH), and serving as a GSH substitute [8, 9].

Case Report▴Top 

A 20-year-old man with no significant past medical history presented with palpitations after ingesting 2 g of methamphetamine. He soon after became obtunded and was intubated for airway protection. He was later found to be hypertensive with a pressure of 160/86 mm Hg, hyperthermic with a temperature of 42 °C and tachycardic with a heart rate of 112 beats per minute. A few hours later, the patient was found to be hypotensive with a pressure of 82/59 mm Hg with minimal response to fluids, central line was placed and patient was started on norepinephrine. Physical exam showed an obtunded individual, with normal breath sounds in bilateral lung fields and an increased heart rate, with normal rhythm without murmurs.

On admission, the patient’s urine toxicology was positive for amphetamines, and laboratory findings (labs) showed an aspartate transaminase (AST) of 121 IU/L with an alanine transaminase (ALT) of 32 U/L and a protime/prothrombin time (PT) of 19.4 s with a partial thromboplastin time (PTT) of 36.5 s with an international normalized ratio (INR) of 1.61, and a normal bilirubin.

Poison control was contacted and recommended supportive care with the initiation of NAC. Intravenous (IV) NAC loading dose followed by a maintenance dose was started around 6 h after admission.

Within 24 h of admission, the patient started to develop multi-organ failure including ALF with an AST of 1,324 IU/L, an ALT of 217 U/L, a PT of 25.8 s, a PTT of 43 s, an INR of 2.32 and a bilirubin of 0.6 mg/dL. On day 3 of hospital admission, the patient’s labs showed a bilirubin of 1.6 mg/dL, an AST of 2,350 IU/L, an ALT of 2,145 U/L, an INR of 3.19, a PTT of 44.8 s and a PT of 33.1 s. Conversely, his serum total protein and serum albumin reached a nadir around the same time period.

After 3 - 4 days of NAC therapy, there was a significant recovery in liver enzymes. The starting of normalization of AST, ALT and PT/INR/PTT was observed by day 5.

Discussion▴Top 

Hepatotoxicity secondary to recreational drug use, such as cocaine, methylenedioxymethamphetamine (MDMA) and amphetamines, has been documented in the literature, but no clear recommendations on its management have yet been given [3, 6]. Although dialysis is a very effective method of removing the drugs, NAC has shown promising effects in the management of ALF secondary to drug use [6]. Studies have shown that NAC has a hepatoprotective effect and is suggested to be via multiple mechanisms of action, which includes antioxidant and anti-inflammatory effects [10-13]. The antioxidant ability of NAC to reduce the effect of oxidative stress is thought to be due to NAC’s ability to decrease free radicals via replenishment of depleted intra-hepatocytes GSH, and the stimulation of a few enzymes, including superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) [11]. It had been previously reported in a study conducted on the hepatocytes of rats, that NAC has been used to protect from cocaine-induced liver injury by up-regulating antioxidant enzymes, such as SOD [14]. NAC also has an anti-inflammatory effect, by decreasing the level of inflammatory cytokines released, and blocking tumor necrosis factor (TNF) alpha activation by modulating TNF alpha receptors [13]. On a cellular level, L-cysteine (L-cys) is a tripeptide (γ-glutamyl cysteinyl glycine) and is the rate-limiting amino acid needed for GSH synthesis, but it is poorly penetrated into the cells. NAC however, easily penetrates the cells and is then deacetylated into L-cys, thereby promoting GSH synthesis for reducing the effect of the oxidative stress that is responsible for the liver injury [9].

Conclusions

Although not yet widely tested on human subjects, NAC has been shown to have anti-inflammatory effects that may help with drug-induced liver injury. It was successfully used in treating our patient’s amphetamine-induced acute hepatic failure. Therefore, more studies need to be conducted to investigate the extended role of NAC in treating such cases of acute liver injury/failure.

Acknowledgments

None to declare.

Financial Disclosure

None to declare.

Conflict of Interest

None to declare.

Informed Consent

Informed consent was granted by the patient prior to writing this manuscript.

Author Contributions

Saif Affas: literature review, preparation, writing and editing of entire manuscript. Mohamad Fekredeen Ayas: literature review, preparation, writing and editing of entire manuscript. Ihab A. Kassab: literature review, preparation and writing part of discussion section.

Data Availability

Information was collected from a PubMed search using the keywords “Amphetamines, N-acetylcysteine, acute liver failure”. All other data were collected from the eCare system of Ascension St. John Hospital.


References▴Top 
  1. Steinkellner T, Freissmuth M, Sitte HH, Montgomery T. The ugly side of amphetamines: short- and long-term toxicity of 3,4-methylenedioxymethamphetamine (MDMA, 'Ecstasy'), methamphetamine and D-amphetamine. Biol Chem. 2011;392(1-2):103-115.
    doi pubmed
  2. Vasan S, Olango GJ. Amphetamine toxicity. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020.
    pubmed
  3. Jones AL, Simpson KJ. Review article: mechanisms and management of hepatotoxicity in ecstasy (MDMA) and amphetamine intoxications. Aliment Pharmacol Ther. 1999;13(2):129-133.
    doi pubmed
  4. De Flora S, Balansky R, La Maestra S. Rationale for the use of N-acetylcysteine in both prevention and adjuvant therapy of COVID-19. FASEB J. 2020;34(10):13185-13193.
    doi pubmed
  5. Pacht ER, Timerman AP, Lykens MG, Merola AJ. Deficiency of alveolar fluid glutathione in patients with sepsis and the adult respiratory distress syndrome. Chest. 1991;100(5):1397-1403.
    doi pubmed
  6. Ansari M, Arshed S, Islam M, Sen S, Yousif A. A case of reversible drug-induced liver failure. Clin Case Rep. 2017;5(7):1181-1183.
    doi pubmed
  7. De Flora S, Grassi C, Carati L. Attenuation of influenza-like symptomatology and improvement of cell-mediated immunity with long-term N-acetylcysteine treatment. Eur Respir J. 1997;10(7):1535-1541.
    doi pubmed
  8. de Andrade KQ, Moura FA, dos Santos JM, de Araujo OR, de Farias Santos JC, Goulart MO. Oxidative stress and inflammation in hepatic diseases: therapeutic possibilities of N-acetylcysteine. Int J Mol Sci. 2015;16(12):30269-30308.
    doi pubmed
  9. Lu SC. Regulation of glutathione synthesis. Mol Aspects Med. 2009;30(1-2):42-59.
    doi pubmed
  10. Arranz L, Fernandez C, Rodriguez A, Ribera JM, De la Fuente M. The glutathione precursor N-acetylcysteine improves immune function in postmenopausal women. Free Radic Biol Med. 2008;45(9):1252-1262.
    doi pubmed
  11. Caglikulekci M, Pata C, Apa DD, Dirlik M, Tamer L, Yaylak F, Kanik A, et al. The effect of N-acetylcysteine (NAC) on liver and renal tissue inducible nitric oxide synthase (iNOS) and tissue lipid peroxidation in obstructive jaundice stimulated by lipopolysaccharide (LPS). Pharmacol Res. 2004;49(3):227-238.
    doi pubmed
  12. Hayakawa M, Miyashita H, Sakamoto I, Kitagawa M, Tanaka H, Yasuda H, Karin M. Evidence that reactive oxygen species do not mediate NF-κB activation. EMBO J. 2003;22:3356-3366.
    doi pubmed
  13. Hou Y, Wang L, Yi D, Ding B, Yang Z, Li J, Chen X, et al. N-acetylcysteine reduces inflammation in the small intestine by regulating redox, EGF and TLR4 signaling. Amino Acids. 2013;45(3):513-522.
    doi pubmed
  14. Zaragoza A, Diez-Fernandez C, Alvarez AM, Andres D, Cascales M. Effect of N-acetylcysteine and deferoxamine on endogenous antioxidant defense system gene expression in a rat hepatocyte model of cocaine cytotoxicity. Biochim Biophys Acta. 2000;1496(2-3):183-195.
    doi


This article is distributed under the terms of the Creative Commons Attribution Non-Commercial 4.0 International License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.


Journal of Medical Cases is published by Elmer Press Inc.

 

Browse  Journals  

 

Journal of Clinical Medicine Research

Journal of Endocrinology and Metabolism

Journal of Clinical Gynecology and Obstetrics

 

World Journal of Oncology

Gastroenterology Research

Journal of Hematology

 

Journal of Medical Cases

Journal of Current Surgery

Clinical Infection and Immunity

 

Cardiology Research

World Journal of Nephrology and Urology

Cellular and Molecular Medicine Research

 

Journal of Neurology Research

International Journal of Clinical Pediatrics

 

 
       
 

Journal of Medical Cases, monthly, ISSN 1923-4155 (print), 1923-4163 (online), published by Elmer Press Inc.                     
The content of this site is intended for health care professionals.
This is an open-access journal distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License, which permits unrestricted
non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Creative Commons Attribution license (Attribution-NonCommercial 4.0 International CC-BY-NC 4.0)


This journal follows the International Committee of Medical Journal Editors (ICMJE) recommendations for manuscripts submitted to biomedical journals,
the Committee on Publication Ethics (COPE) guidelines, and the Principles of Transparency and Best Practice in Scholarly Publishing.

website: www.journalmc.org   editorial contact: editor@journalmc.org
Address: 9225 Leslie Street, Suite 201, Richmond Hill, Ontario, L4B 3H6, Canada

© Elmer Press Inc. All Rights Reserved.