Acetaminophen
side effects, nutrient depletions, herbal interactions and health notes:
Data provided by Applied Health
• N-acetyl cysteine has been shown to improve liver damage caused by acetaminophen overdose.1
• Use of over three grams of vitamin C has been associated with decreased acetaminophen clearance time.2
• Foods high in carbohydrates, pectin and vegetables like broccoli, brussel sprouts, cabbage, etc. can interfere with acetaminophen absorption.3
• Acetaminophen consumption is especially risky for individuals who regularly consume excess amounts of alcohol as they can develop liver toxicity at lower levels of acetaminophen intake.4
• Individuals taking acetaminophen should refrain from fasting, Being in a fasting state greatly increases the chance of liver damage5
• In a study involving five healthy adult volunteers Houston and Levy found that oral administration of 3 g of ascorbic acid 1.5 hours after an oral dose of 1 g of acetaminophen caused a rapid and pronounced decrease in the excretion rate of acetaminophen sulfate. Later research by Mitra et al using rodents supported the conclusion that ascorbyl stearate provided protection against acetaminophen-induced hepatotoxicity by reducing the reactive intermediate back to the parent compound. They also note that the combination enhanced therapeutic efficacy against fever.These initial studies indicate that individuals with conditions commonly treated by acetaminophen might be able to use lower doses of the drug, achieve equal or superior clinical results, and reduce side effects from the drug by combining it with some form of vitamin C. In fact, a survey of current clinical reality might reveal that such a combination is often the unsupervised practice of many patients. Nevertheless, individuals taking acetaminophen should consult with their physician and/or pharmacist before reducing doses of the drug based on simultaneous use of vitamin C.6
• Many studies have looked into the efficacy and appropriateness of using NAC to treat patients suffering from acute toxic effects of acetaminophen. Such treatment of acetaminophen intoxication with N-acetylcysteine (NAC), both oral and intravenous, is standard hospital protocol in many countries. NAC is generally considered safe with relatively few side effects. However, individuals suffering from acetaminophen intoxication require emergency care and use of NAC in this capacity is only appropriate in such a setting7
• Acetaminophen is generally well tolerated with few short-term side effects. However, the drug is inherently toxic to the liver, and to some degree the kidneys also, and an overdose of acetaminophen can result in liver toxicity, liver failure, and even death. The signs and symptoms of liver toxicity may not become apparent for 2-3 days after a toxic overdose. Patients with liver and kidney disease should exercise special caution in taking acetaminophen to avoid toxicity.8
• Overdosage of acetaminophen causes fatal hepatic failure and acute renal failure.9
• Acetaminophen may interfere with home blood-glucose-measurement systems.10
• Oral administration of 3 g of ascorbic acid 1.5 hr after an oral dose of 1 g of acetaminophen caused a rapid and pronounced decrease in the excretion rate of acetaminophen sulfate in five healthy adult volunteers. There was a statistically significant increase in the fractions of the dose of acetaminophen excreted as such as as acetaminophen glucuronide but a decrease in the fraction excreted as acetaminophen sulfate. Ascorbic acid, which itself is metabolized in part to the sulfate, inhibits the conjugation of acetaminophen with sulfate by competing for available sulfate in the body.11
• Avoid or limit alcohol intake Those who take acetaminophen more than occasionally should avoid drinking alcohol because of the increased risk of liver damage.12
• Milk Thistle Extract helps prevent liver damage from hepatotoxins, including acetaminophen research: Acetaminophen exerts several toxic effects upon the liver, perhaps most importantly through lipid peroxidation and its depletion of glutathione. Numerous studies, primarily with animals, have demonstrated that Silybum marianum, particularly silymarin, a key set of flavonoids, can reduce oxidative stress, inhibit lipid peroxidation and support glutathione levels. Several teams of researchers have found positive results when focusing on the efficacy of Silybum and its constituents in reducing or reversing the toxic effects of acetaminophen on the liver.herbal support: Silymarin appears capable of providing specific benefits against the types of liver damage most closely associated with long-term use of acetaminophen. However, as of yet, no clinical studies involving humans have confirmed the efficacy of such a therapeutic approach or established protocols for dosage. Nevertheless, in such circumstances, many practitioners of natural medicine advise taking 200 mg Silybum, standardized to contain 70-80% silymarin, three times per day. Individuals using acetaminophen on a regular basis for extended periods of time, especially over one year, should consult their prescribing physician and/or a healthcare professional trained in herbal medicine to discuss possible benefits of taking Silybum, or an extract such as silymarin.13
• Tobacco decreases blood levels of acetaminophen14
• Several studies have been conducted examining the hepatoprotective effects of various species of Artemesia used in Chinese medicine, specifically an extract identified as DA-9601. Using rats Ryu et al found that DA-9601, from Artemisia asiatica, reduced liver damage induced by acetaminophen (APAP) and carbon tetrachloride (CCl4) as evidenced by serum ALT, AST, LDH and histopathological changes such as centrilobular necrosis, vacuolar degeneration and inflammatory cell infiltration dose-dependently. They also found that DA-9601 also prevented APAP-induced hepatic glutathione (GSH) depletion in a dose-dependent manner.While these research findings are encouraging and consistent with other studies of Artemisia species, inadequate clinical research with human subjects has been conducted to confirm the value of Artemisia as a therapy against the toxic side effects of acetaminophen. Individuals using acetaminophen on a regular basis for extended periods of time, especially over one year, should consult their prescribing physician and a healthcare professional trained in Chinese herbal medicine to determine whether the use of Artemisia, alone or as part of a traditional formula, would be appropriate. However, the particular species of Artemesia used in this study are not typically used in Chinese herbal medicine, or at least not known by the names cited.15
• Acetaminophen is well known for its toxic effects, especially upon the liver. Specifically acetaminophen induces elevation of serum aminotransferase activity and hepatic lipoperoxides content. It is also associated with observable histological damage to the liver cells. Schisandra is an herb commonly used in Chinese herbal medicine. Researchers have investigated the use of gomisin A, a lignan component of Schisandra fruits, in the treatment of acetaminophen-induced liver damage. Using rats, Yamada found that gomisin A inhibited the elevation of serum aminotransferase activity and hepatic lipoperoxides content and reduced the occurrence of adverse changes such as degeneration and necrosis of hepatocytes. Lin et al found that pathological changes of hepatic lesions in rats caused by three hepatotoxicants were improved after administration of certain fractions of Schisandra. However, gomisin A did not prevent gluatathione depletion as compared to Silymarin which provided such protection. Takeda et al have suggested that gomisin A facilitates liver protein synthesis and causes liver enlargement as an adaptive response involving the induction of drug-metabolizing enzymes.herbal support: While these research findings are encouraging and consistent with other studies of Schisandra, inadequate clinical research with human subjects has been conducted to confirm the value of Schisandra as a therapy against the toxic side effects of acetaminophen. Individuals using acetaminophen on a regular basis for extended perioods of time, especially over one year, should consult their prescribing physician about alternatives methods of addressing the symptoms and their underlying cause. Further, a healthcare professional trained in Chinese herbal medicine might help determine whether the use of Schisandra, alone or as part of a traditional formula, would be appropriate.16
References1 Vale JA, Proudfoot AT. Paracetamol (acetaminophen) poisoning. Lancet 1995;346:547-52
2 Houston JB, Levy G. Drug biotransformation interactions in man. VI: Acetaminophen and ascorbic acid. J Pharm Sci 1976;65:121-21.
3 Holt GA. Food & Drug Interactions. Chicago: Precept Press, 1998, 2.
4 Whitcomb DC, Block GD. JAMA 1994 Dec 21;272(23):1845-1850
5 Whitcomb DC, Block GD. JAMA 1994 Dec 21;272(23):1845-1850
6 Houston JB, Levy G. J Pharm Sci 1976;65:1218-1221; Mitra A, et al. J Biochem Toxicol. 1991 Summer;6(2):93-100; Mitra A, et al. Toxicol Lett. 1988 Nov;44(1-2):39-46.)
7 Zed PJ, Krenzelok EP. Am J Health Syst Pharm 1999 Jun 1;56(11):1081-1091; Salgia AD, Kosnik SD. Postgrad Med. 1999 Apr;105(4):81-84, 87, 90; Montoya-Cabrera MA, et al. Gac Med Mex. 1999 May-Jun;135(3):239-243; Schmidt LE, Dalhoff KP. Ugeskr Laeger. 1999 May 3;161(18):2669-2672
8 Brzeznicka EA, Piotrowski JK. Pol J Occup Med. 1989;2(1):15-22; Kamiyama T, et al. Toxicol Lett. 1993 Jan;66(1):7-12; Vale JA, Proudfoot AT. Lancet 1995;346:547-552; Fairhurst S, et al. Toxicology. 1982;23(2-3):249-259.)
9 Fukuoka Igaku Zasshi 1997 Nov;88(11):352-7 -- The risk factors of death from the acetaminophen poisoning with antipyretic-analgesic drugs in Japan. -- Washio M, Inoue N.
10 Am J Hosp Pharm 1985 Oct;42(10):2202-7 -- In vitro drug interference with home blood-glucose-measurement systems. -- Rice GK, Galt KA.
11 J Pharm Sci 1976 Aug;65(8):1218-21 -- Drug biotransformation interactions in man VI: acetaminophen and ascorbic acid. -- Houston JB, Levy G.
12 Pronsky, Z Food Medication Interactions, 11th edition, 1999
12 Whitcomb DC, Block GD. JAMA 1994 Dec 21;272(23):1845-1850
13 Brinker, F Herb Contraindications and Drug Interactions, Eclectic Medical Publications, 1998
13 Campos, R. et al. Silybin Dihemisuccinate protects against glutathione depletion and lipid peroxidation induced by acetaminophen on rat liver. Planta Medica. 1989: 55:417.
13 Campos R, et al. Prog Clin Biol Res. 1988;280:375-378; Campos R, et al. Planta Med. 1989 Oct;55(5):417-419; Garrido A, et al. Pharmacol Toxicol. 1991 Jul;69(1):9-12; Muriel P, et al. J Appl Toxicol. 1992 Dec;12(6):439-442; Chrungoo VJ, et al. Indian J Exp Biol. 1997 Jun;35(6):611-617
14 Brinker, F Herb Contraindications and Drug Interactions, Eclectic Medical Publications, 1998
15 Janbaz KH, Gilani AH. J Ethnopharmacol 1995 Jun 23;47(1):43-47; Ryu BK, et al. Arch Pharm Res 1998 Oct;21(5):508-513.)
16 Takeda S, et al. Nippon Yakurigaku Zasshi. 1986 Feb;87(2):169-187; Yamada S, et al. Biochem Pharmacol 1993;46:1081-1085; Shiota G, et al. Res Commun Mol Pathol Pharmacol. 1996 Nov;94(2):141-146; Lin CC, et al. J Ethnopharmacol 1997 May;56(3):193-200
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Disclaimers
The information in Drug Watch is provided as a courtesy to NewsTarget readers by Applied Health Solutions in cooperation with Healthway Solutions. Although the information is presented with scientific references, we do not wish to imply that this represents a comprehensive list of considerations about any specific drug, herb or nutrient. Nor should this information be considered a substitute for the advice of your doctor, pharmacist, or other healthcare practitioner. Please read the disclaimer about the intentions and limitations of the information provided on these pages. It is important to tell your doctor and pharmacist about all other drugs and nutritional supplements that you are taking if they are recommending a new medication. Copyright © 2007 by Applied Health Solutions, Inc. All rights reserved.
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