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Liver Damage / Tylenol


liftsiron
(@liftsiron)
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posted by DADAWG on PremierMuscle

liver damage / tylenol

this article is from yahoo news . just think what our livers go through when we combine drinking,a oral steroid cycle AND over the counter pain meds like tylenol .
WASHINGTON - Think popping extra pain pills can't hurt? Think again: Accidental poisonings from the nation's most popular pain reliever seem to be rising, making acetaminophen the leading cause of acute liver failure.

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Use it correctly and acetaminophen, best known by the Tylenol brand, lives up to its reputation as one of the safest painkillers. It's taken by some 100 million people a year, and liver damage occurs in only a small fraction of users.

But it's damage that can kill or require a liver transplant, damage that frustrated liver specialists insist should be avoidable.

The problem comes when people don't follow dosing instructions — or unwittingly take too much, not realizing acetaminophen is in hundreds of products, from the over-the-counter remedies Theraflu and Excedrin to the prescription narcotics Vicodin and Percocet.

"The argument that it's the safest sort of has overruled the idea that people cannot take any amount they feel like," says Dr. William Lee of the University of Texas Southwestern Medical Center, who laments that acetaminophen is popped like M&Ms.;

Acetaminophen bottles currently recommend that adults take no more than 4,000 milligrams a day, or eight extra-strength pills.

Just a doubling of the maximum daily dose can be enough to kill, warns Dr. Anne Larson of the University of Washington Medical Center.

Yet, "if two is good, 10 is better in some patients' minds," she says with a sigh.

The Food and Drug Administration has long wrestled with the liver risk, warning two years ago that more than 56,000 emergency-room visits a year are due to acetaminophen overdoses and that 100 people die annually from unintentionally taking too much.

A study published this month by Larson and Lee has agency officials weighing whether to revisit the issue.

Over six years, researchers tracked 662 consecutive patients in acute liver failure who were treated at 22 transplant centers. (Acute liver failure is the most severe type, developing over days, unlike chronic liver failure that can simmer for years because of alcohol abuse or viral hepatitis.)

Almost half were acetaminophen-related. More remarkable was the steady increase: Acetaminophen was to blame for 28 percent of the liver poisonings in 1998, but caused 51 percent of cases in 2003.

That makes acetaminophen the most common cause of acute liver failure, the researchers report in the journal Hepatology.

While most patients pulled through with intensive care, 74 died and 23 others received a transplant.

Some 44 percent of the cases were suicide attempts.

But more, 48 percent, were unintentional overdoses, which "isn't hard to do," Larson says.

Say you take Tylenol Cold & Flu Severe for the flu's aches and stuffiness — 1,000 mg of acetaminophen, every six hours. A headache still nags so between doses you pop some Excedrin — 500 mg more of acetaminophen. Switch to Nyquil Cold/Flu at bedtime, another 1,000 mg.

Maybe you already use arthritis-strength acetaminophen for sore joints — average dose 1,300 mg.

Depending on how often they're taken, the total acetaminophen can add up fast.

That's the nonprescription realm. Surprisingly, 63 percent of unintentional overdoses involved narcotics like Vicodin and Percocet that contain from 325 mg to 750 mg of acetaminophen inside each pill.

Some were chronic pain sufferers taking more and more narcotics as their bodies adjusted to the powerful painkillers, not knowing they were getting ever-higher acetaminophen at the same time. Or they added over-the-counter products for other complaints.

Just this month, Larson treated an 18-year-old whose liver crashed after using Vicodin for three or four days for car-crash injuries. "She was just taking too much because her pain was bothering her."

Led by Tylenol manufacturer McNeil Consumer & Specialty Pharmaceuticals, most over-the-counter products now voluntarily list acetaminophen on front labels.

McNeil also runs ads about the risk, saying "if you're not going to read the label, then don't buy our products," says spokeswoman Kathy Fallon.

But how strongly labels warn varies by product. A rule to standardize warnings, urged by FDA's scientific advisers in 2002, still is working its way through the agency.

While FDA runs a consumer education campaign about the liver risk, nonprescription drugs chief Dr. Charles Ganley says the new study suggests the agency may need to further target narcotic-acetaminophen combinations.

Lee wants to copy Britain, which saw a 30 percent drop in severe liver poisonings after restricting how much acetaminophen could be bought at once.

That's unlikely. Meanwhile, the advice is simple: Read drug labels and add up all your acetaminophen, avoiding more 4,000 mg a day. For extra safety, Lee advises no more than 2,000 to 3,000 mg for more vulnerable people, who regularly use alcohol or have hepatitis.

liftsiron is a fictional character and should be taken as such.


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guijr
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Good post, specially because acetaminophen (brand name: Tylenol) is one of the most popular painkillers ever made, and as we know it's an over-the-counter medicine. But if the damage is already done maybe NAC can help with intoxication due to acetaminophen intake.

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Tsai CL, Chang WT, Weng TI, Fang CC, Walson PD. A patient-tailored N-acetylcysteine protocol for acute acetaminophen intoxication. Clin Ther. 2005;27(3):336-41.

ABSTRACT

BACKGROUND: Hepatotoxicity as a result of acetaminophen(APAP) intoxication has become an important problem, but early intervention with N-acetylcysteine (NAC) is effective in preventing hepatic injury. Two NAC regimens are currently approved for acute APAP intoxication: NAC administered orally every 4 hours for 72 hours, and NAC administered intravenously for 20 hours within 8 to 10 hours after ingestion of a potentially hepatotoxic amount of APAP. However, clinical observations suggest that a variable treatment duration may be more appropriate than use of these predetermined, fixed-duration protocols. OBJECTIVES: This study investigated the tolerability and efficacy of a patient-tailored NAC protocol for acute APAP intoxication by comparing the incidence of hepatotoxicity in patients receiving this protocol and in historical controls receiving 1 of 2 fixed-duration protocols: oral NAC for 72 hours and intravenous NAC for 20 hours within 8 to 10 hours after ingestion of a potentially hepatotoxic amount of APAP. METHODS: This was a retrospective case series study that included all patients admitted through the emergency department (ED) of the National Taiwan University Hospital with a diagnosis of APAP intoxication between October 1997 and October 2002. According to the patient-tailored protocol, which had been used in the ED since 1997, patients with a serum APAP concentration above the limit for possible risk based on a modified Rumack-Matthew nomogram received oral treatment with NAC 140 mg/kg, followed by maintenance doses of 70 mg/kg every 4 hours. NAC treatment was discontinued when the APAP concentration was <10 mg/L and serum aspartate aminotransferase (AST) was <40 IU/L. For the purposes of assessing clinical outcomes, patients were divided into 3 groups based on duration of treatment: the short-course group (</=36 hours), the intermediate-course group (37-72 hours), and the long-course group (>/=73 hours). The primary outcome measure was development of hepatotoxicity, defined as a serum AST or alanine aminotransferase concentration >1000 IU/L. RESULTS: Twenty-seven patients were included in the study, 17 in the short-course group, 4 in the intermediate-course group, and 6 in the long-course group. The mean (SD) durations of NAC treatment in the respective groups were 22.1 (5.5) hours, 45.0 (8.2) hours, and 97.3 (33.2) hours. All 6 patients (22%) in the long-course group had hepatotoxicity (peak AST range, 1083-9770 IU/L); their treatment duration ranged from 80 to 164 hours. No patients in the short- or intermediate-course group had evidence of hepatotoxicity. One woman in the long-course group in whom initiation of NAC treatment was delayed by 28 hours died of fulminant hepatic failure. The overall incidence of hepatotoxicity was similar to that in the historical controls. CONCLUSIONS: In this retrospective case series inpatients who received patient-tailored NAC therapy for acute APAP intoxication, the incidence of hepatotoxicity was low and comparable to that in historical controls who received treatment with 1 of 2 fixed-duration regimens. Use of this protocol may have the potential to shorten hospital stays without increasing the risk to patients. However, the sample size was small, and the findings require confirmation in prospective clinical trials.

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Kolacinski Z, Rusinski P. Paracetamol: therapeutic action, pathogenesis and treatment of acute poisonings complicated by severe liver damage. Przegl Lek. 2003;60(4):218-22.

ABSTRACT

The biosynthesis of prostaglandins proceeds in the presence of fatty acid cycloxygenases (COX-1, COX-2). COX-1 is responsible for the synthesis of prostaglandins indispensable for normal homeostasis, while COX-2 regulates local expression of pro-inflammatory prostaglandins. Paracetamol is a selective inhibitor of COX-2 thus having an analgesic and antipyretic potential. The drug is metabolised primarily in the liver. About 5% of the dose transforms into N-acetylo-p-benzoquinoneimine (NAPQI), a highly active compound. Ingestion of a single paracetamol dose higher than 8 g leads to a depletion of hepatic glutathione reserves and a loss of the detoxifying property of the liver. As a result, hepatic necrosis develops. The specific antidote is N-acetylcysteine (NAC). If applied within 10-15 h since the poisoning it enables complete survival. The efficacy of specific treatment decreases after 24 h but blood paracetamol is an indication for NAC therapy. The surviving patients with advanced paracetamol poisoning require long-lasting conservative treatment with ornithine and phospholipids as well as a light diet.

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Pajoumand A, Jalali N, Abdollahi M, Shadnia S. Successful treatment of acetaminophen overdose associated with hepatic failure. Hum Exp Toxicol. 2003;22(8):453-8.

ABSTRACT

Acetaminophen is the most widely used antipyretic and analgesic drug in the world. Acetaminophen poisoning and the following hepatic failure are not rare and are the most common indications of liver transplantation in the USA and Europe. In this case report, the patient was a 25-year old woman with hepatic failure who was brought to Loghman-Hakim Poison Centre 24 hours after attempted suicide with 100 tablets of acetaminophen, 325 mg. She was treated with N-acetylcysteine (NAC) and discharged from the hospital 12 days after admission and followed up for 1 month. In conclusion, acetaminophen poisoning should be considered in the differential diagnoses of hepatic failure. In acetaminophen-induced hepatic damage the administration of NAC must always be considered even after 24 hours of overdose.

=================================

Kozer E, McGuigan M. Treatment strategies for early presenting acetaminophen overdose: a survey of medical directors of poison centers in North America and Europe. Hum Exp Toxicol. 2002;21(3):123-7.

ABSTRACT

BACKGROUND: Acetaminophen is frequently used in self-poisoning in Western countries. Although treatment with N-acetylcysteine (NAC) reduces liver injury, no consensus exists on the preferred management of acetaminophen toxicity. OBJECTIVES: To describe the approach taken by toxicologists in North America and Europe toward the management of acetaminophen toxicity. Methods: Medical directors of poison centers in the US, Canada, and Europe were surveyed by means of a questionnaire presenting two clinical scenarios of acetaminophen overdose: a healthy adolescent with no risk factors who had an acute ingestion of acetaminophen, and an adult with both acute ingestion and possible risk factors. For each case, several questions about the management of these patients were asked. RESULTS: Questionnaires were sent to medical directors of 76 poison centers in North America and 48 in Europe, with response rates of 62% and 44%, respectively. Forty percent of responders suggested using charcoal 4 hours after ingestion of a potential toxic dose of acetaminophen, and 90% recommended treatment with NAC when levels were above 150 microg/mL but below 200 microg/mL 4 hours after ingestion. Duration of treatment with oral NAC ranged from 24 to 96 hours; 38 responders suggested a duration of 72 hours. Of 49 centers recommending oral NAC, 18 (36.7%) said they might consider treatment for less than 72 hours. Eleven of 29 (37.9%) responders suggested treatment with intravenous NAC for more than 20 hours as their usual protocol or a protocol for specific circumstances. CONCLUSIONS: Our study showed large variability in the management of acetaminophen overdose. Variations in treatment protocols should be addressed in clinical trials to optimize the treatment for this common problem.

More to read:

1) http://www.truestarhealth.com/Notes/1072008.html.

"The medals don't mean anything and the glory doesn't last. It's all about your happiness. The rewards are going to come, but my happiness is just loving the sport and having fun performing" ~ Jackie Joyner Kersee.


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liftsiron
(@liftsiron)
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Thanks for the studies bro.

liftsiron is a fictional character and should be taken as such.


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jboldman
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I alwaysthink twice before taking pain killers. NAC is great stuff, i take it every day.

jb


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jboldman
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This is a really important point, acetominophen when taken by itself is fairly safe unless taken in large doses or for long periods of time but if taken with alcohol the dose to damage ratio changes dramatically! I think many reach for the tylenol bottle for any excuse including hangovers. This excerpt taken from liverdisease.com points out the ironic fact that acetominophen is the pain killer of choice for those with liver disease but when taken incorrectly becomes a great danger!
'excerpt from liverdisease.com"
<<Painkillers and Liver Disease/Hepatitis

Acetaminophen (Tylenol) is a medication used to control pain (known as an analgesic) and fever (known as antipyretic). It does this without producing the stomach discomfort often experienced with aspirin and other nonsteroidal anti-inflammatories (NSAIDs). This characteristic has made acetaminophen a very popular alternative to NSAIDs. In small doses (less than 4 grams per day, or eight pills taken over a twenty-four hour period of time) acetaminophen is quite safe for the liver—unless combined with alcoholic beverages (see below). (Note: each acetaminophen tablet or pill typically contains 500 milligrams of acetaminophen.) In fact, acetaminophen is the recommended medication for relieving minor aches, pains, and headaches in people with liver disease.

However, when taken in excessive quantities or when combined with alcohol, acetaminophen may cause death due to liver failure. In fact, an overdose of acetaminophen is the most common cause of fulminant hepatic failure as well as the most common cause of drug-induced liver disease in the United States. After acetaminophen became readily available in 1960 as an over-the-counter medication, it became one of the most popular means of attempting suicide. For liver injury to occur, acetaminophen must generally be consumed in quantities exceeding 15 grams within a short period of time, such as in a single dose. Although uncommon, ingestion of 7 to 10 grams at one time may cause liver damage.

The consumption of alcohol in conjunction with acetaminophen significantly increases the likelihood that a person will incur severe liver damage. Therefore, people who consume alcohol on a regular basis should probably limit acetaminophen intake to a maximum of 1 to 2 grams per day (that is, two to four pills within a twenty-four hour period). Still, the best advice for people with liver disease is to totally abstain from alcohol.>>

jb


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guijr
(@guijr)
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Good read, Jbol.

"The medals don't mean anything and the glory doesn't last. It's all about your happiness. The rewards are going to come, but my happiness is just loving the sport and having fun performing" ~ Jackie Joyner Kersee.


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guijr
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Posted by: Dodnof
Just got back from the ICU at the hospital..... the girl I've been dating for about 3 years was admitted today by her mother..... she found her delerious a few hours ago and rushed her to the hospital.... they found very high levels of acetaminophen in her system.... her mom later found about 18 excedrin pm missing..... they are holding her and I cant see her until tomorrow...... I really dont have a clue what to do for her at this point, as she is claiming she took an ambien and it made her loopy and she doesnt remember taking anything after that.

That's too bad. I wish her best of luck and hope to hear the good news.

Well, you may ask her physician if she is taking NAC or other medicines specially flumazenil infusion (enable rapid detoxification promoted by the Zolpidem [generic name Ambien]) which is used as a sleeping pill to treat insomnia.

IMHO, one would better be careful before taking these kind of stuff, specially when drugs like that are combined.

==============================

Swainston Harrison T, Keating GM. Zolpidem: a review of its use in the management of insomnia. CNS Drugs. 2005;19(1):65-89.

ABSTRACT

Zolpidem (Ambien, Stilnox, Myslee, an imidazopyridine, is a nonbenzodiazepine hypnotic indicated for the short-term treatment of insomnia. Zolpidem improves sleep in patients with insomnia. Its overall tolerability is favourable when administered according to the manufacturer's prescribing information, with a low propensity to cause clinical residual effects, withdrawal, dependence or tolerance. In addition, most evidence suggests that the drug is associated with minimal rebound insomnia. In the only clinical trials that investigated the use of a hypnosedative drug in an 'as-needed' regimen, zolpidem produced a global improvement in sleep. Thus, zolpidem continues to be a useful therapeutic option in the pharmacological treatment of patients with insomnia.

==============================

Mahoney JE, Webb MJ, Gray SL. Zolpidem prescribing and adverse drug reactions in hospitalized general medicine patients at a Veterans Affairs hospital. Am J Geriatr Pharmacother. 2004 Mar;2(1):66-74.

ABSTRACT

BACKGROUND: Zolpidem is prescribed for sleep disruption in hospitalized patients, but data on the incidence of adverse drug reactions (ADRs) are based largely on outpatient studies. Thus, the incidence of ADRs in hospitalized patients may be much higher. OBJECTIVE: The goal of this study was to describe prescribing patterns of zolpidem for hospitalized medical patients aged 50 years, the incidence of ADRs possibly and probably associated with its use, and the factors associated with central nervous system (CNS) ADRs. METHODS: This case series was conducted in 4 general medicine wards at a Veterans Affairs hospital and was a consecutive sample of patients aged 50 years who were hospitalized between 1993 and 1997 and received zolpidem as a hypnotic during hospitalization, but had not received it in the previous 3 months. Chart review was conducted by 2 evaluators. Data extracted from the medical records included admission demographic characteristics, medications, comorbidities, and levels of function in performing basic and instrumental activities of daily living. The main outcome measure was ADRs possibly or probably related to zolpidem use. The association between zolpidem and the occurrence of CNS ADRs (eg, confusion, dizziness, daytime somnolence) was analyzed separately. RESULTS: The review included 119 medical patients aged > or =50 years who had newly received zolpidem for sleep disruption during hospitalization. The median age of the population was 70 years; 86 (72.3%) patients were aged 65 years. The initial zolpidem dose was 5 mg in 42 patients (35.3%) and 10 mg in 77 patients (64.7%). Twenty-three patients had a respective 16 and 10 ADRs possibly and probably related to zolpidem use (19.3% incidence). Of a total of 26 ADRs, 21 (80.8%) were CNS ADRs, occurring with both zolpidem 5 mg (10.8% of users) and 10 mg (18.3% of users). On univariate analyses, the only factor significantly associated with a CNS ADR was functional impairment at baseline (P = 0.003). Zolpidem was discontinued in 38.8% of patients experiencing a CNS ADR CONCLUSIONS: In this case series in medical inpatients, there was a high frequency of ADRs, particularly CNS ADRs, associated with zolpidem use. Zolpidem should be used cautiously in the hospital setting.

==============================

Quaglio G, Lugoboni F, Fornasiero A, Lechi A, Gerra G, Mezzelani P. Dependence on zolpidem: two case reports of detoxification with flumazenil infusion. Int Clin Psychopharmacol. 2005;20(5):285-7.

ABSTRACT

Zolpidem is a hypnotic drug that is chemically distinct from benzodiazepines (BDZ). It has been suggested that it acts selectively on gamma-aminobutyric acid receptors. However, recent evidence has shown that the behavioural effects of zolpidem are generally similar to those of BDZs. Flumazenil is usually considered to be a BDZ antagonist. Nonetheless, in chronic BDZ users, it acts as a partial, bland agonist. We describe two cases of zolpidem dependence that were detoxified by the use of flumazenil infusion. BDZ dependence is usually treated with tapering of the medication. As an alternative, abrupt discontinuation of the medication and rapid detoxification using flumazenil has been used. Flumazenil may represent an alternative to detoxification treatment by employing a tapering approach, or by replacement therapy with BDZs with a long half-life, particularly where patients are hard to treat or have low compliance to treatment.

==============================

Yang W, Dollear M, Muthukrishnan SR. One rare side effect of zolpidem--sleepwalking: a case report. Arch Phys Med Rehabil. 2005;86(6):1265-6.

ABSTRACT

Zolpidem is an imidazopyridine agent indicated for the short-term treatment of insomnia. Sleepwalking is a rare side effect of zolpidem. A review of the literature produced only 2 cases. We report a case of a male rehabilitation inpatient in his mid fifties with a history of alcoholism and traumatic brain injury who had undergone a right hip hemiarthroplasty. He had no history of somnambulism or insomnia but walked in his sleep on 2 nonconsecutive nights after taking zolpidem. He had exhibited no such behavior before taking zolpidem, on the intervening night that was he was not given medication, and after the medication was discontinued. We conclude that zolpidem can cause sleepwalking, and patients who have suffered a brain injury may be more susceptible to this side effect. Here we describe the clinical presentation and review the relevant literature on zolpidem and sleepwalking.

"The medals don't mean anything and the glory doesn't last. It's all about your happiness. The rewards are going to come, but my happiness is just loving the sport and having fun performing" ~ Jackie Joyner Kersee.


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Bilter
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Good read. I did not realize all of the OTC meds out there that contain acetominophen. Time for me to start reading the ingeidients on this stuff.


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jboldman
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i hope she did not take a high dose of acetominophen as permanent liver damage can result.

jb


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RippedRon
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Posted by: Bilter
Good read. I did not realize all of the OTC meds out there that contain acetominophen. Time for me to start reading the ingeidients on this stuff.

Don't forget that every NSAID out there may cause liver damage, not just acetaminophen. I've always been a big believer in Advil for one reason or another, and will only take it if absolutely necessary.

I'll reference a snippet from one of my texts : Introduction to Organic Laboratory Techniques, A small scale approach, by Pavia, Lampman, Kriz and Engel, page 63.

"...An important advantage of ibuprofen is that it is a very powerful pain reliever. One 200-mg tablet is as effective as two tablets (650mg) of aspirin. Furthermore, ibuprofen has a more advantageous dose-response curve, which means that taking two tablets of this drug is approximately twice as effective as one tablet for certain types of pain. Aspirin and acetaminophen reach their maximum effective dose at two tablets. Little additional relief is gained at doses above that level. Ibuprofen, however, continues to increase its effectiveness up to the 400-mg level (the equivalent of four tablets of aspirin or acetaminophen). Ibuprofen is a relatively safe drug, but its use should be avoided in cases of aspirin allergy, kidney problems, ulcers, asthma, hypertension, or heart disease."

Take home message I guess, any drug you take can be bad if used improperly (which generally means taking too much of it!)

- RR
" Go hard or go home !"

"Lightweight baby!"


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