Liver Cancer - Painkillers May Protect Liver

Painkillers May Protect Liver

By Crystal Phend, Senior Staff Writer, MedPage Today
Published: November 29, 2012
Reviewed by Zalman S. Agus, MD; Emeritus Professor, Perelman School of Medicine at the University of Pennsylvania and Dorothy Caputo, MA, BSN, RN, Nurse Planner

View Video at MedPage Today

Nonsteroidal anti-inflammatory drugs, especially aspirin, may help prevent serious liver problems, a large observational study suggested.

Aspirin users were 41% less likely to develop hepatocellular carcinoma and 45% less likely to die from chronic liver disease than non-users, both statistically significant differences, Vikrant V. Sahasrabuddhe, MBBS, DrPH, of the National Cancer Institute in Rockville, Md., and colleagues reported.

Other NSAIDs were also associated with reduced mortality from chronic liver disease, but not with less liver cancer, among the more than 300,000 middle-age and older participants in the National Institutes of Health-AARP Diet and Health Study cohort.

"These associations are prominent with the use of aspirin, and if confirmed, might open new vistas for chemoprevention of hepatocellular carcinoma and chronic liver disease," the researchers wrote in the Dec. 5 issue of the Journal of the National Cancer Institute.

The findings were not unexpected based on prior results in colorectal and other cancer types, Boris Pasche, MD, PhD, an oncologist at the University of Alabama at Birmingham, noted in an interview with MedPage Today.

"We are seeing a growing body of evidence suggesting that taking aspirin long-term prevents the development of several types of cancer" in populations taking the NSAID for cardiovascular event prevention, he explained.

However, aside from being a possible additional benefit when indicated for cardioprotection, aspirin might not be either necessary or that useful for protecting the liver, according to other experts.
For one thing, there are already good strategies that don't raise bleeding risk the way NSAIDs do, Isra G. Levy, MBBCh, MSc, and Carolyn P. Pim, MD, both of the University of Ottawa and Ottawa Public Health in Ontario, noted in an accompanying editorial.

"In practice," they wrote, "we know and understand the causes of most cases of chronic liver disease and primary liver cancer: viral infections, especially hepatitis B virus (HBV) and hepatitis C virus (HCV), and alcohol. And we already have cheap, readily available interventions to prevent a substantial majority of such diseases."

Furthermore, the risk of developing hepatocellular carcinoma is low enough in the general population that chemoprevention wouldn't make sense when weighed against the bleeding risk, commented Mary Ann Huang, MD, a hepatologist at Henry Ford Hospital in Detroit.

The higher-risk population for whom preventive strategies are needed -- those with cirrhosis -- likely wouldn't be good candidates either because they are also at higher risk of bleeding, Huang told MedPage Today in an interview.

Still the NIH-AARP study results may be good enough to warrant a prospective trial to see whether the benefit would outweigh the risk in that population, Pasche suggested.

The joint Diet and Health study included 300,504 adults ages 50 to 71 years at enrollment who reported their NSAID use on a baseline questionnaire.

The cohort was pulled from six states (California, Florida, Louisiana, New Jersey, North Carolina, and Pennsylvania) and two metropolitan areas (Atlanta and Detroit).
Among the respondents, 73% reported aspirin use and 56% used other NSAIDs.

Altogether, any aspirin or non-aspirin NSAID use was associated with reduced relative risks of:

• 0.63 for developing hepatocellular carcinoma (95% CI 0.46 to 0.87)
• 0.49 for risk of death due to chronic liver disease (95% CI 0.39 to 0.61)

Aspirin use specifically, regardless of other NSAID use, came out significantly protective on both counts as well, with relative risks of 0.59 for developing hepatocellular carcinoma (95% CI 0.45 to 0.77) and 0.55 for death from chronic liver disease (95% CI 0.45 to 0.67).

The effect was even greater, with relative risks of 0.51 and 0.50, when looking at those participants who exclusively used aspirin versus those who didn't take any NSAIDs.

Other NSAID use was associated with a reduced risk of chronic liver disease mortality, with a relative risk of 0.74 (95% CI 0.61 to 0.90) that dropped to 0.66 (95% CI 0.48 to 0.91) when looking at those who used only non-aspirin NSAIDs versus no NSAIDs.

But the effect on hepatocellular carcinoma incidence wasn't significant in either case with non-aspirin NSAIDs, and the effect on death from chronic liver disease was significant only in those who used it on a monthly rather than daily or weekly basis.

Aspirin's effects were independent of frequency of use.

All the results were adjusted for age, sex, race or ethnicity, body mass index, cigarette smoking, alcohol consumption, and diabetes.

The researchers suggested that the apparent advantage of NSAID use in the cohort may have been due to anti-inflammatory or other mechanisms.

They acknowledged, though, that the lack of dose response and finding of only monthly links to non-aspirin NSAID use "suggests that the findings should be interpreted with some caution, because they may also reflect an unmeasured confounder."
Huang pointed to the lack of data on cirrhosis and hepatitis status and the single time point of NSAID use ascertainment.

Although there wasn't any reporting of duration or indication for NSAID use, a sensitivity analysis excluding participants who said they had a history of heart disease or hypertension as "a proxy for cardiovascular indication and longer duration of NSAID use, particularly low-dose aspirin), yielded hazard rate ratios similar to those of the overall cohort and suggested minimal potential for confounding by indication."

Primary source: Journal of the National Cancer Institute
Source reference:
Sahasrabuddhe VV, et al "Nonsteroidal Anti-inflammatory Drug Use, Chronic Liver Disease, and Hepatocellular Carcinoma" J Natl Cancer Inst 2012: 104; 1808–1814.

Additional source: Journal of the National Cancer Institute
Source reference:
Levy IG, Pim CP "An Aspirin a Day: The Allure (and Distraction) of Chemoprevention" J Natl Cancer Inst 2012: 104.

Hepatitis C Review - Acetaminophen -Tylenol

Hepatitis C Review - Acetaminophen -Tylenol 

In 2011 Johnson & Johnson reduced the maximum daily dose of its Extra Strength Tylenol pain reliever, lowering the risk of accidental overdose from the drugs active ingredient acetaminophen.

Today on the blog those label changes are highlighted with the hepatitis C patient in mind.

Stay updated by viewing future articles related to - Acetaminophen Safety.

What We Know

For the average healthy person acetaminophen-Tylenol is a remarkably safe and effective drug when taken at the recommended dose, yet acetaminophen has caused hundreds of deaths per year.

Why?

 .

The Answer

In November of last year MSNBC author Rachel Rettner wrote an article about a study published in the British Journal of Clinical Pharmacology . The study found that "staggered overdoses" of acetaminophen were more deadly than single overdoses. The journalist explains:

The study looked at what are called "staggered overdoses," in which a person repeatedly exceeds the daily recommendation through small overdoses. This is in contrast to the more familiar single overdose, when a person takes too many pills at once.

In the study, staggered overdoses of acetaminophen  (which is found in Tylenol and other pain reliever's) were more deadly than single overdoses, even though people who experienced staggered overdoses typically took smaller total amounts of acetaminophen than those who experienced a single overdose.

Doctors may not identify staggered overdoses right away, researchers added. People with a staggered overdose may have levels of the drug in their blood below what a standard blood test would indicate as an overdose, even when their liver is badly damaged.

Continue Reading...

In a related article at TIME  journalist  Maia Szalavitz reported the highest health risks from "staggered overdose" were seen in older people and people who drink a lot of alcohol.

Heavy drinkers and older patients were at highest risk of staggered overdose. Alcohol alone can damage the liver and those who drink more than three drinks a day are advised not to use drugs that contain acetaminophen.

People who misuse opioid painkillers are also at risk of staggered acetaminophen overdose because common opioid drugs like Vicodin include it. While long-term users develop tolerance to the effects of the opioid component of these drugs, this does not affect the potential of acetaminophen to damage the liver.

Continue Reading...

In  January of 2011 the FDA  asked acetaminophen-manufacturers to lower the strength of acetaminophen in prescription drug products to 325 milligrams per pill. Although, MSNBC reported taking a pill of this dosage every four hours could still put a person at risk from "staggered overdose" from acetaminophen. As noted below Tylenol was not included in the FDA action.

The U.S. Food and Drug Administration (FDA) is asking drug manufacturers to limit the strength of acetaminophen in prescription drug products, which are predominantly combinations of acetaminophen and opioids. This action will limit the amount of acetaminophen in these products to 325 mg per tablet, capsule, or other dosage unit, making these products safer for patients.

In addition, a Boxed Warning highlighting the potential for severe liver injury and a Warning highlighting the potential for allergic reactions (e.g., swelling of the face, mouth, and throat, difficulty breathing, itching, or rash) are being added to the label of all prescription drug products that contain acetaminophen.

These actions will help to reduce the risk of severe liver injury and allergic reactions associated with acetaminophen.

Acetaminophen is widely and effectively used in both prescription and over-the-counter (OTC) products to reduce pain and fever. It is one of the most commonly-used drugs in the United States. Examples of prescription products that contain acetaminophen include hydrocodone with acetaminophen (Vicodin, Lortab), and oxycodone with acetaminophen (Tylox, Percocet).

OTC products containing acetaminophen (e.g., Tylenol) are not affected by this action. Information about the potential for liver injury is already required on the label for OTC products containing acetaminophen. FDA is continuing to evaluate ways to reduce the risk of acetaminophen related liver injury from OTC products. Additional safety measures relating to OTC acetaminophen products will be taken through separate action, such as a rulemaking as part of the ongoing OTC monograph proceeding for internal analgesic drug products.

Acetaminophen-ALT elevations in non-drinkers

I thought this was interesting, in 2010 a study published in "The Journal of Human Pharmacology and Drug Therapy" researchers found that daily use of acetaminophen - at the daily maximum dose of 4 g/day for 10 days causes asymptomatic ALT elevations in non-drinkers.

2010 Study/Full Text:

Serum alanine aminotransferase elevation during 10 days of acetaminophen administration in non-drinkers

In conclusion, administration of the maximum daily recommended dose of acetaminophen, 4 g/day to healthy non-drinkers for more than 4 consecutive days is associated with asymptomatic ALT elevation in most subjects. ALT elevations are generally between 1.5 and 2 times their pre-treatment measurements are not accompanied by other laboratory findings or symptoms of liver injury and all ALT elevations resolved once acetaminophen administration was stopped.

Hepatitis C And Tylenol

Under the supervision of a doctor, and depending on the condition of the liver, people undergoing HCV therapy are often prescribed Tylenol for joint aches, pain and fever relief, without risk or complications. 

Someone please tell me what is the recommended dose of Tylenol is for people with HCV ?

.

The Recommended dose of acetaminophen (Tylenol®) for patients with hepatitis C

According to "The Department of Veterans Affairs" website (updated: July 21, 2011) the maximum recommended dose of acetaminophen (Tylenol®) for patients with hepatitis C is two grams (four 500mg tablets) per day.

Tylenol Label Changes

 The Maximum Recommended Dose For "Healthy Patients"

In the fall of 2011 new dosing instructions for TYLENOL were put in place by Johnson & Johnson. The maximum daily dose was changed from 8 pills (4,000 milligrams) per day to 6 pills (3,000 milligrams) per day. The drug company also changed the dosing interval from every 4-6 hours to every 6 hours.

*The 2011 label changes for extra strength Tylenol are listed below, the company says it will cut the maximum dosage of Regular Strength Tylenol and other acetaminophen-containing products in 2012..

* Patients with cirrhosis should avoid pain medications called “non‐steroidal antiinflammatories (NSAIDS)”

Please know with every mention of HCV therapy there are far too many people who have not benefited from new or old drugs that treat this virus. For these people who have advanced liver damage, managing pain or sleep aids can be a daily struggle. Check out the website for an article written by Jennifer Pate, covering the commonly used sleep medications in patients with liver disease

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Pain Medications In Patients With Cirrhosis

Source- U of M Cirrhosis Patient Tool Kit   

Medications

Patients with cirrhosis should avoid pain medications called “non‐steroidal antiinflammatories (NSAIDS)”. These include over‐the‐counter medications such as ibuprofen (Motrin, Advil), naprosyn (Aleve), as well as some prescription medications. Ask your doctor if any of your medications are NSAIDS.

For mild to moderate aches and pains, it is safe to use Tylenol (acetaminophen) at doses of 2,000 mg/day or less (no more than 6 regular strength or no more than 4 extra strength each day AND no more than 20 regular strength or no more than 15 extra strength each week). Some cold medicines and prescription pain medicines contain acetaminophen, so read the labels and make sure you don’t

take too much by mistake.

Medications - Decompensated Liver Disease 

A 2011 review article published in the International Journal of Hepatology titled:  

Prescribing Medications in Patients with Decompensated Liver Cirrhosis

Extra Strength TYLENOL New dosing instructions

Once again the new dosing instructions reduce the maximum daily dose from 8 pills per day to 6 pills per day and change the dosing interval for Extra Strength TYLENOL^® from every 4-6 hours to every 6 hours. These labeling changes will be consistent across all single-ingredient Extra Strength TYLENOL^® products. We are working closely with other manufacturers of acetaminophen products to help ensure consistency in dosing instructions.

Changes affect the labels of the following Extra Strength TYLENOL® products

Extra Strength TYLENOL^® Rapid Release Gels - 500 mg in each gelcap

Extra Strength TYLENOL^® Caplets - 500 mg in each tablet

Extra Strength TYLENOL^® EZ Tabs - 500 mg in each tablet

Extra Strength TYLENOL^® Rapid Blast Liquid - 500 mg in each

15 mL = 1 tablespoon

 *Regular strength Tylenol 

*Consider a lower acetaminophen dose found in regular-strength Tylenol, which is 325 mg. It could be adequate enough to relieve minor pain or treatment side effects.

Regular strength Tylenol - 325 mg in each tablet

Warnings

Regular strength Tylenol

Liver warning:

This product contains acetaminophen. Severe liver damage may occur if

• adult takes more than 12 tablets in 24 hours, which is the maximum daily amount
• child take more than 5 doses in 24 hours
• taken with other drugs containing acetaminophen
• adult has 3 or more alcoholic drinks every day while using this product

Do not use

• with any other drug containing acetaminophen (prescription or nonprescription). If you are not sure whether a drug contains acetaminophen, ask a doctor or pharmacist
• if you are allergic to acetaminophen or any of the inactive ingredients in this product

*Ask a doctor before use if the user has liver disease

Extra Strength TYLENOL

Caplets, Rapid Release Gels, EZ Tabs

Liver warning:

This product contains acetaminophen. The maximum daily dose of this product is 6 caplets, gelcaps, or tablets (3,000 mg) in 24 hours. Severe liver damage may occur if you take

• more than 4,000 mg of acetaminophen in 24 hours
• with other drugs containing acetaminophen
• 3 or more alcoholic drinks every day while using this product

Rapid Blast Liquid

Liver warning:

This product contains acetaminophen. The maximum daily dose of this product is 90 mL (6 TBSP) (3 FL OZ) (3,000 mg) in 24 hours. Severe liver damage may occur if you take

• more than 4,000 mg of acetaminophen in 24 hours
• with other drugs containing acetaminophen
• 3 or more alcoholic drinks every day while using this product

Do not use

• with any other drug containing acetaminophen (prescription or nonprescription). If you are not sure whether a drug contains acetaminophen, ask a doctor or pharmacist.
• if you are allergic to acetaminophen or any of the inactive ingredients in this product

****Ask a doctor before use if you have liver disease.

TYLENOL - Why the Label Instructions Have Changed.

Today, more than 600 over-the-counter and prescription medicines contain acetaminophen.These include medicines to treat symptoms of allergies, cold and flu, and pain with trouble sleeping.

Some people accidentally exceed the recommended dose when taking multiple products at the same time, often without realizing they contain acetaminophen or by not reading and following the dosing instructions. Acetaminophen –the active ingredient in TYLENOL^®–is safe when used as directed, but when taken in overdose amounts, it can cause liver damage.

Some Common Medications That Contain Acetaminophen*

It’s important to be aware of the ingredients in all medications that you may be taking. Acetaminophen (APAP) is a common component of many different over-the-counter and prescription medications. You should not take two or more products that contain acetaminophen at the same time.

Taking more than the recommended dose (overdose) of acetaminophen may cause liver damage.

Some Common Prescription Drugs That Contain Acetaminophen*

• Darvocet®
• Endocet®
• Fioricet®
• Hycotab
• Hydrocet®
• Hydrocodone Bitartrate
• Lortab®
• Percocet®
• Phenaphen®
• Sedapap®
• Tapanol®
• Ultracet®
• Vicodin®
• Zydone®
  
  

Some Common Over-the-Counter Drugs That Contain Acetaminophen*

• Actifed®
• Anacin®
• Benadryl®
• Cepacol®
• Contac®
• Coricidin®
• Dayquil®
• Dimetapp®
• Dristan®
• Elixir®
• Excedrin®
• Feverall®
• Formula 44®
• Goody’s® Powders
• Liquiprin®
• Midol®
• Nyquil®
• Panadol®
• Robitussin®
• Saint Joseph® Aspirin-Free
• Singlet®
• Sinutab®
• Sudafed®
• Theraflu®
• Triaminic®
• TYLENOL® Brand Products
• Vanquish®
• Vicks®
• Zicam®

*This is NOT a complete list.

In addition to the new dosing instructions on the OTC label, the makers of TYLENOL® launched Get Relief Responsibly™, an initiative designed to educate consumers about the appropriate use of OTC and prescription medications, particularly those containing acetaminophen, and the importance of reading and following medication labels. As a part of this initiative, the makers of TYLENOL® have created a new website www.getreliefresponsibly.com. The site includes an interactive Acetaminophen Finder tool to help consumers identify products that contain acetaminophen and build a personal acetaminophen medication list to share with their healthcare provider or pharmacist.

Related Updates

DDW-Patients May Receive Too Much Acetaminophen in Hospital

Study uncovers the extent of OTC acetaminophen overdose risk

Pain Reliever Safety: Some Red Flags

Pain Reliever Safety: Some Red Flags

For many people, pain relievers are wonder drugs, allowing them to carry on with their lives despite disabling arthritis, for instance, or recurrent headaches. But all pain relievers, whether sold over-the counter (OTC) or by prescription, have potential risks. Recent studies have amplified the concerns.

The most recent warning came from a large Danish study, in Circulation, of people who previously had a heart attack. Those who took certain pain relievers, including ibuprofen (but not aspirin or naproxen), had about a 50 percent increased risk of having another heart attack or dying during the next three months—even after just a week’s use. Last year another large study from the same group of Danish researchers found that the drugs also increased cardiovascular risk in healthy people.

You may be surprised to hear that those innocuous-looking tablets can increase the risk of heart attacks, but the evidence about this has been growing. That’s why two years ago the FDA ruled that the labels of all OTC pain relievers should carry tougher warnings about this and/or other risks.

The basics: Though there are many brands of OTC pain relievers, there are two basic types: acetaminophen (such as Tylenol) and NSAIDs (nonsteroidal anti-inflammatory drugs), all available in generic form. These nonprescription NSAIDs are aspirin, ibuprofen (such as Motrin and Advil) and naproxen (such as Aleve). Some NSAIDs are also sold by prescription.

What to watch out for

The following issues relate primarily to people who take these drugs at least several times a week:

• Cardiovascular risk. In a 2007 report, the American Heart Association concluded that, with the exception of aspirin and probably naproxen, NSAIDs increase the risk of heart attacks, particularly in people who already have cardiovascular disease or are at high risk for it. The so-called COX-2 inhibitors (Celebrex, sold by prescription, is the only one still marketed) are riskiest, followed by ibuprofen.

• Blood pressure. NSAIDs can raise blood pressure. This may be at least partly responsible for the increased risk of heart attack and stroke. The evidence about acetaminophen is inconsistent.

• Gastrointestinal (GI) bleeding. NSAIDs can damage the stomach lining and cause bleeding and ulcers. This has long been considered their major drawback, as the labels warn. The risk is greatest in long-term users, those over 60, heavy drinkers, those with a history of GI bleeding or ulcers and those taking certain medications, such as blood-thinning drugs or steroids.

• Liver damage. Acetaminophen, the No. 1 nonprescription pain reliever, does not cause GI bleeding, but long-term frequent use or even large single doses can cause severe liver damage. In fact, acetaminophen overdosing is the most common cause of acute liver failure in the U.S., often as the result of suicide attempts. Most people still don’t know about this risk and don’t realize that acetaminophen is in hundreds of OTC cold, allergy and headache products and some prescription pain relievers. Check labels for acetaminophen, and don’t take more than 4 grams—equal to eight Extra Strength Tylenol tab--lets—a day from all sources. Alcohol (three drinks or more at a time) and certain other drugs increase the risk. Heavy drinkers and those with liver disease should avoid, or at least limit, acetaminophen. Taking the drug while fasting also increases the risk.

• Kidney damage. NSAIDs (and acetaminophen to a lesser extent) can damage the kidneys. If you have kidney disease, talk to your doctor about pain reliever safety.

Here’s our advice

For healthy people who take OTC pain relievers as directed, the risks are relatively small. However, because these drugs are so popular, thousands of Americans are affected every year. Don’t let these concerns prevent you from taking the drugs if you need them, but do follow this advice, especially if you take pain relievers often:

• Try nondrug treatments for chronic pain first. For arthritis or back pain, for instance, that means physical therapy, exercise, weight loss, and heat or cold therapy. It’s easier to pop a pill, but these treatments may work just as well or even better.

• Talk to your doctor about which pain reliever is best for you to take regularly. Weigh the potential risks and benefits, especially if have heart disease (or are at high risk for it) or uncontrolled hypertension, or if you drink moderately or heavily.

• Consider acetaminophen first, then aspirin or naproxen. But the best choice depends on the cause and severity of your pain, along with your medical history. Acetaminophen is safest for the GI tract, though it may not provide enough relief, since unlike NSAIDs it doesn’t reduce inflammation. Your doctor may recommend a prescription drug instead of long-term use or high doses of OTC products. Celebrex should be used only as a last resort.

• Take the lowest effective dose for the shortest time possible, whatever the pain reliever.

• Do not exceed the doses listed on the labels or take for more than 10 days, unless your doctor has said it’s okay.

• Consult your doctor before starting aspirin therapy to protect your heart or to reduce the risk of colon cancer. Ibuprofen can block aspirin’s anti-clotting effect, so don’t take it during the eight hours before or half hour after you take low-dose aspirin, the FDA advises.


NSAIDS + SSRIs + S.O.S.

Besides the many well-known interactions OTC pain relievers can have with other drugs, a new one was recently discovered. Depressed people taking NSAIDs are about 25 percent less likely to have their symptoms relieved by the widely used antidepressants called SSRIs (selective serotonin reuptake inhibitors), such as Prozac and Paxil, according to a recent study in the Proceedings of the National Academy of Sciences. This is a double whammy, since earlier research found that combining SSRIs and NSAIDs greatly increases the risk of gastrointestinal bleeding. Acetaminophen is thus a better option for people taking SSRIs.


UC Berkeley Wellness Letter, August 2011

About the
Wellness Letter

(NSAIDs); Colon Complications from Anti-Inflammatory Drugs?

Colon Complications from Anti-Inflammatory Drugs?

Posted on April 28, 2011
by Kristine Novak, PhD, Science Editor

Aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) are known to cause stomach problems, but a large prospective study by Lisa Strate et al. in the May issue of Gastroenterology shows that they can also damage the colon, causing diverticulitis and diverticular bleeding.

Strate et al. tracked the use of aspirin, non-aspirin NSAIDs and other factors in 47,210 men in the US for 22 years. They identified men with diverticulitis or diverticular bleeding based on responses to questionnaires.
Compared with men that did not take these drugs, men who used aspirin regularly (twice a week or more) had a 1.25-fold greater risk for diverticulitis and a 1.70-fold greater risk for diverticular bleeding.  Men that regularly took non-aspirin NSAIDs had a 1.72-fold greater risk for diverticulitis and a 1.74-fold greater risk for diverticular bleeding. For diverticulitis, the risk appeared to be somewhat greater among regular users of NSAIDs than of aspirin.

The highest risk of diverticular bleeding was observed in men who used aspirin at a moderately high frequency (4–6 days/week; 3.13-fold increase in risk) or at moderately high doses (2–5.9 tablets/week; 2.32-fold increase in risk).

“We found that the use of both drugs together did not significantly increase the risk of either outcome compared to either drug alone” added Strate in a video abstract.

How do aspirin and NSAIDs damage the colon? 

These drugs can cause direct injury to colon tissue and also impair synthesis of prostaglandins, reduce mucosal integrity, increase permeability and promote an influx of bacteria and toxins. Diverticulitis, defined by the presence of micro- or macro-perforations that can lead to abscess formation, is thought to result from impairments to the mucosal barrier and increased intracolonic pressure. Diverticular bleeding occurs when a nutrient artery ruptures into the colon lumen, and frequently involves local mucosal ulceration in the absence of inflammation. NSAIDs, including aspirin, can also promote blood loss from existing lesions by inhibiting platelet aggregation.

Although previous studies have associated aspirin and NSAID use with diverticular complications, this study was the first to differentiate between diverticulitis and diverticular bleeding, and to analyze separately the effects of aspirin and NSAID use, including dose, frequency, and duration.
Strate et al. state that these findings are important because of the prevalence of diverticular disease and NSAID use—particularly among the elderly. They warn that analgesia should be selected carefully for individuals with diverticulosis—especially those with previous complications. Future studies are needed to identify individuals at greatest risk for diverticular complications and to find ways to lower the gastrointestinal toxicity of NSAIDs.

More Information on Diverticulitis:

• The National Institute Health (NIH) Web site on Diverticulitis

Read the article online. This article has an accompanying podcast and  CME.
Strate LL, Liu YL, Huang ES, et al.  Use of aspirin or nonsteroidal anti-inflammatory drugs increases risk for diverticulitis and diverticular bleeding. Gastroenterology 2011;140:1427–1433.

http://agajournals.wordpress.com/2011/04/28/colon-complications-from-anti-inflammatory-drugs/

Hepatitis C: Headache? Joint Pain? Choose the Right Over-the-Counter Painkiller

Headache? Joint Pain? How to Choose the Right Over-the-Counter Painkiller

Choosing a painkiller off the drug store shelf can be, well, painful. To offer some relief, Consumer Reports Health released its "Best Buy Drugs" -- a 22-page report that compares the effectiveness, safety and price of some of the top brands (and generics) for pain killing.

The report focuses on non-steroidal anti-inflammatories (NSAIDs), which commonly are used to treat pain associated with arthritis.

But NSAIDs are only one type of painkiller. Depending on the ache, another type might be better. And depending on the sufferer, some drugs can be dangerous.
ABC News asked pain experts to weigh in on what drugs to take for various aches and pains, and when to avoid the drugs.

Acetylsalicylic Acid
The drug commonly referred to as aspirin has been around since 400 B.C., when people used salicin-containing willow tree bark to treat pain and inflammation. It was the discovery of salicin as the bark's pain relieving ingredient that led the development of stomach-friendlier acetylsalicylic acid (ASA) in 1838.

"Aspirin was the 'original' headache medication," said Dr. Timothy Collins, assistant professor of medicine and neurology at Duke University Medical Center's Pain and Palliative Care Clinic.
But ASA's anti-inflammatory properties make it good for other types of pain, too, including muscle pain, joint pain from arthritis and toothaches. It's also relatively cheap.
The drug is an NSAID that works by suppressing the production of prostaglandins -- hormone-like molecules that play an important role in inflammation. Unfortunately, the same molecules help to protect the stomach lining.
Acetylsalicylic acid also interferes with blood-clotting thromboxanes. Some people take a daily dose to reduce the risk of heart attack and stroke.
Because of its effects on the stomach and the blood, acetylsalicylic acid isn't right for everyone. People with ulcers, bleeding disorders or kidney or liver problems should avoid it, as should anyone who might be allergic to it.

"There are a lot of other non-steroidal anti-inflammatory drugs (NSAIDs) that have fewer side effects than aspirin so, in many cases, aspirin is not a first choice," said Dr. Mike Schmitz, director of pediatric pain medicine at Arkansas Children's Hospital in Little Rock.
Acetylsalicylic acid use in kids with fevers has been linked to Reye's syndrome -- a potentially fatal disease that attacks the brain and liver. It should only been used in people under 19 under specific orders from a doctor.

Ibuprofen
Another NSAID, ibuprofen, has pain relieving effects similar to those of acetylsalicylic acid. But it tends to work better even at a lower dose and have milder side effects.
"It is a very good anti-inflammatory medication, originally developed to treat arthritis," said Duke's Collins. "It also lowers fever, and helps with symptoms from the common cold."
The brand name version of ibuprofen is Advil. But only the generic form of ibuprofen was named a "best buy" NSAID by Consumer Reports Health today.
Like acetylsalicylic acid, ibuprofen inhibits prostaglandin synthesis. So it can irritate the stomach and increase the risk for ulcers. It also can cause bruising and bleeding in people who use blood thinners. Ibuprofen should be avoided in people with ulcers, bleeding disorders or kidney disease. But it is not associated with Reye's syndrome and, therefore, can be used in children.

Naproxen
A relative newcomer to the pharmacy shelves, naproxen (Aleve) only was approved by the Food and Drug Administration for over-the-counter use in 1994.
Naproxen is an NSAID with a pain-killing mechanism similar to that of ibuprofen. The drugs have comparable effects and side effects, so the choice comes down to personal preference.
"The anti-inflammatory medications like ibuprofen and naproxen are very good for the common muscle aches from 'overdoing it' (like at the gym or working in the yard) and also help with common arthritis pain," said Collins.
Naproxen -- both Aleve and the generic form -- also was named a "best buy" NSAID by Consumer Reports Health.

When taking NSAIDs, hydration is important because the drugs may reduce blood flow to the filtering mechanism of the kidneys. According to the National Institutes of Health, NSAIDs other than acetylsalicylic acid also can increase the risk of stroke and heart attack.
Talk to a doctor about cardiovascular risk factors before taking NSAIDs regularly.

Acetaminophen
The drug known by most people as Tylenol is another mild pain reliever. It is not an NSAID, so it won't quell inflammation. However, it won't irritate the stomach, either

"Acetaminophen is better for people who have stomach troubles," Schmitz said. "It has been a good drug for children as well."
The drug is good for treating aches and pains not related to injury or inflammation. But because it's metabolized in the liver, it can have serious side effects if taken at high doses or with alcohol.
"The most significant danger of high doses acetaminophen is liver damage and even liver failure," said Dr. Doris Cope, professor and vice chairman of pain at the University of Pittsburgh School of Medicine.
Acetaminophen use should be avoided in people who have consumed alcohol or are dehydrated, or who have kidney or liver problems.

Because of its potential to cause serious harm at high doses, people should be careful when taking combination drugs that contain acetaminophen, according to Dr. Carol Warfield, chair of anesthesia, critical care and pain medicine at Beth Israel Deaconess Medical Center in Boston.
Certain prescription painkillers also contain acetaminophen, opening the door for unintentional overdoses.
"In a recent study, fewer than 15 percent of patients knew that commonly prescribed pain medications [such as Percocet and Vicodin] contained acetaminophen," said the University of Pittsburgh's Cope.

Combination Drugs
Over-the-counter medications designed to treat multiple symptoms often contain painkillers in combination with other drugs. Cold and flu medications often contain painkillers as well as decongestants. And menstrual pain relievers often provide diuretics, too.
"I am not a big fan of combination drugs," Schmitz said. "I recommend that people know what they are taking, take specific medicines for specific problems or symptoms, and read the package before they purchase it so that they know what is in it."

Talk to a Doc
When in doubt, ask a doctor or pharmacist for a recommendation or an explanation of a particular drug's ingredients. And during pregnancy, it's important to talk to a doctor before taking any over-the-counter medication.

http://abcnews.go.com/Health/Wellness/counter-painkillers-choose/story?id=12932012&page=4

Aspirin Dose Linked to Risk of Upper GI Bleeding

The study by Huang et al. provides further evidence that use of aspirin increases the risk of major GI bleeding and that this risk increases with increasing dose of aspirin. Meta analysis of randomized trials of low-dose aspirin (75-325 mg daily)for cardiovascular prophylaxis indicates approximately a 2-fold increase in major GI bleeding, similar to the results of this analysis.

In addition, increasing the dose above 325 mg daily also has been shown to significantly increase the risk of bleeding. Since regular use of low-dose aspirin provides approximately100% inhibition of cyclooxygenase-1 and thromboxane, the increased risk of upper GI bleeding with higher-dose aspirin presumably relates to increased mucosal injury (likely due to greater cyclooxygenase-2 inhibition).

This study did not show a significant risk of 325 mg of aspirin taken 2-5 times per week. However,prior large randomized controlled trials have documented a significant increase in major GI bleeding even when low-dose aspirinis taken every other day.The statement that longer duration of use was not significantly associated with an increased risk of upper GI bleeding should not be taken to suggest that risk does not continue with longer-term use of aspirin. Prospective randomized trials of aspirin and other NSAIDs document that the cumulative incidence of GI complications continues to increase over time. Despite the GI risk, patients with established cardiovascular disease clearly benefit from the use of low-dose aspirin and, in general, this benefit out weighs the risk of GI bleeding. Current consensus recommendations from cardiology and GI organizations state that the GI risk needs to be determined in individual patients, and if low-dose aspirin is required in patients with increased GI risk, then cotherapy is recommended.

LOREN A. LAINE, M.D., AGAF,is Professor of Medicine, KeckSchool of Medicine, University of Southern California, Los Angeles,and is Vice President of the AGAInstitute. P E


Aspirin Dose Linked to Risk of Upper GI Bleeding

BY HEIDI SPLETEE
lsevier Global Medical News SAN ANTONIO –

Men who took more than 14 aspirin per week were more than twice as likely to report upper gastrointestinal bleeding as were men who reported no aspirin use, but increased duration of use did not appear to raise the risk of GI bleeding, said Dr. EdwardHuang at the annual meeting of the American College of Gastroenterology.

Evidence regarding the impact of aspirin use on GI bleeding is conflicting because of the limitations of previous studies, said Dr. Huang ofMassachusetts General Hospital in Boston.

To examine the long-term effects of aspirin dose and duration on GI bleeding, Dr.Huang and his colleagues conducted a prospective study of32,989 participants in the Health Professionals Follow up Study, a longitudinal studyof male health professionals in the United States. In 2006 and 2008, participants were asked to report any past episodes of GI bleeding severe enough to require hospitalization or blood transfusion.

The average age of the men when they enrolled in the study was 60 years, and those with a history of peptic ulcer disease were excluded. During a mean 14-year follow-up period, 707 men had an episode of major GI bleeding. After adjustment for risk factors including use of NSAIDs, age, smoking, exercise ,and body mass index, the risk ratios for upper GI bleeding were 1.05 (95% confidence interval [CI], 0.71-1.52) for men who took 0.5-1.5 standard(325 mg) aspirin tablets per week, 1.31 (95% CI, 0.88-1.95) for those who took 2-5 tablets per week, 1.63 (95%CI, 1.15-2.32) for those who took 6-14 tablets per week, and 2.40 (95% CI, 1.10-5.22) for those who took more than 14 tablets per week, compared with men who reported no aspirin use (P less than .001). Short-term aspirin use was defined as less than 5 years, and long-term use was defined as 5 years or longer.

“The dose-response relationship is significant regardless of duration of use,” Dr. Huang noted. By contrast, longer duration of use was not significantly associated with an increased risk of upper GI bleeding, Dr.Huang said. However, individuals who use aspirin the longest tend to use the highest dose, he added.

Dr. Neena S. Abraham said in an interview, “This longitudinal study re-iterates the importance of a high-average daily dose of aspirin as an independent risk factor for subsequent upper gastrointestinal hemorrhage, and helps debunk the clinical myth that duration of treatment is the only relevant risk factor.”“Not only is this study consistent with other longitudinal studies, such as theNurses Heath Study, it complements observationa lstudies that have shown a substantial dose-response relationship between aspirin and the risk of GI bleeding,”said Dr. Abraham, a gastroenterologistat the Michael E. DeBakey VA Medical Center and associate professor of medicine at Baylor College of Medicine,both in Houston.“Given this data, gastroenterologists should re-double their efforts to educate both patients and their providers that the best dose of aspirin is the lowest possible dose for the clinical indication being treated,” she added.

The results suggest that both short term and long-term aspirin users can minimize the risk of upper GI bleeding by using the lowest effective dose, Dr.Huang said.Dr. Huang had no financial conflicts to disclose.

Taking Low Dose Aspirin and NSAIDs? Know Your Risk.

Acetaminophen is an active ingredient in more than 200 other medications, including Nyquil and Anacin 3 as well as most over the counter standard pain killers. Despite the painkiller alternatives for hepatitus (HCV), it is advisable to speak with your doctor before trying anything to confirm that the painkiller is safe for you to use as most drugs may place additional liver strain on anyone living with Hepatitis C.

Ibuprofen – (Motrin, Advil, Nuprin and others) reduces high body temperature, is an anti-inflammatory and inhibits normal platelet function. A non-steroidal anti-inflammatory drug (NSAID), ibuprofen can cause gastrointestinal upset and bleeding. Those at risk of portal hypertension are already at risk for gastrointestinal bleeding, intensifying this risk. Studies have demonstrated that at certain dosages, ibuprofen can stress the liver and elevate liver enzymes in people with Hepatitis C. Ibuprofen must be used with extreme caution in the later stages of liver disease and for those on interferon therapy.

Aspirin – (Bayer, Anacin, Excedrin and others) reduces fever, relieves pain, and acts as an anti-inflammatory and blood thinner. In addition to influencing liver test results, aspirin’s effect on blood platelets temporarily limits the clotting process and prolongs bleeding. In chronic liver disease where the body’s production of clotting factors is naturally decreased, aspirin can increase the risk of bleeding. Although there is no actual drug interaction between aspirin and the drugs used in interferon therapy, both can disrupt blood clotting, which must be monitored if used together. When taken in high doses (more than 2,000 mg per day) aspirin can cause liver injury.

Im Taking an Herbal Medicine. Can I Take an NSAID?

Summary:

An expert explains how NSAIDs in herbal medicines may contribute to the risk of GI or Gastrointestinal Side Effects from aspirin and other NSAIDs. NSAIDs include ibuprofen (Motrin, Advil), naproxen (Aleve) and ketoprofen (Orudis, Oruvail)..

Transcript:

Q: I’m taking an herbal medicine.

Can I take an NSAID?

BYRON CRYER, MD: NSAIDs are available in multiple forms. Clearly, they’re available in prescribed medicines and over-the-counter medicines, but one of the unrecognized forms in which we find NSAIDs are in dietary supplements and herbal medicines. Several of those medicines contain NSAID-like substances, and so what a person does when they combine their herbal medicine or their dietary supplement along with another NSAID is they’ve increased the risk of a gastrointestinal problem because they’ve increased their overall dose of NSAID. So it’s important for patients to recognize that dietary supplements and herbal medicines are also medicines that should be discussed with their physician when they’re discussing the list of medicines that they’re on, because some of those herbal products can have an NSAID.

An expert explains how NSAIDs in herbal medicines may contribute to the risk of GI or gastrointestinal side effects from aspirin and other NSAIDs. Additional important FDA safety information on NSAIDs:

source

Taking Low Dose Aspirin and NSAIDs? Know Your Risk.



Summary:

Combining low dose aspirin with other NSAIDs can increase the risk of GI side effects. Listen as specialists describe the risks, and how to minimize them.

Transcript:

ANNOUNCER: Millions of Americans take low dose aspirin to reduce their risk of heart attack and stroke. Aspirin is a drug called an NSAID - for non-steroidal, anti-inflammatory drug. NSAIDS may cause side effects because they reduce the body's protection from stomach acid.

BYRON CRYER, MD: NSAIDs have a range of gastrointestinal side effects, ranging from mild levels of symptoms such as stomach discomfort, nausea, to more severe abdominal pain, to more concerning side effects such as ulcers, gastrointestinal bleeding or perforation -- perforation being a hole in the stomach that could be caused by an NSAID.

ANNOUNCER: Unless a person has a history of gastrointestinal problems, the risk posed by low dose aspirin is small.

STANLEY ROCKSON, MD: It's quite low so that we don't certainly limit ourselves in any way from prescribing it if somebody does not have an overt history of having had problems in the past.

ANNOUNCER: But what about when a person needs another NSAID, such as ibuprofen or naproxen, for pain relief or to fight inflammation in addition to their low dose aspirin?

STUART SPECHLER, MD: One of the risk factors for developing a complication of NSAIDs is to take more than one NSAID at the same time. Well, aspirin is an NSAID, so if you're taking another NSAID at the same time, you are at increased risk for developing an ulcer complication.

BYRON CRYER, MD: When an individual combines low-dose aspirin along with an NSAID, the risk of having a gastrointestinal complication markedly increases. In fact, it increases about nine fold.

ANNOUNCER: The actual risk varies from person to person.

LAUREN GERSON, MD: The patients who are at risk for GI problems from NSAIDs include patients who have had previous peptic ulcer disease, complicated ulcers that have bleeding requiring hospitalization, patients of older age, patients who are taking steroids, blood thinners, and patients who are taking higher dosage of these drugs.

ANNOUNCER: There are steps people can take to lower GI risk.

BYRON CRYER, MD: There are a couple of strategies that can be pursued for the person who needs to take a chronic NSAID who also needs to take low-dose aspirin. One of the strategies would be to change the NSAID, to change the NSAID to a different class of NSAIDs, such as a COX-2 inhibitor.

ANNOUNCER: COX-2 selective NSAIDs do not interfere with low dose aspirin's cardio-protective effects. But there is still a GI risk.

BYRON CRYER, MD: Another strategy for reducing the gastrointestinal risk of people who are required to take NSAIDs along with aspirin would be to take this class of medicines, this acid blocker class of medicine, the proton pump inhibitors, along with the NSAID plus the low-dose aspirin to reduce the likelihood of a gastrointestinal complication.

ANNOUNCER: Another strategy would be to switch to acetaminophen. But ask your doctor if you should take a proton pump inhibitor or switch to acetaminophen because these medications also have risks. Patients and their doctors must also consider non-GI side effects from NSAIDs. While low dose aspirin reduces cardiovascular risk, doctors have learned that the other NSAIDs may actually increase that risk.

STUART SPECHLER, MD: Aspirin, which is a non-steroidal anti-inflammatory drug, has actually been shown to protect your heart. Now, in contrast to that protective effect of aspirin, a number of the other non-steroidal anti-inflammatory drugs may increase your risk for developing a heart attack, and that many people find confusing. We physicians find it a bit confusing as well.

ANNOUNCER: At recommended doses, doctors say the cardiovascular risk of NSAIDs is very low. But caution is appropriate as all NSAIDs including the COX-2 drugs may increase your cardiovascular risk.

STANLEY ROCKSON, MD: We really don't have a way to predict with accuracy who's at risk and how much increased risk will exist if they take an NSAID -- in the heart or in the circulation. And consequently, we again have to invoke the same rule, which is that if you need the medication you should take it, but ideally you should be able to take it at the lowest feasible dose to get the benefit of the medication to minimize the risk to the heart.

ANNOUNCER: Patients should talk with their doctors about the choice of NSAID. Some may be tolerated better than others. Doctors can help patients evaluate the benefits and risks of NSAIDs, especially when a patient is also taking low dose aspirin.

STANLEY ROCKSON, MD: They're very efficacious at doing what they're designed to do, which is to reduce inflammation and reduce pain. And inflammation plays a role in so many disease states, and so many patients need the benefit of this kind of anti-inflammatory effect, and they get it at a very low cost in terms of the downside. But having said all of that, it's always prudent to think about, is this the right case to do it? And what's the smallest effective dose and the smallest time frame in which I can get away with using it, and thereby maximize the benefit and minimize the risk?

BYRON CRYER, MD: We don't want to alarm the patients excessively about these risks to the extent that they don't take the medicines as they need it for controlling their pain, controlling their inflammation, controlling their arthritis. But at the same time, they need to be aware of the risk. And so what we're trying to do is strike a balance between the benefits and the risk.