Acetaminophen (Tylenol)
Hepatotoxicity from acetaminophen is due
to the toxic metabolite NAPQI. This metabolite is generated by cytochrome
P-450-2E1. Alcohol and other drugs induce cytochrome P-450-2E1 and may result
in enhanced toxicity. In adults, a dose of 7.5-10 g produces hepatic necrosis,
but the dose is difficult to assess because of early vomiting and unreliable
history. Nonetheless, doses as low as 4-8 g/d may produce liver injury in
persons with alcoholism and people with underlying liver disease. For details
about acetaminophen toxicity, refer to Toxicity,
Acetaminophen.
An overdose of acetaminophen can damage the liver. The
probability of damage as well as the severity of the damage depends on the dose
of acetaminophen ingested; the higher the dose, the more likely it is that
there will be damage and the more likely it is that the damage will be severe.
(The reaction to acetaminophen is dose-dependent and predictable; it is not
idiosyncratic - peculiar to the individual.) The liver injury from an overdose
of acetaminophen is a serious matter since the damage can be severe and result
in liver failure and death.
For the average healthy adult, the
recommended maximum dose of acetaminophen during a 24-hour period is 4 grams
(4000 mg) or eight extra-strength tablets. (Each extra-strength tablet contains
500 mg, while each regular strength tablet contains 325 mg.) Among children,
the dose of acetaminophen is determined on the basis of each child's weight and
age, explicitly stated in the package insert. If these guidelines for adults
and children are followed, acetaminophen is safe and carries essentially no
risk of liver injury. A person who drinks more than two alcoholic beverages per
day, however, should not take more than 2 grams (2000 mg) of acetaminophen over
24 hours, as discussed below, since alcohol makes the liver susceptible to
damage from lower doses of
acetaminophen.
Other factors that
increase a person's risk for damage from acetaminophen include the fasting
state, malnutrition, and concomitant administration of some other drugs such as
phenytoin (Dilantin), phenobarbital, carbamazepine [(Tegretol) (anti-seizure
medications)] or isoniazid [(Nydrazid, Laniazid) (anti-TB drug)].
Statins
Statins are the most widely used
medications to lower "bad" (LDL) cholesterol in order to prevent heart
attacks and strokes.
Most doctors believe that statins are safe for long-term use, and important
liver injury is rare. Nevertheless, statins can injure the liver. The most
common liver-related problem caused by statins is mild elevations in blood
levels of liver enzymes (ALT and AST) without symptoms. Clinical studies have
found elevations in 0.5% to 3% of patients who take statins. These
abnormalities usually improve or completely resolve upon stopping the statin or
reducing the dose. There is no permanent liver damage.
Patients with obesity have an
increased chance of developing diabetes, non-alcoholic fatty liver disease
(NFALD), and elevated blood cholesterol levels. Patients with fatty liver often
have no symptoms, and the abnormal tests are discovered when routine blood testing
is done. Recent studies have found that statins can be used safely to treat
high blood cholesterol in patients who already have fatty liver and mildly
abnormal liver
blood tests when the statin
is started. In these patients, doctors may choose to use statins at lower doses
and monitor liver enzyme levels regularly during treatment.
Nicotinic acid (Niacin)
Niacin,
like the stains, has been used to treat elevated blood
cholesterol levels as well as
elevated triglyceride levels. Also like the statins, niacin can damage the
liver. It can cause mild transient elevations in blood levels of AST and ALT,
jaundice, and, in rare instances, liver failure. Liver toxicity with niacin is
dose-dependent; toxic doses usually exceed 2 grams per day. Patients with
pre-existing liver diseases and those who drink alcohol regularly are at higher
risk for developing niacin toxicity. The sustained-release preparations of
niacin also are more likely to cause liver toxicity than the immediate-release
preparations.
Fluconazole:
The spectrum of hepatic reactions
ranges from mild transient elevations in transaminase levels to hepatitis,
cholestasis, and fulminant hepatic failure. In fluconazole-associated
hepatotoxicity, hepatotoxicity is not obviously related to the total daily dose,
duration of therapy, or sex or age of the patient. Fatal reactions occur in
patients with serious underlying medical illness. Fluconazole-associated
hepatotoxicity is usually, but not always, reversible upon discontinuation of
therapy.
Diclofenac:
Elderly females are more susceptible to
diclofenac-induced liver injury. Elevations of one or more liver test results
may occur. These laboratory abnormalities may progress, may remain unchanged,
or may be transient with continued therapy. Borderline or greater elevations of
transaminase levels occur in approximately 15% of patients treated with
diclofenac. Of the hepatic enzymes, ALT is recommended for monitoring liver
injury. Meaningful (>3 times the upper limit of the reference range)
elevations of ALT or AST occur in approximately 2% of patients during the first
2 months of treatment. In patients receiving long-term therapy, transaminase
levels should be measured periodically within 4-8 weeks of initiating
treatment. Some may also have positive ANA findings. In addition to the
elevation of ALT and AST levels, cases of liver necrosis, jaundice, and
fulminant hepatitis with and without jaundice have occurred.
Amiodarone
Amiodarone is an important
medication that is used to treat irregular heart rhythms such as atrial
fibrillation and ventricular
tachycardia. Amiodarone can cause liver damage ranging from mild and
reversible liver blood enzyme abnormalities, to acute liver failure and
irreversible cirrhosis. Mild liver blood test abnormalities are common and
typically resolve weeks to months after stopping the drug. Serious liver damage
occurs in less than 1% of patients.
Amiodarone differs from most other
drugs because a substantial amount of amiodarone is stored in the liver. The
stored drug is capable of causing fatty liver, hepatitis, and, more
importantly, it can continue to damage the liver long after the drug is
stopped. Serious liver damage can lead to acute liver failure, cirrhosis, and
the need for liver transplantation.
No comments:
Post a Comment