Herbs
Which May Cause Liver Problems
The
following herbs have been described to cause a variety of liver problems:
(This
information was supplied by Ca. Pacific Medical Center)
Latin
name Western
or common name
----------------------------------------------------------------------------
lycopodium
serratum
Jin Bu Huan (chinese name)
Teucrium chamaedrys
Germander (mint family) Scutelleria
Skullcap Stephania
Corydalis Senecio longilobus
groundsel Symphytum
comfrey
valerian
asfetida
hops
gentian
mistletoe
margosa oil
mate`tea
gordolobo
yerba tea
pennyroyal (squawmint) oil
chaparral (creoosote bush, greasewood)
source:
http://www.medscape.com/IMNG/ClinPsychNews/1998/v26.n03/cpn2603.28.01.html
St. John's Wort Tied to Serotonin Syndrome
By: Kathryn Demott, Senior Writer
[Clinical Psychiatry News 26(3):28,
1998. © 1998 International Medical News Group.]
People who take St.
John's wort, a trendy herbal remedy for depression, in combination with selective
serotonin reuptake inhibitors, may be at risk for serotonin syndrome, said
Dr. James Stockard of the department of psychiatry and neurology at Northwestern
University in Chicago.
In a yet-to-be-published
study, Dr. Stockard and his associates describe two patients who developed
what appeared to be classic serotonin syndrome. The syndrome developed in
one patient who took St. John's wort alone. The syndrome also was seen in
another patient who took St. John's wort and trazodone, a weak selective serotonin
reuptake inhibitor (SSRI), 6 days after the patient stopped taking the SSRI.
Still, these are very
early and speculative findings, emphasized Dr. Stockard. At this point it
is not clear whether it was the St. John's wort that caused the serotonin
syndrome, the trazodone that the one patient was taking, or the combination.
Neither of the patients
died, but they did have symptoms commonly associated with moderate serotonin
syndrome, such as mental confusion, muscle twitching, sweating, flushing,
and ataxia, said Dr. Elliott Richelson, a coauthor of the report and professor
of psychiatry and pharmacology at the Mayo Medical School in Rochester, Minn.
Dr. S. Nassir Ghaemi,
a psychiatrist at George Washington University in Washington, told this newspaper
that full-blown serotonin syndrome can cause acute delirium and blood pressure
changes. When it gets to that stage, the patient needs to be hospitalized
and given supportive care, such as intravenous fluids if the person can't
eat or drink. There's little medical treatment and there is a mortality risk.
If nothing else, identifying
this possible side effect of St. John's wort underscores the fact that "people
shouldn't think that just because it's an herbal drug [that] it's not without
potential side effects," Dr. Richelson told this newspaper.
On the other hand,
raising questions about its adverse effects is not an indictment of St. John's
wort, said Dr. Stockard.
"St. John's wort
probably is a very promising drug and would be a good addition to our armamentarium
for treating depression," he said.
Any antidepressant
medication can interact adversely with other drugs. "That doesn't mean
that we shouldn't use them. But it does mean that we need knowledge about
how to use them. And that's the problem with St. John's wort. There's very
little research," said Dr. Ghaemi.
No one really knows
exactly how St. John's wort works.
Hypericum, the most
studied compound of St. John's wort, was thought to act as a monoamine oxidase
inhibitor. Now researchers are not so sure. Packages of St. John's wort recommend
taking three 300-mg doses per day, standardized to 0.3% hypericum. But now
"no one even knows if that's the active ingredient," Dr. Stockard
told this newspaper.
It's difficult to study
the mechanisms of a plant extract that literally has hundreds of compounds.
"It's an impossible task," said Dr. Richelson.
There's tremendous
variation from one formulation to the next, added Dr. Stockard. In addition,
there's no mechanism for checking if what is purported to be in an herbal
remedy is really in there.
Last year St. John's
wort started flying off the shelves of health food stores in the wake of increased
media attention. Case in point: In 1 year, sales of St. John's wort nearly
tripled for Nutrition Now Inc., a Vancouver, B.C.-based manufacturer and distributor
of the remedy, according to a spokesperson.
"If I had to guess,
I'd say that about one-fourth of my patients have tried St. John's wort, are
on it, or are thinking about taking it," said Dr. Ghaemi.
The three physicians
interviewed for this article strongly urge physicians to start asking their
patients specifically about St. John's wort in the course of a general history.
When listing medications,
patients often don't think of an herbal remedy that they bought in a health
food store as a drug, Dr. Richelson said.
"I tell people
whom I treat with [SSRIs] that they definitely should not take St. John's
wort," Dr. Ghaemi said.
But if they are dead
set on trying it, he advises them to at least talk with him first.
Then again, the majority
of people experimenting with St. John's wort probably are not seeing a mental
health care professional in the first place--all the more reason to ask patients
about it during a general medical history.
source: http://www.ccspublishing.com/journals/surg/adynamic%20illeus%20st%20john's%2
0wort.htm
November, 1997--Volume 125, Number 16, pp 1022-1087
Adynamic Ileus Associated with the Use of
St. John's Wort
Thuan L. Tran, MD
Department of Family
Practice Kaiser Foundation Medical Center Fontana, California
From the Department
of Family Practice, Kaiser Foundation Medical Center, Fontana, California
92335
Source
Information
Please send to all
correspondence to: Kaiser Medical Clinic 250 W. San Jose Street, Claremont,
CA 91711 (909) 399-2049. Fax: (909) 398-2173; E-mail: thuan.tran@kp.org
Introduction
The use of herbal products
for treatment of common illnesses has been rising significantly over the last
decade. The sale of herbs in America was estimated to be over 500 million
dollars in 1995, a 22-fold increase from 1991 (1). Despite growing evidence
of their potential toxicity and adverse interaction with established medications
(2), (3), (4), herbal products are considered to be food supplements, and
these products do not require any premarketing safety or efficacy testing,
according to the Dietary Supplement Health and Education Act, which was passed
by Congress in 1994 (5). We present a case of a healthy woman who developed
adynamic ileus after two weeks of St. John's wort usage.
Report
of a Case
The patient
is a 67 year-old Caucasian woman with a history of diabetes mellitus, which
had been adequately controlled with glyburide and diet. She began to notice
a gradual increase in abdominal distention, bloating and discomfort, associated
with decreased bowel movements. She was seen several times in the clinic with
diagnoses of constipation and was treated with a stool softener, laxatives,
and enemas, none of which provided any relief . Her abdominal radiographic
series revealed diffused dilation of the large intestine, with moderate amount
of air-fluid levels in the small bowels, consistent with adynamic ileus. Her
metabolic work-up was within normal limits. Her symptoms continue to worsen
and five days after the onset of her illness, the patient was admitted to
the hospital. On admission, the patient appeared very uncomfortable but was
in no acute distress. Her vital signs were within normal limits. Physical
examination revealed a massively distended abdomen with moderate tenderness
and increased tympani on percussion, but no rigidity or guarding. Her bowel
sounds were hypoactive. There was no palpable mass or organomegaly. There
was no fecal impaction on digital examination and Guaiac test was negative
for occult blood. Radiographic studies including Gastografin enema and computerized
tomography of the chest, abdomen and pelvis confirmed the presence of massively
dilated colon. The patient was treated conservatively with intravenous hydration,
low-pressured nasogastric suction, and omeprazole, which slowly decreased
her distention and discomfort. Since there was no identifiable cause for her
ileus, the patient was questioned further regarding any change in her life
style, diet, or medication prior to this illness. The patient then informed
the health care team that she had started taking an over-the-counter herbal
remedy called St John's wort about two weeks prior to the onset of her symptoms.
She had been taking this product continuously throughout her illness and only
stopped it when she was admitted to the hospital. Her condition continued
to improve with conservative treatment. The nasogastric tube was removed and
she was started on liquid, then solid diet, which she tolerated well, and
she was discharged on the seventh day of hospitalization. The follow-up visit,
one week later, revealed complete resolution of her abdominal symptoms with
normal examination.
Discussion
The active ingredient
in St. John's wort is Hypericum perforatum L., an aromatic perennial herb
belonging to the family Hypericaceae (6). The plant is native to Europe, but
it can be found throughout the United States and Australia. It is a short
plant with long stems, small bright yellow flowers, and lots of small leaves
with translucent spots (thus the Latin name H. perforatum). If rubbed between
the fingers, the liquid in these translucent pockets will turn bright red
upon being released. It is usually harvested around the birthday of John the
Baptist, giving the plant its common name of St. John's wort ("wort"
is the old English word for plant).
Throughout the centuries,
extracts of Hypericum, which consists of the dried above-ground part collected
shortly before or during the flowering period, have been used to treat a wide
range of ailments, from childhood enuresis to infected wounds, peptic ulcer
disease, or even cancer (7). However, it is now most commonly used in the
management of depressive illnesses, especially in Europe. Extracts of St.
John's wort are licensed in Germany for the treatment of anxiety, depressive
and sleep disorders. More than 2.7 millions prescription were written in 1993
(8). In the United States, the plant has been relatively obscured until recently
when its popularity was enhanced by national media, including magazines and
television program (9).
There is evidence from
randomized trials that hypericum extracts are more effective than placebo
for the treatment of mild to moderate depressive disorder. In addition, there
is inadequate data to establish whether hypericum is as effective as, or whether
it has fewer side effects than, other antidepressants (10). Despite its wide
use in the treatment of depression, the mechanism of action of Hypericum extracts
is still unclear (11). The extracts contain at least ten constituents or groups
of components which may contribute to the pharmacological effects. Some studies
suggest that the antidepressant activity of Hypericum extract is due to an
inhibition of serotonin uptake by postsynaptic receptors (12). The therapeutic
dosage has not be established. The amount of Hypericum extract being used
in different studies has varied from 300 mg/day to 1000 mg/day (10). The toxicity
level is also unknown.
Even though no death
from the consumption of Hypericum extracts has been reported, the plant is
not without side effects. Meta-analysis of randomized trials of Hypericum
preparations revealed that up to 19.8% of patients reporting having adverse
reactions, with a total drop-out rate of 4.0% (10). The most common side effects
were gastrointestinal disturbance and photosensitivity dermatitis (13).
There are reports of
the extracts being used to relax the colon during radiographic procedures
(14). The possible MAO and serotonin reuptake inhibiting properties of St.
John's wort may explain its negative effect on intestinal motility. Thus,
it is possible to postulate that the use of St. John's wort extract was related
to the development of adynamic ileus in the patient presented here. Her symptoms
started two weeks after starting taking the extracts, with no other identifiable
cause, and resolved gradually and completely after its discontinuation.
More studies are needed
to fully evaluate the mechanism of action of Hypericum, to determine its benefits
and adverse reactions. Until then, physicians should be aware of the potential
side effects of this widely-used herb.
References
1.Emerich E: Industry Growth: 22.6%. Natural Foods Merchandiser 1996;
17: 22-39 2.Huxtable RJ: The myth of beneficent nature: The risks of herbal
preparations. Ann Intern Med 1992; 117: 165-166 3.Koff RS: Herbal hepatotoxicity:
Revisiting a dangerous alternative. JAMA 1995; 273: 502 4.Farley D: Dietary
supplements: Make sure hypes doesn't overwhelm science. FDA Consumer 1993;
27:9-13 5.McNamara SH: FDA Regulation of ingredients in dietary supplements
after passage of the Dietary Supplement Health and Education Act of 1994:
an update. Food and Drug Law J. 1996; 51: 313-318 6.Tyler V: The Honest Herbal.
New York, NY, Pharmaceutical Product Press, 1993, pp. 275-276 7.Bloomfield,
HH, Nordfors, M, Mc Williams, P.: Hypericum & Depression. Los Angeles,
CA, Prelude Press, 1966, pp. 55 8.Lohse MJ, Muller-Oerlinghausen B: Psychopharmaka.
In: Schwabe U, Paffrath D, eds. Arzneiverordnungreport '94. Stuttgart: Gustav
Fischer, 1994: 354-70 9.20/20, American Broadcasting Company, 6/27/97, 10
PM EST 10.Linde K, Ramirez G, Mulrow CD, et al: St. John's wort for depression-an
overview and meta-analysis of randomised clinical trials, Br Med J 1996; 313:
253-258 11.Wagner H, Bladt S.: Pharmaceutical quality of hypericum extracts.
J Geriatr Psychiatry Neurol 1994; 7 Supple 1: S65-S68 12.Perovic, S, Muller,
WE: Pharmacological profile of hypericum extract. Effect on serotonin uptake
by postsynaptic receptors. Arzneimittelforschung 1995; 45: 1145-1148 13.Woelk
H, Burkard G, Grunwald J: Benefits and risks of the hypericum extract LI 160:
drug monitoring study with 3250 patients. J Geriatr Psychiatry Neurol 1994;
7 Suppl 1: S34-S38 14.Omarov MA: Use of St. John's wort for the X-ray study
of the large intestine. Vestn Rentgenol Radiol 1979; 4:86-87
St. John's Wort Linked to Cataracts
LONDON — St. John’s wort, a herb often billed as a natural alternative
to the anti-depressant Prozac, could cause cataracts if people taking it are
exposed to bright light and sunshine, New Scientist magazine said.
A study by Joan Roberts and researchers at Fordham University in New York
showed that hypericin, the active ingredient in the herb reacts with ultraviolet
light to produce chemicals in the body called free radicals that damage cells.
"If this product is consumed - one should avoid exposure to
bright light to prevent damage to the eye," the magazine quoted Roberts
as saying.
In laboratory experiments she and her colleagues found that hypericin
and bright light damaged proteins in the eye that could lead to cataracts.
They warned that people taking St. John’s wort for seasonal affective
disorder, a winter depression due to the lack of daylight, and light-box therapy
should be particularly careful.
"Certainly never take this drug and use light therapy,"
she said, adding that users should also be cautious while skiing and sunbathing.
St. John’s wort is a very popular herb which research has shown is
effective in treating mild to moderate depression.
Roberts said scientists are looking into ways of harnessing the side
effect of the herb as a potential cancer treatment.
"Its side effect is being used as a potential therapy for killing
cancer cells," she said.
Drugs
That May Cause Liver Dysfunction or Damage
The liver is the principal organ
that is capable of converting drugs into forms that can be readily eliminated
from the body. Given the diversity in use today and the complex burden
they impose upon the liver, it is not surprising that a
broad spectrum of adverse drugs
effects on liver functions and structures has been documented. The reactions
range from mild and transient changes in the results of liver function tests
to complete liver failure with death of the
host. Many drugs may affect
the liver adversely in more than one way, as cited below in several listings.
The use of the following drugs requires careful monitoring of their effects
on the liver during the entire course of treatment.
Drugs that may cause ACUTE DOSE-DEPENDENT LIVER DAMAGE (resembling
acute viral hepatitis)
acetaminophen
salicylates (doses over 2 grams daily)
|
acebutolol
allopurin
atenolol
cimetidine
dantrolene
diclofenac
diltiazem
enfluraneethambutol
ethionamide
halothane
ibuprofen indomethacin
|
ol labetalo
isoniazidketo
conazolecarb
amazepine
maprotiline
metoprolo
mianserin
naproxen
para-aminosalicylic acid
penicillins
phenelzine
phenindione
phenobarbital |
phenylbutazone
phenytoin
piroxicam
probenecid
pyrazinamide
quinidine
quinine
ranitidine
sulfonamides
sulindac
tricyclic antidepressants
valproic acid
verapamil |
Drugs that may cause ACUTE FATTY INFILTRATION
OF THE LIVER
|
adrenocortical steroids
antithyroid drugs
isoniazid
methotrexate
|
phenothiazines phenytoin
salicylates
|
sulfonamides
tetracyclines
valproic acid
|
Drugs that may cause CHOLESTATIC JAUNDICE
actinomycin
D
amoxicillin/clavulanate
azathioprine
captopril
carbamazepine
carbimazole
cephalosporins
chlordiazepoxidechlorpropamide
cloxacillin
cyclophosphamide
cyclosporine
danazol
diazepam
disopyramide enalapril |
erythromycin
flecainide
flurazepam
flutamide
glyburide
gold
griseofulvin
haloperidol
ketoconazole
mercaptopurine
methyltestosterone
nifedipine
nitrofurantoin
|
norethandrolone
nonsteroidal anti-inflammatory drugs
oral contraceptives
oxacillin
penicillamine phenothiazines
phenytoin
propoxyphene
sulfonamides
tamoxifen
thiabendazole
tolbutamide
tricyclic antidepressants
troleandomycin
verapamil |
Drugs that may cause LIVER GRANULOMAS (chronic inflammatory
nodules)
allopurinol
aspirin
carbamazepine
chlorpromazine
diltiazem
disopyramide |
gold
hydralazine
isoniazid
nitrofurantoin
penicillin
phenylbutazone |
phenytoin
procainamide
quinidine
sulfonamides
tolbutamide |
Drugs that may cause active chronic hepatitis
acetaminophen
uisoniazid |
dantrolene
nitrofurantoin |
methyldopa |
Drugs that may cause liver cirrhosis or fibrosis
(scarring)
| methotrexate |
nicotinic acid |
Drugs that may cause chronic cholestasis (resembling
primary biliary cirrhosis)
chlorpromazine/valproic
acid (combination)
chlorpropamide/erythromycin (combination)
imipramine |
phenothiazines
phenytoin
thiabendazole
tolbutamide |
Drugs that may cause LIVER TUMORS (benign and malignant)
anabolic steroids
danazol
oral contraceptives |
thorotrast
testosterone |
Drugs that may cause DAMAGE TO LIVER BLOOD
VESSELS
adriamycin
anabolic steroids
azathioprine
carmustine
cyclophosphamide/cyclosporine (combination) |
dacarbazine
mercaptopurine
methotrexate
mitomycin
oral contraceptives |
thioquanine
vincristine
vitamin A (excessive doses) |
SOURCE: The Essential Guide to Prescription
Drugs, 1994 Edition, by James W. Long and James J. Rybacki. ISBN 0-06-273211-0
TOP
"10" KILLER HOUSEHOLD CHEMICALS
AIR
FRESHENERS: Most air fresheners
interfere with your ability to smell by coating your nasal passages with an
oil film, or by releasing a nerve deadening agent. Known toxic chemicals
found in an air freshener: Formaldehyde: Highly toxic, known carcinogen.
Phenol: When phenol touches your skin it can cause it to swell, burn, peel,
and break out in hives. Can cause cold sweats, convulsions, circulatory collapse,
coma and even death!!
AMMONIA:
It is a very volatile chemical, it is very damaging to your eyes, respiratory
tract and skin.
BLEACH:
It is a strong corrosive. It will irritate or burn the skin, eyes and respiratory
tract. It may cause pulmonary edema or vomiting and coma if ingested. WARNING:
never mix bleach with ammonia it may cause fumes which can be DEADLY.
CARPET
AND UPHOLSTERY SHAMPOO: Most formulas
are designed to over power the stain itself, they accomplish the task but
not without using highly toxic substances. Some include: Perchlorethylene:
Known carcinogen damages liver, kidney and nervous system damage. Ammonium
Hydroxide: Corrosive, extremely irritable to eyes, skin and respiratory passages.
DISHWASHER
DETERGENTS: Most products contain
chlorine in a dry form that is highly concentrated. # 1 cause of child poisonings,
according to poison control centers.
DRAIN CLEANER: Most drain cleaners contain lye, hydrochloric acid
or trichloroethane. Lye: Caustic, burns skin and eyes, if ingested will damage
esophagus and stomach. Hydrochloric acid: Corrosive, eye and skin irritant,
damages kidneys, liver and digestive tract. Trichloroethane: Eye and skin
irritant, nervous system depressant; damages liver and kidneys.
FURNITURE POLISH: Petroleum Distillates:
Highly flammable, can cause skin and lung cancer. Phenol: (see Air fresheners,
Phenol.) Nitrobenzene: Easily absorbed through the skin, extremely toxic.
MOLD AND MILDEW CLEANERS: Chemicals
contained are: Sodium hypochlorite: Corrosive, irritates or burns skin and
eyes, causes fluid in the lungs which can lead to coma or death. Formaldehyde:
Highly toxic, known carcinogen. Irritant to eyes, nose, throat, and skin.
May cause nausea, headaches, nosebleeds, dizziness, memory loss and shortness
of breath.
OVEN CLEANER: Sodium Hydroxide (Lye):
Caustic, strong irritant, burns to both skin and eyes. Inhibits reflexes,
will cause severe tissue damage if swallowed.
ANTIBACTERIAL CLEANERS: may contain:
Triclosan: Absorption through the skin can be tied to liver damage.
LAUNDRY ROOM PRODUCTS: Sodium or calcium
hypocrite: Highly corrosive, irritates or burns skin, eyes or respiratory
tract. Linear alkylate sulfonate: Absorbed through the skin. Known liver
damaging agent. Sodium Tripolyphosphate: Irritates skin and mucous membranes,
causes vomiting. Easily absorbed through the skin from clothes.
TOILET BOWL CLEANERS: Hydrochloric
acid: Highly corrosive, irritant to both skin and eyes. Damages kidneys and
liver. Hypochlorite Bleach: Corrosive, irritates or burns eyes, skin and
respiratory tract. May cause pulmonary edema, vomiting or coma if ingested.
with other chemicals may cause chlorine fumes which may be fatal.
OTHER NASTY THINGS THAT ARE AROUND YOUR
HOME
PESTICIDES: Most pesticides have ingredients
that affect the nervous system of insects. Imagine what these extremely poisonous
chemicals do to your body or your baby's. Dimpylate: Better known as Diazinon,
extremely toxic. Impairs the central nervous system. Chlorinate Hydrocarbons:
Suspected carcinogen and mutantagen. Accumulates in food and in fatty tissue.
Will attack the nervous system. Organophosphates: Toxic and poisonous. If
you can smell it, your lungs are absorbing it.
FLEA POWDERS: Why put toxins on "man's
(or woman's) best friend." Carbaryl: Very toxic, causes skin, respiratory
and cardiovascular system damage. Chlordane: Accumulates in the food chain,
may damage eyes, lungs, liver, kidney and skin. Dichlorophene: Skin irritation:
May damage liver, kidney, spleen and central nervous system.
LICE SHAMPOO: Especially vulnerable
are children. Lindane: Inhalation, ingestion, or ABSORPTION through the SKIN
causes vomiting, diarrhea, convulsions and circulatory collapse. May cause
liver damage, stillbirths, birth defects and cancer.
CAR WASH AND POLISH: Petroleum Distillates:
Associated with skin and lung cancer, irritant to skin, eyes, nose and lungs.
Entry into the lungs may cause fatal pulmonary edema, most marked Danger,
Harmful or Fatal.
TAR AND BUG REMOVER: Contains XYLENE
and PETROLEUM DISTILLATES.
J Clin Psychiatry 1998 Jun;59(6):313-316
Disulfiram use in patients with abnormal
liver function test results.
Saxon AJ, Sloan KL,
Reoux J, Haver VM
Addictions Treatment Center, Department
of Psychiatry and Behavioral Sciences, VA Puget Sound Health Care System,
University of Washington, Seattle, USA. asaxon@u.washington.edu
[Medline record in process]
BACKGROUND: Concern about the precipitation
of severe hepatitis by disulfiram often causes clinicians to avoid using this
effective treatment in patients who have elevated baseline transaminase levels,
even though no empirical evidence has so far shown severe hepatotoxicity to
be related to such laboratory abnormalities. This study examines the effects
of disulfiram in alcohol-dependent patients with elevated liver function test
results and/or serologic evidence of hepatitis C virus (HCV) infection. METHOD:
Hepatitis serologies and baseline transaminase levels were obtained for 57
male alcoholics starting treatment with disulfiram. Sequential liver function
test results were obtained for up to 12 weeks while subjects took disulfiram.
RESULTS: Although subjects with elevated baseline transaminase levels and
serologic evidence of HCV infection were the most likely to evidence marked
elevations in transaminase levels while taking disulfiram, most subjects took
disulfiram without other adverse consequences. In only 1 subject did elevations
appear directly related to disulfiram. CONCLUSION: Monitoring of liver function
test results is warranted for patients taking disulfiram and permits most
patients with moderately elevated transaminase levels to take it safely.
PMID:
9671344, UI: 98334419
Pediatric
Anesthesiologists May Risk Halothane-Related Liver Injury
source: http://www.pslgroup.com/dg/88f9a.htm
BALTIMORE, MD -- June 26, 1998 -- Some anesthesiologists
may be accidentally inhaling too much of the potent anesthetic gas halothane
when they tend to their patients, possibly putting themselves at high risk
for liver injury, according to a study by researchers at Johns Hopkins and
the National Institutes of Health.
The investigators found that 23 percent of
pediatric anesthesiologists and nine percent of general anesthesiologists
showed higher than normal levels of antibodies to p-58, a liver protein generally
found in people with hepatitis caused by exposure to halothane. The antibody
level in the doctors was similar to that of one in five patients tested who
had halothane hepatitis. However, none of the anesthesiologists showed signs
of outright liver disease.
"It's still too early to tell whether
the antibodies mean the anesthesiologists will get liver disease, or if the
antibodies may be protecting them," said Dolores Njoku, M.D., lead author
of the study and an instructor of anesthesiology and critical care medicine
at Hopkins. "But there are safety precautions that anesthesiologists
should take, such as making sure their masks fit tightly and not leaving the
gas on during operating room preparation."
Results of the study were presented at a recent
meeting of the Society for Pediatric Anesthesia in Phoenix.
Researchers collected blood samples from 53
general anesthesiologists, 13 pediatric anesthesiologists, 21 patients who
had developed hepatitis as a result of exposure to halothane and 21 patients
who had no exposure to anesthetic gases. They then measured autoantibodies
to p-58 and P4502EI, another protein linked to halothane hepatitis.
When testing for P4502E1, the researchers found
that eight percent of the pediatric anesthesiologists, four percent of the
general anesthesiologists and 62 percent of the halothane hepatitis patients
had significant levels of antibodies.
"The findings of this study indicate that
some anesthesiologists are sensitised to the same liver proteins that have
been associated with halothane hepatitis," Njoku said. "It remains
to be determined why these individuals have not developed liver injury."
source: http://www.pslgroup.com/dg/87e2a.htm
Duract
Voluntarily Withdrawn Due To Liver Problems
ST. DAVIDS, PA -- June 22, 1998
-- Wyeth-Ayerst Laboratories has voluntarily withdrawn Duract(R) (bromfenac
sodium capsules), a non-steroidal, anti-inflammatory analgesic indicated for
the short-term (10 days or less) management of acute pain.
The company is taking this action based on
postmarketing reports of severe hepatic failure resulting in four deaths and
eight liver transplants. All but one of those 12 cases involved patients using
Duract for longer than 10 days -- the maximum recommended duration of treatment.
The exception involved a patient with pre-existing significant liver disease.
Duract was introduced in July 1997 and approximately
2.5 million prescriptions have been dispensed -- the great majority of these
for 10 days or less. In February 1998, the company and the United States Food
and Drug Administration agreed on labelling changes to further emphasise that
Duract should be used for 10 days or less. These changes were initiated in
response to earlier reports of serious events associated with longer-term
use.
Wyeth-Ayerst has sent letters of notification
to more than 600,000 health care professionals in the United States. They
are being advised to stop prescribing and dispensing Duract immediately. In
addition, they have been asked to consider ing patients who may be using the
product longer than 10 days or who have a history of liver disease and advise
these patients to discontinue treatment. Patients are advised to discuss concerns
related to Duract with their physician.
Ned Tijdschr Geneeskd 1997 Mar 15;141(11):540-542
Severe
hepatitis attributed to paroxetine.
[Article in Dutch]
de Man RA
Academisch Ziekenhuis Rotterdam-Dijkzigt,
afd. Maag-, Darm- en Leverzieklen.
A 52-year-old man suffering from chronic hepatitis
B related liver cirrhosis was treated for depression with paroxetine (Serotax)
5 mg and subsequently 15 mg once daily. A severe hepatitis with liver failure
(jaundice, hypoalbuminaemia, edemas, and ascites) developed. After the drug
was withdrawn the patient recovered completely. The adverse reaction may be
explained by a change in the pharmacokinetics of the drug caused by the liver
cirrhosis. Caution is required in prescribing long-term paroxetine therapy
for patients with documented liver cirrhosis. The liver function should be
monitored and administration of the drug should be discontinued when functional
disturbances are noticed.
PMID: 9190513, MUID: 97248929
Special
note- I am pleased to announce that the Canadian government has finally taken
this drug off the market (2000) -Diabetes Drug, Liver Damage Linked
Tuesday, November 4, 1997; 10:23 a.m. EST WASHINGTON
(AP) -- The Food and Drug Administration recommends that diabetics who use
the new drug Rezulin get repeated liver tests after it linked the medicine
to rare but potentially serious liver problems.
The FDA said Monday that it had received 35
reports of liver injuries from among the estimated 500,000 Americans treated
since the drug went on sale last spring. Problems ranged from mildly elevated
liver enzymes to liver failure that led to one transplant and one death.
The FDA cautioned that Rezulin may not be solely
responsible because some patients had other risks.
But manufacturer Warner-Lambert Co. agreed
to change the drug's label to warn about the liver reaction and recommend
testing and wrote doctors nationwide about the warning.
Rezulin, known chemically as troglitazone, is used by Type II, or adult-onset
diabetics. It can help resensitize the body to insulin, allowing many patients
to reduce their daily shots of the vital hormone.
The FDA recommended that doctors test the blood
of Rezulin users within the first one to two months of therapy to see if they
have elevated levels of liver transaminase enzymes. Patients then should be
tested every three months for the first year of therapy, as should any patient
with such symptoms as vomiting, abdominal pain, fatigue, loss of appetite
or dark urine, the FDA said.
Patients suspected of liver dysfunction --
expected to be about 2 percent of Rezulin users -- should stop taking the
drug, the agency said.
Few, if any, of these patients will go on to
develop permanent liver damage if the drug is stopped, the FDA said.
© Copyright 1997 The Associated Press
Toxic
Oil Bought Via Internet
[©
1997, Reuters Health eLine]
NEW YORK (Reuters) -- A report in this week's issue of The
New England Journal of Medicine tells of a 31-year-old man who was poisoned
after drinking a substance he purchased through the Internet.
The toxic liquid was essential oil of wormwood,
the active ingredient of the liqueur absinthe, a "tart" drink of
"dazzling blue-green color" popular in the 1800s, and favored by
artists and writers such as Vincent van Gogh, Henri de Toulouse-Lautrec, and
Oscar Wilde say researchers at George Washington University Medical Center
in Washington, D.C.
Although absinthe -- a distillation of wormwood,
alcohol, herbs, and seeds -- is illegal in the United States, that did not
prevent the patient from finding a description of the drink on the World Wide
Web. He then ordered oil of wormwood over the Internet from a commercial provider
of oils used in aromatherapy.
"He drank about a thimbleful of the essential
oil, like a liqueur, assuming it was absinthe," says one of the report's
authors, Dr. Paul Kimmel, a professor of nephrology at the university.
Several hours later, the patient's father found
him at home in an agitated, incoherent, and disoriented state. Paramedics
were called, and they noted that the man suffered muscle seizures and decorticate
posturing -- a sign of potential brain damage.
In the hospital, after having been calmed with
a potent anti-psychotic drug, the man complained of soreness in his legs.
Blood tests indicated muscle tissue destruction. He was also diagnosed with
congestive heart failure and kidney failure.
The patient survived and was discharged from
the hospital eight days after admission. Seventeen days after becoming ill,
the man had no further symptoms and his blood tests returned to normal.
"While the Internet is touted as a great
source for health information, it also can be the source for health-damaging
products," Kimmel warns. "Consumers need to be extremely cautious
before buying any health product or recreational product through the Internet."
In the mid-19th century, physicians published
reports on absinthism, "a syndrome of hallucinations, sleeplessness,
tremors, convulsions, and paralysis associated with long-term ingestion of
the liqueur," write the report authors.
Claiming that absinthe contributed to psychosis
and suicide, France banned the drink in 1915, followed by other European nations
and the United States. But it is still a popular drink in the bars of the
Czech Republic.
"The essential ingredient in this ancient
potion was purchased in this case by means of up-to-the-minute technology,"
they note. "Should the medical community brace itself for future cases
of Internet-mediated toxic diseases?"
SOURCE: The New England Journal of
Medicine (1997;337:825-827)
JAMA
Letters - June 4, 1997
Fatality
Associated With Combined Fluoxetine-Amitriptyline Therapy
To the Editor.--To our knowledge, this is the
first published report of a death associated with fluoxetine-tricyclic antidepressant
(TCA) interaction.
Report of a Case.--A 36-year-old man with recurrent
major depression was prescribed amitriptyline, 150 mg/d, and fluoxetine, 40
mg/d. He died approximately 6 weeks later, and his body was found in his house
several weeks after death. An autopsy revealed no anatomical cause of death.
Investigation revealed no evidence of suicide by an acute overdose.
Toxicological testing revealed only amitriptyline,
fluoxetine, their respective metabolites, nortriptyline and norfluoxetine,
and ethanol, the level of which was 9 mg/dL (and could be solely because of
postmortem formation by microorganisms). Analyses were performed on gastric
contents and on samples from the liver, kidney, and brain (Table).
Comment.--Given these findings, the most plausible
explanation for the death of this patient is chronic intoxication with amitriptyline
because of a reduction in its clearance caused by fluoxetine.
Tricyclic antidepressants at high concentrations
slow intracardiac conduction and may result in fatal arrhythmias.[1] Such
concentrations usually are associated with acute overdose, which is ruled
out in this case by the following observations: no pill fragments found in
the stomach, no unaccounted for pills from the patient's prescription, no
suicide note, and the fact that the amitriptyline:nortriptyline ratios in
the gastric contents and deep systemic compartments (ie, brain and kidney)
are the same. In acute overdose, patients typically die during the drug absorption
phase, and hence, the ratio would be distorted by the unabsorbed and unmetabolized
amitriptyline in the stomach.[2, 3] The amitriptyline:nortriptyline ratio
also has the advantage that it is not affected by postmortem autolysis, which
can increase the apparent blood levels of amitriptyline and nortriptyline
as a result of drug and metabolite mobilization from tissue compartments into
the blood.[2,3]
The coadministration of fluoxetine would be
expected to increase the functional daily dose of amitriptyline in this case
to 600 to 1050 mg/d. Such a dose is sufficient to produce toxic levels normally
associated with an acute overdose. The elimination of TCAs in more than 90%
of humans is principally dependent on the cytochrome P450 enzyme, CYP 2D6.[4]
At a dose of 20 mg/d fluoxetine produces sufficient inhibition of this enzyme
to produce a 4- to 7-fold increase in TCA plasma levels.[4] This patient was
prescribed 40 mg/d of fluoxetine. Hence, the functional dose of amitriptyline
would have been the prescribed dose multiplied by the expected increase in
plasma levels (ie, 150 mg/d x 4-7=600-1050 mg/d).
The implications of this case are not restricted
to amitriptyline or TCAs. Instead, it illustrates the significant effect that
fluoxetine can have when coprescribed with drugs that are dependent on CYP
2D6 for clearance. In addition to CYP 2D6, fluoxetine at 20 mg/d also substantially
reduces the clearance of drugs metabolized by CYP 2C isoenzymes.[4] Depending
on the pharmacological profile of the specific drug affected (eg, therapeutic
index), the clinical consequences of fluoxetine-induced reduction in clearance
may range from minimal tolerability problems to medically serious toxicity.
By being knowledgeable about this phenomenon, physicians can avoid adverse
outcomes by adjusting the dose of the affected drug or avoiding specific drug
combinations. Drugs that should be used cautiously in combination with fluoxetine
include, by way of example, but not limited to all TCAs, methadone, phenytoin,
propanolol, and perphenazine.
Sheldon H. Preskorn, MD University of Kansas School of Medicine
Bryan Baker, RN, MSM Psychiatric Research Institute Wichita,
Kan
eferences 1. Preskorn SH, Fast G. Therapeutic drug monitoring
for antidepressants: safety, efficacy, and cost-effectiveness. J Clin Psychiatry.
1991;52:23-33. 2. Prouty RW, Anderson WH. Postmortem redistribution of drugs.
In: The International Association of Forensic Toxiologists: Proceedings of
the 24th International Meeting, July 28-31, 1987. Edmonton, Alberta: International
Association of Forensic Toxicologists; 1988:1-21.
3. Apple FS, Bandt
CM. Liver and serum postmortem tricyclic antidepressant concentrations. In:
The International Association of Forensic Toxicologists: Proceedings of the
24th International Meeting, July 28-31, 1987. Edmonton, Alberta: International
Association of Forensic Toxicologists; 1988:55-69.
4.
Harvey AH, Preskorn SH. Cytochrome P450 enzymes: interpretation of their interactions
with selective serotonin reuptake inhibitors, I and II. J Clin Psychopharm.
1996;16:273-285, 345-355.
(JAMA.
1997;277:1682)
source: http://www.ama-assn.org/sci-pubs/journals/most/recent/issues/surg/pc7023a.htm
Morbid
Prognostic Features in Patients With Chronic Liver Failure Undergoing Nonhepatic
Surgery
Arch Surg. 1997;132:880-885
Henry E. Rice, MD; Grant E. O'Keefe,
MD; W. Scott Helton, MD; Kaj Johansen, MD, PhD
Background: Although the risk of portal decompression
surgery is accurately predicted by objective scoring systems (Child classification
and Pugh score), few useful prognostic criteria exist regarding nonhepatic
surgery in patients with chronic liver failure.
Objective: To evaluate the clinical findings
associated with perioperative mortality in patients with chronic liver failure
undergoing nonhepatic surgery.
Design: A retrospective cohort study.
Setting: University teaching hospitals.
Patients: Forty consecutive patients with an
International Classification of Diseases, Ninth Revision (ICD-9), diagnosis
of chronic liver failure and one or more of the following: jaundice, cirrhosis,
chronic hepatitis, or alcoholism.
Interventions: Forty operations, including
28 abdominal procedures, 2 coronary artery bypass grafts, 5 orthopedic procedures,
and 5 miscellaneous procedures.
Main Outcome Measures: Thirty-day mortality
as related to 19 preoperative clinical and laboratory variables.
Results: Eleven (28%) of the patients died
within 30 days of surgery. By univariate analysis, the following variables
were significantly (P<.05, Pearson chi2 test for categorical data or Mann-Whitney
U test for continuous data) associated with nonsurvival: encephalopathy, congestive
heart failure, the need for emergent surgery, infection, hyperbilirubinemia,
international normalized ratio greater than 1.6, hypoalbuminemia, and an elevated
creatinine level. By multiple logistic regression analysis, an international
normalized ratio greater than 1.6 and encephalopathy were associated with
a greater than 10- and 35-fold increased mortality risk, respectively. Child
classification and Pugh score failed to predict 30-day mortality.
Conclusions: We identified 8 clinical and laboratory
variables associated with death within 30 days in patients with chronic liver
failure undergoing nonhepatic surgery. Two factors—international normalized
ratio greater than 1.6 and encephalopathy—independently predicted mortality
by multivariate analysis. Neither Child classification nor Pugh score was
prognostically helpful. Nonhepatic surgery confers a substantial mortality
risk in patients with chronic liver failure.
-------------------------------------------
Gastroenterol
1998 May;36(5):385-9
[Article in German]
Hackstein
H, Mohl W, Puschel W, Stallmach A, Zeitz M
Klinik fur Innere Medizin II, Universitatskliniken
des Saarlandes
Diclofenac is an anti-inflammatory
analgesic which is widely used in the therapy of inflammatory joint pain.
Diclofenac hepatotoxicity ranges from asymptomatic elevation of transaminase
activity to significant liver disease. 31 cases of diclofenac-induced hepatitis
with five associated deaths have been already reported in the English, French
and Spanish literature. We report the case of a 64-year-old patient who was
admitted to the hospital with an icteric hepatitis of sudden onset. The only
drug that was taken before admission was diclofenac in a daily dose of 150-200
mg because of a spondylodiscitis. Work-up of the patient included ERCP, laparoscopy
and liver biopsy and excluded other reasons of a cholestatic hepatitis. Discontinuation
of diclofenac resulted in normalization of transaminase activity and bilirubin
concentration within four months. The frequent use of diclofenac and the possibility
of fatal liver damage highlights the need that diclofenac-toxicity should
be considered in the differential diagnosis of acute cholestatic hepatitis.
PMID: 9654706, UI: 98318775
-------------------------------------------------------
Am
J Gastroenterol 1998 Sep;93(9):1563-5
Ibuprofen-induced
hepatotoxicity in patients with chronic hepatitis C: a case series.
Riley TR 3rd,
Smith JP
Penn State Geisinger Health System,
The Milton S. Hershey Medical Center, The Pennsylvania State University, Department
of Medicine, Hershey 17033-0850, USA.
Hepatitis C is a common chronic infection.
Nonsteroidal anti-inflammatory drugs are commonly ingested both over-the-counter
and by prescription. This case report describes three cases where ibuprofen
use leads to a marked rise in hepatic transaminases with one case repeating
on rechallenge. These cases support the recommendation of acetaminophen over
nonsteroidal antiinflammatory drug use in patients with chronic hepatitis
C.
PMID: 9732947, UI:
98401783
Preventing Liver Damage
Even low doses of over-the-counter ibuprofen can cause liver
damage in patients with hepatitis C, according to a recent study. As a result,
patients with the joint pain that often accompanies the disease should take
low doses of acetaminophen instead.
“Many physicians don’t want to prescribe [acetaminophen]
because it has a reputation for causing liver damage,” said Thomas Riley III,
MD, director of the liver transplant program at the Milton S. Hershey Medical
Center of Penn State Geisinger Health System. But as long as acetaminophen
is prescribed in low doses, Riley called it “definitely the best treatment.”
He said patients with hepatitis C could safely take about 2 g of acetaminophen
per day to relieve joint pain.
In a report published in the September issue of the American Journal of Gastroenterology, Riley
and his colleagues described three patients with chronic hepatitis C who experienced
ibuprofen-induced hepatotoxicity. They reported that over-the-counter ibuprofen
can result in a 10-fold increase in liver enzymes. The researchers cautioned
that taking too much of the medication could accelerate the development of
cirrhosis of the liver.
There are 120
citations on ibuprofen induced acute renal failure.
--------------------------
Am
J Med 1998 Nov 2;105(5A):17S-21S
Nonsteroidal anti-inflammatory drug-associated toxicity of the
liver, lower gastrointestinal tract, and esophagus.
Bjorkman
D
University of Utah Medical Center,
Salt Lake City 84132, USA.
Although upper gastrointestinal
(GI) adverse events are the most common consequences of nonsteroidal anti-inflammatory
drug (NSAID) use, there are other GI side effects that can contribute to the
morbidity and mortality associated with these drugs. NSAID-associated toxicity
of the large and small bowel is increasingly recognized in clinical practice,
as enteroscopic procedures become more frequently used. This lower GI toxicity
may have several different manifestations: ulcerations, strictures, colitis,
or exacerbation of inflammatory bowel disease. Hepatic injury, most likely
due to an idiosyncratic reaction resulting from an immunologic response or
altered metabolic pathways, is another sequela of NSAID use that is usually
reversible. Although hepatotoxicity is listed as a class warning for NSAIDs,
aspirin, diclofenac, and sulindac are most commonly associated with this problem.
Surveillance for hepatic injury is not always reliable, and the low frequency
of both hepatic and lower GI toxicity in NSAID users renders these events
difficult to characterize. An increase in awareness, surveillance, and reporting
of these events can lead to a better understanding of the risk factors and
etiology associated with NSAID toxicity.
Publication Types:
·
Review
·
Review, tutorial
PMID: 9855171, UI: 99070813
------------------------------------------
GUT 1999;44:270-273 ( February )
Anti-inflammatory drugs and variceal bleeding:
a case-control study
V De Lédinghen,a D Heresbach,b O Fourdan,c
P Bernard,d M P Liebaert-Bories,e J B Nousbaum,f A Gourlaouen,g M C Becker,h
D Ribard,i P Ingrand,a C Silvain,a M Beauchanta a CHU, Poitiers, France, b
CHU, Rennes, c CHU, Paris-St Antoine, d CHU, Bordeaux, e CHU, Limoges, f CHU,
Brest, g CHU, Morlaix, h CHU, Besançon, i CHU, Nîmes Correspondence to: Dr
M Beauchant, Service d'Hépato-gastroentérologie, University Hospital, BP 577,
86021 Poitiers, France.
Accepted for publication 2 September 1998 Background[]Non-steroidal
anti-inflammatory drugs (NSAIDs) can have severe gastrointestinal effects
and cause peptic ulcers to bleed. Acute bleeding from oesophageal varices
is a major complication of cirrhosis of the liver.
Aims[] To investigate the role, using a case-control
study, of NSAIDs in first bleeding episodes associated with oesophageal or
cardial varices in cirrhotic patients.
Patients/Methods[] A structured interview was
conducted of 125 cirrhotic patients with bleeding mainly related to oesophageal
varices and 75 cirrhotic controls with oesophageal varices who had never bled.
Results Cirrhotic patients who were admitted
for bleeding related to portal hypertension were more likely to have used
NSAIDs during the week before the index day (31 of 125 (25%)) than the cirrhotic
controls (eight of 75 (11%); odds ratio = 2.8, p = 0.016). Use of aspirin
alone or combined with other NSAIDs was also more prevalent in the cases (21
of 125 (17%)) than in the controls (three of 75 (4%); odds ratio = 4.9, p
= 0.007). Logistic regression analysis showed that NSAID use (p = 0.022, odds
ratio = 2.9, 95% confidence interval = 1.8 to 4.7) and variceal size (p<0.001,
odds ratio = 4.0, 95% confidence interval = 1.4 to 11.5) were the only variables
independently associated with the risk of bleeding.
Conclusions[] Aspirin, used alone or combined
with other NSAIDs, was associated with a first variceal bleeding episode in
patients with cirrhosis. Given the life threatening nature of this complication,
the possible benefit of this treatment should be weighed against the risk
shown here. No firm conclusions could be drawn on non-aspirin NSAIDs used
alone.
(GUT 1999;44:270-273)
New
Arthritis Drug:
A new drug developed in Canada
that treats the grinding joint pain of osteoarthritis has raised hopes of
doctors and patients. The reason? Rofecoxib (Vioxx) has virtually no side
effects and does not cause ulcers or internal bleeding, which in a minority
of cases can be life threatening.
Doctors have typically prescribed nonsteriodal
anti-inflammatory drugs (NSAIDs) such as Aspirin or naproxen (Naprosyn) for
pain. However, common side effects of NSAIDs are heartburn and indigestion.
Two to four per cent of NSAID users develop ulcers or internal bleeding. It
has also been shown that in individuals with Portal Hypertension the use of
NSAIDs can lead to variceal bleeds.
Vioxx which is also an NSAID, provides pain
relief equivalent to other NSAIDs. However, as with any new drug, it doesn’t
have a long term safety profile. It is a new class of anti inflammatory called
COX 2 Inhibitors. Typical NSAIDs are inhibit both COX 1 and 2. COX 1 inhibitors
cause the reduction in mucous production in the gut which is what increases
the risk of ulcer formations.
While Vioxx costs about $ 1.30 a day, generic
NSAIDs cost only pennies daily. But for people with sensitive digestive tracts
or who are on long term NSAID therapy, Vioxx proves less expensive because
they no longer have to buy another medication to protect their stomachs. And
even with the extra protection regular NSAIDs still can cause problems in
sensitive individuals.
Vioxx is in the same class of drug as celecoxib
(Celebrex). People who are allergic to sulfonamide cannot take Celebrex but
can take Vioxx - Susan Pedwell
