Liver & Drug Interaction
Sometimes you, or a family member, need to take more than one
medication at a time. Whenever this happens, there is the risk of
one drug affecting how another drug acts. Usually this results in
only minor changes that you don't even notice, but occasionally the
outcome is more serious. Nobody knows exactly how often drug
interactions cause problems in the population at large, but we do
know that certain combinations of drugs increase your risk of
A drug interaction is a change in the effect of one drug when
taking a second drug concomitantly. This change may be desirable,
adverse, or inconsequential. An example of a desirable drug
interaction is cancer treatment: patients with cancer often receive
combinations of drugs that act in concert to fight the
Most adverse drug interactions result in an increase or decrease
in the effect of one of the drugs, but sometimes a combination of
drugs results in a new reaction not seen with either of the drugs
When one drug causes an "increased effect" of another
medication, this effect may be associated with various undesirable
symptoms, such as sweating, nausea, rapid heartbeat, etc.; the type
of symptoms that develop, as well as their severity, depends on the
specific drugs being taken as well as the individual variability of
your own body. If severe undesirable symptoms develop, the
increased effect is termed a "toxic" effect.
How Do Drugs Interact?
To understand better how drugs interact with each other, let's
follow a drug on its journey through your body. Most drugs are
taken orally, and dissolved in the stomach.
Once absorbed - mostly by the small intestine - the drug is
distributed throughout your body in the bloodstream, often hitching
a ride on blood proteins (such as albumin). Some of the drug goes
to the tissues and organs where it will produce its beneficial
effect, usually by attaching to specific chemical landing pads
called "receptors." By this time the body has also begun the
process of eliminating the drug. Some drugs are soluble enough in
water so that they are excreted by the kidneys and appear in the
urine. Most drugs, however, must be altered by the body before the
kidneys can get rid of them.
The LIVER usually accomplishes this by taking the drug molecule
into a LIVER cell, and then either removing certain parts of the
drug molecule, or adding chemical groups onto the molecule. The
altered drug, now more water-soluble and called a "metabolite," is
then expelled from the LIVER cell back into the bloodstream. The
metabolite has lost most of its ability to produce effects (good or
bad) in the body and can now be eliminated in the urine.
If you look at almost any drug interaction, one medication can
be considered the object drug--the drug whose effect is altered by
the interaction-and one medication can be considered the
precipitant drug-the drug that causes, or precipitates, the altered
effect in the object drug.
Some precipitant drugs bind with object drugs in the stomach or
the intestine and inhibit their ability to be absorbed into your
bloodstream. Antacids, for example, bind tightly with drugs such as
ciprofloxacin and tetracyclines, thus dramatically reducing their
absorption. If you take the antibiotic ciprofloxacin with most
antacids, the combination will dramatically reduce the amount of
antibiotic getting into your bloodstream. The bacteria romping and
reproducing in your system have a reprieve, while the antibiotic
sails down your intestine only to be excreted from your body.
Medicines other than antacids that can sometimes bind drugs in
the stomach and the intestine include cholestyramine (Questran),
colestipol (Colestid), and antidiarrheal agents, such as
kaolinpectin (Donnagel-PG) and attapulgite (Donnagel).
The LIVER is the site of many important drug interactions. Some
precipitant drugs, called "enzyme inhibitors," slow down the drug
metabolizing machinery in the LIVER, so that the LIVER cannot
metabolize drug molecules properly. This results in accumulation of
the affected drug in the blood, and may increase the risk of side
effects and toxicity. Examples of enzyme inhibitors are cimetidine
(Tagamet), ciprofloxacin (Cipro), diltiazem (Cardizem),
erythromycin (E-Mycin, Erythrocin), ketoconazole (Nizoral), and
verapamil (Calan, Isoptin).
Other drugs, called "enzyme inducers," have the opposite effect
in the LIVER; they speed up drug metabolism by adding more enzymes
to the system. This results in more rapid elimination of the object
drug, and tends to reduce its effect. Examples of enzyme inducers
are anticonvulsants such as carbamazepine (Tegretol),
phenobarbital, phenytoin (Dilantin), primidone (Mysoline), and the
antibiotic rifampin (Rifadin, Rimactane).
Though not as common a site of drug interactions as the LIVER,
the kidney is important in the elimination of some drugs such as
lithium carbonate (Lithane, Lithobid) and methotrexate (Mexate).
When another drug interferes with this process, lithium or
methotrexate accumulates in the body and serious toxicity can
It's important to understand that serious consequences may ensue
not only when two drugs interact, but also when one of the two
interacting drugs is either reduced in dosage or discontinued
altogether. For example, when propoxyphene (Darvon), a
pain-relieving medication, is given with carbamazepine (Tegretol),
a drug used to control seizures, an increased amount of
carbamazepine in the body results, which may lead to carbamazepine
Generally, when an interaction such as this occurs, your doctor
will adjust the dose of the medication to alleviate adverse side
effects (in this case, the doctor may choose to reduce the dose of
the carbamazepine so that drug toxicity will not occur) while
ensuring that both drugs are working properly. Getting just the
right amount in your body so that it can do its job properly
without serious side effects is called "titrating" the dose (only
your doctor should do this).
In this case, if the pain-reliever is discontinued, the
therapeutic dose of the anti-seizure drug is no longer a true
therapeutic dose, but subtherapeutic, or less than the dose needed
to control seizures.
There are several ways to try to avoid combinations with adverse
effects. For most disorders several different medicines can be used
for treatment, and it may be possible to select alternatives to the
Sometimes the dose of the object drug is adjusted to correct for
the alteration caused by the drug interaction. Sometimes the doctor
will monitor your response to the object drug more carefully in
order to catch the interaction before it does any harm. Sometimes
the interaction can be prevented by spacing the doses of the
interacting drugs appropriately, or by giving one of the drugs by a
different route of administration. Use of these and other methods
can typically prevent the adverse effects of drug interactions. But
prevention must be a cooperative effort among you, your doctor, and
How To Avoid Problems
Do not take drugs unless they are necessary. Sometimes the
obvious needs repeating: The more drugs you take the greater the
chance that you will eventually take a combination that doesn't mix
well. For example, a 1989 report in the Journal of Clinical
Psychiatry described four women with depression taking phenelzine
(Nardil) who had severe hypertensive reactions after using
nonprescription cold products containing decongestants. One woman
Keep your doctors informed of all drugs you are taking. If you
have to go to specialists (cardiologists, gastroenterologists, or
rheumatologists, for example), you need to have a primary physician
(usually a family physician or internal medicine physician) who is
looking at the "big picture." It is important to keep this primary
physician informed of all of the medications prescribed by the
other doctors, dentists, and anyone else involved in your
treatment. You should make sure that the specialists you are seeing
know about all of the drugs you are taking.
Unfortunately, drug interactions sometimes occur no matter how
well-informed doctors are kept. There are hundreds of drug
interactions and new ones are discovered every month. Another
important line of defense against drug interactions is your
Pharmacists are trained in drug interactions and can work with
your doctor to reduce the risk of adverse drug interactions. But
your pharmacist needs your cooperation. If possible, have all your
prescriptions filled at the same pharmacy. A growing number of
pharmacies have computerized drug interaction screening programs
that alert pharmacists if a new prescription you are having filled
interacts with any of your other medications.
Ask questions. When your doctor prescribes a new medication, ask
whether there are any nonprescription drugs that you should avoid.
Ask whether you should reduce or abstain from drinking alcohol.
Your pharmacist is also a good source for this kind of
Follow directions. If you have been advised to take your
ciprofloxacin (Cipro) two hours before your antacid, that is to
make sure that the ciprofloxacin gets absorbed into your blood
before the antacid has a chance to prevent its absorption.
It is also important not to stop taking a medication before you
are supposed to without checking with the doctor who prescribed it.
Sometimes a person is stabilized on two interacting drugs. Stopping
the precipitant drug may throw the object drug out of whack and
cause an adverse effect.
This is probably what happened to one boy who was receiving
theophylline for his asthma along with carbamazepine (Tegretol) for
seizures. Carbamazepine enhances the ability of the LIVER to
inactivate theophylline, so a larger dose of theophylline was
required. When the carbamazepine was stopped, the theophylline
blood concentrations skyrocketed, resulting in a severe reaction
and permanent brain damage in this unfortunate child.
Don't take other people's medicine. When you do this, you
circumvent the normal process for detecting drug interactions.
Become an informed consumer of health care. The practice of
medicine and the use of drugs to treat disease has become so
complicated that it is not possible for any one doctor or
pharmacist to know every bit of information about every single
drug. One authoritative source to consult is Advice for the
Patient: Drug Information in Lay Language, published by the U.S.
Pharmacopeial Convention, Inc. It should be available at a local
Gone are the days when all the doctor had was morphine, aspirin,
and penicillin. Many wonderful new drugs are available that have
made a tremendous positive impact on people's lives. But these
medications have their darker side as well.
By Jeff Schein
All articles on this website are for information purposes ONLY.
Always ask your private physician about any new treatments, drugs
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