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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 adverse effects.

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 malignancy.

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 alone.

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 result.

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 toxicity.

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 interacting drugs.

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 your pharmacist.

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 died.

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 pharmacist.

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 information.

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 library.

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 or procedures.

Follow these links for related information

Drugs That May Cause Liver Dysfunction or Damage

Amoxicillin-Clavulanic Acid: Higher Risk Of Hepatotoxicity Than With Amoxicillin Alone

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