Adverse Drug Reactions are the 4th leading cause of death in the United States and a primary reason for malpractice payouts. The clinician must consider both the efficacy and safety of a drug when making a therapeutic medication recommendation for their patients. However, not only does the response to drugs vary between individuals and ethnic populations, but often in adverse reactions it is the interaction between various medications and herbs, over-the-counter items and many foods that put people at risk.

Pharmacogenetics

Cytochrome P450 enzymes are essential to the production of cholesterol, steroids, protacyclins and thromboxane A, but they are also necessary for the detoxification of foreign substances and the metabolism of drugs. CYP450 enzymes are named such because they bind to membranes within a cell (cyto) and contain a heme pigment (chrome and P) that absorbs light at a wavelength of 450 nm when exposed to carbon monoxide. Although these enzymes are predominantly found in the liver, they are also present in the lungs, placenta, kidneys and small intestine.

There are more than fifty P450 enzymes, but only six (CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A4, and CYP3A5) metabolize 90% of all drugs. Individuals vary in their ability to detoxify and eliminate drugs due to genetic variance of these liver enzymes, and polymorphism is responsible for drug response among patients of differing ethnic origins. For example, 7% of Caucasians and 2-7% of African Americans are poor metabolizers of drugs dependent on CYP2D6, which metabolize many beta-blockers, opiates and antidepressants. 20% of Asians are poor metabolizers of drugs dependent on CYP2C19 and process Phenobarbital, Dilantin, Prilosec and other drugs. Severe toxicity can result even for normal metabolizers if CYP450 enzyme-inhibiting drugs are added to benzodiazepines, antipsychotics, cyclosporine, statins or warfarin.

Identifying how different cultures metabolize drugs is prudent in medicine. Additionally, because many drugs act as either a substrate or inhibitor, they have the potential to interact with other medications and place the patient at an even greater risk.

Drug Interactions

Many drug interactions are the results of CYP450 metabolism. The non-sedating antihistamines astemizole (Hismanal) and terfenadine (Seldane), and the gastrointestinal agent cisapride (Propulsid), were all withdrawn from the market in the United States because metabolic inhibition by other drugs led to life-threatening arrhythmias. In 1998, the calcium channel blocker mibefradio was withdrawn from the U.S. market because it was a potent enzyme inhibitor that resulted in toxic levels of other cardiovascular drugs.

Drugs interact in several ways – they may be metabolized by only one enzyme (e.g., metoprolol by CYP2D6) or by multiple enzymes (Coumadin by CYP3A4, CYP2D6, and CYP1A2) and act as either an inhibitor or inducer. Inhibitiors block the activity of one or more enzymes, but the extent depends upon factors such as the dose and ability of the inhibitor to bind to the enzyme. For instance, Sertraline (Zoloft) is a mild inhibitor of CYP2D6 at a 50 mg dose, but at 200 mg it becomes a potent inhibitor.

Inducers increase the CYP450 enzyme activity, but there is usually a delay depending on the half-life of the inducing drug. It can take up to one week after beginning Phenobarbital, an inducer with a very long half-life. Tegretol is another potent enzyme inducer that should be initiated at a low dose and increased at weekly intervals as its half-life gradually decreases over time.

GeneMedRx Software

GeneMedRx explains the mechanism of each drug interaction, the level of significance (major, minor, moderate) and in some instances it can provide a course of action to manage the interaction. Interactions between medications, foods and herbal items will also be displayed.

The GeneMedRx software offers additional safety to manage patient prescriptions.

For a Free Trial Subscription, click here.

Using the Program:

1. Input patient prescription, over-the-counter items, herbal regimens, foods and patient factors (pregnancy, cigarette smoking, etc).

2. Click “Check Interactions” for potential drug-drug interactions based on the metabolism of the drugs in question. Please note that results do not include the minority of drug-drug interactions for which metabolism is not understood.

3. Determine the effect removing or adding a particular drug has on the predicted change.

4. If needed, pick an alternate drug or dosage based on the predicted change profile.

How It Works:

1. Input patient variables such as prescription drugs, over-the-counter items, herbs/foods as well as other factors such as pregnancy and cigarette smoking.

2. Scan the results for potential drug-drug or drug-herb-food interactions based on the metabolism of the drugs in question. Please note that results do not include the minority of drug-drug interactions for which metabolism is not understood. 



3. Determine the effect removing or adding a particular drug has on the predicted change. 



4. If needed, pick an alternate drug or dosage based on the predicted change profile

GeneMedRx software is provided for the medical community. Individuals using the drug interaction software should print the report and discuss the results with your physician.

Drug Interaction Software - 1 Year Subscription / $199.00

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