A 1998 medical report in the Journal of the American Medical Association estimated that ADRs to prescribed medicines kill about 106,000 americans annually, three times as many as are killed by automobiles, six times as many as are killed by illegal drugs. This makes prescription drugs the fourth leading killer in the US, after heart disease, cancer, and stroke. The report followed the World Health Organization definition of ADRs and included only drug reactions that resulted from proper dosage and under normal circumstances, excluding drug reactions that were a result of errors.

Of the 106,000 people killed each year by ADRs to prescription drugs, about 40% were initially admitted to the hospital because of the ADR. The other 60% were hospitalized for some other cause but developed a fatal reaction to a prescription drug received while hospitalized. The report found that 3.2 out of every 1000 hospitalized patients die each year in every hospital in the US as the result of ADR.

As alarming as these numbers are, they don't begin to suggest the full toll. The JAMA study only counted ADRs in hospitals, not including all other venues where they occur, especially nursing homes. More importantly, ADRs are grossly under recognized and severly under reported. Some health care professionals estimate only 1% get reported. The FDA, for example, currently averages 82 reports a year about ADRs caused by Digoxin. Medicare records, however indicate of almost 30,000 annually. In addition there are ADRs to over-th-counter drugs, natural medicines, and vitamins and supplements.

The number of ADRs in America can be expected to increase because of the:
* Rising number of drugs perscribed.
* Ever-increasing number of new drugs on the market.
* Way these drugs are tested and marketed.
* Lack of a formal system for monitoring ADRs.

Older people are at especially high risk of having an adverse drug reaction, primarily because they're likely to have chronic or multiple illnesses for which they are taking several prescription and over-the-counter drugs. The average person over 60 not in a care facility takes at least four different drugs. People in care facilities, such as nursing homes, typically take six-eight. this makes drug-drug interactions a major concern. Kidney and liver function and the ability to rid the body of drugs also decline with age. Patients 60 and older account for 51% of ADR deaths.

*CYP2D6 (cytochrome P450 2D6) is the best studied of the DMEs (drug metabolizing enzymes) and acts on one quarter of all prescription drugs. Approximately ten percent of the population have a slow acting form of this enzyme and five percent a super-fast acting form. Drugs that interact with CYP2D6 include: Prozac, Zoloft, Paxil, Effexor, Oxycontin, Hydrocodone, Amitriptyline, Claritin, Cyclobenzaprine, Haldol, Metoprolol, Rythmol, Tagamet, Tamaxifen, and over-the-counter-diphenylhydramine drugs, Allegra, Dytuss and Tusstat.

*CYP2C9 (cytochrome P450 2C9) is the primary route of metabolism for Coumadin (Warfarin), Dilantin, Amaryl, Isoniazid, Sulfa and Ibuprofen. Clinical studies suggest that the use od genetic testing may be especially helpful with Warfarin administration. Other drugs metabolized by 2C9 include: Amitriptyline, Hyzaar, THC (tetrahydrocannabinol), Naproxen and viagra.