Drugs: Toward Personalized Prescriptions

When a patient has any one of a number of infections, his physician may write on a prescription blank: “Tetracycline, 250 mg. #16. Sig. 1 caps, q.i.d.” That dosage of 250 milligrams is standard for any adolescent or adult, whether a 100-lb. girl or a 300-lb. man. Equally standard is the one capsule four times a day for about four days.

Such stereotyped prescribing is extremely unsound, says Pharmacologist Sumner Kalman of Stanford University. “There is no average man who always needs a particular dose of this or that drug on a certain daily schedule,” Dr. Kalman notes. Even patients who are identical in sex and size do not absorb a drug into the bloodstream at the same rate. Their systems do not metabolize the drug at the same rate. Moreover, their reactions to a drug may range all the way from nil to collapse and sudden death as a result of severe allergic shock. “The fate of a drug in the body is a personal affair, as peculiar in a way as a personality trait,” says Kalman. “How dare we consider all patients the same? We have to study the drug in the individual patient so that he can be placed upon a proper schedule.”

Across Ethnic Lines. The need for such procedures is being emphasized by a growing body of biochemical knowledge. “As a patient’s health changes, or as other drugs are used,” says Kalman, “the blood level of an important drug may change.” One example is the use of barbiturates in combination with digitalis. If a patient is on digitoxin, one of the digitalis products, and then uses barbiturates for a while, his heart-medicine dosage should be checked, and possibly adjusted, twice. Barbiturates speed up the metabolism of digitalis-type drugs, which are critical within a narrow range. Even a modest overdose may precipitate a dangerous, abnormal heart rhythm.

Precise drug dosages for individuals are undoubtedly years off, for Kalman’s is a counsel of pharmacological perfection. Nonetheless, he and two fellow pharmacologists at Stanford, Drs. Avram Goldstein and Lewis Aronow, have given it considerable impetus with their exhaustive, 884-page study, Principles of Drug Action (Hoeber Medical Division of Harper & Row). The differences among patients in their reactions to drugs may be caused by race, individual heredity, personal idiosyncrasy, or allergic reaction. Enzyme deficiencies and abnormal hemoglobins are found among Negroes and some Mediterranean peoples. In as many as 10% of Negro males, normal doses of the antimalarial drug primaquine will precipitate an acute and potentially fatal blood-destroying anemia. Many individuals with this peculiarity are almost equally sensitive to sulfas and several other drugs.

One of the common drug reactions involves isoniazid, the most widely used drug against tuberculosis. One of the rarer reactions is found among victims of porphyria (see following story), who suffer acute attacks if they take barbiturates; they may also be sensitive to the sulfas. At the opposite end of the reaction scale, some victims of an unusual form of rickets need more than 1,000 times the normal quantity of vitamin D before they respond.

No Useful Purpose. Exposure to a drug may sensitize a patient and cause a dangerous allergic reaction on the next exposure. But, the California authors complain, it may do no good for the doctor to ask a patient whether he has previously had a reaction to a certain drug. “Patients are commonly unaware of what medication they receive, multiple irrational drug mixtures abound, and memories tend to be much less persistent than antibody-forming capacity.” Reaction to penicillin injections cause an estimated 100 deaths annually in the U.S. What is most tragic about these deaths, say Kalman and his colleagues in citing a number of cases, is that the penicillin was injected for a sprained tee, an injured finger, and mild upper respiratory infections. “Penicillin could have served no useful purpose in these instances.”

The pharmacologists also complain about the way doctors write their prescriptions. “Writing prescriptions in Latin is an obsolete affectation, conducive to misunderstanding and error,” they say. With rare exceptions, the medicine bottle should be labeled with the name of the drug. “The obsolete apothecary system of grains, ounces and drachms is dangerous and unnecessary. The ancient symbols for ounce and drachm are nearly alike, and fatal over doses have resulted. The abbreviation gr. (meaning grain, 60 mg.) is easily mistaken for gram (1,000 mg.), also with catastrophic consequences.” Instead of a dubious decimal point, the doctor should use a vertical line.

When it comes to telling the patient how to take his medicine, the Stanford professors advise doctors and druggists to use “terms of common household measures like teaspoonful or tablespoonful.” That way the patient knows what he is doing. He can only hope that his doctor does too.