Prescribing Drugs in the 21st Century

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When we started practicing 30 years ago, prescribing medications involved using a cookbook formulary that listed 1 or 2 drugs by name and dose. The more cutting-edge documents might have included both generic and brand names, but little else was included. Today the number of drugs prescribers must know has increased exponentially, and information regarding how to prescribe rationally continues to emerge. Simple formulary information is a very small portion of what one needs to consider prior to prescribing any drug today.

For example, the timing of administration can be crucial. Chronopharmacology, a subsection of the larger field of chronobiology, is the study of pharmacology and biorhythms. One common example involves the drug category of statins that need to be taken in the evening because the human body releases the most cholesterol during the evening/night. Chronopharmacology may hold the key to other mysteries of pharmacokinetics and pharmacodynamics. Multiple studies have reported contradictory results regarding the use of low-dose aspirin (ASA) to reduce the risk of adverse perinatal outcomes, especially preeclampsia. A Spanish team of investigators lead by Hermida investigated aspirin and preeclampsia, intrauterine growth restriction, and preterm birth among 341 women.1 When ASA was taken upon awakening, there was no statistically significant difference between control or treatment groups. However, when ingested at bedtime, the incidence of the aforementioned perinatal complications was 1.7%, 3.4%, and 0% respectively, compared to values of 14.3%, 16.1%, and 17.9% for women in the control group who took a placebo at the same time (P < .001).1 Chronopharmacology is now a major component of new designer drugs. Old drugs also may be newly reformulated as more information is found about optimal timing. Already multiple agents are available in extended-release delivery systems. These systems are used both to facilitate a stable plasma release and maximize convenience of administration.2

In years past, the use of multiple drugs was termed polypharmacy and was usually reserved for discussion of prescribing medications to the elderly. Today, polypharmacy is becoming common for persons of all age groups.3 A woman who is newly diagnosed with type 2 diabetes mellitus will most likely find herself taking a daily antihypoglycemic agent (or 2), a low-dose antihypertensive, and a statin. Even the “healthy” woman often consumes multiple various vitamins and/or botanicals for prophylactic reasons.

Thus, polypharmacy is a more important consideration than ever before, especially with the information now available about pharmacogenetics/pharmacogenomics. One individual with her unique genetic make-up can have adverse effects when taking a specific agent that another person will not.4 A common example in midwifery practice is the prescription of hydrocodone, a variant of codeine that is metabolized into the pharmacologically active agent hydromorphone. Drugs that are a combination of hydrocodone and acetaminophen (eg, Vicodin, Lorcet, Lortab) are often prescribed for treatment of pain secondary to several obstetric or gynecologic conditions. However, approximately 10% of the Caucasian population are genetically poor metabolizers of codeine, and these individuals obtain very little pain relief when taking hydrocodone.5

Adverse effects are more frequent when genetics and multiple drugs interact as in the case of polypharmacy. Drugs administered simultaneously may potentiate adverse reactions, inhibit therapeutic effects, or attenuate the expected effects for a specific individual. Although it still may be a few years before a custom genetic workup is required before a drug is prescribed, that action is being advocated for some very toxic and expensive chemotherapeutic drugs today. More information about pharmacogenetics also is aiding providers in understanding some puzzles from the past. Dextromethorphan is a widely used over-the-counter antitussive whose major untoward effect for the average person is minor gastrointestinal upset. However, an inquisitive adolescent who is a rapid metabolizer with the CYP2D6 polymorphism may have just found a cheap drug of abuse with similar effects to ecstasy.6

Some of the articles in this issue focus on pharmaceutical treatment of a disease, details on drugs themselves, or even an historical perspective on prescribing. All point to the finding that this is a burgeoning field, constantly growing and challenging providers. Cookbooks belong in the kitchen.

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