Issues for the Practitioner in Drug Therapy
Virginia P. Arcangelo
Veronica F. Wilbur
Drug therapy is often the mainstay of treatment of acute and chronic diseases. An important role of health care practitioners is to develop a treatment plan with the patient; an integral part of the treatment plan of disease and health promotion is drug therapy. According to the Health in the United States (2014), from 2009 to 2012, of those persons aged 55 to 64, 55.6% used one to four prescription drugs and 20.3% used five or more during the last 30 days. Additionally, according to the National Ambulatory Medical Survey (2010), there were 2.6 billion drugs (75.1%) prescribed during office visits, 329.2 million drugs (72.5%) prescribed during visits to a hospital outpatient department, and 286.2 million drugs (80.3%) prescribed during visits to a hospital emergency department. The overall growth in spending on prescription drugs has slowed to 2.9% by 2011, but the overall spending equals $263 billion and accounts for a large share of national health care expenditures (CDC, FastStats, 2014). Therefore, it is imperative that prescribers have the best knowledge about principles of prescribing.
In developing a treatment plan that includes drug therapy, the prescribing practitioner considers many issues in achieving the goal of safe, appropriate, and effective therapy. Among them are drug safety and product safeguards, the practitioner’s role and responsibilities, the step-by-step process of prescribing therapy and writing the prescription, and follow-up measures. Particularly important are promoting adherence to the therapeutic regimen and keeping up-to-date with the latest developments in drug therapy.
DRUG SAFETY AND MARKET SAFEGUARDS
In the United States, drug safety is ensured in many ways, but primarily by the U.S. Food and Drug Administration (FDA), which is the federal agency charged with conducting and monitoring clinical trials, approving new drugs for market and manufacture, and ensuring safe drugs for public consumption. Although the federal government provides guidelines for a pure and safe drug product, guidelines for prescribers of drug therapy are dictated both by state and federal governments and by licensing bodies in each state.
Clinical Trials
Various legislated mechanisms are in place to ensure pure and safe drug products. One of these mechanisms is the clinical trial process by which new drug development is carefully monitored by the FDA. Every new drug must successfully pass through several stages of development (see Figure 1.1). The first stage is preclinical trials, which involve testing in animals and monitoring efficacy, toxic effects, and untoward reactions. Application to the FDA for investigational use of a drug is made only after this portion of research is completed.
Clinical trials, which begin only after the FDA grants approval for investigation, consist of four phases and may last up to 9 years before a drug is approved for general use. During clinical trials, performed on informed volunteers, data are gathered about the proposed drug’s purity, bioavailability, potency, efficacy, safety, and toxicity.
Phase I of clinical trials is the initial evaluation of the drug. It involves supervised studies on 20 to 100 healthy people and focuses on absorption, distribution, metabolism (sometimes interchangeable with biotransformation), and elimination of the drug. In phase I, the most effective administration routes and dosage ranges are determined. During phase II, up to several hundred patients with the disease for which the drug is
intended are subjects. The testing focus is the same as in phase I, except that drug effects are monitored on people with disease.
intended are subjects. The testing focus is the same as in phase I, except that drug effects are monitored on people with disease.
 FIGURE 1.1 Phases of drug development. |
Phase III begins once the FDA determines that the drug causes no apparent serious adverse effects and that the dosage range is appropriate. Double-blind research methods (in which neither the study and control subjects nor the investigators know who is receiving the test drug and who is not) are used for data collection in this phase, and the proposed drug is compared with placebo. Usually several thousand subjects are involved in this phase, which lasts several years and during which most risks of the proposed drug are discovered. At the completion of phase III, the FDA evaluates data presented and accepts or rejects the application for the new drug. Approval of the application means that the drug can be marketed—but only by the company seeking the approval.
Once on the market, the drug enters phase IV or postmarketing surveillance. Objectives at this stage are (1) to compare the drug with others on the market, (2) to monitor for long-term effectiveness and impact on quality of life, and (3) to analyze cost-effectiveness (Center Watch, 2015). During postmarketing surveillance, drugs can be taken off the market or restricted due to additional findings about the drug and side effects.
BOX 1.1
Scheduled Drugs
Scheduled Drugs
Schedule 1 drugs have a high potential for abuse. There is no routine therapeutic use for these drugs, and they are not available for regular use. They may be obtained for “investigational use only” by applying to the U.S. Drug Enforcement Agency. Examples include heroin and LSD.
Schedule 2 drugs have a valid medical use but a high potential for abuse, both psychological and physiologic. In an emergency, a Schedule 2 drug may be prescribed by telephone if a written prescription cannot be provided at the time. However, a written prescription must be provided within 72 hours with the words authorization for emergency dispensing written on the prescription. These prescriptions cannot be refilled. A new prescription must be written each time. Examples include certain amphetamines and barbiturates.
Schedule 3 drugs have a potential for abuse, but the potential is lower than for drugs on Schedule 2. These drugs contain a combination of controlled and noncontrolled substances. Use of these drugs can cause a moderate to low physiologic dependence and a higher psychological dependence. A verbal order can be given to the pharmacy, and the prescription can be refilled up to five times within 6 months. Examples include certain narcotics (codeine) and nonbarbiturate sedatives.
Schedule 4 drugs have a low potential for abuse. They can cause psychological dependency but limited physiologic dependency. Examples include nonnarcotic analgesics and antianxiety agents, such as lorazepam (Ativan).
Schedule 5 drugs have the least potential for abuse. They contain a moderate amount of opioids and are used mainly as antitussives and antidiarrheals. Examples include antitussives and antidiarrheals with small amounts of narcotics.
Prevention of Harm and Misuse
The passage of the FDA’s Controlled Substances Act of 1970 established the schedule of ranking of drugs that have the potential for abuse or misuse. Drugs on the schedule are considered controlled substances. These drugs have the potential to induce dependency and addiction, either psychologically or physiologically. Box 1.1 defines the five categories of scheduled drugs, with Schedule 1 drugs having the greatest potential for abuse and Schedule 5 drugs the least.
Schedule drugs can be prescribed only by a practitioner who is registered and approved by the U.S. Drug Enforcement
Agency (DEA), and in some states, practitioners must possess a controlled substance (CS) license as well. The DEA issues approved applicants a number, which must be written on the prescription for a controlled substance for the prescription to be valid. The prescriber’s DEA number must also appear on a prescription that is being filled in another state.
Agency (DEA), and in some states, practitioners must possess a controlled substance (CS) license as well. The DEA issues approved applicants a number, which must be written on the prescription for a controlled substance for the prescription to be valid. The prescriber’s DEA number must also appear on a prescription that is being filled in another state.
Currently, in the United States, overdose emergencies and abuse of schedule drugs have become epidemic with over 259 million prescriptions written for painkillers (CDC Vital Statistics, 2014). To assist health care providers with safe prescribing practices, many states have enacted prescription drug monitoring programs (PDMPs). These programs are established and run by individual states through electronic databases that collect information on designated substances dispensed in the state. The DEA does not have involvement in any state PDMP program. According to the National Association of State Controlled Substance Authorities (NASCSA), in 2014, only one state did not have a PDMP. The program allows prescribers of controlled substance to look up patients for previous prescriptions of controlled substances including type of medication, amount, and name of the prescriber. The information obtained from this program helps to reveal those patients who prescriber shop and are receiving too many controlled substances. It also helps to start a conversation with the patients, exploring their health care needs.
National Provider Identifier
The Administrative Simplification provisions of the Health Insurance Portability and Accountability Act of 1996 (HIPAA) mandated the adoption of standard unique identifiers for health care providers and health plans. This identification system improves the efficiency and effectiveness of electronically transmitting health information. The Centers for Medicare & Medicaid Services (CMS) has developed the National Plan and Provider Enumeration System (NPPES) to assign each provider a unique National Provider Identifier (NPI). Covered health care providers and all health plans and health care clearinghouses must use NPIs in the administrative and financial transactions adopted under HIPAA. The NPI is a 10-position, intelligence-free numeric identifier (10-digit number). The NPI does not carry other information about the health care provider, such as the health care provider’s specialty or in which state he or she practices. The NPI must be used in lieu of legacy provider identifiers in HIPAA standard transactions. Covered providers must also share their NPI with other providers, health plans, clearinghouses, and any entity that may need it for billing purposes.
The purpose of the NPI is to identify all health care providers by a unique number in standard transactions such as health care claims. NPIs may also be used to identify health care providers on prescriptions, in internal files to link proprietary provider identification numbers and other information, in coordination of benefits between health plans, in patient medical record systems, in program integrity files, and in other ways. HIPAA requires that covered entities (i.e., health plans, health care clearinghouses, and those health care providers who transmit health information in electronic form in connection with a transaction for which the Secretary of Health and Human Services has adopted a standard) use NPIs in standard transactions. The NPI is the only health care provider identifier that can be used in standard transactions by covered entities.
A health care provider may apply for an NPI through a web-based application process at https://nppes.cms.hhs.gov or by filling out and mailing a paper application to the NPI Enumerator. A copy of the application (CMS-10114), which includes the NPI Enumerator’s mailing address, is available upon request through the NPI Enumerator at 1-800-465-3203, TTY 1-800-692-2326.
When applying for an NPI, providers are asked to include their Medicare identifiers as well as those issued by other health plans. A Medicaid identification number must include the associated state name. The legacy identifier information is critical for health plans to aid in the transition to the NPI. When the NPI application information has been submitted and the NPI assigned, NPPES sends the health care provider a notification that includes their NPI. This notification is proof of NPI enumeration and helps to verify a health care provider’s NPI.
Prescription versus Nonprescription Drugs
Many drugs may now be obtained that were previously available only with a prescription, and at the prescription dosage. Although these drugs are commonly and legally obtained over the counter (OTC) without a prescription, approval for the drug must still be obtained from the FDA for specific uses in specific doses.
These drugs carry user warnings on the labels. Many have the potential for interacting adversely with prescribed drugs or complicating existing disease. The self-prescribed use of OTC drugs may delay diagnosis and treatment of potentially serious problems. On the other hand, the use of OTC drugs can be beneficial for treatment of self-limiting disorders that are not serious.
Generic Drugs versus Brand Name Drugs
Substituting a generic drug for a brand name drug is a common practice. In many states, it is required. When the patent on a brand name drug expires, other drug manufacturers can then produce the same drug formula under its generic name (the generic name and formula of a drug are always the same; only the brand names change). This practice not only benefits the manufacturer but also decreases the cost to the consumer.
To ensure safety, the FDA must grant approval for these drugs, and rigorous testing is again required to ensure that all generic drugs meet specifications for quality, purity, strength, and potency. Generic drugs must demonstrate therapeutic equivalence to the brand name equivalent. They must be manufactured under the same strict standards and meet the same batch requirements for identity, strength, purity, and quality as the brand name drug. To obtain FDA approval, the generic drug is administered in a single dose to at least 18 healthy human subjects. Next, peak serum concentration
and the area under the plasma concentration curve (AUC) are measured. The values obtained for the generic drug must be within 80% to 125% of those obtained for the brand name drug. Most generic drugs have a mean AUC within 3% of the brand name drug. There has been no reported therapeutic difference of a serious nature between brand name products and FDA-approved generic products. For more information, see Table 1.1, which presents FDA equivalency ratings for brand name and generic drugs.
and the area under the plasma concentration curve (AUC) are measured. The values obtained for the generic drug must be within 80% to 125% of those obtained for the brand name drug. Most generic drugs have a mean AUC within 3% of the brand name drug. There has been no reported therapeutic difference of a serious nature between brand name products and FDA-approved generic products. For more information, see Table 1.1, which presents FDA equivalency ratings for brand name and generic drugs.
Complementary and Alternative Medicine
In the United States, the use of herbal preparations as treatments for disease and disease prevention has increased tremendously. According to the National Center for Complementary and Integrative Health, in 2012 approximately 33% of adults and 11% of children use some form of complementary approach to health care. The findings mirror similar surveys from 2007. The most popular products for adults (7.8%) and children (1.1%) are fish oils/Omega-3 fatty acids. These are followed by glucosamine and/or chondroitin (2.6%), probiotics/prebiotics (1.6%) and melatonin (1.3%) for adults, and for children melatonin (0.7%) (Clarke et al., 2015).
Historically, herbs were the first healing system used. Herbal medicines are derived from plants and thought by many to be harmless because they are products of nature. Some prescription drugs in current use, however, such as digitalis, are also “natural,” which is not synonymous with “harmless.” Before 1962, herbal preparations were considered to be drugs, but now they are sold as foods or supplements and therefore do not require FDA approval as drugs. Hence, there are no legislated standards on purity or quantity of active ingredients in herbal preparations. The value of herbal therapy is usually measured by anecdotal reports and not verified by research. Like synthetic products, herbal preparations may interact with other drugs and may produce undesirable side effects as well.
TABLE 1.1 FDA Therapeutic Equivalence Ratings | ||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| ||||||||||||||||||||||||||||||||||||||||||
The Dietary Supplement Health and Education Act (1994) requires labeling about the effect of herbal products on the body and requires the statement that the herbal product has not been reviewed by the FDA and is not intended to be used as a drug. Complementary and alternative medicine (CAM) is discussed in Chapter 9.
Foreign Medications
In today’s global society, practitioners will experience encounters with patients from many countries. These individuals may request refills of drugs for treating their chronic conditions. These drugs may have unrecognizable names, different dosages/dosage forms, or different active ingredients. Additionally, patients may get their drugs from online pharmacies in other countries because they are less expensive. Today, there is a proliferation of these online pharmacies, and only 3% comply with U.S. pharmacy laws (FDA, 2013). According to the World Health Organization, 80% of drugs are counterfeited in some countries (FDA, 2014). The Food and Drug Administration (FDA) has many resources for the practitioner to guide patients toward sound decision making about prescription drug acquisition.
Disposal of Medications
Many medications can be potentially harmful if taken by someone other than the person for whom they are prescribed. Understand that improperly disposed drugs can leak into the environment, and the best disposal method is through community drug take-back programs. Almost all medicines can be safely disposed of if they are mixed with an undesirable substance, such as cat litter or coffee grounds, and placed in a closed container. Any personal information should be removed from the container by using a black marker or duct tape. Many communities have a drug take-back program for disposal, or drugs can be disposed of when the community collects hazardous material. Drugs should not be flushed down the toilet or drain unless the dispensing directions say this is permitted. Drugs permitted to be flushed can be found on the Web site http://www.fda.gov/Drugs/ResourcesForYou/Consumers/BuyingUsingMedicineSafely/EnsuringSafeUseofMedicine/SafeDisposalofMedicines/ucm186187.htm.
PRACTITIONER’S ROLE AND RESPONSIBILITIES IN PRESCRIBING
Before prescribing therapy, the practitioner has a responsibility to gather data by taking a thorough history and performing a physical examination. Once the data are gathered and evaluated, one or more diagnoses are formulated and a treatment plan established. As noted, the most frequently used treatment modality is drug therapy, usually with a prescription or OTC drug.
If a drug is deemed necessary for therapy, it is essential for the practitioner to understand the responsibility involved in prescribing that drug or drugs and to consider seriously which class of medication is most appropriate for the patient. The decision is reached based on a thorough knowledge of diagnosis and treatment.
Drug Selection
To determine which therapy is best for the patient, the practitioner conducts a risk-benefit analysis, evaluating the therapeutic value versus the risk associated with each drug to be prescribed. The practitioner then selects from a vast number of pharmacologic agents used for treating the specific medical problem. Factors to consider when selecting the drug or drugs are the subtle or significant differences in action, side effects, interactions, convenience, storage needs, route of administration, efficacy, and cost. Another factor in the decision may involve the patient pressuring the practitioner to prescribe a medication (because that is the expectation of many patients at the beginning of a health care encounter). Clearly, many responsibilities are inherent in prescribing a medication, and serious consequences may result if these responsibilities are not taken seriously and the prescription is prepared incorrectly.
BOX 1.2
Questions to Address When Prescribing a Medication
Questions to Address When Prescribing a Medication
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
