Книги фарма 2 / Bertram G. Katzung-Basic & Clinical Pharmacology(9th Edition)

The United States government recognizes two classes of drugs: (1) over-the-counter (OTC) drugs and (2) those that require a prescription from a licensed prescriber (Rx Only). OTC drugs are those that can be safely self-administered by the layman for self-limiting conditions and for which appropriate labels can be written for lay comprehension. Half of all drug doses consumed by the American public are OTC drugs.

Physicians, dentists, podiatrists, and veterinarians—and, in some states, specialized pharmacists, nurses, physician's assistants, and optometrists—are granted authority to prescribe dangerous drugs (those bearing the federal legend statement, "Rx Only") on the basis of their training in diagnosis and treatment (see Who May Prescribe?). Pharmacists are authorized to dispense prescriptions pursuant to a prescriber's order provided that the medication order is appropriate and rational for the patient. Nurses are authorized to administer medications to patients subject to a prescriber's order.

Prescription drugs are controlled by the United States Food and Drug Administration as described in Chapter 5: Basic & Clinical Evaluation of New Drugs. The federal legend statement as well as the package insert are part of the packaging requirements for all prescription drugs. The package insert is the official brochure setting forth the indications, contraindications, warnings, and dosing for the drug.

The prescriber, by writing and signing a prescription order, controls who may obtain prescription drugs. The pharmacist may purchase these drugs, but they may be dispensed only on the order of a legally qualified prescriber. Thus, a "prescription" is actually three things: the physician's order in the patient's chart, the written order to which the pharmacist refers when dispensing, and the patient's medication container with a label affixed.

While the federal government controls the drugs and their labeling and distribution, the state legislatures control who may prescribe drugs through their licensing boards, eg, the Board of Medical Examiners. Prescribers must pass examinations, pay fees, and—in the case of some states and some professions—meet other requirements for relicensure such as continuing education. If these requirements are met, the prescriber is licensed to order dispensing of drugs.

The federal government and the states further impose special restrictions on drugs according to their perceived potential for abuse (Table 66–3). Such drugs include opioids, hallucinogens, stimulants, depressants, and anabolic steroids (see Chapter 32: Drugs of Abuse). Special requirements must be met when these drugs are to be prescribed. The Controlled Drug Act requires prescribers and dispensers to register with the Drug Enforcement Agency (DEA), pay a fee, receive a personal registration number, and keep records of all controlled drugs prescribed or dispensed. Every time a controlled drug is prescribed, a valid DEA number must appear on the prescription blank.

Table 66–3. Classification of Controlled Substances.

Prescriptions for substances with a high potential for abuse (schedule II) cannot be refilled. Prescriptions for schedule III, IV, and V drugs can be refilled, but there is a five-refill maximum, and in no case may the prescription be refilled after 6 months from the date of writing. Schedule II drug prescriptions may not be transmitted over the telephone, and some states require a special state-issued prescription blank. These restrictive prescribing laws are intended to limit the amount of drugs of abuse that are made available to the public.

Unfortunately, the inconvenience occasioned by these laws—and an unwarranted fear by medical professionals themselves regarding the risk of patient tolerance and addiction—continues to hamper adequate treatment of patients with terminal conditions. This has been shown to be particularly true in children and elderly patients with cancer. There is no excuse for inadequate treatment of pain in a terminal patient; not only is addiction irrelevant in such a patient, it is actually uncommon in patients who are being treated for pain (see Chapter 31: Opioid Analgesics & Antagonists). Some states have recognized the underutilization of pain medications in the treatment of pain associated with chronic and terminal conditions. California, for example, has enacted an "intractable pain treatment" act that reduces the difficulty of renewing prescriptions for opioids. Under the provisions of this act, upon receipt of a copy of the order from the prescriber, eg, by fax, a pharmacist may write a "triplicate" prescription* for a Schedule II substance for a patient under hospice care or living in a skilled nursing facility or in cases where the patient is expected to live less than 6 months; the word "exemption" with regulatory code number is written on a typical prescription, thus providing easier access for the terminally ill.

* The "triplicate" is the special California prescription form required for Schedule II substances.

Labeled & Unlabeled Uses of Drugs

In the USA, the FDA approves a drug only for the specific uses proposed and documented by the manufacturer in its New Drug Application (NDA; see Chapter 5: Basic & Clinical Evaluation of New Drugs). These approved (labeled) uses or indications are set forth in the package insert that accompanies the drug. For a variety of reasons, these labeled indications may not include all the conditions in which the drug might be useful. Therefore, a clinician may wish to prescribe the agent for some other, unapproved (unlabeled) clinical condition, often on the basis of adequate or even compelling scientific evidence. Federal laws governing FDA regulations and drug use place no restrictions on such unapproved use.‡

‡"Once a product has been approved for marketing, a physician may prescribe it for uses or in treatment regimens or patient populations that are not included in the approved labeling. Such 'unapproved' or, more precisely, 'unlabeled' uses may be appropriate and rational in certain circumstances, and may, in fact, reflect approaches to drug therapy that have been extensively reported in medical literature."—FDA Drug Bull 1982;12:4.

Even if the patient suffers injury from the drug, its use for an unlabeled purpose does not in itself constitute "malpractice." However, the courts may consider the package insert labeling as a complete listing of the indications for which the drug is considered safe unless the clinician can show that other use is considered safe by competent expert testimony.

Katzung PHARMACOLOGY, 9e > Section X. Special Topics > Chapter 66. Rational Prescribing & Prescription Writing >

Who May Prescribe?*

The right to prescribe drugs and much of the legal responsibility for any harm that derives from the prescription were largely limited to just two groups in the past: physicians and osteopaths. In recent years, this power has diffused and now includes—in a number of states and in varying degrees— pharmacists, nurse practitioners, physician's assistants, and optometrists (see Table 66–2). This development began with the growth of a sense of independence within different health professions and was actively promoted by their professional societies. The more recent development of large health maintenance organizations has greatly strengthened the movement because it offers these extremely powerful economic bodies a way to reduce their expenses.

Table 66–2. Prescribing Authority of Certain Allied Health Professionals in Selected States.

1Under protocol: see Who May Prescribe.

2In collaboration with or under the supervision of a physician.

For example, under a plan of pharmacist care, a patient diagnosed as asthmatic by a physician might be referred to a pharmacist for coordination and follow-up of therapy. The pharmacist would be responsible for generating a problem list, prescribing and dispensing the appropriate drugs after consultation with the physician, educating the patient with regard to his or her disease and medications, and then following the patient's responses to the medications by means of appropriate tests (peak airflow metering, etc).

The primary organizations controlling the privilege of prescribing in the USA are the state boards, under the powers delegated to them by the state legislatures. As indicated in Table 66–2, many state boards have attempted to reserve some measure of the primary responsibility for prescribing to physicians by requiring that the ancillary professional work with or under a physician according to a specific "protocol." In the state of California, this protocol must include a statement of the training, supervision, and documentation requirements of the arrangement and must specify referral requirements, limitations to the list of drugs that may be prescribed (ie, a formulary), and a method of evaluation by the supervising physician. The protocol must be in writing and must be periodically updated (An Explanation of the Scope of RN Practice, 1994).

* This Section Prepared with the Assistance of Ronda Malone, PharmD.

Socioeconomic Factors

Generic Prescribing

Prescribing by generic name offers the pharmacist flexibility in selecting the particular drug product to fill the order and the patient a potential savings if there is price competition. The brand name of a popular sedative is, for example, Valium by Roche. The generic (public nonproprietary) name of the same chemical substance adopted by United States Adopted Names (USAN) and approved by the Food and Drug Administration (FDA) is diazepam. All diazepam drug products in the USA meet the pharmaceutical standards expressed in United States Pharmacopeia (USP). However, there are several manufacturers, and prices vary greatly. For some drugs in common use, the difference in cost between the trade-named product and generic products varies from less than twofold to more than 100-fold.

In most states and in many hospitals, pharmacists have the option of supplying a generically equivalent drug product even if a proprietary name has been specified in the order. If the physician wants a particular brand of drug product dispensed, handwritten instruction to "dispense as written" or words of similar meaning are required. Some government-subsidized health care programs and many third-party insurance payers require that pharmacists dispense the cheapest generically equivalent product in the inventory. However, the principles of drug product selection by private

pharmacists do not permit substituting one therapeutic agent for another (therapeutic substitution)— ie, dispensing trichlormethiazide for hydrochlorothiazide would not be permitted without the prescriber's permission even though these two diuretics may be considered pharmacodynamically equivalent. Pharmacists within managed care organizations may follow different policies; see below.

It should not be assumed that every generic drug product is as satisfactory as the trade-named product, though most generics are satisfactory. Bioavailability—the effective absorption of the drug product—varies between manufacturers and sometimes between different lots of a drug produced by the same manufacturer. In the case of a very small number of drugs, which usually have a low therapeutic index, poor solubility, or a high ratio of inert ingredients to active drug content, a specific manufacturer's product may give more consistent results. In the case of life-threatening diseases, the advantages of generic substitution are probably outweighed by the clinical urgency so that the prescription should be filled as written.

In an effort to codify bioequivalence information, the FDA publishes Approved Drug Products With Therapeutic Equivalence Evaluations, with monthly supplements, commonly called "the Orange Book." The book contains listings of multisource products in one of two categories: Products coded "A" are considered bioequivalent to all other versions of that product with a similar "A" coding. Products not considered bioequivalent are coded "B." Of the approximately 8000 products listed, 90% are coded "A."

Mandatory drug product selection on the basis of price is common practice in the USA as thirdparty payers (insurance companies, health maintenance organizations, etc) enforce money-saving regulations. If outside a managed care organization, the prescriber can sometimes override these controls by writing "dispense as written" on a prescription that calls for a brand-named product.

However, in such cases, the patient may have to pay the difference between the dispensed product and the cheaper one.

Within most managed care organizations, formulary controls have been put in place that force the selection of less expensive medications whenever they are available. In a managed care environment, the prescriber often selects the drug group rather than a specific agent, and the pharmacist dispenses the formulary drug from that group. For example, if a prescriber in such an organization decides that a patient needs a thiazide diuretic, the pharmacist will automatically dispense the single thiazide diuretic carried on the organization's formulary.

Other Cost Factors

The private pharmacy bases its charges on the cost of the drug plus a fee for providing a professional service. Each time a prescription is dispensed, there is a fee. The prescriber controls the frequency of filling prescriptions by authorizing refills and specifying the quantity to be dispensed. Thus, the prescriber can save the patient money by prescribing standard sizes (so that drugs do not have to be repackaged) and, when chronic treatment is involved, by ordering the largest quantity consistent with safety, expense, and third-party plan. Optimal prescribing for cost savings often involves consultation between the prescriber and the pharmacist. Because of continuing increases in the wholesale prices of drugs in the USA, prescription costs have risen dramatically over the past 3 decades (see The Cost of Prescriptions).

The Cost of Prescriptions

The cost of prescriptions has risen dramatically in the last several decades. The average price for a single prescription in the USA in 2003 was more than $50.00. This rise is occasioned by new technology, marketing costs, and stockholder expectations. The pharmaceutical industry typically posts double-digit profits annually while the retail business sector shows a 3% profit. The cost to the patient for many new drugs like "statins" exceeds $1000 per year. Pharmaceuticals are the highest out-of-pocket health-related cost for the health sector because many other health care services are covered by health insurance whereas prescriptions are often not.

These high drug costs have caused payers and consumers alike to seek alternative sources or to ask the government to subsidize personal pharmaceutical needs. Because the Canadian government has done a better job in controlling drug prices, their prices are less than those in the United States. This fact has caused a number of United States citizens to purchase their drugs "off-shore" for "personal use" in quantities up to a 3-month supply—at substantial savings. However, there is no assurance that these drugs are what they are purported to be or that they will be delivered in a timely manner—or that there is a traditional doctor-pharmacist-patient relationship and the safeguards that such a relationship offers. Pharmacists and physicians are asking the question: Why can't we purchase drugs at "off-shore" prices and thus lower the overall cost to the patients? The Veterans Administration system for controlling costs through bulk purchases of drugs and serious negotiation of prices with manufacturers shows that it is possible.

Appendix I: Vaccines, Immune Globulins, & Other Complex

Biologic Products

Vaccines, Immune Globulins, & Other Complex Biologic Products: Introduction

Vaccines and related biologic products constitute an important group of agents that bridge the disciplines of microbiology, infectious diseases, immunology, and immunopharmacology. A listing of the most important preparations is provided here. The reader who requires more complete information is referred to the sources listed at the end of this appendix.

Katzung PHARMACOLOGY, 9e > Section X. Special Topics > Appendix I: Vaccines, Immune Globulins, & Other Complex Biologic Products >

Active Immunization

Active immunization consists of the administration of antigen to the host to induce formation of antibodies and cell-mediated immunity. Immunization is practiced to induce protection against many infectious agents and may utilize either inactivated (killed) materials or live attenuated agents (Table I–1). Desirable features of the ideal immunogen include complete prevention of disease, prevention of the carrier state, production of prolonged immunity with a minimum of immunizations, absence of toxicity, and suitability for mass immunization (eg, cheap and easy to administer). Active immunization is generally preferable to passive immunization—in most cases because higher antibody levels are sustained for longer periods of time, requiring less frequent immunization, and in some cases because of the development of concurrent cell-mediated immunity. However, active immunization requires time to develop and is therefore generally inactive at the time of a specific exposure (eg, for parenteral exposure to hepatitis B, concurrent hepatitis B IgG [passive antibodies] and active immunization are given to prevent illness).

Table I–1. Materials Commonly Used for Active Immunization in the United States.1