Basic Principles of Pharmacology

At the completion of this chapter the reader should be able to do the following:

1. Describe the regulation of pharmaceuticals, including the management of prescription and nonprescription medication in an athletic training facility

2. Describe the basics of pharmaceutics and pharmacokinetics including dosage forms, routes of administration, and drug storage

3. Access various drug information resources to obtain more information about a drug

Introduction

This chapter introduces the reader to the regulatory, pharmacological, and pharmaceutical information that athletic trainers or other allied health professionals must be familiar with and understand. Important regulatory agencies discussed include the U.S. Food and Drug Administration (FDA), the U.S. Drug Enforcement Administration (DEA), and the National Collegiate Athletic Association (NCAA). The basic principles of pharmacology cover pharmacokinetics, routes of administration, drug storage and resources, pharmacodynamics, indications and contraindications, and special considerations for athletes. Drug information resources also are reviewed and include web-based and mobile options. This chapter is designed as an overview and lists additional sources for continued reading and expanded content. Information about specific drug classifications is found in Chapter 5.

Regulation of Pharmaceuticals

It is important for athletic trainers to understand the legal regulations that apply to the use of medications. Two entities of the U.S. federal government are charged to control the use of pharmaceutical products: the Food and Drug Administration (FDA) and the Drug Enforcement Administration (DEA). The agency in Canada equivalent to the FDA is the Canadian Health Products and Food Branch (HPFB). The HPFB is responsible for regulating food and health products, including pharmaceuticals, biological agents, and genetic therapies.¹ The HPFB is one of nine branches of Health Canada, which all report to the deputy and associate deputy ministers of health.

Drug Enforcement Administration

The DEA lies within the Department of Justice. Its function is to ensure compliance with the Controlled Substances Act of 1970 and implement the regulations found in Title 21, Code of Federal Regulations, Part 1300 to the end. The DEA registers health care practitioners who will be prescribing or dispensing those drugs that are considered controlled substances and advises them on compliance with controlled substance regulations.

Controlled substances are drugs that have a high potential for abuse (e.g., morphine and codeine). The DEA has established five categories or “schedules” of controlled substances (I-V). Table 4-1 lists drugs that are classified as controlled substances and are placed into one of these five categories on the basis of their likelihood for abuse.

TABLE 4-1

Drug Enforcement Administration Schedules of Controlled Substances

Schedule	Description	Examples of Drugs^∗
I	Drugs with no accepted medical use in the United States High abuse potential	Opium Hallucinogens (heroin, LSD, mescaline) Marijuana
II	Drugs with high abuse potential Severe psychic or physical dependence liability Tightly controlled prescribing requirements including written prescription (no verbal orders) from physician No refills without additional prescription from physician	Morphine Cocaine Oxycodone Oxycodone combination products (Percocet) Methamphetamine
III	Drugs with less abuse potential than those in schedule I or II	Benzphetamine Stimulants Depressants Clortermine Narcotic drugs Anabolic steroids
IV	Drugs with less abuse potential than those in schedule II	Barbital Phenobarbital Oxazepam
V	Drugs with less abuse potential than those in schedule IV Class consists of preparations containing limited quantities of certain narcotic ingredients generally for antitussive and antidiarrheal purposes	<200 mg of codeine or opium per 100 g

LSD, Lysergic acid diethylamide.

^∗Examples of drugs in each schedule do not represent an all-inclusive list.

Food and Drug Administration

The FDA is an agency of the U.S. Department of Health and Human Services. Its mission is to “promote and protect the public health by helping safe and effective products reach the market in a timely way and monitoring products for continued safety after they are in use.”²

The FDA is responsible for approving manufacturers who may produce medications for consumption, approving new chemical formulations for marketing and sale as either prescription or nonprescription such as over-the-counter products, and approving generic drug products that must exhibit bioequivalence to a brand-name product.

The FDA is also charged with determining how drugs may be marketed and sold in the United States, including a drug’s indications, information contained in the product’s package insert, and

KEY POINTS

BIOEQUIVALENCE

Bioequivalence is the quality of having the same drug strength and providing an equivalent amount of drug to the target tissue in the same dosage form as another sample of a given drug substance. For example, for two drugs to be considered bioequivalent, they must meet the following criteria:

• Have the same dosage form (e.g., tablet or suspension)

• Have the same drug strength

• Provide equivalent blood levels or tissue levels of the drug

how the drug is manufactured. Pharmaceutical product manufacturers must meet stringent manufacturing guidelines and pass FDA inspections. The drug products that they produce must consistently pass dissolution and bioequivalence tests. It is important to remember that the FDA does not oversee the marketing or sale of food supplements and herbal products, many of which are used by athletes, and neither does any other government agency.

Administration versus Dispensing

States have regulations that address both the administration and dispensing of drugs. It is important that the athletic trainer understand the differences between these two actions. Dispensing is the act of delivering a medication to an ultimate user pursuant to a medical order issued by a practitioner authorized to prescribe. This includes the packaging, labeling, or compounding necessary to prepare the medication for such delivery. Administration is the act of applying a medication by injection, inhalation, ingestion, or any other means to the body of a patient in a single dose.³

KEY POINTS

ADMINISTRATION VERSUS DISPENSING

• Administration is the direct application of a single dose of a drug.

• Dispensing is the act of delivering a medication to an ultimate user pursuant to a medical order issued by a practitioner authorized to prescribe.

• Facilities that dispense medications must have a Drug Enforcement Agency (DEA) certificate on file.

Both dispensing and administration require a written prescription from a physician. In some states, dispensing medications is beyond the scope of the athletic training profession. It is important that the athletic training facility comply with both state and federal regulations governing prescription medications.⁴ Some states require that an athletic training facility have a signed agreement with a physician allowing the athletic training staff to serve as agents of the physician in the care of the physician’s patients. At no time does the agent make any discretionary decisions about the administration or dosage of a medication.³ Prescription medications that may be used for on-the-field treatments must be secured and accessed only by the physician.⁴ Companies such as SportPharm, Inc. are used by several major colleges and universities as well as by professional athletic teams to help ensure compliance with state and federal regulations. The 50 states have different legislation about administration and dispensing of medications. The athletic trainer, team physician, and team pharmacist must work together to ensure that state and federal regulations are being met.

Pharmacology

Pharmacology is the study of drugs and includes pharmacokinetics and pharmacodynamics. Pharmacodynamics describes the actions of a drug on the body, including its mechanism of action and medicinal effect (i.e., the biochemical and physiological effects of the drug). This may involve a stimulatory or inhibitory reaction at the drug’s receptor type. Pharmacokinetics, on the other hand, describes how the body acts on the drug. Pharmacokinetics includes the absorption, distribution, metabolism, and elimination of the drug in the body.

To better understand how drugs work within the body, it is important to know the process by which a drug gets into the body, is distributed, is metabolized, and finally is eliminated from the body. The methods of absorption, distribution, metabolism, and elimination are discussed here.

KEY POINTS

PHARMACOKINETICS

• Absorption: Getting the drug into the body through a variety of routes, including oral, rectal, vaginal, intravenous, intramuscular, inhalation, and topical application to the skin

• Distribution: Delivering the drug throughout the tissues and fluids of the body; whether a drug is fat or water soluble is a factor; the medication’s ability to cross the blood–brain barrier will also affect distribution

• Metabolism: When the drug is changed into chemical entities in the body different from the parent drug

• Elimination: Getting the drug out of the body

Absorption is the process of getting a drug into the body. Drugs may be absorbed through various routes including via rectal, intestinal, and dermal tissue. Which route is used depends on many different patient-related and drug-related factors. Patient-related considerations include the patient’s age, level of consciousness, and disease being treated; drug-related factors include solubility and stability. The desired route of absorption will determine the formulation used. For example, rectal absorption will generally indicate using a suppository, but tablets, capsules, liquids, and suspensions may also be absorbed rectally.

Absorption exerts a major influence on the bioavailability of a drug. The bioavailability of a drug describes how much of the drug is available to the tissues after its administration. Bioavailability is an important concept in drug development, especially as it pertains to generic drugs. For any generic drug to be considered equivalent to a brand-name preparation, it must be demonstrated that its bioavailability is equal to that of the brand-name product.

Distribution refers to the process of moving the drug throughout the body. Most drugs are distributed throughout most or all of the body’s tissues, but this distribution is not necessarily even. For example, many drugs do not cross the blood–brain barrier to enter the central nervous system (CNS). Factors such as the drug’s pH, hydrophilicity (i.e., water solubility), and lipophilicity (i.e., fat solubility) will affect its distribution throughout the body. The concept of volume of distribution is used to describe the effective space in the body available to contain a drug. It is the ratio of the total amount of drug in the body to the plasma concentration of drug. Drugs with a high volume of distribution have lower plasma concentrations and are more greatly distributed into extravascular spaces. Drugs with a lower volume of distribution have higher plasma concentration and less distribution into extravascular tissues.

Metabolism is the complex process by which a drug is changed into one or more chemical entities that differ from the parent drug. These entities may be active metabolites that have a pharmacological effect or inactive metabolites with no pharmacological effect. Drug metabolism occurs primarily in the liver through the action of various hepatic enzymes, although some metabolism does occur in a few other tissues in the body (e.g., the lung).

Elimination is the process of getting a drug out of the body. A drug and its metabolites are eliminated through some combination of renal or fecal excretion. Although some drugs are completely eliminated either through renal or fecal excretion, most drugs and their metabolites undergo elimination through a combination of these two mechanisms. In individuals with renal or hepatic impairment, the rate of drug elimination will be slowed to a degree dependent on the level of impairment. This means that the dose of a drug or the frequency of taking the drug will often need to be adjusted in individuals with renal or hepatic dysfunction.

Two concepts used to describe the elimination of a drug from the body are clearance and half-life. Clearance is the measure of the body’s ability to eliminate a drug. It describes the volume of blood that is cleared of a drug over a given period of time, usually expressed as milliliters per minute. Drugs with a higher clearance rate will be removed from the body more quickly. Creatinine clearance is the rate of removal of creatinine from the serum into the urine. It is used as a measure of renal function. The normal creatinine clearance for men is 100 ml/min; for women it is 85 ml/min. In individuals with impaired renal function, it is important to know the creatinine clearance. In pharmaceutical reference books, dosage adjustments for renal impairment are given on the basis of creatinine clearance.

Half-life is the length of time that it takes for blood levels or tissue levels of a drug to decrease by one half. The clearance rate of a drug and the drug’s volume of distribution will determine the half-life of the drug. The half-life is directly proportional to the volume of distribution and inversely proportional to the clearance. This means that a drug with a high clearance rate and a small volume of distribution will have a short half-life and be eliminated from the body very quickly. A drug with a large volume of distribution and a low clearance rate will have a long half-life.

KEY POINTS

HALF-LIFE

The half-life of a drug describes the length of time it takes for the drug level to decrease by one half; it is determined by the volume of distribution and clearance rate (elimination) of the drug.

A drug’s half-life is one of the major factors determining how often the drug will be given. As a rule, a drug with a long half-life will have a long dosage interval. A drug with a short half-life will have a short dosage interval. If the clearance rate of a drug is decreased by renal or hepatic dysfunction, this will increase the half-life of the drug and necessitate an increase in the dosage interval. Individuals with an altered volume of distribution because of disease (e.g., ascites) also will have an altered drug half-life. It is important to know the effect of a disease on a drug’s half-life, so that changes in the dosage regimen may be made.

Routes of Administration

Drugs can enter the body through a variety of routes (Box 4-1), and these paths of administration promote the drug’s absorption. The oral route is certainly the most common for the administration of drugs, but often it is appropriate to use a parenteral (nonoral) route of administration. The preferred route is determined by multiple factors including ease of administration, patient adherence, desired onset of action, local versus systemic distribution, and properties of the drug itself. An example is the destruction of insulin in the gastrointestinal tract, which necessitates its administration through a nonoral route.

BOX 4-1 ROUTES OF DRUG ADMINISTRATION