Understanding the basics of pharmacology is an essential nursing responsibility. Pharmacology is the science that deals with the physical and chemical properties as well as the biochemical and physiologic effects of drugs. It includes the areas of pharmacokinetics, pharmacodynamics, pharmacotherapeutics, pharmacognosy, and toxicodynamics.

The Nurse’s Drug Handbook deals primarily with pharmacokinetics, pharmacodynamics, and pharmacotherapeutics—the information you need to administer safe and effective drug therapy (discussed as follows). Pharmacognosy is the branch of pharmacology that deals with the biological, biochemical, and economic features of naturally occurring drugs.

Toxicodynamics is the study of the harmful effects that excessive amounts of a drug produce in the body; in a drug overdose or drug poisoning, large drug doses may saturate or overwhelm normal mechanisms that control absorption, distribution, metabolism, and excretion.

Drug Nomenclature

Most drugs are known by several names—chemical, generic, trade, and official—each of which serves a specific function. (See How drugs are named.) However, multiple drug names can also contribute to medication errors. You may find a familiar drug packaged with an unfamiliar name if your institution changes suppliers or if a familiar drug is newly approved in a different dose or for a new indication.

Drug Classification

Drugs can be classified in various ways. Most pharmacology textbooks group drugs by their functional classification, such as psychotherapeutics, which is based on common characteristics. Drugs can also be classified according to their therapeutic use, such as antipanic or antiobsessional drugs. Drugs within a certain therapeutic class may be further divided into subgroups based on their mechanisms of action. For example, the therapeutic class antineoplastics can be further classified as alkylating agents, antibiotic antineoplastics, antimetabolites, antimitotics, biological response modifiers, antineoplastic enzymes, and hormonal antineoplastics.

Pharmacokinetics

Pharmacokinetics is the study of a drug’s actions—or fate—as it passes through the body during absorption, distribution, metabolism, and excretion.

ABSORPTION

Before a drug can begin working, it must be transformed from its pharmaceutical dosage form to a biologically available (bioavailable) substance that can pass through various biological cell membranes to reach its site of action. This process is known as absorption. A drug’s absorption rate depends on its route of administration, its circulation through the tissue into which it is administered, and its solubility—that is, whether it is more water soluble (hydrophilic) or fat soluble (lipophilic).

Although drugs may penetrate cellular membranes either actively or passively, most drugs do so by passive diffusion, moving inertly from an area of higher concentration to an area of lower concentration. Passive diffusion may occur through water or fat. Passive diffusion through water—aqueous diffusion—occurs within large water-filled compartments, such as interstitial spaces, and across epithelial membrane tight junctions and pores in the epithelial lining of blood vessels. Aqueous diffusion is driven by concentration gradients. Drug molecules that are bound to large plasma proteins, such as albumin, are too large to pass through aqueous pores in this way. Passive diffusion through fat—lipid diffusion—plays an important role in drug metabolism because of the large number of lipid barriers that separate the aqueous compartments of the body. The tendency of a drug to move through lipid layers between aqueous compartments often depends on the pH of the medium—that is, the ability of the water-soluble or fat-soluble drug to form weak acid or weak base.

Drugs with molecules that are too large to readily diffuse may rely on active diffusion, in which special carriers on molecules, including amino acids, glucose, and peptides, transport the drug through the membranes. However, some molecules with selective membrane carriers can expel foreign drug molecules; this is why many drugs can’t cross the blood–brain barrier.

Drug absorption begins at the administration route. The three main administration route categories are enteral, parenteral, and transcutaneous. Depending on its nature or chemical makeup, a drug may be better absorbed from one site than from another.

Enteral Administration

Enteral administration consists of the oral, gastric or nasogastric, and rectal routes.

Oral: Drugs administered orally are absorbed in the GI tract and then proceed by the hepatic portal vein to the liver and into the systemic circulation. Although generally considered the preferred route, oral drug administration has several disadvantages:

• The oral route doesn’t always yield sufficiently high blood concentrations to be effective.
• Bioavailability may be less than optimal because of incomplete absorption and first-pass elimination (the part of metabolism that occurs during transit through the liver before the drug reaches the general circulation).
• Drug absorption may be incomplete if the drug is degraded by digestive enzymes or the acidic pH in the stomach or if it is excreted from the liver into the bile.
• Food in the GI tract, gastric emptying time, and intestinal motility may also impede drug absorption.

Gastric or nasogastric: Drugs administered through a gastric or nasogastric tube enter the stomach directly and are absorbed in the GI tract.

Rectal: Rectal drugs and suppositories also enter the GI tract directly after being inserted in the rectum and absorbed through the rectal mucosa. After being absorbed into the lower GI tract, rectal drugs enter the circulation through the inferior vena cava, bypassing the liver and thus avoiding first-pass metabolism. Suppositories, however, tend to travel upward into the rectum, where veins, such as the superior hemorrhoidal vein, lead to the liver. As a result, drug absorption by this route is often unreliable and difficult to predict.

Parenteral Administration

Parenteral routes may be used whenever enteral routes are contraindicated, inadequate, or unavailable. These routes include intramuscular (I.M.), intravenous (I.V.), subcutaneous (SubQ), and intradermal (I.D.) administration. Drug absorption is much faster and more predictable after parenteral administration than after enteral administration.

I.M.: Drugs administered by the I.M. route are injected deep into the muscle, where they’re absorbed relatively quickly. The rate of drug absorption depends on the vascularity of the injection site, the physiochemical properties of the drug, and the solution in which the drug is contained.

I.V.: I.V. drug administration involves injecting or infusing the drug directly into the blood circulation, allowing for rapid distribution throughout the body. This route usually provides the greatest bioavailability.

Subcutaneous: Drugs administered by the subcutaneous route are injected into the connective tissue just below the skin and are absorbed by simple diffusion from the injection site. The factors that affect I.M. absorption also affect subcutaneous absorption. Absorption by the subcutaneous route may be slower than by the I.M. route.

Intradermal: Drugs administered intradermally, such as purified protein derivative (PPD), are injected into the dermis, from which they diffuse slowly into the local microcapillary system.

Transcutaneous Administration

Transcutaneous drug administration allows drug absorption through the skin or soft-tissue surface. Drugs may be inhaled, inserted sublingually, applied topically, or administered to the eyes, ears, nose, or vagina.

Inhalation: Inhaled drugs may be given as a powder and aerosolized or mixed in solution and nebulized directly into the respiratory tract, where they’re absorbed through the alveoli. Inhaled drugs are usually absorbed quickly because of the abundant blood flow in the lungs, though some inhaled drugs have low systemic absorption.

Sublingual: Sublingual drug administration involves placing a tablet, troche, or lozenge under the tongue. The drug is absorbed across the epithelial lining of the mouth, usually quickly. This route avoids first-pass metabolism.

Topical: Topical drugs—creams, lotions, ointments, and patches—are placed on the skin and then cross the epidermis into the capillary circulation. They may also be absorbed through hair follicles, sweat glands, and other skin structures. Absorption by the skin is enhanced if the drug is in a solution.

Ophthalmic: Ophthalmic drugs include solutions and ointments that are instilled or applied directly to the cornea or conjunctiva as well as small, elliptical disks that are placed directly on the eyeball behind the lower eyelid. The movements of the eyeball promote distribution of these drugs over the surface of the eye. Although ophthalmic drugs produce a local effect on the conjunctiva or anterior chamber, some preparations may be absorbed systemically and therefore produce systemic effects.

Otic: Drops administered into the external auditory canal, otic drugs are used to treat infection or inflammation and to soften and remove ear wax. Otic solutions exert a local effect and may result in minimal systemic absorption with no adverse effects.

Nasal: Nasal solutions and suspensions are applied directly to the nasal mucosa by instillation or inhalation to produce local effects, such as vasoconstriction to reduce nasal congestion. Some nasal solutions, such as mometasone furoate monohydrate, are administered by this route specifically to produce systemic effects.

Vaginal: Vaginal drugs include creams, suppositories, and troches that are inserted into the vagina, sometimes using a special applicator. These drugs are administered locally to treat such conditions as bacterial and fungal infections.

DISTRIBUTION

Distribution is the process by which a drug is transported by the circulating fluids to various sites, including its sites of action. To ensure maximum therapeutic effectiveness, the drug must permeate all membranes that separate it from its intended site of action. Drug distribution is influenced by blood flow, protein binding, and tissue availability. Drugs that cannot distribute to the tissues in which they are needed are not effective.

METABOLISM

Drug metabolism is the enzymatic conversion of a drug’s structure into substrate molecules or polar compounds that are either less active or inactive and are readily excreted. Drugs can also be synthesized to larger molecules. Metabolism may also convert a drug to a more toxic compound. Because the primary site of drug metabolism is the liver, children, older people, and patients with impaired hepatic function are at risk for altered therapeutic effects.

Biotransformation is the process of changing a drug into its active metabolite. Compounds that require metabolic biotransformation for activation are known as prodrugs. During phase I of biotransformation, the parent drug is converted into an inactive or partially active metabolite. Much of the original drug may be eliminated during this phase. During phase II, the inactive or partially active metabolite binds with available substrates, such as acetic acid, glucuronic acid, sulfuric acid, or water, to form its active metabolite. When biotransformation leads to synthesis, larger molecules are produced to create a pharmacologic effect.

EXCRETION

The body eliminates drugs by both excretion and metabolism. Drug metabolites—and, in some cases, the active drug itself—are eventually excreted from the body, usually through bile, feces, and urine. The primary organ for drug elimination is the kidney. Impaired renal function may alter drug elimination, thereby altering the drug’s therapeutic effect. Other excretion routes include evaporation through the skin, exhalation from the lungs, and secretion into breast milk or salvia.

A drug’s elimination half-life is the amount of time required for half of the drug to be eliminated from the body. The half-life roughly correlates with the drug’s duration of action and is based on normal hepatic and renal function. Typically, the longer the half-life, the less often the drug has to be given and the longer it remains in the body.

Pharmacodynamics

Pharmacodynamics is the study of the biochemical and physiologic effects of drugs and their mechanisms of action. A drug’s actions may be structurally specific or nonspecific. Structurally specific drugs combine with cell receptors, such as glycoproteins or proteins, to enhance or inhibit cellular enzyme actions. Drug receptors are the cellular components affected at the site of action. Many drugs form chemical bonds with drug receptors, but a drug can bond with a receptor only if it has a similar shape—much the same way that a key fits into a lock. When a drug combines with a receptor, channels are either opened or closed and cellular biochemical messengers, such as calcium or cyclic adenosine monophosphate ions, are activated. Once activated, cellular functions can be turned either on or off by these messengers.

Structurally nonspecific drugs, such as biological response modifiers, don’t combine with cell receptors; rather, they produce changes within the cell membrane or interior.

The mechanisms by which drugs interact with the body are not always known. Drugs may work by physical action (such as the protective effects of a topical ointment), by chemical reaction (such as an antacid’s effect on the gastric mucosa), by modifying the metabolic activity of invading pathogens (such as an antibiotic), or by replacing a missing biochemical substance (such as insulin).

AGONISTS

Agonists are drugs that interact with a receptor to stimulate a response. They alter cell physiology by binding to plasma membranes or intracellular structures. Partial agonists can’t achieve maximal effects even though they may occupy all available receptor sites on a cell. Strong agonists can cause maximal effects while occupying only a small number of receptor sites on a cell. Weak agonists must occupy many more receptor sites than strong agonists to produce the same effect.

ANTAGONISTS

Antagonists are drugs that attach to a receptor but don’t stimulate a response; instead, they inhibit or block responses that would normally be caused by agonists.

• Competitive antagonists bind to receptor sites that are also compatible with an agonist, thus preventing the agonist from binding to the site.
• Noncompetitive antagonists bind to receptor sites that aren’t occupied by an agonist; this changes the receptor site so that it is no longer recognized by the agonist.
• Irreversible antagonists work in much the same way that noncompetitive ones do, except that they permanently bind with the receptor.

Antagonism plays an important role in drug interactions. When two agonists that cause opposite therapeutic effects are combined, such as a vasodilator and a vasoconstrictor, the effects cancel each other out. When two antagonists are combined, such as morphine and naloxone, both drugs may become inactive.

Pharmacotherapeutics

Pharmacotherapeutics is the study of how drugs are used to prevent or treat disease. Understanding why a drug is prescribed for a certain disease can assist you in prioritizing drug administration with other patient care activities. Knowing a drug’s desired and unwanted effects may help you uncover problems not readily apparent from the admitting diagnosis. This information may also help you prevent such problems as adverse reactions and drug interactions.

A drug’s desired effect is the expected or intended clinical response to the drug. This is the response you start to evaluate as soon as a drug is given. Dosage adjustments and the continuation of therapy often depend on your accurate evaluation and documentation of the patient’s response.

An adverse reaction is any noxious and unintended response to a drug that occurs at therapeutic doses used for prophylaxis, diagnosis, or therapy. Adverse reactions associated with excessive amounts of a drug are considered drug overdoses. Be prepared to follow your institution’s policy for reporting adverse drug reactions.

An idiosyncratic response is a genetically determined abnormal or excessive response to a drug that occurs in a particular patient. The unusual response may indicate that the drug has saturated or overwhelmed mechanisms that normally control absorption, distribution, metabolism, or excretion, thus altering the expected response. You may be unsure whether a reaction is adverse or idiosyncratic. Once you report the reaction, the prescriber usually determines the appropriate course of action.

An allergic reaction is an adverse response that results from previous exposure to the same drug or to one that’s chemically similar to it. The patient’s immune system reacts to the drug as if it were a foreign invader and may produce a mild hypersensitivity reaction, characterized by localized dermatitis or photosensitivity. Allergic reactions should be reported to the prescriber immediately as some reactions may become serious or even life-threatening, requiring the drug to be discontinued. Follow-up care may include giving drugs, including antihistamines and corticosteroids, to counteract the allergic response.

An anaphylactic reaction involves an immediate hypersensitivity response characterized by angioedema, pruritus, and urticaria. Left untreated, an anaphylactic reaction can lead to systemic involvement, resulting in shock. It is often associated with life-threatening hypotension and respiratory distress. Be prepared to assist with emergency life-support measures, especially if the reaction occurs in response to I.V. drugs, which have the fastest rate of absorption.

A drug interaction occurs when one drug alters the pharmacokinetics of another drug—for example, when two or more drugs are given concurrently. Such concurrent administration can decrease or increase the therapeutic or adverse effects of either drug. Some drug interactions are beneficial. For example, when taken with penicillin, probenecid decreases the excretion rate of penicillin, resulting in higher blood levels of penicillin. Drug interactions also may occur when a drug’s metabolism is altered, often owing to the induction of or competition for metabolizing enzymes. For example, H₂-receptor agonists, which reduce secretion of the enzyme gastrin, may alter the breakdown of enteric coatings on other drugs. Drug interactions due to carrier protein competition typically occur when a drug inhibits the kidneys’ ability to reduce excretion of other drugs. For example, probenecid is completely reabsorbed by the renal tubules and is metabolized very slowly. It competes with the same carrier protein as sulfonamides for active tubular secretion and decreases the renal excretion of sulfonamides. This particular competition can lead to an increased risk of sulfonamide toxicity.

Special Considerations

Although every drug has a usual dosage range, certain factors such as a patient’s age, weight, culture and ethnicity, gender, pregnancy status, and hepatic and renal function may contribute to the need for dosage adjustments. When you encounter special considerations such as these, be prepared to reassess the prescribed dosage to make sure that it is safe and effective for your patient.

CULTURE AND ETHNICITY

Certain drugs are more effective or more likely to produce adverse effects in particular ethnic groups or races. For example, Asian patients being treated for hyperlipidemia with rosuvastatin require a smaller dose to decrease the risk of adverse reactions, while African Americans have an increased risk of developing angioedema with ACE inhibitors. A patient’s cultural or religious background also may call for special consideration. For example, a drug made from porcine products may be unacceptable to a Jewish or Muslim patient.

ELDERLY PATIENTS

Because aging produces certain changes in body composition and organ function, older patients present unique therapeutic and dosing problems that require special attention. For example, the weight of the liver, the number of functioning hepatic cells, and hepatic blood flow all decrease as a person ages, resulting in slower drug metabolism. Renal function may also decrease with aging. These processes can lead to the accumulation of active drugs and metabolites as well as increased sensitivity to the effects of some drugs in older patients. Because they’re also more likely to have multiple chronic illnesses, many older patients take multiple prescription drugs each day, thus increasing the risk of drug interactions.

CHILDREN

Because their bodily functions aren’t fully developed, children—particularly those under age 12—may metabolize drugs differently than do adults. In infants, immature hepatic and renal functions delay metabolism and excretion of drugs. As a result, pediatric drug dosages are very different from adult dosages.

The FDA has provided drug manufacturers with guidelines that define pediatric age categories. Unless the manufacturer provides a specific age range, use these categories as a guide when administering drugs:

• neonates—birth up to age 1 month
• infants—ages 1 month to 2 years
• children—ages 2 to 12
• adolescents—ages 12 to 16

CHILDBEARING CONSIDERATIONS

The many physiologic changes that take place in the body during the childbearing process may affect a drug’s pharmacokinetics and alter its effectiveness. In addition, exposure to drugs may pose risks for the developing fetus. Before administering a drug to a pregnant patient, be sure to check the new more comprehensive text for drugs and intervene appropriately.