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PART ONE Pharmacology Basicsdeterioration of at least one of the drugs when the two substances are mixed together. (p. 37)
Medication error (ME) Any preventable ADE involving inappropriate drug use by a patient or health care pro- vider; it may or may not cause patient harm. (p. 38)
Medication use process The prescribing, dispensing, and administering of drugs, and the monitoring of their effects. (p. 38)
Metabolite A chemical form of a drug that is the product of one or more biochemical (metabolic) reactions involv- ing the parent drug. (p. 22)
Onset of action The time required for a drug to elicit a therapeutic response after dosing. (p. 33)
Parent drug The chemical form of a drug that is admin- istered before it is metabolized by the body’s biochemical reactions into its active or inactive metabolites. (p. 22)
Peak effect The time required for a drug to reach its max- imum therapeutic response in the body. (p. 33)
Peak level The maximum concentration of a drug in the body after administration, usually measured in a blood sample for therapeutic drug monitoring. (p. 33)
Pharmaceutics The science of preparing and dispensing drugs, including dosage form design (e.g., tablets, cap- sules, injections, patches, etc.). (p. 22)
Pharmacodynamics The study of the biochemical and physiological interactions of drugs at their sites of activ- ity. (p. 22)
Pharmacogenetics The study of the influence of genetic factors on drug response, including the nature of genetic aberrations that result in the absence, overabundance, or insufficiency of drug-metabolizing enzymes; also called
pharmacogenomics. (p. 38)
Pharmacognosy The study of drugs that are obtained from natural plant and animal sources. (p. 22)
Pharmacokinetics The rate of drug distribution among body compartments after a drug has entered the body. (p. 22)
Pharmacology Broadest term for the study or science of drugs. (p. 21)
Pharmacotherapeutics The treatment of pathological conditions through the use of drugs. (p. 22)
Prodrug An inactive drug dosage form that is converted to an active metabolite by biochemical reactions once it is inside the body. (p. 22)
Receptor A molecular structure within or on the outer surface of cells to which specific substances (e.g., drug molecules) bind. One or more corresponding cellular effects (drug effects) occur as a result of this drug–receptor interaction. (p. 22)
Steady state The physiological state in which the amount of drug removed via elimination is equal to the amount of drug absorbed with each dose. (p. 33)
Substrate A substance (e.g., drug or natural biochemical in the body) on which an enzyme acts. (p. 30)
Chemical name The name that describes the chemical composition and molecular structure of a drug. (p. 21)
Contraindication Any condition, especially one related to a disease state or other patient characteristic, including current or recent drug therapy, that renders a particular form of treatment improper or undesirable. (p. 35)
Cytochrome P450 General name for a large class of enzymes (found especially in the liver) that play a signifi- cant role in drug metabolism. (p. 30)
Dissolution The process by which solid forms of drugs disintegrate in the gastrointestinal tract, become soluble, and are absorbed into the circulation. (p. 22)
Drug Any chemical that affects the physiological processes of a living organism. (p. 21)
Drug actions The cellular processes involved in the inter- action between a drug and cell (e.g., the action of a drug on a receptor); also referred to as mechanism of action. (p. 22)
Drug effects The physiological reactions of the body to a drug. (p. 33)
Drug-induced teratogenesis The development of con- genital anomalies or defects in the developing fetus that are caused by the toxic effects of drugs. (p. 39)
Drug interaction Alteration of the pharmacological activity of a given drug caused by the presence of one or more addi- tional drugs; it is usually related to effects on the enzymes required for metabolism of the involved drugs. (p. 37)
Duration of action The length of time in which the con- centration of a drug in the blood or tissues is sufficient to elicit a therapeutic response. (p. 33)
Enzymes Protein molecules that catalyze one or more of a variety of biochemical reactions, including those related to the body’s own physiological processes as well as those related to drug metabolism. (p. 34)
Evidence-informed practice (EIP) Continuous interactive process involving the explicit, conscious, and judicious consideration of the best research evidence available to make collaborative decisions between the health care team and the patient and family when providing patient care. (p. 41)
First-pass effect The initial metabolism in the liver of a drug absorbed from the gastrointestinal tract before the drug reaches the systemic circulation through the blood- stream. (p. 24)
Generic name The name given to a drug approved by Health Canada; also called the nonproprietary name or the
official name. (p. 21)
Half-life In pharmacokinetics, the time required for one half of an administered dose of drug to be eliminated by the body; also called elimination half-life. (p. 32)
Idiosyncratic reaction An abnormal and unexpected response to a drug, other than an allergic reaction, that is peculiar to an individual patient. (p. 38)
Incompatibility The quality of two parenteral drugs or solutions that leads to a reaction resulting in chemical
Pharmacological Principles CHAPTER 2
21
Toxic The quality of being poisonous (i.e., injurious to health or dangerous to life). (p. 22)
Toxicity The condition of producing adverse bodily effects because of poisonous qualities. (p. 33)
Toxicology The study of the effects of drugs, poisons, and other chemicals in living systems, their detection, and treatments to counteract their poisonous effects. (p. 22)
Trade name The commercial name given to a drug prod- uct by its manufacturer; also called the proprietary name. (p. 21)
Trough level The lowest concentration of a drug reached in the body after it falls from the peak level, usually meas- ured in a blood sample for therapeutic drug monitoring. (p. 33)
O V E R V I E W
Any chemical that affects the processes of a living organ- ism can broadly be defined as a drug. The study or sci- ence of drugs is known as pharmacology. This study may incorporate knowledge from a variety of areas: • Absorption • Biochemical effects • Biotransformation (metabolism) • Distribution • Drug history • Drug origin
• Drug receptor mechanisms • Excretion
• Mechanisms of action
• Physical and chemical properties • Physical effects
• Therapeutic (beneficial) effects • Toxic (harmful) effects
Knowledge of these areas of pharmacology enables the nurse to better understand how drugs affect humans. Without a sound understanding of basic pharmaco- logical principles, the nurse cannot fully appreciate the therapeutic benefits and potential toxicity of drugs.
Pharmacology is an extensive science that incorpor- ates several interrelated sciences: pharmaceutics, phar- macokinetics, pharmacodynamics, pharmacotherapeutics, pharmacognosy, and toxicology. The drugs discussed in each chapter of this text are described from the stand- point of one or more of these six areas.
Synergistic effects Drug interactions in which the effect of a combination of two or more drugs with similar actions is greater than the sum of the individual effects of the same drugs given alone (compare with additive effects). (p. 37)
Therapeutic drug monitoring The process of measuring drug peak and trough levels to gauge the level of a patient’s drug exposure and allow adjustment of dosages with the joint goals of maximizing therapeutic effects and minimiz- ing toxicity. (p. 34)
Therapeutic effect The desired or intended effect of a particular drug. (p. 34)
Therapeutic index The ratio between the toxic and thera- peutic concentrations of a drug. (p. 36)
Throughout the process of development, a drug will acquire at least three different names. The chemical name describes the drug’s chemical composition and molecular structure. The generic name, or nonpropri- etary name, is given to the drug and approved by Health Canada under the Food and Drugs Act and Food and Drug Regulations. It is often much shorter and simpler than the chemical name. The generic name is used in most official drug compendiums to list drugs. The trade name, or proprietary name, indicates that the drug has a registered trademark and that its commercial use is restricted to the owner of the patent for the drug until the patent expires. The owner is usually the manufac- turer of the drug. Trade names are generally created by the manufacturer with marketability in mind. For this reason, trade names are usually shorter and easier to pro- nounce and remember than generic names. The company that researches and manufactures the drug retains sole rights to sell the drug without competition for a specified number of years owing to patent protection. The patent life of a newly discovered drug molecule in Canada is 20 years from the time of filing. After the patent period expires, competing manufacturers may produce and sell generic versions of the drug with the same active ingredi- ents. At this point, the price of the drug usually falls substantially, which offers many patients and third-party payers the benefits of savings on the generic (versus the original brand-name) drug (Figure 2-1).
Three basic phases of drug activity—pharmaceutics, pharmacokinetics, and pharmacodynamics—describe
CH CH CH3 CH2 CH3 CH3 COOH Chemical name
(⫹/⫺)-2-(p-isobutylphenyl) propionic acid Generic name
ibuprofen Trade name Motrin, others
FIG. 2-1 Chemical structure of the common analgesic ibuprofen and the chemical, generic, and trade names for the drug.
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PART ONE Pharmacology Basicsconsidered to be relatively minor but are expected to occur in a percentage of the population receiving a given drug. The severity of effects occurs on a continuum. More ser- ious adverse effects may result in changes in prescribed drug therapy after weighing the risk-to-benefit ratio of a drug in a specific clinical situation. Toxic effects are often an extension of a drug’s therapeutic action. Therefore, toxicology often involves overlapping principles of both pharmacotherapy and toxicology.
The study of natural (versus synthetic) drug sources (both plants and animals) is called pharmacognosy. This science was formerly called materia medica (medicinal materials) and is concerned with the botanical or zoological origin, biochemical composition, and therapeutic effects of nat- ural drugs, their derivatives, and their constituents.
In summary, pharmacology is a dynamic science incorporating several different disciplines. Traditionally, chemistry has been seen as the primary basis of pharma- cology, but pharmacology also relies heavily on physiol- ogy and biology.
P H A R M A C E U T I C S
Different drug dosage forms have different pharma- ceutical properties. Dosage form design determines the rate at which a drug undergoes dissolution (dissolving of solid dosage forms and their absorption [e.g., from the relationship between the dose of a drug given to
a patient and the effectiveness of that drug in treating the patient’s disorder. Pharmaceutics includes the study of how different dosage forms (e.g., injection, capsule, controlled-release tablet) influence the way in which the body metabolizes a drug and the way in which the drug affects the body. Pharmacokinetics includes the study of what the body does to the drug molecules. It includes the phases of absorption, distribution, metabolism, and excretion of drugs. These four phases and their rela- tionship to drug and drug metabolite concentrations are determined for different body sites over specified periods. A metabolite is the product of one or more biochemical (metabolic) reactions involving the parent drug (the original drug administered). A parent drug that is not pharmacologically active is called a prodrug. A prodrug is then metabolized to pharmacologically active metabolites. Often, a prodrug is more readily absorbed than its active metabolite, hence the need for its develop- ment. Inactive metabolites lack pharmacological activity and are simply drug waste products awaiting excretion from the body (e.g., via the urinary, gastrointestinal, or respiratory tract). The onset of action, the peak effect of a drug, and the duration of action of a drug are all part of the drug’s pharmacokinetics.
Pharmacodynamics, on the other hand, is the study of what the drug does to the body. It examines the physico- chemical properties of drugs and their pharmacological interactions with body receptors. Receptors are special- ized protein molecules embedded in the outer surfaces of cells or within cells to which drug molecules bind to exert their effects. Receptor theory assumes that all drugs perform their unique actions at chemically specific recep- tor sites in various tissues. Not all mechanisms of action, however, have been identified for all drugs. Thus, a drug may be said to have an unknown or unclear mechan- ism of action, even though it has observable therapeutic effects in the body. Figure 2-2 illustrates the three phases that affect drug activity, starting with the pharmaceutical phase, proceeding to the pharmacokinetic phase, and finishing with the pharmacodynamic phase.
Pharmacotherapeutics (also called therapeutics) focuses on the use of drugs and the clinical indications for administering drugs to prevent and treat diseases. It defines the principles of drug actions—the cellular processes that change in response to the presence of drug molecules. Therefore, an understanding of pharmaco- therapeutics is essential for nurses when implementing drug therapy. Empirical therapeutics refers to drug therapy that is effective but for which the mechanism of drug action is unknown. Rational therapeutics is drug therapy in which specific evidence has been obtained for the mechanisms of drug action. Recall that some drug mech- anisms of action are more clearly understood than others.
The study of the adverse effects of drugs and other chemicals on living systems is known as toxicology. An adverse effect is a direct response to one or more drugs that results in an undesirable effect. These effects are generally
Dose of formulated drug Pharmaceutical phase Administration Pharmacokinetic phase Disintegration of dosage form Dissolution of drug Drug available for absorption Absorption, distribution, metabolism, excretion Drug available for action Pharmacodynamic phase Effect I II III Drug–receptor interaction
FIG. 2-2 Phases of drug activity. From McKenry, L. M., Tessier, E., & Hogan, M. (2006). Mosby’s pharmacology
Pharmacological Principles CHAPTER 2
23
Many topically applied dosage forms work directly on the surface of the skin. Therefore, when the drug is applied, it is already in a dosage form that allows it to act immediately. With other topical dosage forms, the skin acts as a barrier through which the drug must pass to get to the circulation; once there, the drug is carried to the site of action (e.g., fentanyl transdermal patch for pain).
Dosage forms administered via injection are called parenteral forms. They must have certain characteristics to be safe and effective. The arteries and veins that carry drugs throughout the body can easily be damaged if the drug is too concentrated or corrosive. The pH of injections must be similar to the blood to be safely administered. Parenteral dosage forms that are injected intravenously or intra-arterially are immediately placed into solution in the bloodstream and do not have to be dissolved in the body. Therefore, 100% absorption is assumed to occur immediately upon intravenous or intra-arterial injection. The intra-arterial route is used much less commonly than the intravenous route but may be used in critical care units and oncology care settings.
P H A R M A C O K I N E T I C S
A particular drug’s onset of action, peak effect, and dur- ation of action are all characteristics defined by pharma- cokinetics. Pharmacokinetics is the study of what actually happens to a drug from the time it is put into the body until the parent drug and all metabolites have left the body. Thus, drug absorption into, distribution and metabolism within, and excretion from a living organism represent the combined focus of pharmacokinetics.
Absorption
Absorption is the movement of a drug from its site of administration into the bloodstream for distribution to the tissues. A term used to express the extent of drug absorption is bioavailability. For example, a drug that is absorbed from the gastrointestinal tract travels via the venous portal system to the liver before it reaches the systemic circulation. If the drug is metabolized in gastrointestinal tract fluids]). A drug to be ingested orally
may be taken in either a solid form (tablet, capsule, or powder) or a liquid form (solution or suspension). Table 2-1 lists some drug preparations and the relative rate at which they are absorbed. Oral drugs that are liquids (e.g., elixirs, syrups) are already dissolved and are usually absorbed more quickly than solid dosage forms. Enteric-coated tablets, by contrast, have a coating that prevents them from being broken down in an acidic pH environment and thus are not absorbed until they reach the higher (more alkaline) pH of the intestines. This pharmaceutical property results in slower dissolu- tion and slower absorption. Sometimes the size of the particles within a capsule can make different capsules containing the same drug dissolve at different rates, become absorbed at different rates, and thus have dif- ferent onsets of action. A prime example of this is the difference between micronized (meaning tiny particles) and nonmicronized forms of a drug. The micronized formulation of the lipid-modifying drug fenofibrate, for example,reaches a maximum concentration peak faster than would a nonmicronized formulation because of how the dosage form is pharmaceutically engineered.
A variety of dosage forms exist to provide both accur- ate and convenient drug delivery systems (Table 2-2). These delivery systems are designed to achieve a desired therapeutic response with minimal adverse effects. Many dosage forms have been developed to encourage patient adherence with the medication regime. Convenience of administration correlates strongly with medication adherence. Many of the extended-release oral dosage forms were designed with this in mind as they often require fewer daily doses.
The specific characteristics of the different dosage forms have a large impact on how and to what extent the drug is absorbed. If a drug is to work at a specific site in the body, it must either be applied directly at that site in an active form or have a way of getting to that site. Enteral (sys- temic) administration refers to drugs administered via the gastrointestinal tract. Oral dosage forms rely on gastric and intestinal enzymes and pH environments to break the medication down into particles that are small enough to be absorbed into the circulation. Once absorbed through the mucosa of the stomach or intes- tines, the drug is then transported to the site of action by blood or lymph.
TABLE
2-1
Drug Absorption of Various Oral Preparations Liquids, elixirs, and syrups Fastest Suspension solutions
Powders Capsules Tablets Coated tablets
Enteric-coated tablets Slowest
TABLE
2-2
Dosage Forms
Route Forms
Enteral Tablets, capsules, pills, timed-release capsules, sublingual or buccal tablets, elixirs, suspensions, syrups, timed-release tablets, enteric-coated tablets, emulsions, solutions, lozenges or troches, caplets, suppositories (rectal), pessary (vaginal) Parenteral Injectable forms, solutions, suspensions, emulsions, powders for reconstitution Topical Aerosols, sprays, ointments, creams,
pastes, powders, solutions, foams, gels, transdermal patches, inhalers
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PART ONE Pharmacology Basicsorally administered drugs are absorbed from the intes- tinal lumen into the mesenteric blood system and con- veyed by the portal vein to the liver. Once the drug is in the liver, the liver microsomal P450 enzyme system metabolizes it, and it is passed into the general circula- tion. As noted previously, this initial metabolism of a drug and its passage from the liver into the circulation is called the first-pass effect (Figure 2-3). If a large proportion of a drug is chemically processed into inactive metabol- ites in the liver, then a much less active drug will make it into circulation. Such a drug would have a high first-pass effect. Consequently, the oral dose has to be calculated to compensate for the lower bioavailability. For example, nitroglycerin administered orally undergoes rapid liver metabolism and, as a result, has almost no pharmaco-