Pharmacologic Principles



Pharmacologic Principles


Objectives


When you reach the end of this chapter, you will be able to do the following:



1 Define the common terms used in pharmacology (see Key Terms).


2 Understand the general concepts such as pharmaceutics, pharmacokinetics, and pharmacodynamics and their application in drug therapy and the nursing process.


3 Demonstrate an understanding of the various drug dosage forms as related to drug therapy and the nursing process.


4 Discuss the relevance of the four aspects of pharmacokinetics (absorption, distribution, metabolism, excretion) to professional nursing practice as related to drug therapy for a variety of patients and health care settings.


5 Discuss the use of natural drug sources in the development of new drugs.


6 Develop a nursing care plan that takes into account general pharmacologic principles, specifically pharmacokinetic principles, as they relate to the nursing process.


Key Terms


Additive effects Drug interactions in which the effect of a combination of two or more drugs with similar actions is equivalent to the sum of the individual effects of the same drugs given alone. For example, 1 + 1 = 2 (compare with synergistic effects). (p. 33)


Adverse drug event Any undesirable occurrence related to administering or failing to administer a prescribed medication. (p. 33)


Adverse drug reaction Any unexpected, unintended, undesired, or excessive response to a medication given at therapeutic dosages (as opposed to overdose). (p. 34)


Adverse effects A general term for any undesirable effects that are a direct response to one or more drugs. (p. 31)


Agonist A drug that binds to and stimulates the activity of one or more receptors in the body. (p. 30)


Allergic reaction An immunologic hypersensitivity reaction resulting from the unusual sensitivity of a patient to a particular medication; a type of adverse drug event. (p. 34)


Antagonist A drug that binds to and inhibits the activity of one or more receptors in the body. Antagonists are also called inhibitors. (p. 30)


Antagonistic effects Drug interactions in which the effect of a combination of two or more drugs is less than the sum of the individual effects of the same drugs given alone (1 + 1 equals less than 2); it is usually caused by an antagonizing (blocking or reducing) effect of one drug on another. (p. 33)


Bioavailability A measure of the extent of drug absorption for a given drug and route (from 0% to 100%). (p. 22)


Biotransformation One or more biochemical reactions involving a parent drug. Biotransformation occurs mainly in the liver and produces a metabolite that is either inactive or active. Also known as metabolism. (p. 27)


Blood-brain barrier The barrier system that restricts the passage of various chemicals and microscopic entities (e.g., bacteria, viruses) between the bloodstream and the central nervous system. It still allows for the passage of essential substances such as oxygen. (p. 27)


Chemical name The name that describes the chemical composition and molecular structure of a drug. (p. 19)


Contraindication Any condition, especially one related to a disease state or patient characteristic, including current or recent drug therapy, that renders a particular form of treatment improper or undesirable. (p. 31)


Cytochrome P-450 The general name for a large class of enzymes that play a significant role in drug metabolism and drug interactions. (p. 27)


Dependence A state in which there is a compulsive or chronic need, as for a drug. (p. 32)


Dissolution The process by which solid forms of drugs disintegrate in the gastrointestinal tract and become soluble before being absorbed into the circulation. (p. 21)


Drug Any chemical that affects the physiologic processes of a living organism. (p. 19)


Drug actions The processes involved in the interaction between a drug and body cells (e.g., the action of a drug on a receptor protein); also called mechanism of action. (p. 20)


Drug classification A method of grouping drugs; may be based on structure or therapeutic use. (p. 20)


Drug effects The physiologic reactions of the body to a drug. They can be therapeutic or toxic and describe how the body is affected as a whole by the drug. The terms onset, peak, and duration are used to describe drug effects (most often referring to therapeutic effects). (p. 29)


Drug-induced teratogenesis The development of congenital anomalies or defects in the developing fetus caused by the toxic effects of drugs. (p. 35)


Drug interaction Alteration in the pharmacologic or pharmacokinetic activity of a given drug caused by the presence of one or more additional drugs; it is usually related to effects on the enzymes required for metabolism of the involved drugs. (p. 32)


Duration of action The length of time the concentration of a drug in the blood or tissues is sufficient to elicit a response. (p. 29)


Enzymes Protein molecules that catalyze one or more of a variety of biochemical reactions, including those related to the body’s physiologic processes as well as those related to drug metabolism. (p. 30)


First-pass effect The initial metabolism in the liver of a drug absorbed from the gastrointestinal tract before the drug reaches systemic circulation through the bloodstream. (p. 22)


Generic name The name given to a drug by the United States Adopted Names Council. Also called the nonproprietary name. The generic name is much shorter and simpler than the chemical name and is not protected by trademark. (p. 19)


Glucose-6-phosphate dehydrogenase (G6PD) deficiency A hereditary condition in which red blood cells break down when the body is exposed to certain drugs. (p. 34)


Half-life In pharmacokinetics, the time required for half of an administered dose of drug to be eliminated by the body, or the time it takes for the blood level of a drug to be reduced by 50% (also called elimination half-life). (p. 29)


Idiosyncratic reaction An abnormal and unexpected response to a medication, other than an allergic reaction, that is peculiar to an individual patient. (p. 34)


Incompatibility The characteristic that causes two parenteral drugs or solutions to undergo a reaction when mixed or given together that results in the chemical deterioration of at least one of the drugs. (p. 33)


Intraarterial Within an artery (e.g., intraarterial injection). (p. 23)


Intraarticular Within a joint (e.g., intraarticular injection). (p. 23)


Intrathecal Within a sheath (e.g., the theca of the spinal cord, as in an intrathecal injection into the subarachnoid space). (p. 23)


Medication error Any preventable adverse drug event (see above) involving inappropriate medication use by a patient or health care professional; it may or may not cause patient harm. (p. 33)


Medication use process The prescribing, dispensing, and administering of medications, and the monitoring of their effects. (p. 33)


Metabolite A chemical form of a drug that is the product of one or more biochemical (metabolic) reactions involving the parent drug (see later). Active metabolites are those that have pharmacologic activity of their own, even if the parent drug is inactive (see prodrug). Inactive metabolites lack pharmacologic activity and are simply drug waste products awaiting excretion from the body (e.g., via the urinary, gastrointestinal, or respiratory tract). (p. 34)


Onset of action The time required for a drug to elicit a therapeutic response after dosing. (p. 29)


Parent drug The chemical form of a drug that is administered before it is metabolized by the body’s biochemical reactions into its active or inactive metabolites (see metabolite). A parent drug that is not pharmacologically active itself is called a prodrug. A prodrug is then metabolized to pharmacologically active metabolites. (p. 22)


Peak effect The time required for a drug to reach its maximum therapeutic response in the body. (p. 29)


Peak level The maximum concentration of a drug in the body after administration, usually measured in a blood sample for therapeutic drug monitoring. (p. 30)


Pharmaceutics The science of preparing and dispensing drugs, including dosage form design. (p. 20)


Pharmacodynamics The study of the biochemical and physiologic interactions of drugs at their sites of activity. It examines the physicochemical properties of drugs and their pharmacologic interactions with body receptors. (p. 20)


Pharmacoeconomics The study of economic factors impacting the cost of drug therapy. (p. 20)


Pharmacogenomics 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; see Chapter 8). (p. 34)


Pharmacognosy The study of drugs that are obtained from natural plant and animal sources. (p. 20)


Pharmacokinetics The study of what happens to a drug from the time it is put into the body until the parent drug and all metabolites have left the body. Pharmacokinetics represent the drug absorption into, distribution and metabolism within, and excretion from the body. (p. 20)


Pharmacology The broadest term for the study or science of drugs. (p. 19)


Pharmacotherapeutics The treatment of pathologic conditions through the use of drugs. (p. 20)


Prodrug An inactive drug dosage form that is converted to an active metabolite by various biochemical reactions once it is inside the body. (p. 27)


Receptor A molecular structure within or on the outer surface of a cell. Receptors bind specific substances (e.g., drug molecules), and one or more corresponding cellular effects (drug actions) occurs as a result of this drug-receptor interaction. (p. 30)


Steady state The physiologic state in which the amount of drug removed via elimination is equal to the amount of drug absorbed with each dose. (p. 29)


Substrates Substances (e.g., drugs or natural biochemicals in the body) on which an enzyme acts. (p. 27)


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. For example, 1 + 1 is greater than 2 (compare with additive effects). (p. 33)


Therapeutic drug monitoring The process of measuring drug levels to identify a patient’s drug exposure and to allow adjustment of dosages with the goals of maximizing therapeutic effects and minimizing toxicity. (p. 30)


Therapeutic effect The desired or intended effect of a particular medication. (p. 30)


Therapeutic index The ratio between the toxic and therapeutic concentrations of a drug. (p. 32)


Tolerance Reduced response to a drug after prolonged use. (p. 32)


Toxic The quality of being poisonous (i.e., injurious to health or dangerous to life). (p. 20)


Toxicity The condition of producing adverse bodily effects due to poisonous qualities. (p. 30)


Toxicology The study of poisons, including toxic drug effects, and applicable treatments. (p. 20)


Trade name The commercial name given to a drug product by its manufacturer; also called the proprietary name. (p. 19)


Trough level The lowest concentration of drug reached in the body after it falls from its peak level, usually measured in a blood sample for therapeutic drug monitoring. (p. 30)


image


http://evolve.elsevier.com/Lilley



Overview


Any chemical that affects the physiologic processes of a living organism can broadly be defined as a drug. The study or science of drugs is known as pharmacology. Pharmacology encompasses a variety of topics, including the following:



Pharmacology includes the following several subspecialty areas: pharmaceutics, pharmacokinetics, pharmacodynamics, pharmacogenomics (pharmacogenetics), pharmacoeconomics, pharmacotherapeutics, pharmacognosy, and toxicology. Knowledge of pharmacology enables the nurse to better understand how drugs affect humans. Without understanding basic pharmacologic principles, the nurse cannot fully appreciate the therapeutic benefits and potential toxicity of drugs.


Throughout the process of its 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 nonproprietary name, 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, is the drug’s registered trademark, and indicates that its commercial use is restricted to the owner of the patent for the drug (Figure 2-1). The patent owner is usually the manufacturer of the drug. Trade names are generally created by the manufacturer with marketability in mind. For this reason, they are usually shorter and easier to pronounce and remember than generic drug names. The patent life of a newly discovered drug molecule is normally 17 years. This is the length of time from patent approval until patent expiration. Because the research processes for new drug development normally require about 10 years, a drug manufacturer generally has the remaining 7 years for sales profits before patent expiration. A significant amount of these profits serves to offset the multimillion-dollar costs for research and development of the drug.



After the patent for a given drug expires, other manufacturers may legally begin to manufacture generic drugs with the same active ingredient. At this point, the drug price usually decreases substantially. Due to the high cost of drugs, many institutions have implemented programs in which one drug in a class of several drugs is chosen as the preferred agent, even though the drugs do not have the same active ingredients. This is called therapeutic equivalence. Before one drug can be therapeutically substituted for another, the drugs must have been proven to have the same therapeutic effect in the body.


Drugs are grouped together based on their similar properties. This is known as a drug classification. Drugs can be classified by their structure (e.g., beta-adrenergic blockers) or by their therapeutic use (e.g., antibiotics, antihypertensives, antidepressants). Within the broad classification, each class may have subclasses; for example, penicillins are a subclass within the group of antibiotics and beta-adrenergic blockers are a subclass within the group of antihypertensives.


Three basic areas of pharmacology—pharmaceutics, pharmacokinetics, and pharmacodynamics—describe the relationship between the dose of a drug given to a patient and the activity of that drug in treating the patient’s disorder. Pharmaceutics is the study of how various dosage forms influence the way in which the drug affects the body. Pharmacokinetics is the study of what the body does to the drug. Pharmacokinetics involves the processes of absorption, distribution, metabolism, and excretion. Pharmacodynamics, on the other hand, is the study of what the drug does to the body. Pharmacodynamics involves drug-receptor relationships. Figure 2-2 illustrates the three phases of 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 clinical use of 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. Some drug mechanisms of action are more clearly understood than others. Drugs are categorized into pharmacologic classes according to their physiologic functions (e.g., beta-adrenergic blockers) and primary disease states treated (e.g., anticonvulsants, antiinfectives). The U.S. Food and Drug Administration (FDA) regulates the approval and clinical use of all drugs in the United States, including the requirement of an expiration date on all drugs. This textbook focuses almost exclusively on current FDA-approved indications for the drugs discussed in each chapter and on drugs that are currently available in the United States at the time of this writing. Only FDA-approved indications are permitted to be described in the manufacturer’s written information, or labeling, for a given drug product. At times, prescribers may elect to use drugs for non–FDA-approved indications. This is known as off-label prescribing and often requires seasoned clinical judgment on the part of the prescriber. Evolving over time in clinical practice, previously off-label indications often become FDA-approved indications for a given drug.


The study of the adverse effects of drugs and other chemicals on living systems is known as toxicology. Toxic effects are often an extension of a drug’s therapeutic action. Therefore, toxicology frequently involves overlapping principles of both pharmacotherapy and toxicology. The study of natural (versus synthetic) drug sources (i.e., plants, animals, minerals) is called pharmacognosy. Pharmacoeconomics focuses on the economic aspects of drug therapy.


In summary, pharmacology is a very dynamic science that incorporates several different disciplines. Traditionally, chemistry has been seen as the primary basis of pharmacology, but pharmacology also relies heavily on physiology and biology.


Pharmaceutics


Different drug dosage forms have different pharmaceutical properties. Dosage form determines the rate at which drug dissolution (dissolving of solid dosage forms and their absorption, e.g., from gastrointestinal [GI] tract fluids) occurs. A drug to be ingested orally may be in either a solid form (tablet, capsule, or powder) or a liquid form (solution or suspension). Table 2-1 lists various oral 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, on the other hand, have a coating that prevents them from being broken down in the acidic pH environment of the stomach and therefore are not absorbed until they reach the higher (more alkaline) pH of the intestines. This pharmaceutical property results in slower dissolution and therefore slower absorption.



Particle size within a tablet or capsule can make different dosage forms of the same drug dissolve at different rates, become absorbed at different rates, and thus have different times to onset of action. An example is the difference between micronized glyburide and nonmicronized glyburide. Micronized glyburide reaches a maximum concentration peak faster than does the nonmicronized formulation. Dosage form design for injectable drugs tends to be more straightforward than that for oral dosage forms. However, some injections are carefully formulated to reduce drug toxicity (e.g., liposomal amphotericin B).


Combination dosage forms contain multiple drugs in one dose. Examples of these combination forms include the cholesterol and antihypertensive medications atorvastatin/amlodipine tablets called Caduet and bacitracin/neomycin/polymyxin B/hydrocortisone ointment (generic). There are large numbers of such combination dosage forms; key examples are cited in the various chapters of this book.


A variety of dosage forms exist to provide both accurate 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 regimen. Extended-release tablets and capsules release drug molecules in the patient’s GI tract over a prolonged period of time. This ultimately prolongs drug absorption as well as duration of action. This is the opposite of immediate-release dosage forms, which release all of the active ingredient immediately upon dissolution in the GI tract. Extended-release dosage forms are normally easily identified by various capital letter abbreviations attached to their names. Examples of this nomenclature are SR (slow release or sustained release), SA (sustained action), CR (controlled release), XL (extended length), and XT (extended time). Convenience of administration correlates strongly with patient adherence, because these forms often require fewer daily doses. Extended-release oral dosage forms must not be crushed, as this could cause accelerated release of drug from the dosage form and possible toxicity. Enteric-coated tablets also are not recommended for crushing. This would cause disruption of the tablet coating designed to protect the stomach lining from the local effects of the drug and/or protect the drug from being prematurely disrupted by stomach acid. The ability to crush a tablet or open a capsule can facilitate drug administration when patients are unable or unwilling to swallow a tablet or capsule and also when medications need to be given through an enteral feeding tube. Capsules, powder, or liquid contents can often be added to soft foods such as applesauce or pudding, or dissolved in a beverage. Granules contained in capsules are usually for extended drug release and normally should not be crushed or chewed by the patient. However, they can often be swallowed when sprinkled on one of the soft foods. Consultation with a pharmacist, reading the product literature, or use of other suitable source is necessary if any question exists as to whether a drug can be crushed or mixed with specific food or beverages.



An increasingly popular dosage form is drug products that dissolve in the mouth and are absorbed through the oral mucosa. These include orally disintegrating tablets as well as thin wafers that also dissolve in the mouth. Depending on the specific drug product, the dosage form may dissolve on the tongue, under the tongue, or in the buccal (cheek) pocket.


The specific characteristics of various dosage forms have a large impact on how and to what extent the drug is absorbed. For a drug to work at a specific site in the body, either it must be applied directly at the site in an active form or it must have a way of getting to that site. 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 intestines, the drug is then transported to the site of action by blood or lymph.


Many topically applied dosage forms work directly on the surface of the skin. Once the drug is applied, it is already in a form that allows it to act immediately. However, with other topical dosage forms, the skin acts as a barrier through which the drug must pass to get into the circulation; once there, the drug is then carried to its site of action (e.g., fentanyl transdermal patch for pain).


Dosage forms that are 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 very similar to that of the blood for these drugs to be administered safely. Parenteral dosage forms that are injected intravenously 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 injection.


Pharmacokinetics


A drug’s time to onset of action, time to peak effect, and duration of action are all characteristics defined by pharmacokinetics. Pharmacokinetics is the study of what 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 the body 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. Bioavailability is the term used to express the extent of drug absorption. For example, a drug that is absorbed from the intestine must first pass through the liver before it reaches the systemic circulation. If a large proportion of a drug is chemically changed into inactive metabolites in the liver, then a much smaller amount of drug will pass into the circulation (i.e., will be bioavailable). Such a drug is said to have a high first-pass effect (e.g., oral nitrates). First-pass effect reduces the bioavailability of the drug to less than 100%. Many drugs administered by mouth have a bioavailability of less than 100%, whereas drugs administered by the intravenous route are 100% bioavailable. If two medications have the same bioavailability and same concentration of active ingredient, they are said to be bioequivalent (e.g., a brand-name drug and the same generic drug).


Various factors affect the rate of drug absorption. How a drug is administered, or its route of administration, affects the rate and extent of absorption of that drug. Although a number of dosage formulations are available for delivering medications, they can all be categorized into three basic routes of administration: enteral (GI tract), parenteral, and topical.



Enteral Route


In enteral drug administration, the drug is absorbed into the systemic circulation through the mucosa of the stomach and/or small or large intestine. The rate of absorption can be altered by many factors. Orally administered drugs are absorbed from the intestinal lumen into the blood system and transported to the liver. Once the drug is in the liver, hepatic enzyme systems metabolize it, and the remaining active ingredients are passed into the general circulation. Many factors can alter the absorption of drugs, including acid changes within the stomach, absorption changes in the intestines, and the presence or absence of food and fluid. Various factors that affect the acidity of the stomach include the time of day; the age of the patient; and the presence and types of medications (e.g., H2 blockers or proton pump inhibitors [see Chapter 50]), foods, or beverages. Enteric-coating is designed to protect the stomach by having drug dissolution and absorption occur in the intestines. Taking an enteric-coated medication with a large amount food may cause it to be dissolved by acidic stomach contents and thus reduce intestinal drug absorption and negate the coating’s stomach-protective properties. Anticholinergic drugs slow GI transit time (or the time it takes for substances in the stomach to be dissolved for eventual transport to and absorption from the intestines). This may reduce the amount of drug absorption and therapeutic effect for acid-susceptible drugs that become broken down by stomach acids. The presence of food may enhance the absorption of some fat-soluble drugs or of drugs that are more easily broken down in an acidic environment.


Drug absorption may also be altered in patients who have had portions of the small intestine removed because of disease. This is known as short bowel syndrome. Similarly, bariatric weight loss surgery reduces the size of the stomach. As a result, medication absorption can be altered, because stomach contents are delivered to the intestines more rapidly than usual after such surgery. This is called gastric dumping. Examples of drugs to be taken on an empty stomach and those to be taken with food are provided in Box 2-1. The stomach and small intestine are highly vascularized. When blood flow to this area is decreased, absorption may also be decreased. Sepsis and exercise are examples of circumstances under which blood flow to the GI tract is often reduced. In both cases, blood tends to be routed to the heart and other vital organs. In the case of exercise, it is also routed to the skeletal muscles.


Only gold members can continue reading. Log In or Register to continue

Related posts:

  1. Pituitary Drugs
  2. Cholinergic-Blocking Drugs
  3. Acid-Controlling Drugs
  4. Analgesic Drugs

Stay updated, free articles. Join our Telegram channel
Tags:
May 9, 2017 | Posted by in NURSING | Comments Off on Pharmacologic Principles

Full access? Get Clinical Tree
Get Clinical Tree app for offline access