PH 3 Principles of Pharmacology PDF

3 Principles of Pharmacology LEARNING OUTCOMES 1. Define the keywords used in pharmacology and drug administration. 2. Explain the differences between the chemical, generic, and brand names of drugs. 3. Compare the drug actions of agonists, partial agonists, and antagonists. 4. Describe the four ba...

3 Principles of Pharmacology LEARNING OUTCOMES 1. Define the keywords used in pharmacology and drug administration. 2. Explain the differences between the chemical, generic, and brand names of drugs. 3. Compare the drug actions of agonists, partial agonists, and antagonists. 4. Describe the four basic physiologic processes that affect drug actions in the body. 5. Explain the differences between side effects and adverse effects. 6. Discuss personal factors that influence drug therapy. 7. Describe how drugs affect persons at different lifespan changes. KEY TERMS absorption (ăb-SŎRP-shŭn, p. 24) Drugs enter the body and pass into the circulation to reach the part of the body it needs to affect through the processes of diffusion, osmosis, and filtration. additive effect (ĂD-ĭ-tĭv, p. 28) When two drugs are given together and either make one drug stronger or make the action of the two drugs more powerful. adverse reaction (ăd-VŬRS, p. 27) Severe symptoms or problems that can cause great harm. agonist (ĂG-ō-nĭst, p. 24) Drugs that work by activating or unlocking cell receptors causing the same actions as the body's own chemicals. allergy (ĂL-ĕr-jē, p. 27) An antigen-antibody response that can cause hives, rashes, itching, or swelling. anaphylactic reaction (ăn-ă-fĭ-LĂK-tĭk, p. 27) A severe life-threatening form of an allergic reaction. antagonist (ăn-TĂG-ŏ-nĭst, p. 24) Drugs that attach at a drug receptor site but do not activate or unlock the receptor. bioequivalent (BĪ-ō-ĭ-KWĬV-ĭ-lent, p. 28) Drug products that are chemically the same or identical. biotransformation (BĪ-ō-trăns-fŏr-MĀ-shŭn, p. 25) The transformation or altering of a drug into either active or inactive chemicals after it has been absorbed. brand name (p. 23) The proprietary name that a manufacturer gives to a specific 64 drug. Also known as a trade name. buccal (BŬ-kěl, p. 24) Drug placement against the cheek. chemical name (KĔM—ĭ-kăl, p. 23) The names of the chemicals that actually form the drug. desired action (ĂK-shŭn, p. 27) The drug does what it is supposed to do. distribution (dĭs-trĭ-BŪ-shŭn, p. 25) Movement of a drug in the body to reach its site of action by way of the blood and lymph system. drug interaction (ĭn-tĕr-ĂK-shŭn, p. 28) When one drug changes the action of another drug. enteral (route) (ĔN-tĕr-ăl, p. 24) Giving a drug by way of the gastrointestinal system; oral, feeding tube, sublingual, and rectally. first-pass (effect) (p. 26) After they are consumed, drugs are inactivated in the liver before being distributed to other parts of the body. generic name (jĕn–ĔR-ĭk, p. 23) The most common drug name used by the manufacturer in all countries. Also known as the nonproprietary name. half-life (p. 26) The time it takes the body to remove 50% of the drug from the body. hepatotoxic (hĕp-ă-tō-TŎK-sĭk, p. 27) Adverse drug effects that can result in liver damage. hypersensitivity (hĭ-pĕr-sĕn-sĭ-TĬV-ĭ-tē, p. 27) An exaggerated response to a drug. An allergy is an example of a hypersensitive response. idiosyncratic response (ĭd-ē-ō-sĭn-KRĂ-tĭk, p. 27) Responses to a drug that are peculiar and unpredicted. intramuscular (IM) (īn-trě-MŬ-skyě-lěr, p. 24) Giving a drug by way of an injection deep into the muscle. intravenous (IV) (in-tră-VĒ-nŭs, p. 24) Giving a drug by way of an injection into a vein or giving the drug into tubing that is connected to a catheter that is inserted into to a vein. nephrotoxic (nĕf-rō-TŎK-sĭk, p. 27) Adverse drug effects that can result in kidney damage. parenteral (route) (pĕ-RĔN-tĕr-ăl, p. 24) Giving a drug by way of an injection or an infusion underneath the skin. partial agonist (PĂR-shăl ĂG-ō-nĭst, p. 24) Drugs that attach to the receptor site but produce only a partial effect rather than a full effect (agonist). percutaneous (route) (pĕr-kū-TĀ-nē-ŭs, p. 24) Giving a drug by way of absorption through the skin. Topical creams, patches, or devices under the skin are common examples. pharmacodynamics (FĂRM-ă-kō-dĭ-NĂM-ĭks, p. 23) The effects of a drug on body function (what a drug does to the body). pharmacokinetics (FĂRM-ă-kō-kĭ-NĔT-ĭks, p. 23) The metabolism of a drug within the body (what the body does to a drug). pharmacotherapeutics (FĂRM-ă-kō-thĕr-ă-PŪ-tĭks, p. 23) The use of drugs in the 65 treatment of disease. prodrug (p. 25) Drugs that must be metabolized before they are active. receptor site (rē-SĔP-tŏr, p. 23) Small “lock-like” areas of cell membranes that control what substances either enter the cell or change its activity. side effect (SĪD ĕf-FĔCT, p. 27) Mild but annoying responses to the drug. Nausea and headache are common and usual side effects to many drugs. solubility (sŏl-ū-BĬL-ĭ-tē, p. 24) The ability of a drug to dissolve in body fluids. subcutaneous (sŭb-kyū-TĀ-nē-ăs, p. 24) Drug placement into fatty tissue. sublingual (sŭb-LĬNG-gwăl, p. 24) Drug placement under the tongue. synergistic effect (sĭn-ĕr-JĬS-tĭk, p. 28) The effect of two drugs taken at the same time is greater than the sum of the effects of each drug given alone. trade name (TRĀD), (p. 23) The proprietary name that a manufacturer gives to a specific drug. Also known as a brand name. This chapter provides an overview of very basic information from chemistry, physics, anatomy, and physiology that explains the action of drugs in the body (pharmacokinetics, or what the body does to the drug). This involves the processes of absorption, distribution, metabolism/biotransformation, and excretion. It also covers basic information on the effects of drugs on body functions (pharmacodynamics, or what the drug does to the body). This information is vital in understanding pharmacotherapeutics, or the use of drugs in the treatment of disease. Drug Names Drugs have several different names that may be confusing when you first learn to work with drugs. It is very important to know the different names of a drug so that the wrong drug is not given to a patient. Sometimes a drug is ordered by one name for the drug and the pharmacist labels it with another name for the same drug. For example, Valium (trade name) is also known as diazepam, its generic name. It is also common that one trade name drug is substituted for another trade name in the pharmacy. For example, Atarax (hydroxyzine) and Vistaril (hydroxyzine): hydroxyzine is the generic name, whereas Atarax and Vistaril are two different trade names (brand names) of hydroxyzine made by two different manufacturers. When one drug name is ordered and a drug with another name is supplied, it is important for you to know whether the drug is the same or a different drug. The most common drug name used is the generic name. This is the name the drug manufacturer uses for a drug, and it is the same in all countries. It is also called the nonproprietary name, which is given to a drug before there is any specific trade name or when the drug has been available for many years and more than one company makes the drug. Examples would be ibuprofen and acetaminophen. The American Pharmaceutical Association, the American Medical Association, and the US Adopted Names Council assign generic names. Generic names are not capitalized when written. It is becoming common in hospitals, extended care facilities, and other settings for drugs to be ordered by their generic names. The trade name, or brand name, is the proprietary name or the name for the drug 66 manufactured by one company. This name is often followed by the symbol ®, which indicates that the name is registered to a specific drug maker or owner and no one else can use that name for a drug. This is the drug name used in advertisements and is often descriptive, easy to spell, or catchy sounding so that prescribers will remember it easily and be more likely to use it. The first letters of the trade name are capitalized. Examples of trade names are Motrin, Tylenol, and Mylanta. Chemical names are often difficult to remember because they include all of the chemicals that make up the drug. These names are usually long and hyphenated, and they describe the atomic or molecular structure. An example is ethyl 1-methyl-4phenylisonipecotate hydrochloride, the chemical name for meperidine (Demerol). The chemical name is rarely, if ever, used by nurses or physicians and does not need to be remembered for safe drug administration. Drug Attachment Drugs take part in chemical reactions that change the way the body acts. They do this most commonly when the drug forms a chemical bond at specific sites on body cells. Receptor sites are small, “lock-like” areas of cell membranes that control what substances either enter the cell or change their activity (Fig. 3.1). The chemical reactions between a drug and a receptor site are possible only when the receptor site and the drug can fit together like pieces of a jigsaw puzzle or a key fitting into a lock. The drug attaches to the receptor site and activates the receptor. The drug will have a similar effect to the body's own chemical effect. When drugs activate or unlock receptors and have the same actions as the body's own chemicals, they are known as receptor agonists. Here is an example: morphine (key) activates the opiate receptors (lock) and produces analgesia (pain relief). In the body, deep breathing (key) triggers the same opiate receptors (lock) to release the body's own endorphins to decrease pain. (You can teach patients to use this technique to decrease pain.) FIG. 3.1 (A) Possible drug receptor actions. (B) Complete attachment as in an agonist. (C) An attachment that does not give a response or blocks a response as in an antagonist. (D) A small response as in a partial agonist. (From Clayton BD, Stock YN, Cooper S: Basic pharmacology for nurses, ed 15, St Louis, 2010, Mosby.) Some drugs attach to the receptor site but produce only a partial effect. These drugs are called partial agonists. Buspirone (BuSpar) is an example of a partial agonist. When given, the drug partially locks into the serotonin receptors and helps relieve anxiety and depression. Although buspirone can be used alone, it is frequently used to boost the effects of other drugs for depression like Prozac, which are full serotonin agonists. When a drug attaches at a drug receptor site but does not activate or unlock it, there is no increase in cell activity and the drug is an 67 antagonist. An important feature of an antagonist is that as long as the antagonist is attached to a receptor site, agonists cannot bind there. This antagonist effect blocks the action of agonists. Narcan (naloxone) is an example of an antagonist. In an opiate overdose, naloxone is given to completely reverse the effects of the opiate that is bound to the opioid receptor sites. The Memory Jogger box summarizes the various types of receptor site activity, and this is key information to memorize and understand. Memory Jogger Agonist: Drug attaches at receptor site and activates the receptor; the drug has an action similar to the body's own chemicals. Antagonist: Drug attaches at drug receptor site, but no chemical drug response is produced, and the drug prevents activation of the receptor. Partial agonist: Drug attaches at drug receptor site, but only a slight chemical action is produced. Basic Drug Processes Drugs must be changed chemically in the body to become usable. Four basic processes are involved in drug utilization in the body: absorption, distribution, metabolism, and excretion. Drugs have different characteristics, or pharmacokinetics, that determine to what extent these processes will be used. To safely give and monitor how a drug works in a patient's body, it is important for you to understand each of these processes for the specific drug or drugs prescribed. Absorption Absorption is the way a drug enters the body and passes into the circulation to reach the part of the body it needs to affect. Absorption takes place through processes of diffusion, filtration, and osmosis. These mechanisms of absorption are more fully described in Box 3.1. How fast the drug is absorbed into the body through these processes depends on how easily the drug dissolves, how the drug is introduced into the body (by mouth or by injection), and whether there is good blood flow through the tissue where the drug is located. Box 3.1 Mechanisms Involved in Absorption DIFFUSION Diffusion is the tendency of the molecules of a substance (gas, liquid, or solid) to move from a region of high concentration to one of lower concentration. OSMOSIS Osmosis is the diffusion of fluid through a semipermeable membrane; the flow is primarily from the thicker or more concentrated solution to the thinner or less concentrated solution. 68 FILTRATION Filtration is the passage of a substance through a filter or through a material that prevents passage of certain molecules. Filtration. Diffusion. Osmosis. All drugs must be dissolved in body fluid before they can enter body tissues. The ability of the drug to dissolve is called solubility. To achieve the best possible action, sometimes the drug must be dissolved quickly; at other times it should be dissolved slowly. Solubility is often controlled by the form of the drug. For example, liquids are more soluble than capsules or tablets because a liquid is absorbed faster than a tablet or capsule, which first must be dissolved. An injection with an oil base must be chemically changed before absorption can take place, and this delay in absorption holds the drug in the tissues longer, which may be the desired action, especially if it is an antibiotic. When your patient takes water with a tablet, it not only helps in swallowing but also helps dissolve the drug. That is why a full glass of water should be given with oral drugs unless the patient has a health problem that requires fluid restriction. The route of administration also influences absorption. Drugs can be given in many different ways: the oral route (enteral) through the mouth, a nasogastric or feeding tube, or rectally; by injection (parenteral) underneath the skin; into the fat (subcutaneous); into the muscle (intramuscular [IM]); into the cerebrospinal fluid (epidural); into the bloodstream (intravenous [IV]); on top of the skin (topical or percutaneous); under the tongue (sublingual); against the cheek (buccal); or by way of breathing (inhalation). In areas where the blood flow through tissues is very high, drugs are rapidly absorbed. The IV route delivers drugs directly into the bloodstream, and the drugs are immediately distributed to the tissues. The muscles (IM), the area under the tongue (sublingual), inside the nose (intranasal), and through the lungs (inhalation) have very high blood flow and so drugs given by these routes begin to work very quickly. Fig. 3.2 shows the action of drugs in the body from the fastest to the slowest onset. 69 FIG. 3.2 Fastest to slowest drug absorption and availability. Distribution After a drug enters the body's circulation, it must reach the organ or tissues where it will have its action. Movement of a drug in the body is its distribution, which occurs by way of the blood and lymph system. Distribution of the drug is usually uneven because of differences in how much blood is able to penetrate the tissue (perfusion), types of tissue (bone, fat, and muscle), and how easy it is for the drug to penetrate the cell membranes. For example, the tissue in the placenta and the brain make it difficult for the drug molecules to pass through. Some drugs will also bind together with many blood substances and proteins such as albumin. This binding allows only “free” drug (that which is not bound) to penetrate the tissues. Some drugs are attracted to tissues other than the target receptor sites. For example, drugs that dissolve easily in lipids (fats) prefer adipose, or fat tissue, and stores of the drug may build up in these areas. Eventually this buildup of the drug in the fat cells will be released, making the effect of the drug last a long time. Diazepam (Valium), an antianxiety agent, is a highly lipophilic (fat-loving) drug, and the sedative effects last much longer than lorazepam (Ativan), a less lipophilic antianxiety agent. Metabolism Once the drug is absorbed and distributed in the body, the body transforms or alters the drug into active or inactive chemicals. This process, known as biotransformation, happens mainly in the liver, where there are enzymes that break down the chemicals that make up the drug into its usable and unusable parts. Drugs that are known as prodrugs have to be transformed and activated by these enzymes before they can be used by the body. Biotransformation happens in various sites in 70 the body, but mainly in the liver. Thus liver disease may impair the transformation of the inactive form of the prodrug into an active form of the drug. Drugs move very quickly from the stomach or small intestines to the liver. A lot of the drug is then inactivated on its first pass through the liver before it can be distributed to other parts of the body. That is why some drugs are given sublingually or intravenously; otherwise the drug would be inactivated and patients would not receive the amount of drug they require. Therefore, how a drug is given may affect how much of it is needed. (For example, only 1 mg of propranolol is required intravenously, but 40 mg is required when the drug is given by mouth because so much is inactivated during the first pass through the liver.) Genetic differences in the enzyme pathways in the liver also explain why people respond differently to a drug. Some people grow tolerant to the drug and seem to need larger doses, and some are sensitive to the drug and need only a small dose. These liver enzyme pathways, known as the cytochrome P-450 system, play an important role in adverse drug reactions (ADRs), especially when taking several drugs at the same time or when there are drug–food interactions. Because there are individual genetic differences in the enzyme pathways, different patients may respond differently to the same drug. For example, African American persons with hypertension require higher doses of some antihypertension drugs, and the drugs that they do respond to are different from that of white persons. Excretion or Elimination All inactive chemicals, chemical by-products, and waste (often referred to as metabolites) finally break down through metabolism and are removed from the body through the process of excretion. Fibrous or insoluble waste is usually passed through the gastrointestinal (GI) tract as feces. Chemicals that may be made watersoluble are dissolved and filtered out as they pass through the kidneys and then are lost in the urine. Some chemicals are exhaled from the lungs through breathing or lost through evaporation from the skin during sweating. Very small amounts of drug may also escape in tears, saliva, or the milk of breast-feeding mothers. This concept can be easily understood by the following examples: the smell of penicillin, asparagus, and nicotine in the urine, or the smell of alcohol on the sweat and breath of someone who has consumed large amounts of beer or whiskey. If the patient has poorly functioning kidneys, then these metabolites may build up in the body and become toxic if they cannot be excreted in the urine. This is why it is so important for you to monitor the urine function of very ill patients. The major processes involved in drug utilization in the body are shown in Fig. 3.3. These four processes are basic to understanding how drugs are used in the body. If you understand these four processes well, you will be able to understand many of the ways in which drugs are different. When you understand how drugs are used in the body, you will be better able to identify when patients may have toxic or ill effects of the drugs on the body. Watching the patient especially closely after he or she takes the drug to see his or her response to the drug is important. It is especially important the first time the patient takes the drug and whenever there are changes in the patient's condition, diet, or other drugs that are introduced into the medical regimen. 71 FIG. 3.3 Processes of absorption, distribution, metabolism, and excretion. GI, gastrointestinal. Did You Know? Grapefruit juice affects (usually reduces) the absorption of many drugs, such as antihistamines, cholesterol-lowering drugs, HIV drugs, and transplant drugs. Some drugs enter and leave the body very quickly; other drugs remain for a long time. The standard method of describing how long it takes to metabolize and excrete a drug is the half-life, or the time it takes the body to remove 50% of the drug from the body. Because the rates of metabolism and excretion are usually the same for most people, the half-life helps explain the dose (how much drug should be taken), the frequency (how often it should be taken), and the duration (how long it will last) for different drugs. If a drug has a long half-life, it may need to be taken only once a day. If a person takes too much drug with a long half-life, an adverse reaction may occur because the action of the drug lasts for such a long time. If the half-life of a drug is short, such as for many antibiotics, the person must take frequent doses to keep the correct level in the blood. If a person's liver or kidneys do not function correctly, drugs may not be properly metabolized or excreted, and this would mean that higher doses of the drug will circulate for a longer time and produce symptoms of overdosage. Drugs are often dosed based on kidney and liver function for this reason, which is why kidney and liver function blood work is drawn. Some drugs such as narcotics and antihypertensive drugs come in an extendedrelease or long-acting form for ease of administration. Many of these drugs end in contin, LA, or ER. Top Tip for Safety Long-acting or extended-release drugs must never be crushed, chewed, opened (if it is a capsule), or cut because this will result in an overdosage. Drug Actions When a drug is given to a patient, it is usually possible to predict the chemical 72 reaction that will result and a change seen. However, because each patient is different, some unexpected chemical reactions are also possible. With each patient, giving a drug is somewhat of an experiment, so watching patients closely to monitor their reaction to the drug is an important role of the nurse. This is most important the first time a patient is given a newly prescribed drug. The expected response of the drug is called the desired action. This is when the drug does what is desired, and the therapeutic goal is reached; for example, a fentanyl patch (Duragesic) relieves pain. Because a drug may influence many body systems at the same time, the effect of the drug is often not restricted to the desired action. Other actions called side effects or adverse reactions may also take place. Side effects are usually seen as mild but annoying responses to the drug. Side effects are expected effects. For example, the drug used to relieve pain may make the patient very sleepy. Certain side effects, such as nausea, may be stopped if the dosage is reduced or the drug is given with food or a full glass of water. Some side effects are such a problem that the drug must be changed or stopped. An example of this is insomnia (inability to sleep) or making the patient pass out (syncope). Expected side effects that are very common are usually related to the GI system: nausea, constipation, and diarrhea. Adverse reactions, or adverse effects, imply more severe symptoms or problems that develop because of the drug. Some adverse effects may require the patient to be hospitalized or may even be life-threatening. Examples include a necrotic skin condition called Steven-Johnsons syndrome or anaphylactic shock. If severe adverse effects such as damage to the kidney (nephrotoxic drug) or liver (hepatotoxic drug) or bleeding develop, the drug often must be stopped. You, as a nurse, are on the front line to notice whether and when an adverse reaction may occur and are responsible for the well-being of your patients. Occasionally a patient may have a drug reaction that is a surprise. Strange, unique, peculiar, or unpredicted responses to drugs are called idiosyncratic responses. These reactions may be the result of missing or defective metabolic enzymes caused by a genetic or hormonal variation of that individual. They often produce either an unexpected result, such as pain or bleeding, or an over response to the drug. These types of reactions are usually rare. One type of idiosyncratic response is called a paradoxical response. In this situation, the patient's reaction may be just the opposite of what would be expected. For example, diphenhydramine (Benadryl) is an antihistamine with sedative (sleep-inducing) effects. It is in many over-the-counter sleep aids like Motrin PM. Instead of sedation, some people have a paradoxical response and remain awake and excited. A second type of unexpected reaction is an increased reaction to a drug (hypersensitivity) or a sensitivity caused by antibody response to a drug (allergy). Some drugs (sulfa products, aspirin, penicillin) and some conditions (asthma) are more likely to produce allergic reactions than others. Allergic reactions usually occur when an individual has taken the drug and the body has developed antibodies to it. When the patient takes the drug again, the antigen–antibody reaction produces hives, rash, itching, or swelling of the skin. This type of allergic reaction is very common, so ask all patients about whether they have ever had a drug reaction. Patients with an allergy to one drug may be more likely to develop an allergy to another drug, but individuals may also develop a reaction to drugs they have taken before without problems or have been taking for a long time and only now show 73 signs of an allergy. Did You Know? Allergic reactions to antibiotics can happen even after the first time a patient takes a drug because he or she may have been previously exposed to the antibiotics in milk or food that was fed to livestock. Occasionally the allergic reaction is so severe the patient has trouble breathing, and the heart may stop. This life-threatening response is called an anaphylactic reaction. A patient who has a mild allergic reaction to a drug is much more likely to develop the more severe anaphylactic reaction if the drug is given again. An anaphylactic reaction is a true medical emergency because the patient may suffer severe breathing problems including swelling of their lips, throat, and trachea that prevent air from entering the lungs. Top Tip for Safety Always warn patients who have anaphylactic reactions about their allergy so they will not take the drug again. Teach them to wear a medical alert bracelet or necklace, or carry identification about their allergy. Some patients may need to carry an adrenaline (epinephrine)-filled syringe that they can use to inject themselves to prevent anaphylaxis when symptoms begin. Patients often confuse an allergy with side effects, both of which may produce unpleasant symptoms. If a patient reports an “allergy” to a drug, make sure you ask the right questions to understand the exact past reaction to the drug. If the patient had nausea or stomach pain when taking aspirin, that is a side effect, but not an allergy. If the patient reported sedation when taking an antihypertensive drug, that is also not an allergy. Because patients often do not understand the difference between an allergy and a side effect, it is important for you to clarify the difference when patients say they have had an allergic reaction. Memory Jogger The possible types of drug actions and responses are: • desired effect • side effect • adverse effect or reaction • idiosyncratic response • paradoxical reaction • allergic (hypersensitivity) responses 74 • anaphylactic reaction Bioequivalence After a new drug enters the market, an exclusive patent protects the financial interests of the drug company for some time, usually 17 years, by limiting other companies from producing that drug. After the patent ends, other companies may make the same drug under a generic name. Brand name drugs are usually more expensive than generic drugs because the maker of the brand name drug is attempting to recover the huge sums of money spent on research and drug development. Thus generic products are often less expensive because they do not face those costs. Drug products seen as identical with respect to their active ingredients are known as generic equivalents. However, slight differences in processing or formulation may mean that the action of the generic drug in the body is slightly different from that of the brand name product. These differences most commonly cause variations in absorption, distribution, or metabolism. Thus the product a prescription is written for may vary according to what specific brand the pharmacist dispenses. Some products are chemically the same or identical and are thus bioequivalent. This may be particularly important for some cardiac or antiseizure drugs. An example is a prescription or an order written for Lanoxin, the brand name for digoxin. If the pharmacy dispenses a generic brand that is not considered bioequivalent, then the product may not have the same action on the body. Drug Interactions When one drug changes the action of another drug, a drug interaction is present. These reactions often take place during the process of metabolism (or biotransformation) in the liver and are a result of the cytochrome P-450 enzyme pathways each person inherits genetically from his or her parents. The actions of a number of drugs may be altered when they are taken with other drugs; some examples include some antidepressants, respiratory drugs, anticlotting drugs, antibiotics, and opiates. Some drugs are given together on purpose because the combination produces an additive effect. The drugs work as a team so to speak. For example, probenecid is given with penicillin to increase the amount of penicillin that is absorbed. This is called an additive effect. Other drug interactions produce adverse effects. For example, many antibiotics make birth control tablets less effective, thus making it more likely a woman will get pregnant while taking both drugs if she is sexually active. If one drug interferes with the action of another drug, it has an antagonistic effect. At times, one drug may replace another drug at a receptor site, decreasing the effect of the first drug (displacement). Flumazenil (Romazicon) is a drug that can be given to displace the effects of a sedative like diazepam (Valium). Sometimes incompatibility occurs when drugs do not mix well chemically. Attempts to mix them together, especially in a syringe or IV solution, may cause a chemical reaction, so neither of the drugs can be given. Heparin is an example of such a drug. If heparin is mixed together in a syringe or an IV line with many drugs, a white, hazy precipitate will occur. Finally, if the effect of two drugs taken at the same time is greater than 75 the sum of the effects of each drug given alone, the drugs have a synergistic effect. For example, acetaminophen is given with codeine for added pain relief. Food, Alcohol, and Drug Interactions Food, alcohol, and most drugs taken by mouth must travel through the liver for chemical changes before they can be used by the body. Thus the risk for drug interaction with food or alcohol is high because these products also go through the liver. When taken together, food or alcohol and drugs may alter the body's ability to handle a particular food or drug. Part of these interactions may be caused by activation of the P-450 enzyme system or competition for receptor sites. The classification of antidepressant drugs called monoamine oxidase inhibitors are some of the drugs most noted for drug–food interactions. They cannot be taken with aged cheese, red wine, or many processed foods. Information every patient should know about possible drug interactions includes: 1. Cigarette smoking can decrease the effect of drugs or create other problems with some drugs by increasing metabolism. 2. Caffeine, which is found in coffee, tea, some soft drinks, chocolate, and some drugs, can also affect the action of some drugs. 3. Drugs should never be taken during pregnancy or by a patient trying to get pregnant without the advice of the healthcare provider. 4. If the patient has any problem related to drugs, the healthcare provider or a pharmacist should be contacted immediately. 5. Some drugs are blocked from being absorbed by the body by grapefruit juice, fatty meals, milk products, or other drugs. Some drugs or foods increase or decrease the action of the anticlotting drug warfarin, by increasing or decreasing the blood clotting time, and thus can increase the risk for stroke or heart attacks. Other drugs might raise the blood pressure, increase vasoconstriction in tissues, or cause other vascular changes that might be harmful to the patient. Almost every drug has the potential to have an effect on other drugs that the patient is receiving, so you will need to be aware of potential drug interactions as you learn about different drug categories. The amount of alcohol use is very high in the US population. It has been estimated that approximately 70% of adults consume alcohol at least occasionally. Many patients may not be aware that alcohol is one of the products that react most commonly with drugs. The extent to which a drug dose reaches its site of action is called availability. Alcohol can influence whether a drug is effective by changing its availability. It is estimated that alcohol–drug interactions may be a factor in at least 25% of all emergency department admissions. “According to the National Institute on Alcohol Abuse and Alcoholism (NIAAA), more than 150 drugs have harmful additive or interactive effects when combined with alcohol.” Narcotics, antianxiety agents, antidepressants, antihistamines, antihypertensive agents, and antibiotics are just a few of the drugs that will cause problems when combined with alcohol. Older adults are more likely to suffer drug side effects compared with younger persons, and these effects tend to be more severe with advancing age. 76 Personal Factors That Influence Drug Therapy Some personal factors affect how effective drugs are for any specific patient. All drug therapy requires adequate hydration and blood flow for drugs to be distributed to target tissues. So any problem that interferes with blood flow decreases drug effectiveness. Such problems include dehydration, overhydration, low blood pressure, shock, heart failure, or reduced blood flow to one or more body areas. Use of other prescribed, over-the-counter, or illicit drugs, as well as alcohol intake often increase the activity of metabolic enzyme systems. This change increases the rate at which some drugs are deactivated and eliminated, often requiring that the doses be increased and/or given more frequently to be effective. For example, opioid drugs for pain are metabolized and eliminated much faster in the person who drinks alcohol on a daily basis. The dose then may need to be higher for the person to obtain pain relief. Any person who has problems of the liver or the kidneys will retain a drug much longer, increasing the risk for adverse and toxic effects. For the patient who has either liver dysfunction or kidney problems, dosages usually need to be reduced and the drug given less frequently. Body size and lean-to-fat ratios also affect drug therapy responses. For many drugs, bigger people (adults or children) require larger dosages of drugs. Drug dosages are based on kilogram of body weight or body surface area for children, as well as for drugs that are considered dangerous (e.g., heparin, chemotherapy drugs). Ethnicity and genetic makeup change the expected drug response as well. For example, many people of Asian descent have a greater-than-usual response to the anticoagulant drug warfarin, which greatly increases their risk for excessive bleeding, hemorrhage, and stroke. As a result, the starting dosage of warfarin is lower for Asians and increased at a slower rate until the individual patient's response is known. There is great variation in the activity of the P-450 system enzymes from one person to the next as a result of genetic differences. A person may be a rapid metabolizer of drugs and require higher-than-expected dosages to achieve the same desired effect. Another person may be a slow metabolizer and have more problems with side effects, adverse reactions, and toxic effects even from what are considered “normal” drug dosages. These personal differences in drug therapy require all healthcare professionals to be aware of the possibility of unexpected patient responses. Thus one size does NOT fit all when it comes to drug therapy. This is especially true for drugs that have a narrow therapeutic range, which means that the dose that is effective is very close to the dose that causes adverse and toxic reactions. You are on the front line of drug therapy to prevent, as well as to recognize, unexpected patient responses. Drug Therapy and Special Populations People respond to drugs differently at various lifespan stages. These differences are based on body size, water content, organ maturity, and general organ health. Pediatric Drug Therapy Considerations 77 Overview Childhood extends from newborns to adolescents. During these years the processes of drug absorption, distribution, metabolism, and elimination continue to change. As children grow, total body water decreases (but is still greater than an adult's), body size increases, and body fat stores increase. Overall, body metabolism is highest in infants and slowly decreases as the child ages. However, healthy children have a higher metabolism than do adults. These normal changes alter a child's responses to drug therapy. Drug Absorption In neonates (less than 1 month of age), oral drugs are absorbed poorly from the GI tract because no gastric acid is present to help break down drugs, no intestinal bacteria or enzyme function is present to metabolize a drug, and the time it takes for a drug to move through the stomach and intestines is slow. Thus the effectiveness of oral drugs in this age group is not very predictable. In later infancy and childhood these factors change, making oral drugs more effective. Absorption of IM injections is based on muscle mass and muscle blood flow. Neonates and infants have relatively small muscle mass and blood flow, which reduces IM absorption. In older children, muscle size and circulation in the muscles affect how rapidly a drug is absorbed. There is more rapid absorption from the deltoid muscle (shoulder and upper arm) than from the vastus lateralis muscle (thigh), and the slowest absorption is from the gluteal (buttock) muscles. Drug Distribution Distribution of water-soluble drugs is faster and more widespread in neonates, infants, and younger children because of their high percentages of total body water. For older children and adolescents, distribution is affected by the lean-to-fat body mass ratio in the same way that it is for adults. Drug Metabolism In neonates and young infants the systems that metabolize drugs in the liver are immature. As a result, prodrugs (drugs that must be metabolized before they are active) are slower to be activated and to become effective. For drugs that are active when absorbed, deactivation takes longer and drug levels can build up more quickly. This increases the risk for side effects, toxic effects, and overdosages in this age group. Older infants and young children have higher metabolic rates and a rapid turnover of body water. This often results in greater drug dosage requirements per kilogram of body weight than those of the adolescent or adult. Often these young children require more frequent drug dosing to maintain blood drug levels. For example, the dosing of digoxin, a heart drug that can become toxic very easily (narrow therapeutic index) is four times higher in the neonate than in the adult. During adolescent growth spurts, metabolism increases along with body weight. Drug dosages often must be increased at this time, especially for drugs that control seizure disorders. Drug Elimination 78 As with metabolism, the growth and maturity of the child's organs have important effects on the child's ability to excrete drugs, which changes expected drug responses. Preterm infants, neonates, and infants younger than 6 months have less mature kidneys that may not excrete drugs effectively. Careful monitoring of responses and blood drug levels are needed to determine the most effective dosages and scheduling of drug therapy. Older Adult Drug Therapy Considerations Older adult patients also react differently to drugs. Drugs are absorbed, metabolized, and excreted more slowly and less completely in older adults. In adults older than 65 years, problems with drugs are often due to a lack of understanding of the way drugs are processed in the aging body and the body's changed response to drugs. To further complicate matters, people age differently, and their individual body systems may also age at different rates. Many older adults with chronic illnesses take drugs daily. These drugs are helpful in controlling disease, but they also present a very real hazard to older adult patients. ADRs are common in older adults. Issues such as falls, hypotension, delirium, kidney failure, and bleeding are common clinical manifestations. Many of the issues can also be attributed to aging, which leads to ADRs being frequently overlooked in this population. You are the person most likely to notice these ADRs and alert the prescriber to the possibility of the problem. Because many older adult patients take several drugs, interactions among these different drugs may also cause problems for them. These patients may see several specialists, each of whom may prescribe different drugs. This is called polypharmacy. If the specialists do not know about all the different drugs a patient may be taking at the same time, the patient is at risk for adverse interactions. All drugs have some risk or hazard, but those most dangerous to older adults are tranquilizers, sedatives, and other drugs that alter the mind and change what the patient thinks he or she sees, or causes the patient to become dizzy or lose balance. Diuretics and cardiac drugs pose special dangers and must be given with caution and careful observation of how the patient responds. Older adult patients may become dehydrated easily, thus allowing the amount of drug in the blood to increase. This places them at greater risk for side effects and toxicity with normal dosages. Diuretics lead to an increase in urination, and this can lead to loss of electrolytes. Electrolytes are important for electrical energy of all body functions like muscle contraction and nerve impulses, but particularly for the proper electrical function of the heart. Electrolyte levels must be monitored by blood tests, and electrolytes may have to be replaced if they are low. Drug Absorption The overall importance of changes in the absorption of drugs with aging is not completely clear. There may be some delay in the absorption process. Physiologic changes that affect the GI tract include a reduction in acid output, so there is a more alkaline environment, which may affect drugs that require an acid medium for absorption. Reductions in blood flow, enzyme activity, gastric emptying, and bowel motility may delay the absorption of some drugs. Compounds such as iron, calcium, and some vitamins that depend on active transport mechanisms for absorption may 79 be affected by the decreased blood flow in the aging patient's GI tract. Drug Distribution The distribution of drugs in the body may also be affected by the aging process and is linked to the chemical makeup of the agent. There is a decline in total body water and lean body mass with aging that may result in less movement or distribution of water-soluble drugs into some tissues. If the dose of these drugs is not decreased, the patient may develop higher serum concentrations, leading to an increased effect or toxicity. Thus the usual rule is to start drugs using a low dose and then increase the dose slowly in older adult patients. You should be mindful of the distribution of the drug you are giving so you can be alert to possible toxic effects. The distribution of fat-soluble drugs may also be changed by the aging process. With aging, there is usually a decrease in lean body mass and an increase in total body fat. Thus lipid-soluble drugs may be stored in larger amounts in fat tissues and remain in the body for a longer time. This can cause problems with drug toxicity, as well as safety issues for a patient. Another important concern for some older adults is a decrease in serum proteins. When serum proteins are low, greater amounts of unbound drug may circulate and cause adverse or toxic reactions. Drug Metabolism Overall, a decrease in liver mass occurs with age, along with a reduction in liver blood flow. When blood flow is reduced, as may occur with aging, less of the drug is metabolized, so increased amounts of the active form may remain in the blood. In an aging liver, there may also be changes in the phases of metabolism during which certain chemical and molecular changes occur to prepare the drug for metabolism. The drug may stay in the body too long and/or not be eliminated. Drugs that are metabolized by the liver may have less or reduced metabolism because of other changes in the liver and also because of the influence of other diseases. The aging liver often gets smaller, has less blood flow, is affected by changes in nutritional status, and may become overloaded with fluid from diseases such as chronic heart failure or chronic renal failure. These factors may result in a loss of the liver's ability to handle all the different chemicals it must process. In this situation, the patient may have more risk for adverse effects when drugs are added to the existing treatment plan. Drug Elimination Kidney (renal) function is an important factor that causes ADRs. Changes in the aging kidney include decreases in the number of nephrons; decreases in blood flow, glomerular filtration, and tubular secretion rate; and kidney damage. In addition, damage to the arterial walls of blood vessels and lowered cardiac output reduce the amount of blood that flows to the kidneys by 40% to 50%. The creatinine clearance rate is an estimated measure of how well the kidney functions. This rate decreases with age, which allows drugs to remain in an older adult's system longer, increasing the risk for adverse and toxic effects. Important factors to remember when caring for older adults who are taking drugs that will be excreted by the kidneys is that each patient may respond a little 80 differently to the drug. The dosage ordered is adjusted by the prescriber based on the best creatinine clearance estimates, and low doses or longer intervals between doses are used if kidney damage is present. Drugs that depend on the kidneys for elimination include many antibiotics, some antivirals, anticancer drugs, antifungals, analgesics, and many cardiac drugs. Patient Teaching Considerations Many older adults require special teaching about how to take their prescription drugs and about the danger of taking nonprescription drugs at the same time. Failure of older adults to follow their drug therapy plan may be because of the cost of the drug, difficulty in getting it from a pharmacy, poor memory, lack of desire to take the drug regularly, depression, and feelings of being overwhelmed by the responsibility of taking care of themselves. In some cases, arthritis or another disease that causes physical disability may make it difficult to open bottle lids or use an inhaler. Poor eyesight may make it hard to draw up insulin or read labels accurately. Some older adults share drugs and may cut pills in half or skip doses without realizing this action may interfere with the effectiveness of the drug. Drug Therapy Considerations During Pregnancy and Lactation Pregnant and breast-feeding women may have both chronic diseases and acute problems that require drug therapy. In pregnancy the drug is really going to two people, so how the drug may affect the growing fetus is a consideration. The benefit of any drug to a pregnant patient must be carefully weighed against the possible (or potential) risk to the fetus. It is important for pregnant women to avoid as many drugs as possible, especially those drugs with teratogenic potential (i.e., likely to cause malformations or damage in the embryo or fetus). Many drugs have been confirmed as teratogenic in humans. The US Food and Drug Administration (FDA) has new guidelines for drug use during pregnancy. The pregnancy letter categories on prescription drugs will be removed by June of 2020. Instead, additional content will create awareness of the risks involved in taking drugs during pregnancy. Factors such as what drug the mother takes, how much is taken, and the age of the fetus when the drug is taken are related to different types of malformations. Taking a drug during the first 2 weeks after conception (before implantation) results in an allor-nothing effect. The ovum either dies of exposure to a lethal dose of a teratogen or recovers completely with no adverse effects. The critical period for teratogenic effects in humans lasts from about 2 to 10 weeks after the last menstrual period. This period is the time of organ development (14–56 days), during which any teratogenic drug taken by the mother may produce major abnormalities in the embryo. Taking a teratogen later in the pregnancy during the fetal period (57 days to term) may result in minor structural changes, but abnormalities are more likely to involve problems with growth, mental development, and reproductive organ abnormalities. Clearly it would be best if all women could stop taking any drugs before they got pregnant and not resume them until the baby is born. Always ask about the possibility of pregnancy when giving a drug to a woman of childbearing age. 81 As the fetus grows, the placenta allows most drugs and foods to cross from the mother to the baby. However, the reaction of a fetus to a drug is different from that of the mother. Because of an immature blood–brain barrier, many drugs are able to pass into the brain of the fetus. Because of the immaturity of the liver, the fetus does not metabolize drugs well. Many drugs can pass into human breast milk, and this is also a major concern for the baby. Nicotine, cocaine, heroin, marijuana, and angel dust are examples of some illicit drugs that pass into the breast milk. If a mother is given a prescription while she is nursing, she can lessen the infant's drug exposure by taking the drug just before the infant is due to have a lengthy sleep period or right after a feeding. A bottle can then be substituted for the next scheduled feeding, and the affected breast milk can be expressed and discarded. Nevertheless, the infant should be watched for emotional changes, altered feeding habits, sleepiness, or restlessness. If short-term drug therapy is required, the mother may need to consider stopping breast-feeding for a short time and instead pumping and discarding her milk to maintain lactation until drug therapy is finished. Drug Cards Approximately 9000 drugs are on the market, with new drugs becoming approved by the FDA every day. Of these, approximately 200 drugs are frequently prescribed. By now you have realized how important it is for you to understand everything you can about the patient and drug that you will be giving. A good way to learn and remember drugs is to write drug cards on the most popular drugs, as well as any and all drugs you will give to a patient. The golden rule of drug administration is to never give a patient a drug with which you are not fully familiar. A drug card should include both the trade and generic names of the drug, the dosage range, the desired action, expected side effects, adverse effects, how to give the drug, and lastly, important information that you will need to know before giving the drug. As you progress through the text you will notice that many drugs belong to a classification, and part of the drug's generic name provides a hint. For example, what do you notice about the suffix (ending of a word) of each generic drug mentioned in the following list? acebutolol (Sectral) atenolol (Tenormin) bisoprolol (Zebeta) metoprolol (Lopressor, Toprol XL) nadolol (Corgard) nebivolol (Bystolic) propranolol (Inderal) All of these drugs are examples of a classification of antihypertensives known as beta blockers. They all have a suffix of “olol,” and the way they work in the body is similar. They block the action of epinephrine in the body's beta receptor sites. Beta blockers are antagonist drugs. If epinephrine, a neurotransmitter in the body, cannot connect with a beta receptor, then the result will be a decreased heart rate and 82 relaxation of the veins and arteries (vasodilation). The desired action then is to decrease the blood pressure. The dosage range and specific information of each of these drugs may differ, but they all work in the same way. The nurse may want to make one “classification” drug card with all of the drugs listed whenever possible to become acquainted with the drugs that belong in that classification. Table 3.1 provides a list of common suffixes and prefixes. Table 3.1 Common Generic Drug Prefixes and Suffixes SUFFIX OR PREFIX DRUG CATEGORY ACTION cefcephsulf-actone -azoles -azosin -caine -calci -cyclovir -cycline -dipine -drodonate -floxacin -lam and -pam -olol -lone Cephalosporins Cephalosporins Sulfonamides Diuretics Antifungals Alpha blocker Local anesthetics Calcium vitamin D Antivirals Tetracyclines Calcium channel blockers Bisphosphonates Fluoroquinolone Benzodiazepines Beta blockers Corticosteroids Antibiotic Antibiotic Antibiotic Spare potassium, increase urine production Antifungal Relaxes blood vessels Block pain Supplements Antiviral Antibiotics Relax blood vessels, decrease heart workload Prevent loss of bone mass Antibiotic Decrease anxiety Relax blood vessels, decrease heart workload Anti-inflammatory -mycin -prazole -pril -sartan Aminoglycoside/macrolides Proton pump inhibitors Angiotensin-converting enzyme inhibitors Nonsteroidal anti-inflammatory drug Angiotensin II antagonists -sone -tidine -statin -zine Corticosteroids H2 receptor blockers Anticholesterol, antilipemics Phenothiazines -profen EXAMPLES Cefadroxil, cefaclor Cephalexin Sulfadiazine Spironolactone (Aldactone) Fluconazole Doxazosin, prazosin Lidocaine Calciferol Acyclovir, valacyclovir Doxycycline, minocycline Amlodipine, felodipine Alendronate, etidronate Ciprofloxacin, levofloxacin Alprazolam, lorazepam Atenolol, metoprolol Methylprednisolone, triamcinolone Antibiotic Erythromycin, vancomycin Reduces gastric acid Omeprazole, pantoprazole Prevents constriction of blood vessels and excess water in Benazepril, captopril, lisinopril the body Nonsteroidal anti-inflammatory Ibuprofen, ketoprofen Prevent constriction of blood vessels and excess water in the body Anti-inflammatory Decrease gastric acid Decrease cholesterol and lipids Antipsychotics, antiemetic Losartan, valsartan Prednisone, dexamethasone Cimetidine, famotidine Atorvastatin, lovastatin Chlorpromazine, prochlorperazine Get Ready for the NCLEX® Examination! Key Points • An agonist drug increases a cell's or organ's activity, and an antagonist drug slows or stops the activity. • Drug absorption and availability are fastest with the IV and other parenteral routes, and slowest for extended-release oral drugs. • Do not crush or let the patient chew, open (if it is a capsule), or cut long-acting or extended-release drugs because this will result in an overdosage. • Most drugs are metabolized by the liver and eliminated by the kidneys. • Patients with liver or kidney impairment often require drug dosages to be lower to prevent adverse effects. • Side effects are common and usually mild expected reactions to drugs, although they may be annoying. 83 • Adverse reactions or effects are serious and sometimes life-threatening patient responses to drug therapy that may require stopping the drug. • Always warn patients who have anaphylactic reactions about their allergy so they will not take the drug again. • Teach patients with a drug allergy to wear a medical alert bracelet or necklace, or carry identification about their allergy. • Special considerations are needed when giving drugs to pediatric patients, pregnant and breast-feeding women, and older adults. • Distribution of water-soluble drugs is faster and more widespread in neonates, infants, and younger children because of their high percentages of total body water. • The critical period for adverse drug effects during pregnancy is between conception and 57 days. • Older adults taking many different drugs are at risk for serious drug interactions. • Ethnicity and genetics can affect drug action in certain individuals. • All drugs that belong to the same category work in the same way and often have similar side effects. • Agonist drugs activate a receptor and antagonists prevent the receptor from affecting a response. • Alcohol can make a drug either more or less effective. • Ethnicity and genetic makeup can change the expected response of drugs. • Consider barriers in older adults that require special teaching regarding their drugs. • Never give a drug with which you are not fully familiar. Review Questions for the NCLEX® Examination 1. Which drug route has the fastest action? 1. Drugs given by way of a feeding tube. 2. Drugs given by subcutaneous injection. 3. Drugs given sublingually. 4. Drugs given intravenously. 2. The patient is given a drug that will help him sleep. Instead he stays awake all night. What is this outcome known as? 1. Paradoxical response 2. Adverse reaction 3. Side effect 4. Anaphylactic reaction 3. The patient is prescribed a drug that leads to very difficult breathing. What is the reason for this response? 84 1. Adverse reaction 2. Anaphylactic reaction 3. Side effect 4. Idiosyncratic response 4. The nurse is giving a drug that blocks the effect of a receptor. What is this response known as? 1. Displacement 2. Additive effect 3. Antagonistic effect 4. Interference 5. The nurse is giving two drugs and finds that the effect of the two drugs taken together is greater than the sum of the effects of each drug were it given alone. What is this response known as? 1. Interference 2. Synergy 3. Displacement 4. Incompatibility 6. Which organ(s) is (are) mostly responsible for the elimination of drugs? 1. Liver 2. Intestines 3. Kidney 4. Gallbladder 7. The physician has changed an order from morphine 10 mg intravenously every 2 hours to morphine 30 mg by mouth every 4 hours. What does this nurse recognize about this order? 1. The increased dosage is needed because of the “first-pass” effect. 2. The prescriber has made a drug error. 3. The dosage change is needed because the patient excretes oral drugs faster than IV drugs. 4. The change is needed because the patient reports the IV dose is ineffective. 8. A patient on a diuretic (increases urine production) complains of leg cramping. Which is the priority action of the nur