NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.
Open Resources for Nursing (Open RN); Ernstmeyer K, Christman E, editors. Nursing Pharmacology [Internet]. 2nd edition. Eau Claire (WI): Chippewa Valley Technical College; 2023.
• Discuss the processes of pharmacokinetics
• Use multiple professional resources, including technology, to identify pertinent information related to drugs
• Describe the processes of pharmacodynamics
• Consider pharmacodynamic differences across the life span
• Differentiate among prescription drugs, over-the-counter drugs, herbals, and dietary supplements
Safe medication administration is a vital component of the nursing role. Every day, nurses make critical decisions regarding the safety, appropriateness, and effectiveness of the medications administered to their clients. Examples of decisions that a nurse might make during client care are as follows:
Is my client’s heart rate within the correct range to receive this beta-blocker medication? Does my client have adequate renal function prior to administering this dose of antibiotic? Is this pain medication effective in controlling my client’s discomfort?To make safe decisions regarding medication administration, the nurse must have a strong understanding of pharmacology, the science dealing with actions of drugs on the body. Symptom management and a client’s overall well-being are strongly connected to the appropriate administration of medications prescribed in a client’s treatment plan. Before a student nurse reviews a medication order, checks a medication administration record, or removes a medication from a dispensing machine, it is essential to have a foundational understanding of how medications interact with the human body. This chapter will review basic concepts related to pharmacokinetics and pharmacodynamics.
Pharmacokinetics is the term that describes the four stages of absorption, distribution, metabolism, and excretion of drugs. Drugs are medications or other substances that have a physiological effect when introduced to the body. There are four basic stages a medication goes through within the human body: absorption, distribution, metabolism, and excretion. This entire process is sometimes abbreviated ADME.
Absorption is the first stage of pharmacokinetics and occurs after medications enter the body and travel from the site of administration into the body’s circulation. Distribution is the second stage of pharmacokinetics. It is the process by which medication is spread throughout the body. Metabolism is the third stage of pharmacokinetics and involves the breakdown of a drug molecule. Excretion is the final stage of pharmacokinetics and refers to the process in which the body eliminates waste. Each of these stages is described separately in the following sections of this chapter.
Research scientists who specialize in pharmacokinetics must also pay attention to another dimension of drug action within the body: time. Scientists do not have the ability to visualize where a drug is going or how long it is active. To compensate, they use mathematical models and precise measurements of blood and urine to determine where a drug goes and how much of the drug (or breakdown product) remains after the body processes it. Other indicators, such as blood levels of liver enzymes, can help predict how much of a drug is going to be absorbed.
Principles of chemistry are also applied while studying pharmacokinetics because the interactions between drugs and body molecules represent a series of chemical reactions. Understanding the chemical encounters between drugs and biological environments, such as the bloodstream and the oily surfaces of cells, is necessary to predict how much of a drug will be metabolized by the body.
Pharmacodynamics refers to the effects of drugs in the body and the mechanism of their action. As a drug travels through the bloodstream, it exhibits a unique affinity for a drug-receptor site, meaning how strongly it binds to the site. Drugs and receptor sites create a lock and key system (see Figure 1.1[1]) that affect how drugs work and the presence of a drug in the bloodstream after it is administered. This concept is broadly termed as drug bioavailability.
Pharmacodynamics: Drug and Receptor Binding
The bioavailability of drugs is an important feature that chemists and pharmaceutical scientists keep in mind when designing and packaging medicines. However, no matter how effectively a drug works in a laboratory simulation, the performance in the human body will not always produce the same results, and individualized responses to drugs have to be considered. Although many responses to medications may be anticipated, a person’s unique genetic makeup may significantly impact their response to a drug. Pharmacogenetics is defined as the study of how people’s genes affect their response to medicines.[2]
The first stage of pharmacokinetics is known as absorption. Absorption occurs after drugs enter the body and travel from the site of administration into the body’s circulation. Medications can enter the body through various routes. Common routes to administer medications include the following examples:
Oral (swallowing an aspirin tablet) Enteral (administering medication into the gastrointestinal tract via a nasogastric tube) Rectal (administering an acetaminophen suppository) Intranasal (spraying allergy medication into the nose) Inhalation (breathing in asthma medication from an inhaler) Intramuscular (injecting an influenza vaccine into the deltoid muscle) Subcutaneous (injecting insulin into the subcutaneous tissue in the abdomen) Transdermal (wearing a nicotine patch that is absorbed through the skin) Intravenous (administering antibiotics directly into a vein)When a medication is administered orally or enterally, absorption may be significantly hindered in the gastrointestinal (GI) tract. For example, when medications made of protein are introduced into the GI tract, they can be quickly deactivated by enzymes as they pass through the stomach and duodenum. If some of the drug is absorbed from the intestine into the bloodstream, part of the absorbed portion may be broken down by liver enzymes, whereas the remaining part escapes into the general circulation. The portion of the drug that enters the general circulation will either become protein-bound (and thus inactive) or remain free to circulate and create an action at a receptor site. This entire process that results in reduced concentration of active drug available in an individual’s circulation is known as the first-pass effect. Due to the first-pass effect, prescribing providers and nurses administering medications must understand that several doses of an oral medication may be needed before enough free drug stays active in the circulation to exert the desired effect. These metabolic effects are further described in the “Metabolism” section later in this chapter.
A workaround to the first-pass effect is to administer medication using alternate routes to the GI tract. Examples of alternative routes that avoid the first-pass effect include transdermal, nasal, inhalation, injection, or intravenous administration of medication. Alternative routes of medication administration bypass the first-pass effect by entering the bloodstream directly or via absorption through the skin or lungs. For example, pain relievers may be administered directly into the bloodstream (referred to as intravenous medications) so they are quickly available for distribution to tissues within the body.
Alternative routes of medication have other potential considerations. For example, injections are often painful and cause a break in the skin, an important barrier to infection. They can also be costly and difficult to administer daily, may cause localized side effects, or contribute to unpredictable fluctuations in medication blood levels.
Transdermal application of medication is an alternate route that has the primary benefit of slow, steady drug delivery directly to the bloodstream, without passing through the liver first. See Figure 1.2[1] for an image of a client self-administering a transdermal patch. Drugs delivered transdermally enter the blood via a meshwork of small arteries, veins, and capillaries in the skin. This makes the transdermal route of drug delivery particularly useful when a medication must be administered over a longer period of time to control symptoms. For example, transdermal application of fentanyl, a pain medication, can provide effective pain management over a several hours; a scopolamine patch can control motion sickness over the duration of a cruise ship vacation; and a nitroglycerin patch is used to prevent chronic chest pain. Despite their advantages, transdermal patches have a significant drawback in that only very small drug molecules can enter the body through the skin, making this application route inappropriate for some types of medications.
Applying Transdermal Patch
Inhaling drugs through the nose or mouth is another alternative route for rapid medication delivery that bypasses the liver. See Figure 1.3 for an image of a client self-administering an inhaler.[2] Metered-dose inhalers have been a mainstay of asthma therapy for several years, and nasal steroid medications are often prescribed for allergy and sinus problems.
Adult Using Inhaler
Researchers are currently exploring alternative methods of drug delivery such as the use of inhaled insulin powders. Afrezza® is an example of an inhaled insulin approved by the Food and Drug Administration (FDA) to assist with blood sugar control. This technology stems from novel uses of chemistry and engineering to manufacture insulin particles of just the right size for absorption. If too large, the insulin particles could lodge in the lungs; if too small, the particles will be exhaled.[3]
Gastric absorption in neonates and pediatric clients varies from adults. In infants, the acid-producing cells of the stomach are immature until around the age of one to two years. Additionally, gastric emptying may be decreased because of slowed or irregular peristalsis (coordinated muscle movements of the intestines).
The liver of infants and children is not fully mature, resulting in a decrease in first-pass elimination and subsequently higher drug levels in the bloodstream.[4]
As a natural result of aging, older adults will experience decreased blood flow to tissues within the GI tract. In addition, there may be changes in the gastric (stomach) pH that may alter the absorption of certain medications. Older adult clients may also experience variations in available plasma proteins, which can impact drug levels of medications that are highly protein-bound.
Consideration must also be given to the use of subcutaneous and intramuscular injections in older clients experiencing decreased cardiac output because decreased drug absorption of medications can occur when peripheral circulation is decreased. Additionally, as adults age, they often have less subcutaneous fat, resulting in decreased absorption of medication from transdermal patches that require adequate subcutaneous fat stores for proper absorption.[5]
The box below summarizes route considerations that a nurse should consider when administering medication.
Oral (PO) or Enteral (NGT, GT, OGT) Ingestion
Oral route is a convenient route for administration of solid and liquid formulations.Additional variables that may influence the rate and extent of absorption include enteric coating or extended-release formulations, acidity of gastric contents, gastric emptying rate, dietary contents, and presence of other drugs.
First-pass effect: Blood containing the absorbed drug passes through the liver, which can deactivate a substantial amount of the drug and decrease its bioavailability (the percentage of dose that reaches the systemic circulation).
Parenteral Injection
Subcutaneous and intramuscular administration: Injections can be difficult for clients to self-administer at home or to administer on a daily basis. They can be costly and painful. Injections also cause a break in skin that is an important barrier to infection, can cause fluctuation in drug levels, and can cause localized side effects to skin, such as bruising, redness, bleeding, and swelling.
Intravenous (IV): IV drugs are fully available to tissues after administration into the bloodstream, offering complete bioavailability and an immediate effect. However, this route requires intravenous access that can be painful to the client and also increases risk for infection. Medications must be administered in sterile fashion, and if two products are administered simultaneously, their compatibility must be verified. There is also an increased risk of toxicity to the kidneys or liver.
Pulmonary Inhalation
• Inhalation allows for rapid absorption of drugs in gaseous, vaporized, or aerosol form through the lung tissue.
• Absorption of particulates/aerosols depends on particle/droplet size, which influences depth of entry through the pulmonary tree to reach the alveoli.
• The ability of the client to create successful inhalation, especially in the presence of bronchospasm, may also influence depth of entry in the pulmonary tree.
Topical and Transdermal Application
• Topical creams, lotions, and ointments are generally used for local effect; transdermal patch formulations are used for systemic effect.
• Absorption through the buccal or sublingual membranes may be rapid and is used for systemic effect.
• Absorption through skin is generally slower but produces a steady, long-term effect that avoids the first-pass effect. However, absorption of medication is affected by blood flow to the skin.[6] For this reason, heat and cold applications should not be used over transdermal medications.
Fernandez, E., Perez, R., Hernandez, A., Tejada, P., Arteta, M., & Ramos, J. T. (2011). Factors and mechanisms for pharmacokinetic differences between pediatric population and adults. Pharmaceutics, 3(1), 53–72. ↵10.3390/pharmaceutics3010053 [PMC free article : PMC3857037 ] [PubMed : 24310425 ] [CrossRef]
Fernandez, E., Perez, R., Hernandez, A., Tejada, P., Arteta, M., & Ramos, J. T. (2011). Factors and mechanisms for pharmacokinetic differences between pediatric population and adults. Pharmaceutics, 3(1), 53–72. ↵10.3390/pharmaceutics3010053 [PMC free article : PMC3857037 ] [PubMed : 24310425 ] [CrossRef]
This work is a derivative of Principles of Pharmacology by LibreTexts and is licensed under CC BY-NC-SA 4.0 ↵
The second stage of pharmacokinetics is the process known as distribution. Distribution is the process by which a drug is dispersed throughout the body’s blood and tissues. After a drug enters into systemic circulation by absorption or direct administration, it will pass from vascular spaces to tissues where a drug-receptor interaction will occur, creating the effect of the drug.
Drugs are designed to primarily cause one effect, meaning they bind more strongly to one specific receptor site and predictably cause or block an action. However, side effects and adverse effects can occur when the drug binds to other sites in addition to the target tissue, causing an unintended action. These side effects can range from tolerable to unacceptable and can result in the discontinuation of the medication. For example, a person might take the pain reliever ibuprofen (Advil) to treat a sore leg muscle, and the pain may be subsequently relieved, but there may also be stomach irritation as a side effect.
The distribution of a drug throughout the body is dependent on many body-related factors such as blood flow, tissue differences, plasma protein-binding, the blood-brain barrier, and the placental barrier.
The circulatory system transports medications throughout the body in the bloodstream. Many factors can affect the blood flow and delivery of medication, such as decreased blood flow (due to dehydration), blocked vessels (due to atherosclerosis), constricted vessels (due to uncontrolled hypertension), or weakened pumping by the heart muscle (due to heart failure). As an example, when administering an antibiotic to a client with diabetes who has an infected toe, it may be difficult for the antibiotic to move through the blood vessels all the way to the area of the toe that is infected because of blocked vessels in the legs and feet due to atherosclerosis.
Distribution occurs most rapidly into tissues with a greater number of blood vessels that allow high blood flow (such as the lungs, kidneys, liver, brain). Distribution occurs least rapidly in tissues with fewer numbers of blood vessels (such as fat), resulting in low blood flow. However, lipophilic drugs (i.e., drugs that dissolve in lipid environments) disproportionately distribute into adipose tissue in obese subjects.
The permeability of capillaries is tissue-dependent. Capillaries of the liver and kidney are porous, allowing for greater permeability. Distribution rates are relatively slower or nonexistent into the central nervous system because of the tight junction between capillary endothelial cells and the blood-brain barrier.
After a drug enters the bloodstream, a portion of it exists as free drug, dissolved in plasma water, but a portion of it becomes bound to proteins. This is important because only free and unbound drugs will pass from the bloodstream to tissues where drug-receptor interactions will occur, thus producing the first effects of a medication. The other portion of the drug that becomes “protein-bound” is inactive while it is bound. For many drugs, these bound forms can account for 95-98% of the total.[1]
Protein binding can also act as a reservoir as the drug is released slowly, causing a prolonged action. When considering drug distribution, it is important to consider both the amount of free drug that is readily available to tissues, as well as the protein binding that causes the drug to be released over time.
Albumin is one of the most important proteins in the blood. Albumin levels can be decreased by several factors such as malnutrition and liver disease. Therefore, clients with low albumin levels may experience differences in the desired actions of administered medication because of the consequence effect on protein-binding and distribution.
Competition for plasma binding can also impact the effects of drugs. For example, aspirin and warfarin are anticoagulants that compete for the same plasma protein-binding site. Administering both drugs at the same time will increase the amount of unbound drug, thereby increasing their effects and increasing the client’s risk for bleeding.[2]
As an analogy of how protein binding affects the distribution of medications, consider passengers at a bus stop going to their destination. See Figure 1.4[3] for an image of a bus related to this analogy. Many passengers (i.e., drug molecules) want to take a ride on the bus. Everyone is eager to get to their destination (i.e., receptor sites) and tries to find a seat. Some passengers are stronger than others and take all the seats first (such as drug molecules with greater protein-binding ability). When there aren’t enough seats on the bus, some passengers are left at the bus stop and become “free” to move around or walk to their destination. In a similar way, “free” drug molecules that are not protein-bound circulate freely in the bloodstream. The “free” passengers in this analogy may go directly to their destination, or they may stop at other locations along the route. In a similar manner, “free” drug molecules produce the first intended or unintended effects in the body when they attach to receptors. Furthermore, similar to the passengers who had seats on the bus and then later got off at their destination, the medication molecules attached to proteins are eventually released and attach to the receptor sites.
Protein-Binding Like Available Seats on a Bus
Medications destined for the central nervous system (the brain and spinal cord) face an even larger hurdle than protein-binding; they must also pass through a nearly impenetrable barricade called the blood-brain barrier. This blockade is built from a tightly woven mesh of capillaries that protect the brain from potentially dangerous substances, such as poisons or viruses. Only certain medications made of lipids (fats) or those with a “carrier” can get through the blood-brain barrier.
Scientists have devised ways for medications to penetrate the blood-brain barrier. For example, the brand-named medication Sinemet® is a combination of two drugs: carbidopa and levadopa. Carbidopa is designed to carry the levadopa medication across the blood-brain barrier, where it enters the brain and is converted into dopamine to exert its effect on symptoms related to Parkinson’s disease.
Some medications inadvertently bypass the blood-brain barrier and impact an individual’s central nervous system function as a side effect. For example, diphenhydramine is an antihistamine used to decrease allergy symptoms. However, it can also cross the blood-brain barrier, depress the central nervous system, and cause the side effect of drowsiness. In the case of a person who has difficulty falling asleep, this drowsy side effect may be useful, but for a person trying to carry out daily activities, drowsiness can be problematic.
The placenta links mother and fetus, and the blood-placental barrier regulates transfer of molecules between maternal and fetal circulation to protect the fetus. Drug transporters are involved in transport of drugs through the placenta, affecting potential drug distribution to the fetus.[4] The placenta is known to be permeable to some medications, and furthermore, some drugs can cause significant harm to the fetus. However, many medications have not been specifically studied in pregnant clients and their effects on the fetus are unknown.
For this reason, it is always important to consider the potential effects of medication on the fetus if it is administered to a client who is pregnant or who may become pregnant. Nurses play a critical role in notifying the health care provider regarding potential safety concerns if medication can be distributed to the fetus. Nurses must always check a recent, evidence-based drug reference before administering medications to a client who is pregnant or may become pregnant. This imperative is implied in the remaining chapters.
Fat content in infants and children is decreased because of greater total body water. Additionally, protein-binding capacity is decreased, and the developing blood-brain barrier allows more drugs to enter the central nervous system.[5]
At the same body mass index, older adults, on average, tend to have more body fat than younger adults. This increased body fat can result in a longer duration of action for many medications that accumulate in fatty tissues. Serum albumin also decreases, resulting in more active free drug circulating within the body. For these reasons related to distribution, many older adult clients require lower dosages of medication.[6]
Liu, L., & Liu, X. (2019). Contributions of drug transporters to blood-placental barrier. Advances in Experimental Medicine and Biology, 1141, 505–548. ↵10.1007/978-981-13-7647-4_11 [PubMed : 31571173 ] [CrossRef]
Fernandez, E., Perez, R., Hernandez, A., Tejada, P., Arteta, M., & Ramos, J. T. (2011). Factors and mechanisms for pharmacokinetic differences between pediatric population and adults. Pharmaceutics, 3(1), 53–72. ↵10.3390/pharmaceutics3010053 [PMC free article : PMC3857037 ] [PubMed : 24310425 ] [CrossRef]
Fernandez, E., Perez, R., Hernandez, A., Tejada, P., Arteta, M., & Ramos, J. T. (2011). Factors and mechanisms for pharmacokinetic differences between pediatric population and adults. Pharmaceutics, 3(1), 53–72. ↵10.3390/pharmaceutics3010053 [PMC free article : PMC3857037 ] [PubMed : 24310425 ] [CrossRef]
After a drug has been absorbed and distributed throughout the body, it is broken down by a process known as metabolism so that it can be excreted from the body. Drugs undergo chemical alteration by various body systems to create compounds that are more easily excreted.
As previously discussed in this chapter, medications that are swallowed or otherwise administered into the gastrointestinal tract are inactivated by the intestines and liver, known as the first-pass effect. Additionally, everything that enters the bloodstream, whether swallowed, injected, inhaled, absorbed through the skin, or produced by the body itself, is metabolized by the liver. See Figure 1.5[1] for an image of the liver. These chemical alterations are known as biotransformations. The biotransformations that take place in the liver are performed by liver enzymes.
Biotransformations occur by mechanisms categorized as either Phase I (modification), Phase II (conjugation), and in some instances, Phase III (additional modification and excretion.)[2]
Phase I biotransformations alter the chemical structure of the drug. Many of the products of enzymatic breakdown, called metabolites, are less chemically active than the original molecule. For this reason, the liver is referred to as a “detoxifying” organ. An example of a Phase I biotransformation is when diazepam, a medication prescribed for anxiety, is transformed into desmethyldiazepam and then to oxazepam. Both these metabolites produce similar physiological and psychological effects of diazepam.[3]
In some instances, Phase I biotransformations change an inactive drug into an active form called a “prodrug.” Prodrugs improve a medication’s effectiveness. They may also be designed to avoid certain side effects or toxicities. For example, sulfasalazine is a medication prescribed for rheumatoid arthritis. It is prodrug that is not active in its ingested form but becomes active after Phase I modification.
Phase II biotransformations involve reactions that couple the drug molecule with another molecule in a process called conjugation. Conjugation typically renders the compound pharmacologically inert and water-soluble so it can be easily excreted. These processes can occur in the liver, kidney, lungs, intestines, and other organ systems. An example of Phase II metabolism is when oxazepam, the active metabolite of diazepam, is conjugated with a molecule called glucuronide so that it becomes physiologically inactive and is excreted without further chemical modification.[4]
Following Phase II metabolism, Phase III biotransformations may also occur, where the conjugates and metabolites are excreted from cells.[5]
Critical factors in drug metabolism are the type and concentration of liver enzymes. The most important enzymes for medical purposes are monoamine oxidase and cytochrome P450. These two enzymes are responsible for metabolizing dozens of chemicals.[6]
Drug metabolism can be influenced by a number of factors. One major disruptor of drug metabolism is depot binding. Depot binding is the coupling of drug molecules with inactive sites in the body, resulting in the drug not being accessible for metabolism. This action can also affect the duration of action of other medications susceptible to depot binding. For example, tetrahydrocannabinol (THC), the main psychoactive component of marijuana, is highly lipid-soluble and depot binds in the adipose tissue of users. This interaction drastically slows the metabolism of the drug, so metabolites of THC can be detected in urine weeks after the last use.[7]
Another factor in drug metabolism is enzyme induction. Enzymes are induced by repeated use of the same drug. The body becomes accustomed to the constant presence of the drug and compensates by increasing the production of the enzyme necessary for the drug’s metabolism. This contributes to a condition referred to as tolerance and causes clients to require ever-increasing doses of certain drugs to produce the same effect. For example, clients who take opioid analgesics over a long period of time will notice that their medication becomes less effective over time.[8]
In contrast, some drugs have an inhibitory effect on enzymes, making the client more sensitive to other medications metabolized through the action of those enzymes. For example, monoamine oxidase inhibitors (MAOIs) are prescribed as antidepressants because they block monoamine oxidase, the enzyme that breaks down serotonin and dopamine, thus increasing the concentration of these chemicals in the central nervous system. However, this can cause problems when clients taking an MAOI also take other medications that increase the levels of these chemicals, such as dextromethorphan found in cough syrup.[9]
Additionally, drugs that share metabolic pathways can “compete” for the same binding sites on enzymes, thus decreasing the efficiency of their metabolism. For example, alcohol and some sedatives are metabolized by the cytochrome P450 enzyme and only a limited number of these enzymes exist to break these drugs down. Therefore, if a client takes a sedative after drinking alcohol, the sedative is not well-metabolized because most of cytochrome P450 enzymes are filled by alcohol molecules. This results in reduced excretion and high levels of both drugs in the body with enhanced effects. For this reason, the co-administration of alcohol and sedatives can be deadly.
When administering medication, nurses must know how and when the medication is metabolized and eliminated from the body. Most of the time, the rate of elimination of a drug depends on the concentration of the drug in the bloodstream. However, the elimination of some drugs occurs at a constant rate that is independent of plasma concentrations. For example, the ethanol contained in alcoholic beverages is eliminated at a constant rate of about 15 mL/hour regardless of the concentration in the bloodstream.[10]
Half-life refers to the rate at which 50% of a drug is eliminated from the body. Half-life can vary significantly between drugs. Some drugs have a short half-life of only a few hours and must be given multiple times a day, whereas other drugs have half-lives exceeding 12 hours and can be given as a single dose every 24 hours. See Figure 1.6[11] for an illustration of half-life affecting the blood concentration of medication over time.
Half-Life Affecting Blood Concentration of Medication Over Time
Half-life affects the duration of the therapeutic effect of a medication. Many factors can influence half-life. For example, liver disease can prolong half-life if it is no longer effectively metabolizing the medication. Information about half-life of a specific medication can be found in evidence-based medication references. For example, in the “Clinical Pharmacology” section of the DailyMed reference for furosemide, the half-life is approximately two hours.
Depending on whether a drug is metabolized and eliminated by the kidneys or liver, impairment in either of these systems can significantly alter medication dosing, frequency of doses, anticipated therapeutic effect, and even whether a particular medication can be used at all. Nurses must work with other members of the health care team to prevent drug interactions that could significantly affect a client’s health and well-being. Nurses must be alert for signs of a toxic buildup of metabolites or active drugs, particularly if the client has liver or kidney disease, so that they can alert the health care provider. In other cases, drugs such as warfarin and certain antibiotics are dosed and monitored by pharmacists, who monitor serum levels of the drugs, as well as kidney function.
The developing liver in infants and young children produces decreased levels of enzymes. This may result in a decreased ability of the young child or neonate to metabolize medications. In contrast, older children may experience increased metabolism and require higher doses of medications once the hepatic enzymes are fully produced.[12]
Metabolism by the liver may significantly decline in the older adult. As a result, dosages should be adjusted according to the client’s liver function and their anticipated metabolic rate. First-pass metabolism also decreases with aging, so older adults may have higher “free” circulating drug concentrations and thus be at higher risk for side effects and toxicities.[13]
Metabolism can be influenced by many factors within the body. If a client has liver damage, they may not be able to breakdown (metabolize) medications as efficiently. Dosages are calculated according to the liver’s ability to metabolize and the kidney’s ability to excrete.
When caring for a client with cirrhosis, how can this condition impact the dosages prescribed?
Note: Answers to the Critical Thinking activities can be found in the “Answer Key” section at the end of the book.
Did You Know?
Did you know that, in some people, a single glass of grapefruit juice can alter levels of drugs used to treat allergies, heart diseases, and infections? Fifteen years ago, pharmacologists discovered this “grapefruit juice effect” by luck, after giving volunteers grapefruit juice to mask the taste of a medicine. Nearly a decade later, researchers figured out that grapefruit juice affects the metabolizing rates of some medicines by lowering levels of a drug-metabolizing enzyme called CYP3A4 (part of the CYP450 family of drug-binding enzymes) in the intestines.
Paul B. Watkins of the University of North Carolina at Chapel Hill discovered that other juices like Seville (sour) orange juice—but not regular orange juice—have the same effect on the liver’s ability to metabolize using enzymes. Each of ten people who volunteered for Watkins’ juice-medicine study took a standard dose of felodopine, a drug used to treat high blood pressure, diluted in grapefruit juice, sour orange juice, or plain orange juice. The researchers measured blood levels of felodopine at various times afterward. The team observed that both grapefruit juice and sour orange juice increased blood levels of felodopine, as if the people had received a higher dose. Regular orange juice had no effect. Watkins and his coworkers have found that a chemical common to grapefruit and sour oranges, dihydroxybergamottin, is likely the molecular culprit. Thus, when taking medications that use the CYP3A4 enzyme to metabolize, clients are advised to avoid grapefruit juice and sour orange juice.[14]
“Grapefruit” by ExplorerBob is licensed under CC0
This work is a derivative of StatPearls by Susa, Hussain, and Preuss and is licensed under CC BY 4.0 ↵.
This work is a derivative of StatPearls by Susa, Hussain, and Preuss and is licensed under CC BY 4.0 ↵.
This work is a derivative of StatPearls by Susa, Hussain, and Preuss and is licensed under CC BY 4.0 ↵.
This work is a derivative of StatPearls by Susa, Hussain, and Preuss and is licensed under CC BY 4.0 ↵.
This work is a derivative of StatPearls by Susa, Hussain, and Preuss and is licensed under CC BY 4.0 ↵.
This work is a derivative of StatPearls by Susa, Hussain, and Preuss and is licensed under CC BY 4.0 ↵.
This work is a derivative of StatPearls by Susa, Hussain, and Preuss and is licensed under CC BY 4.0 ↵.
This work is a derivative of StatPearls by Susa, Hussain, and Preuss and is licensed under CC BY 4.0 ↵.
This work is a derivative of StatPearls by Susa, Hussain, and Preuss and is licensed under CC BY 4.0 ↵.
“Concentration _vs_number _of_half-life_periodes.png” by OPPSD is licensed under CC BY-SA 3.0 ↵.Fernandez, E., Perez, R., Hernandez, A., Tejada, P., Arteta, M., & Ramos, J. T. (2011). Factors and mechanisms for pharmacokinetic differences between pediatric population and adults. Pharmaceutics , 3(1), 53–72. ↵ 10.3390/pharmaceutics3010053 . [PMC free article : PMC3857037 ] [PubMed : 24310425 ] [CrossRef]
Fernandez, E., Perez, R., Hernandez, A., Tejada, P., Arteta, M., & Ramos, J. T. (2011). Factors and mechanisms for pharmacokinetic differences between pediatric population and adults. Pharmaceutics , 3(1), 53–72. ↵ 10.3390/pharmaceutics3010053 . [PMC free article : PMC3857037 ] [PubMed : 24310425 ] [CrossRef]
Excretion is the final stage of a medication interaction within the body. The body has absorbed, distributed, and metabolized the medication molecules – now what does it do with the leftovers? Remaining parent drugs and metabolites in the bloodstream are often filtered by the kidney, where a portion undergoes reabsorption back into the bloodstream, and the remainder is excreted in the urine. The liver also excretes byproducts and waste into the bile. Another potential route of excretion is the lungs. For example, drugs like alcohol and the anesthetic gases are often eliminated by the lungs.[1]
The most common route of excretion is through the kidneys. As the kidneys filter blood, the majority of drug byproducts and waste are excreted in the urine. The rate of excretion can be estimated by taking into consideration several client factors, including age, weight, biological sex, and kidney function. There are known sex differences in the three main renal functions of glomerular filtration, tubular secretion and tubular reabsorption. Renal clearance is generally higher in men than in women.[2]
Kidney function is measured by lab values such as serum creatinine, glomerular filtration rate (GFR), and creatinine clearance. If a client’s kidney function is decreased, then their ability to excrete medication is affected, and drug dosages must be altered for safe administration.
Renal disorders, such as chronic kidney disease, can reduce kidney function and hinder drug excretion. As kidney function decreases with age, drug excretion becomes less efficient, and dosing adjustments may be needed. Other medical conditions that impact blood flow to the kidneys can also affect drug elimination. For example, heart failure can affect systemic blood flow to the kidney, resulting in decreased filtration and elimination of drugs.
As the liver filters blood, some drugs and their metabolites are actively transported by hepatocytes (liver cells) to bile. Bile moves through the bile ducts to the gallbladder and then on to the small intestine. During this process, some drugs may be partially absorbed by the intestine back into the bloodstream. Other drugs are biotransformed (metabolized) by intestinal bacteria and reabsorbed. Unabsorbed drugs and byproducts/metabolites are excreted in the feces.
If a client has decreased liver function, their ability to excrete medication is affected, and drug dosages must be adjusted. Lab studies used to evaluate liver function are called liver function tests and include measurement of alanine transaminase (ALT) and aspartate aminotransferase (AST) enzymes that the body releases in response to damage to or disease of the liver.
Conditions that cause decreased blood flow to the liver can also affect the metabolism and excretion of drugs. For example, conditions such as shock, hypovolemia, or hypotension cause decreased liver perfusion and may require adjustment of dosages of medication.
Sweat, tears, reproductive fluids (such as seminal fluid), and breast milk can also contain drugs and byproducts/metabolites of drugs. This can pose a toxic threat, such as the exposure of an infant to breast milk containing drugs or byproducts of drugs ingested by the mother. Therefore, nurses must refer to a drug reference and contact a health care provider with any concerns before administering medications to a mother who is breastfeeding.[3]
Neonates and children have immature kidneys with decreased glomerular filtration, resorption, and tubular secretion. As a result, they do not excrete medications as efficiently from the body. Dosing for most medications used to treat infants and pediatric clients is commonly based on weight in kilograms, and a smaller dose is usually prescribed. In addition, pediatric clients may have higher levels of free circulating medication than anticipated and may become toxic quickly. Therefore, it is vital for nurses to diligently recheck dosages before administering medications and closely monitor infants and children for early identification of adverse effects and drug toxicity.[4]
Kidney and liver function often decrease with age, which can lead to decreased metabolism and excretion of medications. Subsequently, medication may have a prolonged half-life with a greater potential for toxicity due to elevated circulating drug levels. Some medications may be avoided or smaller doses recommended for older clients due to these factors, which is commonly referred to as “Start low and go slow.”[5]
Safely administering medications to clients is a significant concern and requires team effort by pharmacists, prescribing health care providers, and nurses. In addition to the factors described in this chapter, there are many other considerations for safe medication administration that are further explained in the “Legal/Ethical” chapter.
When providing care for a client who has chronic kidney disease, how does this condition impact medication excretion?
Note: Answers to the Critical Thinking activities can be found in the “Answer Key” section at the end of the book.
“Pharmacokinetics Quiz” by E. Christman for Open RN is licensed under CC BY 4.0
This work is a derivative of Principles of Pharmacology by LibreTexts and is licensed under CC BY-NC-SA 4.0 ↵
Soldin, O. P., & Mattison, D. R. (2009). Sex differences in pharmacokinetics and pharmacodynamics. Clinical Pharmacokinetics, 48(3), 143–157. ↵10.2165/00003088-200948030-00001 [PMC free article : PMC3644551 ] [PubMed : 19385708 ] [CrossRef]
This work is a derivative of Principles of Pharmacology by LibreTexts and is licensed under CC BY-NC-SA 4.0 ↵
Fernandez, E., Perez, R., Hernandez, A., Tejada, P., Arteta, M., & Ramos, J. T. (2011). Factors and mechanisms for pharmacokinetic differences between pediatric population and adults. Pharmaceutics, 3(1), 53–72. ↵10.3390/pharmaceutics3010053 [PMC free article : PMC3857037 ] [PubMed : 24310425 ] [CrossRef]
Fernandez, E., Perez, R., Hernandez, A., Tejada, P., Arteta, M., & Ramos, J. T. (2011). Factors and mechanisms for pharmacokinetic differences between pediatric population and adults. Pharmaceutics, 3(1), 53–72. ↵10.3390/pharmaceutics3010053 [PMC free article : PMC3857037 ] [PubMed : 24310425 ] [CrossRef]
So far in this chapter, we have learned the importance of pharmacokinetics in how the body absorbs, distributes, metabolizes, and excretes a medication. Now let’s consider how drugs act on target sites of action in the body, referred to as pharmacodynamics.
Mechanism of action is a medical term that describes how a medication works in the body. For example, did you know that an osmotic laxative like magnesium citrate attracts and binds with water? The mechanism of action for this medication is it pulls water into the bowel, which softens stool and increases the likelihood of a bowel movement.
A drug’s mechanism of action may refer to how it affects a specific receptor. Many drugs bind to specific receptors on the surface of cells to cause an action. For example, morphine binds to a specific receptor that inhibits transmission of nerve impulses along the pain pathway and decreases a client’s feelings of pain.
Other medications inhibit specific enzymes for a desired effect. For example, earlier in this chapter we discussed how monoamine oxidase inhibitors (MAOIs) are prescribed as antidepressants because they block monoamine oxidase, the enzyme that breaks down serotonin and dopamine. This blockage increases the concentration of serotonin and dopamine in the central nervous system and increases a client’s feelings of pleasure.
Drugs have agonistic or antagonistic effects on receptor sites. An agonist binds tightly to a receptor to produce a desired effect. An antagonist competes with other molecules and blocks a specific action or response at a receptor site. See Figure 1.7[1] for an illustration of how a beta-blocker, an antagonist cardiac medication, blocks specific action on the beta receptors of a cardiac cell.
Antagonist Action of Beta-Blockers on Beta Receptors of a Cardiac Cell
Agonistic and antagonistic effects on receptors for common classes of medications are further discussed in the “Autonomic Nervous System” chapter.
Atenolol (Tenormin) is an antagonist medication. Does the nurse anticipate this will cause a specific action or block a specific action at a receptor site?
Note: Answers to the Critical Thinking activities can be found in the “Answer Key” section at the end of the book.
“Mechanism of Action” by Dominic Slausen at Chippewa Valley Technical College is licensed under CC BY 4.0 ↵.
There are a variety of drugs and substances that clients may utilize for symptom management or to enhance their wellness. Nurses document clients’ use of prescription medications, over-the-counter medications, herbal substances, and other supplements in the medical record. Some substances have a long half-life and have the potential to interact with new medications, so accuracy is vital. Ensuring an accurate medical record and knowledge of the different types of substances a client is taking is important for an effective nursing plan of care.
Drugs are prescribed by a licensed prescriber for a specific person’s use and regulated through the United States Food and Drug Administration (FDA). More information about FDA approval of medications is described in the “Legal/Ethical” chapter. Prescription medications include brand-name medications and generic medications.[1]
Table 1.8 provides prefixes, suffixes, and roots associated with common prescription medications. As a nurse, familiarizing yourself with the content in the table can help you to quickly organize medications based on their name and recall their mechanism of action and identify potential interactions or side effects. This knowledge can improve your ability to safely administer medications and provide health teaching. Ultimately, this knowledge can lead to improved client outcomes, increased satisfaction, and a reduced risk of adverse events and medication errors.
Common Classes of Medications, Examples, Suffixes, and Roots
| Class of Medication | Example | Common Suffixes | Common Roots |
|---|---|---|---|
| Analgesics | lidocaine | -caine | -morph, -morphe, -morphic |
| Antacids | omeprazole | -azole | -tidine |
| Antibiotics | levofloxacin | -mycin, -floxacin | bacter-, vir-, -cidal |
| Anticoagulants | warfarin | -arin | coagul- |
| Antidepressants | fluoxetine | -oxetine, -ipramine | serotonin, norepinephrine |
| Antihistamines | diphenhydramine | -dine, -mine | hist- |
| Anti-inflammatory | cortisone | -one | -corti-, -flam-, -prost- |
| Antipsychotics | olanzapine | -azine, -apine | dopa-, sero-, -plegia |
| Beta-blockers | metoprolol | -olol | adrenergic, beta- |
| Bronchodilators | albuterol | -terol | bronch-, -pnea |
| Corticosteroids | prednisone | -sone or -solone | |
| Diuretics | furosemide | -semide, -thiazide | -uret-, -osm- |
| Hypoglycemics | glipizide | -ide | gluc-, insulin- |
| Statins | atorvastatin | -statin | cholesterol, lipid- |
Generic medications can be safe and effective alternatives to their brand-name counterparts at a significantly reduced cost. By law, generic medications must have the same chemically active ingredient in the same dose as the brand name (i.e., they must be “bio-equivalent”). However, the excipients (the base substance that holds the active chemical ingredient into a pill form (such as talc) or the flavoring can be different. Some clients do not tolerate these differences in excipients very well. When prescribing a medication, the provider must indicate that a generic substitution is acceptable. Nurses are often pivotal in completing insurance paperwork on the client’s behalf if the brand-name medication is more effective or better tolerated by that particular client.[2]
When studying medications in nursing school and preparing for the NCLEX, it is important to know medications by their generic name because the NCLEX does not include brand names in their questions.
Over-the-counter (OTC) medications do not require a prescription. They can be bought at a store and may be used by multiple individuals. OTC medications are also regulated through the FDA. Some prescription medications are available for purchase as OTC in smaller doses. For example, diphenhydramine (Benadryl) is commonly prescribed as 50 mg every 6 hours, and the prescription strength is 50 mg. However, it can also be purchased OTC in 25 mg doses (or less for children.)[3]
Herbs and supplements may include a wide variety of substances including vitamins, minerals, enzymes, and botanicals. Supplements such as “protein powders” are marketed to build muscle mass and can contain a variety of substances that may not be appropriate for all individuals. Herbals and supplements are often considered complementary and alternative medications (CAM). Complementary and alternative medications (CAM) are types of therapies that are commonly used in conjunction with or as an alternate to traditional medical therapies. These herbal and supplement substances are not regulated by the FDA, and most have not undergone rigorous scientific testing for safety for the public. While clients may be tempted to try these herbals and supplements, there is no guarantee that they contain the ingredients listed on the label. It is also important to remember that there is a potential for adverse effects or even overdose if the herbal or supplement contains some of the same drug that was also prescribed to a client.[4] By understanding the use of CAM therapies, nurses can help their clients make informed decisions and take a holistic approach to their care. Additionally, being knowledgeable about CAM therapies can help nurses to better educate their clients on the potential benefits and risks associated with these therapies, which can help improve client outcomes and satisfaction.
