Nursing Continuing Education

Introduction to Pharmacology

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This is Your Course on Introductory Principles of Pharmacology

Syllabus

Introduction to Pharmacology: Pharmaceutics, Pharmacokinetics, and Pharmacodynamics


Purpose

The purpose of this module is to provide an understanding of the basics of pharmacology including pharmaceutics, pharmacokinetics, and pharmacodynamics. Drug reactions in relation to side and adverse effects; hypersensitivity reactions; drug tolerance, cumulative effects and drug toxicity; drug interactions; precautions and contraindications, are also addressed to provide the nurse with a comprehensive understanding of the knowledge needed for safe medication administration.  Nursing indications are included for each section with a summative list at the end of the module.

 

Objectives

  1. Understand the concept of pharmaceutics, pharmacokinetics, and pharmacodynamics.
  2. Analyze the relevance of the four aspects of pharmacokinetics that include absorption distribution metabolism and excretion.
  3. Discuss the various routes of administration and related effect on the pharmacokinetics of a drug.
  4. Describe factors that can affect the pharmacokinetics of a drug.
  5. Analyze the various chemical changes that take place in the body as a result of the pharmacodynamics of the drug.
  6. Discuss drug-drug and drug-food interactions and their relationship to the development of adverse effects and toxicity.
  7. Explore precipitating factors related to the occurrence of side and adverse effects.
  8. Analyze the etiology of hypersensitivity reactions, including anaphylaxis, and actions taken to manage them.
  9. Differentiate between drug tolerance, cumulative effects of drugs, and drug toxicity.
  10. Review precautions that should be taken when giving a medication and contraindications that can make administering a drug dangerous or detrimental to the patient.

Background

In a study recently done by Johns Hopkins University 10% of all deaths in the United States are attributable to medical errors making them the third-highest cause of death in the United States. Subsequently, a thorough understanding of the drugs being given is needed to minimize the number of errors being made on an individual basis. 

Using the IOM competencies for nursing, the QSEN project sponsored by the Robert Wood foundation, has identified six competencies necessary for safe practice. These are patient centered care, teamwork and collaboration, evidence-based practice, quality improvement, safety, and informatics. Curricula in nursing programs today have been tasked to incorporate into their curricula these concepts to support safe medication administration.  The joint commission as a part of their national patient safety goals has identified two particular areas of interest regarding medication administration. One area addresses medication errors that occur when reading and interpreting new medication orders. A “Do Not Use” list of abbreviations has been developed to prevent confusion that could lead to a medication error.  Appropriate medication labeling and use of anticoagulant medications have also been targeted. The Institute for Safe Medication Practices (ISMP) has provided a list of high alert medications that pose an enhanced risk of causing significant patient harm if given inappropriately.

Special populations have also been targeted as high risk in relation to certain medications and or how medications are administered. One special population is the pregnant woman due to the potential for maternal or fetal adverse drug reactions.  Some drugs can be teratogenic and cause birth defects if given in the first trimester.  Historically these have been rated according to categories but a new system is being developed that allows for more specificity based on research that supports evidence-based prescribing. 

Definitions

ABSORPTION is the movement of the drug from the site of administration to various tissues in the body. 

ADVERSE EFFECTS are the unintended and unexpected effects of a drug that can be severe and even be life-threatening in nature at a therapeutic dose.

AGONIST is a drug that stimulates the activity of one or more receptors in the body.

ALLERGIC REACTION is an immunologic based hypersensitivity response that results from administration of a drug to a person who is sensitive to that drug.

ANTAGONIST is a drug that inhibits the activity of one or more receptors in the body.

BIOTRANSFORMATION is the biochemical reaction that primarily occurs in the liver and produces a metabolite which is either an active or inactive form of the original drug.

BLOOD BRAIN BARRIER is the barrier system that exists in certain parts of the body that selectively restricts the passage of chemicals between the bloodstream and the brain.

DURATION OF ACTION is the length of time a drug is in the blood in sufficient amounts to elicit a response.

CONTRAINDICATION is a disease state or patient characteristic that renders a drug inappropriate to be used due to the potential for adverse effects.

CUMULATIVE EFFECTS occur when the body is unable to metabolize and excrete a drug before the next dose therapeutic if given.

DISTRIBUTION is the movement of the drug by the circulatory system to its intended site of action.

DRUG’S GENERIC NAME is a term referring to the chemical makeup of a drug rather than to the advertised brand name under which the drug is sold.

DRUG’S BRAND NAME is a term referring to the advertised brand name under which the drug is sold.

DRUG-DRUG INTERACTION occurs when two drugs are given that can radically change the action of one or both of the drugs in the body by reducing absorption or increasing risk for toxicity

DRUG-FOOD INTERACTION occurs when a drug is given with a food that can radically change the action of the drug by reducing absorption or increasing risk for toxicity. 

EXCRETION is the elimination of a drug or its metabolites through various parts of the body.

FIRST PASS EFFEFCT is the effect that the liver has on medication as it passes through the liver for the first time deactivating a certain amount of medication

HALF-LIFE is the time it takes for a drug that enters the body to decrease in amount by half.

HYPERSENSITIVITY REACTIONS occur secondary to administration of a drug that a patient’s body sees as a foreign substance precipitating a mild to moderate release of histamine.

METABOLISM is the change that occurs in a drug making it a more or less potent form of the drug.

METABOLITE is a chemical form of a drug that remains after biotransformation that may or may not have a pharmacologic effect.

ONSET OF ACTION is the time it takes for a drug to exert its therapeutic effect.

PEAK LEVEL of a drug is the point in time when a drug is at its highest level in the body.

PHARMACEUTICS are the various pharmaceutical properties a drug possesses based on its form and chemical composition.

PHARMACODYNAMICS are the biochemical changes that occur in the body as a result of taking a drug.

PHARMACOKINETICS refers to how drugs travel through the body where they undergo the biochemical processes of absorption, distribution, metabolism, and excretion. 

PHARMACOLOGY is the study of drugs and their effect on the human body

PRECAUTIONS are actions that should be taken when providers prescribe drugs that have a potential to cause adverse effects in certain populations or in combination with other drugs or certain foods.

SIDE EFFECTS are the unintended effects of a drug that commonly occur in patients and are mild in nature at a therapeutic dose.

SYNERGISTIC EFFECT occurs when two drugs are given with similar actions creating a summative response greater than what would be seen when the drugs were given alone.

THERAPEUTIC EFFECT is the desired effect of a drug.

TOLERANCE the decrease in response to a drug after prolonged use.

TROUGH LEVEL of the drug is the point in time when the drug is at its lowest level in the body.


Pharmacology

Pharmacology is the study of drugs and their effect on the human body.  Drugs can have a positive effect on the body which is called the therapeutic effect, they can have non-therapeutic effects on the body called side effects, or they can have negative effects on the body which are called adverse effects. When administering drugs one must also watch for contraindications that would make a drug dangerous to give to a patient, precautions that should be taken when administering a drug, and interactions, either drug-drug or drug-food, that can increase or decrease the efficacy of the drug.

Drugs are also called medications when given for therapeutic purposes.  When administering a drug to a patient the term medication is more commonly used because it is being given to elicit a specific therapeutic response or to treat a health alteration.  Drugs are also known by two different names: their brand name and their generic name.  A drug’s brand name is a term referring to the advertised brand name under which the drug is sold and a drug’s generic name is a term referring to the chemical makeup of a drug rather than the advertised brand name under which the drug is sold.  An example of a drug’s generic and brand name is acetaminophen whose brand name is Tylenol.  Patient’s may be more familiar with their medication’s brand names but health care providers should use the generic form to prevent confusion because brand names can vary widely.  

Some drugs given for pain have addictive properties and can be abused by patients.  Of major concern is the improper use of opioid drugs by patients that has led to an opioid crisis in our society.  Approximately 20% of people who require pain relief for acute pain such as post-operative pain or have chronic pain related to a health issue such as low back pain are prescribed opioids. Opioids are narcotics and as such have addictive properties.  These drugs are safe if taken over a short period of time however, if taken for extended periods of time or in higher than prescribed amounts a patient becomes at risk for developing an addiction.  It is critical that nurses give these medications as prescribed and educate patients on their proper use and alternative non- opioid drugs that can be taken when pain is subsiding.

Pharmaceutics

Pharmaceutics are the various pharmaceutical properties a drug possesses based on its form and chemical composition.  The ability of a drug to dissolve in a patient’s body is largely dependent on its form.  For example, a drug taken orally in liquid form is going to be absorbed by the body more quickly than a drug in pill form.  Pills with an “enteric” coating delay dissolution of the pill until it reaches the intestinal tract.  This ensures that the acidic pH of the stomach does not break down the chemical composition of a drug rendering it ineffective.  Enteric-coated pills should never be crushed because their action may be lost before leaving the stomach.

The table below illustrates the absorption rate of various forms of oral medication based on their form.

Drug Form

Rate of Absorption

Liquids, elixirs, and syrups

Fastest

Suspensions solutions

 

Powders

Capsules

Tablets

Coated tablets

Enteric-coated tablets

Slowest

 

Drugs can be given in three dosage forms: enterally, parentally, and topically.  Enteral forms are given via the intestinal tract either orally, sublinqually (under the tongue), bucally ( between the gums and cheek), or rectally.  Drugs that require quick absorption may be given sublingually or bucally because the rich supply of blood vessels in the mouth and the ease of transport through the mucous membranes supports immediate absorption by the body. Parenteral forms are given outside the gastrointestinal tract.  They are given intradermally, intramuscularly, subcutaneously, or intravenously.  These forms allow for immediate absorption by the body bypassing the gastrointestinal track and the need for dissolution. Topical forms are given via aerosol, cream, foam, gel, suppository, and through patches.  These drugs may act directly on the skin or may be absorbed through the skin for a systemic response.

Drugs may be chemically formulated to be released over a specific period of time.  Extended-release forms release the drug in the patient’s gastrointestinal track over an extended period of time.  In contrast immediate-release dosage forms release the drug upon contact with the gastrointestinal track.  Nurses must be cognizant in noting when a drug has one of the following abbreviations as a part of its name.  Extended drugs will be administered less often due to their slow release over time.

SR

Slow release

SA

Sustained action

CR

Controlled releases

XL

Extended release

XT

Extended time

 

Pharmacokinetics

Pharmacokinetics refers to how drugs travel through the body where they undergo a variety of biochemical processes that result in absorption, distribution, metabolism, and excretion.

Absorption is the transmission of drugs from the location of administration, including the gastrointestinal tract, muscle, skin, mucous membranes, and subcutaneous tissue into the bloodstream. There are various factors that influence the distribution of medication given through these various routes.

  • Oral drugs must pass through a layer of epithelial cells that line the gastrointestinal tract. The absorption pattern of drugs taken orally varies due to solubility and stability of the medication, the pH of the gastrointestinal tract and its motility, the presence of food in the stomach or intestines, drugs given at the same time, and the form of the medication in regard to whether a medication is a liquid, capsule, tablet, enteric-coated, or time-released.
  • Sublingual and buccal drugs which are placed under the tongue (sublingual) or between the gums and the cheek (buccal) are absorbed before swallowing. This prevents the gastric pH from inactivating the medication. It also enhances the rate of absorption due to its passage through highly vascular membranes.
  • Rectal and vaginal drugs are easily absorbed and can precipitate both local and systemic effects. However, the presence of stool in the rectum or infectious discharge in the vagina limits tissue contact with the medication.
  • Inhalation of medication through the mouth or nose is rapidly absorbed through capillary networks in either the nose or alveoli in the lungs.
  • Intradermal and topical drugs allow slow, gradual absorption of medication. The effects of this type of medication is usually local but systemic effects can occur as well.
  • Subcutaneous and intramuscular drugs may be absorbed quickly or slowly. Water-soluble drugs are absorbed rapidly while non water-soluble drugs have a slower absorption rate. In general, drugs given intramuscularly are absorbed quickly due to the vascularity of muscles however, patients with poor peripheral perfusion may experience delayed absorption.
  • Intravenous drugs are absorbed the most quickly and completely of any of the other routes. Intravenous medication given directly into the bloodstream reaches tissues in its original chemical form.

Distribution is the transportation of drugs to sites of action by bodily fluids. The organs that are exposed to the drug first are the heart, liver, kidneys, and brain due to their vascularity and extensive supply of blood.  Many drugs may be hepatotoxic (can cause liver injury) or nephrotoxic (can cause kidney injury) because drugs pass through these organs in a higher concentration increasing their potential to cause damage to these organs.  There are various factors that influence the distribution of drugs.

  • Circulation is one factor that can either enhance or inhibit perfusion of drugs throughout the body. Health alterations such as cardiac disease or peripheral vascular disease can delay medication distribution.  Dehydration and overhydration can also effect the ability of a drug to perfuse in its intended manner and for the expected amount of time through the body.
  • Permeability of cell membranes is another factor that affects perfusion of medication through tissues and membranes. Drugs must pass through several types of cell membranes before they reach their target tissue.  Oral drugs must pass through cell membranes in the gastrointestinal tract and capillaries to enter the circulation; then leave the circulation to bind with receptors on the target cells; then return to the circulation and pass through the liver where a certain amount of the drug is metabolized by liver enzymes; and then re-enter the circulation to be excreted by the body.  Certain areas of the body have cell membranes that decrease the amount of drug that can pass through.  This is true for the brain (also known and the blood-brain barrier) and placenta.  
  • Plasma protein binding sites also affect the distribution of drugs within the bloodstream. Drugs that bind to proteins (drug-protein complex) will be affected by how much of the medication is given and its transport to target tissues. The drug-protein complex is usually too large to pass through the capillaries into tissues so only unbound or “free” amounts of the drug is pharmacologically active and can exert a therapeutic effect.  Clients who are malnourished or have a negative nitrogen balance are at higher risk of toxicity due to the increased amounts of free drug.  These patients require lower dosages of certain drugs to prevent toxicity.

Metabolism is the biotransformation that changes drugs into less active or inactive forms through the action of enzymes.  The new or altered form of the drug is called a metabolite. Metabolism occurs primarily in the liver but also takes place in the kidney, lungs, intestines, and blood.  Once a drug enters the body and passes through these organs, in particular the liver and kidneys, the body begins to eliminate it by metabolizing it.  An interesting note is that most drugs are lipid soluble but the kidneys can only excrete water soluble substances.  Therefore, it is necessary for the liver to convert lipid soluble drugs to water soluble drugs as they pass through the liver and are metabolized.

  • Age is a factor that can affect the metabolism of a drug. Infants have a limited “medication – metabolizing capacity”.  Metabolism by the liver also tends to decline with age requiring a decrease in dose when older adults are given drugs to avoid inadvertently causing toxicity.
  • Increase in “medication metabolizing enzymes” can cause a drug to be metabolized sooner. This increase may be a result of administering certain drugs over an extended period of time.  This may require an increase in dosage to maintain a therapeutic level. An increase in “medication metabolizing enzymes” can also cause an increase in the metabolism of other drugs being given concurrently.
  • First pass effect results from the liver inactivating a certain amount of a drug after it leaves the gastrointestinal tract and passes through the liver for the first time. Drugs that are inactivated by the liver need to be given by a route that does not pass the gastrointestinal tract.
  • Similar metabolic pathways can alter the metabolism of two drugs given at the same time. The rate of metabolism can decrease for one or both drugs leading to toxicity.
  • Nutritional status of clients affect the availability of a drug and number of metabolizing enzymes available. Clients who are malnourished may have a fewer number of enzymes increasing the risk of toxicity.

Excretion is the elimination of drugs from the body, primarily through the kidneys. Kidney dysfunction can lead to an increase in the duration and intensity of a medication’s response; as a result, the BUN and creatinine levels of at risk patients must be closely monitored. Elimination also takes place through the liver, lungs, intestines, skin, and exocrine glands so sufficient function of these organs is also necessary for effective excretion. 

Renal excretion is supported by glomerular filtration, active tubular reabsorption, and active tubular secretion.
  • The free or unbound water soluble form of a drug or metabolite enters the kidney through passive glomerular filtration.
  • The vasculature that surrounds the nephron may also transport via tubular secretion molecules of the drug into the nephron.
  • Active reabsorption may draw some of the drug back into circulation and redistribute it throughout the body.
  • Biliary excretion supports excretion of a drug through the gastrointestinal in the form of feces.
Half Life
The half-life of a drug is the time it takes after a drug enters the body to decrease in amount by half.  This decrease reflects how quickly and efficiently a drug is metabolized and then excreted.  Drugs are considered to be excreted from the body when approximately five half-lives have occurred.  Drugs with a short half-life may need to administered several times a day as compared to drugs with a long half-life which may only need to be administered once a day. 

Since most drugs are metabolized in the liver and are excreted by the kidneys; a decrease in functioning in either of these organs increases the half-life of a drug. Subsequently, patients with liver or kidney dysfunction may experience toxic effects of drugs much more easily if the dosage or frequency of administration is not decreased.  The nurse should also monitor labs that reflect liver function including alanine transaminase (ALT), aspartate transaminase, (AST), alkaline phosphatase (ALP) and kidney function including blood urea nitrogen (BUN) and creatinine.  The provider should be notified should an increase in any of the values occur.

Onset, Peak, Trough, and Duration

Onset of action is the time it takes for a drug to exert its therapeutic effect.  Onset of action is influenced by the route of administration and patency of patient’s gastrointestinal tract and circulatory system.  Peak level of a drug is the point in time when a drug is at its highest level in the body.  Duration of action is the length of time a drug is in the blood in sufficient amounts to elicit a response.  Duration of action is influenced by the rate of excretion from the body. Trough level of a drug is the point in time when a drug is at its lowest, non-therapeutic level in the body. 

Peak and Trough Levels

The peak and trough level of a drug is very important in regard to maintaining a therapeutic level of a drug in a patient’s body.  If the peak level of a drug is too high the patient runs a risk of toxicity.  If the peak level of a drug is too low the patient runs the risk of receiving a non-therapeutic amount of the drug negating its intended effect.  Determination of the amount of drug in the body during the time when it should be peaking is done by taking a sample of blood and having a laboratory measure the amount of drug in the blood at that point in time.  It is the nurse’s responsibility to monitor the peak and trough level of a drug to ensure the patient is receiving a therapeutic and not a toxic amount of the drug. For example, an antibiotic medication such as gentamycin needs to be maintained at a therapeutic level in order to effectively treat the infection for which it is being given. However, it is also highly nephrotoxic and requires diligent monitoring of the peak level of the drug as well lab values that monitor kidney function to ensure the antibiotic is not being given at a higher than therapeutic level for the client.

Pharmacodynamics

Pharmacodynamics are the biochemical changes that occur in the body as a result of taking a drugAfter a drug has been introduced into the body it enters the circulation and comes into contact with the cells of almost all of the organs and tissues in the body.  The cells that are the target site for a drug are impacted in one of three ways: alteration in cellular function, alteration in cellular environment, and action of enzymes in the body. 
  • Alteration in cellular function
    When a drug comes into contact with a cell it can modify its function by either enhancing or blocking the way in which the cell functions. The joining or binding of a drug with a cell is called the drug – receptor interaction. Drugs bind with receptors on a cell through the formation of chemical bonds between the receptor and the active site on the drug molecule.   

    Drugs given to enhance a physiologic response are called agonists.  Agonists are drugs that bind with a receptor and enhance the typical response.   Morphine is an example of an agonist because it binds with receptors that produce the desirable effect of analgesia.  Antagonists are drugs that bind with receptors and either block or lessen the typical response.  An example is a histamine-2 (H2) blocker such as ranitidine which blocks the histamine induced gastric acid secretion from the parietal cell of the gastric mucosa.
  • Changes in cellular environment
    Changes in the cellular environment occur when a drug changes the structure of a cell.  Changes may be made in the cell wall or one of a cell’s critical processes such as replication.  For example, penicillin-type antibiotics inhibit cell wall synthesis of certain types of bacteria resulting in the destruction and death of the bacteria.  Sulfa-type antibiotics inhibit the replication of certain types of bacteria by preventing folic acid from helping to make DNA and RNA.
  • Changes in enzymatic action
    Through a process called selective interaction a drug may change a target molecule’s typical response by inhibiting or enhancing the action of an enzyme that affects the target molecule. ACE inhibitors such as lisinopril block the “angiotensin converting enzyme” which is needed to create the hormone angiotensin II.  Blocking this hormone relaxes blood vessels making it a good drug to treat hypertension. 

Drug Interactions  

Drug-drug and drug-food interactions can dramatically change the action of a drug in the body.  Precautions should be taken to limit or restrict certain types of food or concurrent administration of certain types of drugs rather than restricting the drug itself. 

 Drug-drug interactions occur when one drug changes the way another drug affects the body.  When the combined effect of two drugs you give together is the same as each drug you give alone in similar doses an additive effect occurs.   An example would be a patient who ingests two drugs that are central nervous system depressants, such as alcohol and opioids.  Their effects add to each other putting the patient at risk for significant and possibly fatal central nervous system depression.  Synergistic effects occur when the effect of one drug is greater if you give it with another drug.   An example would be giving aspirin to a patient who is taking a blood thinner such as warfarin which would increase the patients risk of bleeding and hemorrhage.   Antagonistic effects occur when the effect of one drug is decreased or blocked if you give it with another drug.  An example would be giving ciprofloxacin with an antacid which reduces the absorption of ciprofloxacin decreasing its efficacy to treat infection.  

Drug-food interactions occur when a drug is given with a food that can radically change the action of the drug by reducing absorption or increasing risk for toxicity.  An example would be eating fruit or drinking fruit juice an hour or two before or after taking fexofenadine.  The juice can inhibit the absorption of fexofenadine decreasing or inhibiting its ability to block the release of allergy-related histamine. 

Therapeutic, Side, and Adverse Drug Effects

Therapeutic effects are the desired effects of a drug being given.  Side and adverse effects of a drug are the undesirable effects that occur in response to a drug being given.

Side effects are the unintended effects of a drug that commonly occur in patients and are mild in nature. Side effects occur as a result of a drug's effects on the body.  For example, side effects of diphenhydramine include dry mouth and drowsiness.  Nurses often help patients cope with common and often uncomfortable side effects of prescribed drugs.  A nurse caring for a patient who is receiving diphenhydramine and reports having a dry mouth should ensure water or ice chips are available, offer sugar-free hard candy, and use a saliva substitute as needed.  These patients should also be instructed to avoid driving a car or using heavy machinery when experiencing drowsiness.

Adverse effects are the unintended and unexpected effects of a drug that are more severe and can even be life-threatening at a therapeutic dose. Adverse effects are also side effects of a drug but are more severe in nature.  For example, adverse effects of diphenhydramine in some older adults include confusion, incoordination, and dizziness.  Another example is the risk of serotonin syndrome when taking sertraline, a drug prescribed for major depressive disorder, obsessive compulsive disorder, panic disorder, posttraumatic stress disorder, social anxiety disorder, and premenstrual dysphoric disorder. Serotonin syndrome results from concurrent administration of a selective serotonin reuptake inhibitor (SSRI) or a monoamine oxidase (MAO) inhibitor or any other drug that potentiates serotonin neurotransmission.  Serotonin syndrome is characterized by hypertensive crisis, hyperpyrexia, muscle rigidity, seizure, and extreme agitation that can progress to delirium and coma.  Nurses must recognize when a patient is receiving a drug that has life-threatening side effects and monitor the patient very closely for the first sign of these adverse effects.

Hypersensitivity reactions

Hypersensitivity reactions occur secondary to administration of a drug that a patient’s body sees as a foreign substance.  An allergy to a drug usually occurs after more than one dose of a drug has been given.  It occurs secondary to the release of histamine which can cause generalized inflammation and swelling of tissues (hives), increased mucous production, and in severe cases constriction of the bronchioles.  Mild to moderate cases of hypersensitivity reactions can be treated with an antihistamine such as diphenhydramine.

Anaphylactic shock is an exaggerated response of the body's immune system to a drug which precipitates a massive release of histamine and other chemical mediators into the body.  Symptoms of anaphylactic shock can occur almost immediately after exposure and include:

  • swelling of the eyes face mouth and throat
  • difficulty breathing
  • wheezing
  • rapid heart rate
  • extremely low blood pressure
  • cardiac arrest

A patient in anaphylactic shock must be immediately brought to a medical facility where he or she can receive cardiopulmonary support along with rescue drugs.  Treatment of anaphylactic shock focuses on reestablishment of an airway and oxygen therapy, administration of epinephrine to raise the patient's blood pressure and dilate respiratory bronchi, and administration of diphenhydramine to block the additional release of histamine.

It is very important for nurses to ask patients if they have any allergies to drugs.  Even minor reactions to a drug are notable.  If a patient admits to having an allergy to a drug, ask them what type of reaction they had then note this information on the chart.   The patient’s wristband should list all known allergies and be placed on a patient immediately after admission.  When administering medication be sure to check both the chart and patient’s wrist band for allergies. When checking new orders review the patient’s chart for allergies and bring to the provider’s attention any drug that could precipitate a reaction.  Some drugs can display a cross-sensitivity to another drugs.  Patients who report an allergy to penicillin may have a cross-sensitivity to cephalosporin drugs.  If the patient has not received a cephalosporin on a prior occasion monitor the patient very closely during the first few doses for signs of an allergic reaction.

Drug Tolerance, Cumulative Effects, and Drug Toxicity

Drug tolerance, cumulative effects, and drug toxicity are other undesirable effects related to safe medication administration that the nurse must monitor for when caring for a patient receiving drug therapy. 

Drug tolerance is a body’s decrease in response to a drug it receives over a period of time.  For the drug to continue to exert a therapeutic effect the dosage must be increased.  Tolerance is not synonymous with addiction.  A patient can develop tolerance to a drug and not be addicted.  However, if the patient continues to take the drug in increasing doses over a longer than recommended period of time addiction can occur.  Narcotic analgesics and antianxiety drugs are at high risk for development of tolerance and subsequent addiction.   Nurses must monitor patients for the development of tolerance if one of these medications has been given over an extended period of time or if the prescribed amount of medication is no longer giving the patient relief.

Cumulative effects occur when the body is unable to metabolize and excrete a drug before the next dose is given. If the next dose is given while some of the drug from the previous dose is still in the patient’s body the drug begins to accumulate in the body.  The gradual increase in the amount of the drug in the patient’s body increases the risk of adverse reactions and toxicity. The development of cumulative effects is a common occurrence in older adults who have a decreased cardiac and kidney function and in patients of any age who have liver or kidney disease. The nurse should ensure the proper dose of medication is given to these at risk patients and monitor for adverse effects that could indicate too much of the drug is being given in relation to the body’s ability to excrete it.   

Drug toxicity occurs when a drug is given in amounts greater than what the body is able to excrete.  Drug toxicity may occur when a patient receives drugs in greater than recommended dosages.  It can also occur when impaired excretion of the drug, secondary to impaired liver or kidney function, allows it to build up in the body over a period of time.  Eventually a toxic level is reached causing the patient to experience severe and possibly fatal adverse effects.  Drugs that have a small margin of safety can quickly build up to a toxic level in the body. Patients on drugs with a small margin of need to have their serum drug level regularly drawn and be closely monitored for signs and symptoms of toxicity.  The effects of drug toxicity may be irreversible and life-threatening.  For example, vancomycin, given in toxic amounts may cause permanent damage to cranial nerve VIII resulting in decreased hearing or deafness.  Acetaminophen given in amounts great than 4,000 milligrams per day may cause temporary damage to the liver or permanent damage that results in liver failure.  Nurses must make certain when giving a patient acetaminophen that a review of all the drugs has been done to determine if the patient is receiving additional acetaminophen in any other drugs.  Many drugs for pain are combination drugs that contain an opioid and acetaminophen.  Vicodin is an example of a combination drug which contains 5 milligrams of hydrocodone and 300 milligrams of acetaminophen.  

Precautions and Contraindications

Certain drugs should be given after careful consideration in regard to precautions or avoided completely because they are contraindicated in certain populations.

Take precautions when providers prescribe drugs that have a potential to cause adverse effects in certain populations or in combination with other drugs or certain foods. Patients with certain diseases, are of a certain age, are pregnant or lactating are some of these special populations. These drugs are typically used only when necessary and when the benefits outweigh the risks.  For example, use of meperidine in older adults is discouraged because decreased renal function can lead to accumulation of normeperidine, a neurotoxic metabolite of meperidine. 

Be cognizant of contraindications if a disease state or patient characteristic renders a drug inappropriate for use due to the potential for adverse effects. There are some drugs that providers should not prescribe because they have the potential to cause serious or life-threatening adverse effects with certain populations or in combination with other drugs and certain foods.  Providers should not consider the use of drugs in these situations except under extremely unusual circumstances.  For example, children under eight years of age should not be given tetracyclines because they can permanently stain developing teeth.  Simvastatin should not be taken with grapefruit juice because it can significantly increase blood levels of simvastatin.  Increased blood levels of simvastatin increase the risk of liver damage and breakdown of skeletal muscle tissue.  A high intake of dark green vegetables, beef liver, and soybean-containing foods should be avoided in patients taking warfarin.  These foods interfere with the anticoagulant property of warfarin because they contain high amounts of vitamin K which can decrease the effects of warfarin.

Women who are pregnant or could become pregnant should avoid the use of several types of drugs.  Prior to 2015 the FDA supported a five category labeling system of prescription drugs that indicated their risk of fetal injury when used by a pregnant mother during pregnancy.  This manner of labeling prescription medications has been replaced because the categories often led to prescribing errors based on false conclusions made related to the categories. A new registry system documents known or potential maternal or fetal adverse reactions and pregnancy outcomes for individual drugs.  This registry provides information that supports evidence based decisions in regard to prescribing appropriate and safe medications. 

Nursing Indications

Nurses must be knowledgeable of all drugs they are administering to their patients.  It is important to understand the pharmacokinetics and pharmacodynamics of a drug in order to safely administer the drug while monitoring for side and adverse effects, signs of an allergic response, and toxicity.  Patient characteristics such as age, health alterations, and impairment of liver or kidney function, must also be considered in regard to increased risk for side and adverse effects.  The process of monitoring peak and trough level of drugs that are critical to be maintained at a therapeutic level is also very important knowledge for nurses caring for patients.  All drugs that are prescribed by a provider should be reviewed in relation to other drugs that are being given to prevent drug – drug interactions.  If a potential interaction is discovered or two similar drugs are prescribed increasing the risk for toxicity the provider should be notified and concerns brought to that individual’s attention so a substitution can be made or a drug discontinued. Foods that could precipitate a drug – food interaction must also be restricted from a patient’s diet and patient education provided if the medication will continue to be taken outside of the acute care setting.  In summary, nurses are responsible for a deep understanding of the drugs they are giving in order to administer drugs in a safe and evidence-based manner.

 

References

Wintgerton Edmunds, M. (2016) Introduction to Clinical Pharmacology. St. Louis, MO: Elsevier.

Frandsen, G. & Smith Pennington, S. (2018) Abram’s Clinical Drug Therapy: Rationales for Nursing Practice. Philadelphia, PA: Wolters Kluwer

Lilley, L.L., Rainforth Collins, S. & Snyder, J.S. (2017) Pharmacology and the Nursing Process.  St. Louis, MO: Elsevier.


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