NURS 251 Module 1 Portage Learning

NURS 251 Module 1 Portage Learning Module 1 1.1: An Introduction to Pharmacology Concepts Pharmacology is the study or science of drugs. What is a drug? A drug is any chemical that affects the physiologic processes of a living organism. Commonly, the term drug refers to any medication that is used for diagnosing, curing, or treating disease. Drug Effects Drugs have many different effects on the body including the following: (1) therapeutic effects, (2) side effects, (3) adverse effects, and (4) toxic effects. Therapeutic effect is the desired drug effect to alleviate some condition or symptom. Side effects are the drug effect other than the therapeutic effect that are usually undesirable but not harmful. Adverse effect is a general term for undesirable and potentially harmful drug effects. Toxic effects are undesirable drug effects that implies the drug is poisoning the body and can be harmful or even lifethreatening. Clinically, it is important to recognize the difference between these different ways drugs can affect the body. A simple side effect could be something as harmless as mild nausea after taking a medication that can be managed by taking it with food. The drug therapy can continue without a problem. However, adverse effects need to be assessed to determine whether there is any risk of harm. Drug therapy is often a risk vs. benefit assessment. The patient’s provider should weigh the risk of taking the medication vs. the benefit. It often comes down to the severity of the disease being treated to decide the number of adverse events that will be tolerated. A good example of this is chemotherapy treatments for cancer. There are often adverse events associated with these treatment regimens, yet the treatment is continued because the benefit of treating the cancer is greater than the adverse events the patient experiences. However, there are certainly times when a treatment becomes too toxic, and the patient is unable to tolerate the regimen. This is often a large part of managing a cancer patient’s treatment, to assess how they are handling the adverse effects associated with the treatment regimen and determine whether it is becoming too toxic and needs to be suspended. Basic Concepts There are some basic concepts that are important to understand and that can be applied to any drug. Most important is the drug’s mechanism of action—how a drug produces its effects. This course will cover the accepted mechanism of action of known drugs. When a drug enters the body, it has a targeted site of action—the location within the body where a drug exerts its therapeutic effect, often a specific drug receptor. Generally, these sites of action or receptors are on the surface or inside a cell. Receptors are specific cellular structures that a drug binds to in order to produce a physiologic effect. When a drug binds to a receptor, it can act either as an agonist, works to activate a physiologic response or drug effect, or an antagonist, works to interfere with other drugs or substances from producing a drug-effect. The dose-dependent relationship is a basic principle of pharmacology which states that the response to any drug depends on the amount of drug given. This is referred to as the dose dependent relationship. A dose is the exact amount of drug that is given. As shown in Figure 1.1, the onset of action is the time from the drug administration to the first observable effect. The duration of action is the length of time that the drug continues to produce its effect. All drugs have a therapeutic range defined as when the drug concentration is above the minimum effective concentration and below the maximum tolerate concentration. Figure 1.1 The change in plasma drug concentration over time. The Therapeutic range represented by the area between the Minimum tolerated concentration (MTC) and Minimum effective concentration (MEC). Cmax is the maximum concentration, and tmax is the time it takes to reach the maximum concentration. The time the drug is above the MEC is the duration of action. If the drug concentration goes above the MTC, it is considered the toxic range. Similarly, if the drug concentration is below the MEC, it is in the ineffective range. Nomenclature All drugs are chemicals, and many have long chemical names that define the chemical composition of the drug. In addition, they are given a shorter non-proprietary name or generic name. The generic name, also known as a nonproprietary name, is the name that we will use for assessments throughout the course. Drugs are marketed under a trade name, also called a brand name, by pharmaceutical companies under a patented proprietary name specific to that manufacturer. These names may be somewhat confusing because more often than not, one manufacturer will market a medication that leads to multiple trade names for the same pharmaceutical compound. For example, the common blood pressure medication, lisinopril, is marketed under both Prinivil and Zestril. Beyond this basic nomenclature system, it is important to know that drugs also fall into categories called drug classes. Drug classes represent a group of drugs that all work by a common general mechanism of action. They may have slight differences in their effect on the body in terms of effectiveness or side effect profile; however, generally drugs within the same drug class have many of the same characteristics. Dosage Forms and Routes of Administration Drugs are prepared in various forms for administration. The physical and chemical properties of the drug determine which form will be most effective. All drugs have the active ingredient, the drug itself, and inactive ingredients that help facilitate the administration and absorption of the drug. Common dosage forms are described in Table 1.1 below. Routes of administration are how the drug is introduced to the body. The two most common routes of administration are oral and parenteral. Oral administration is the route of drug administration by way of the mouth through swallowing. Parenteral administration is the route of drug administration that does not involve the GI tract. Although most commonly administered by injection, parenteral administration also technically includes routes such as inhalation and topical administrations because they bypass the GI tract. Oral administration is the safest and most convenient. However, since it must go through the GI tract the onset of action is delayed about 30-60 minutes compared to parenteral administration, which is fairly immediate. Many of the most common routes of administration are listed below in Table 1.2. 1.2: Pharmacokinetics and Pharmacodynamics Pharmacokinetics and Pharmacodynamics There are three main areas of pharmacology: (1) pharmaceutics, (2) pharmacokinetics, and (3) pharmacodynamics. See Figure 1.2 for a visual representation of these three areas. Pharmaceutics is the study of how various dosage forms influence the way in which the drug affects the body. Pharmacokinetics is the study of what the body does to the drug, including absorption, distribution, metabolism, and excretion. Pharmacodynamics is the study of what the drug does to the body. Figure 1.2: Phases of drug activity. The three areas of pharmacology are represented above. Starting with administration of various dosage forms and the study of pharmaceutics. Pharmacokinetics includes the four phases: absorption, distribution, metabolism, and elimination. Last is the pharmacodynamic phase or what effect the drug is having on the body. Pharmaceutics Pharmaceutics is manipulating a chemical compound into something that can be administered to (or taken by) a patient as well as reach the targeted site of action in the body in order to exert its effect. This specific area of pharmacy studies the science behind determining the best dosage form for a particular chemical entity. Many drugs have the potential to be effective clinically, but they need to be incorporated into a dosage form that can reach clinically significant amounts of drug at the site of action. Without the science of pharmaceutics, drugs would not be able to exert their desired effect on the body. Successful pharmaceutics is critical to get the drug substance into a dosage form that can have clinical activity. Pharmacokinetics In its simplest terms, the study of pharmacokinetics should be thought of as what the body does to a drug once it enters the body. There are four main processes that take place: (1) Absorption, (2) distribution, (3) metabolism, and (4) excretion. Absorption is the movement of a drug from its site of administration into the bloodstream ready to be distributed throughout the body. Bioavailability is the measure of the extent of drug absorption for a given drug and route (from 0%-100%). There are various factors that affect the absorption of a drug, the primary one being the route of administration. For example, in enteral administration, meaning the drug is absorbed through the GI tract, the drug is absorbed into circulation via the stomach and/or intestines. The drug then goes to the liver where hepatic enzymes metabolize the drug, and then the remaining active ingredients are passed into general circulation. Many factors can impact the absorption of drugs. For example, stomach acid that can change depending on time of day, age, presence of food or other medications. Enteric coating is an example of a strategy that is designed to protect the stomach by having the absorption occur in the intestines and not the stomach. Note: Not all tablet-like formulations pass through the GI tract. For example, sublingual tablets are absorbed in the highly vascularized tissue under the tongue because of the high blood supply to this area. The drug is absorbed rapidly and bypasses the liver. A contrast to the enteral route is the parenteral route. As discussed previously, this is any route that is not through the GI tract. The most common being intravenous injection. Intravenous injection describes drugs that are injected directly to the bloodstream where it can then be distributed throughout the body. Other types of injection such as intramuscular (directly into the muscle) and subcutaneous (under the skin) are absorbed much more slowly. Topical is another common route that avoids the GI system in most cases. They typically display a much slower onset of action and prolonged duration of action. Topical drugs can be applied to the skin, eyes, ears, nose, lungs, rectum, or vagina. In general, topical administration has erratic or unreliable absorption into the bloodstream. For this reason, most topical medications are used for their local effects. Distribution refers to the transport of a drug by the bloodstream to its site of action. Drugs are first distributed to areas of the body with a high blood supply such as the heart, liver, kidneys, and brain. It takes longer for a drug to reach areas with less blood supply like muscle, skin, and fat. Once a drug is in the bloodstream, it is distributed throughout the body. Simultaneously, the drug is also starting to be eliminated by the two organs that metabolize and excrete the drug which are the liver and kidneys. Metabolism is the biochemical alteration of a drug into an inactive metabolite, a more potent metabolite, or a less active metabolite. The liver is the primary site of metabolism. There is a class of enzymes within the liver called the cytochrome P-450 enzymes that are responsible for the majority of drug metabolism. There are many different enzymes that are labeled with an alpha numeric code. For example, 3A4 is a common enzyme that metabolizes drugs. Many different drugs go through these same enzymatic pathways. Inevitably, this is a major influencer of drug-drug interactions. Drugs can either be substrates of these enzymes, meaning that they are a site where the enzyme acts. The other option is that a drug acts as an enzyme inhibitor, meaning that it prevents the drug from being metabolized. There are also instances where a drug can act as an enzyme inducer, meaning that it stimulates more drug metabolism. Excretion describes the elimination of drugs from the body. The primary organ responsible for the elimination of drugs from the body is the kidney. The actual process of renal excretion is accomplished through glomerular filtration, active tubular reabsorption, and active tubular excretion. Some drugs are excreted through the intestines through a process called biliary excretion. Another important concept is the half-life of a drug. The half-life of a drug is defined as the time it takes 50% of a given drug to be removed from the body. The most important thing to remember about a drug half-life is that after about five half-lives, most drugs are considered to be effectively removed from the body. At that time, about 97% of the drug has been eliminated, and what remains is too small to have any real effect. Steady state refers to the physiologic state in which the amount of drug removed via elimination is equal to the amount absorbed with each dose. It is related to halflife in that it takes about 4-5 half-lives of the administered drug to reach steady state; therefore, the longer the half-life, the longer it takes to reach steady state. Pharmacodynamics Pharmacodynamics is the study of what the drug does to the body. In other words, the main focus of pharmacodynamics is the mechanism of action or how the drug works in the body that leads to the therapeutic effect. Once the drug reaches its site of action, it can modify how the cell functions. Drugs can exert their actions three basic ways: (1) receptors, (2) enzymes, and (3) nonselective interactions. It is also important to note that not all drugs have a known mechanism of action. A receptor is a reactive site on the surface or inside a cell. Simply put, the drug binds to the receptor site, and the pharmacologic response is produced. Drugs can bind with different levels of strength to their receptor sites which can lead to the strength of the response seen. Table 1.3 describes the different types of drug-receptor interactions. Table 1.3 Drug Receptor Interactions Drug Type Action Agonist Drug binds to the receptor and there is a response Partial agonist Drug binds to the receptor but the response is diminished Antagonist Drug binds to receptor and there is no response; prevent the binding of other agonists Competitive Antagonist Drug competes with the agonist, if it binds there is no response Noncompetitive antagonist Drug combines with different parts of the receptor and inactivates it; Agonist then has no effect. Enzymes are substances that catalyze or start biochemical reactions within cells. Drugs can interact with these enzymes and either inhibit (more common) or enhance the action of the enzyme. Nonselective interactions describe drugs that do not target a specific receptor or enzyme but rather target cell membranes and various cell processes. Antibiotics are a common example of drugs with this type of mechanism. Factors Affecting How Someone Responds to Drug Therapy There are many individual factors that can affect how someone responds to a drug. In general, some of these factors include: age, weight, sex, and genetic variation. Infants, children, and the elderly are generally more sensitive to drug actions than younger adults. As people age, all of the changes within their body lead to many changes in how their body processes drugs. See Table 1.4 below: Table 1.4 Age Related Changes in Pharmacokinetics Pharmacokinetic Process Age-related Change Absorption Drug absorption is delayed due to decreased intestinal blood flow, surface area and motility- this slows the onset of action Distribution Distribution is increased leading to increased drug effect due to decreased body water, lean body mass and increased fat content Metabolism Drug metabolism decreases increasing the duration of the drug due to decrease in blood flow to the liver and decrease in liver enzymes Excretion Excretion is decreased due to decreased blood flow to the kidneys and overall decreased renal function as one ages. The size of a person may also impact their response to a drug. Most adult dosages are calculated for a 150-pound adult. If a person is significantly larger or smaller their dose may need to be adjusted. Similarly, body fat can impact drug response. Higher body fat percentage means that there is less body water for the drug to dissolve in; therefore, they may have a greater response to the drug. Genetic factors such as a missing enzyme or alteration in how an enzyme works can also make a person either not respond or respond too much to a particular dug. 1.3: Introduction to Common Drug Interactions A drug interaction is when the actions of one drug are affected by another drug. There are several different ways that two drugs can interfere with one another. Interference can occur during the GI absorption process, distribution, metabolism, or excretion. Drug interactions can increase or decrease the actions of the drugs involved. They can also either be helpful or harmful. See Table 1.5 for a description of the different types of drug interactions. Table 1.5 Terminology of Common Drug Interactions Term Explanation Incompatibility Physical changes that occur to a drug when it is mixed with another prior to administration Additive Effects When the combined effect of two drugs is equal to the sum of each on their own. Synergism When the combined effect of two drugs is greater than the sum of their individual effects. Antagonism When the combined effect of two drugs is less than the sum of their individual effects. The most common drug interactions happen when there is competition between two drugs for metabolizing enzymes within the cytochrome P-450 enzymes. Generally, the competition causes the speed of metabolism to either be increased or decreased leading to a drug depletion and lack of effect or drug build up and the risk of drug toxicity. Table 1.6 provides examples of the different types of drug interactions. Table 1.6 Examples of Drug Interactions Pharmacokinetic Phase Drug Combination Mechanism Result Absorption PPIs and iron The iron requires an acidic environment for absorption Decreases the blood levels of iron leading to it being less effective Distribution Warfarin and amiodarone Compete for protein binding sites There are higher levels of the free drug which increases the action of both drugs Metabolism Grapefruit juice and statins They compete for the same liver enzymes Statin metabolism is decreased resulting in high or toxic levels Excretion Amoxicillin and probenecid Inhibits the excretion of amoxicillin into the kidney Increases and prolongs plasma levels of amoxicillin (could help it to be more effective) Drug Safety The Food and Drug Administration (FDA) is the federal agency that oversees the approval of all prescription medications. Every drug must prove to the FDA that it works or has efficacy for the disease state it will be used for and that is it safe. All drugs go through a very thorough approval process to ensure safety and efficacy. However, it is important to remember that all drugs carry risks, and it is important to continue to monitor for drug safety after drugs come to market. The FDA requires post-marketing surveillance to watch the drug's long term safety profile. It is possible that during this process there is a safety issue that is identified that leads to the medication being taken off the market. A well-known example of this is the once popular arthritis medication Vioxx. After being on the market, it came to light that there was a higher percentage of heart related adverse events for patients taking Vioxx compared to the closely related medication Celebrex. This led to Vioxx being removed from the market. Another major area of concern for safety is around the use of medications in pregnant women. There is not a lot of research done in this area due to the obvious ethical issues of introducing a drug with an unknown effect to a pregnant woman. The FDA has developed Pregnancy categories, see Table 1.7 to help assist providers and patients in knowing what medications are considered safe and what known risks are available. Table 1.7 Description of FDA Pregnancy Categories Category Description Pregnancy Category A Drug studies have not yet demonstrated risk to the fetus Pregnancy Category B Drug studies have not been performed in pregnant women. Animal studies have not demonstrated risk. Pregnancy Category C Drug studies have not been performed in pregnant women or animals or animal studies have revealed some potential risk to the fetus. Pregnancy Category D Drug studies have revealed risk to the fetus. Benefit to risk ratio must be established prior to use in pregnancy. Pregnancy Category X Drug studies have revealed significant risk to the fetus. Drug is contraindicated in pregnancy Pregnancy Category NR Drug has not yet been rated by the FDA. Some adverse drug events are related to human error. Medication errors are defined as any preventable adverse event involving inappropriate medication use by a patient or health care professional; it may or may not cause the patient harm. Prescription medications require the written order or “prescription” from an authorized provider. Laws regarding who can prescribe what may vary by state. Generally, providers with the authority to write prescriptions include physicians (MD, DO), Dentists, Nurse practitioners, and Physician Assistants. Most drugs are considered non-scheduled and can be prescribed by any of the providers above. There are specific laws for each type of provider around scheduled drugs. See Table 1.8 below for a description of the different drug schedules. Over the counter (OTC) or nonprescription medications are available without a prescription and can be purchased at the will of the consumer. Table 1.8 Drug Schedules Schedule Definition Examples Schedule I Drug with high abuse potential and no accepted medical use. Heroin, marijuana (federal law labels marijuana as schedule I; some states have legalized) Schedule II Drug with high abuse potential and accepted medical use. Narcotics (morphine, oxycodone), amphetamines *no refills without written prescription Schedule III Drugs with moderate abuse potential and accepted medical use. Drugs containing codeine *5 refills allowed within 6 months Schedule IV Drugs with low abuse potential and accepted medical use. Anxiety medication like diazepam (Valium), sedatives like zolpidem (Ambien) *5 refills allowed in 6 months Schedule V Drugs with limited abuse potential and accepted medical use. Cough syrups with codeine In some states a registered pharmacist can dispense these without a prescription to patients 18 years or older Chronic Drug Use/Abuse Chronic drug use can lead to physiologic and pharmacologic changes in drug response. Drug tolerance is defined as a decreased effect that occurs after repeated administration. In order for the patient to attain the previous response, the dose must be increased. This is a common occurrence in patients taking pain medications. Over time, they need increasingly higher dosages to experience the same level of pain relief. Drug dependence is a condition wherein reliance on the administration of a particular drug becomes extremely important to the well-being of the individual. This can be psychological and physical. When the patient begins using the drug for non-medical purposes, the term drug abuse is applied. Drug addiction is reserved for cases when drug dependence is particularly severe and compulsive drug behavior dominates all other activities. 1.4: Basic Drug Dosing Calculations There are instances when a drug may be ordered in a dose that is not available. Therefore, some calculations are necessary in order to determine the appropriate amount of drug to be given. Example 1: A physician orders 10mg of a drug be given once daily. The drug is only available in a 20mg and 50mg tablet. What would the dose be? (Desired Dose/ Available dose): 10 mg/20mg = 1/2 The dose for this patient would be to take ½ of the 20mg tablet daily (that tablet would need to be scored for splitting). Example 2: Calculating Dosages using a proportion equation: The physician orders 50mg of a drug that is available in a 22mg/5ml solution. How many ml would the patient need? (22mg / 5mL) = (50mg / x mL) Next: Solve for x: 22 (x) = 50 x 5 22 (x) = 250 X = 11.4mL Example 3: Dosage calculation based on a patient’s weight. The physician orders 7.5mg/kg administered intravenously of a certain antibiotic. The patient weighs 110 pounds. The drug is available in a 100mg per 2ml vial. How many milligrams of drug are required and in what volume? 1. Must convert the patient’s weight to kilograms. There are 2.2 pounds in 1 Kilogram: 110 lbs / 2.2 lbs/kg = 50 kg 2. Determine how many mg of drug are required: 7.5 (mg/kg) x 50 kg = 375 mg 3. Determine how many milliliters of stock solution contain 375 mg using the proportion equation as shown: (100 mg / 2 mL) = (375 mg / x mL) Cross multiply and get: 100(x) = 750 therefore, x = 750 / 100 thus, x = 7.5 mL of vial solution Problem Set Question 1 Describe the difference between a side effect and adverse effect. Side effects are the drug effects other than the therapeutic effect that are undesirable but not harmful. Adverse effect is a general term for undesirable potentially harmful drug effects. Question 2 Define receptors and the two different ways in which they can act. Receptors are specific cellular structures that a drug binds to in order to produce a physiologic effect. agonist—works to activate a physiologic response or drug effect and antagonist—works to interfere with other drugs or substances from producing a drug-effect. Question 3 What is the difference between the onset of action and duration of action? The onset of action is the time from the drug administration to the first observable effect. The duration of action is the length of time that the drug continues to produce its effect. Question 4 Describe the different names that drugs are given: chemical name, brand/trade name/proprietary, generic/nonproprietary. Chemical names- they define the chemical composition of the drug. Drugs are marketed under a trade name or brand name by pharmaceutical companies under a patented proprietary name specific to that manufacturer, drugs may have more than one brand name. Drugs have only one generic or non-proprietary name. Question 5 List some defining characteristics of the following dosage forms: Tablet, capsule, syrup, troche, delayed release tablet, enteric coated tablet, suppository, ointment, transdermal patch. Tablet- convenient oral Capsule- convenient way to ingest a powder or liquid Syrup- formed with water and sugar Troche- dissolves in patients’ mouth Delayed Release- special coating allowing the drug to work over a longer period of time Enteric coated- protects the stomach and delays absorption until the intestines. Suppository- Melts at body temperature Ointment- oily substance applied to the skin Transdermal Patch- releases drug over 24-hour period Question 6 What is the difference between oral and parenteral administration? Oral administration is the route of drug administration by way of the mouth through swallowing. Parenteral administration is the route of drug administration that does not involve the GI tract. Question 7 Please label the boxes below with the appropriate phase. Box 1- pharmaceutics, Box 2- Pharmacokinetics, Box 3- Pharmacodynamics. Question 8 Define the four pharmacokinetic processes Absorption, distribution, metabolism, excretion. Absorption is the movement of a drug from its site of administration into the bloodstream ready to be distributed throughout the body. Distribution refers to the transport of a drug by the bloodstream to its site of action. Metabolism is the biochemical alteration of a drug into an inactive metabolite, a more potent metabolite, or a less active metabolite. Excretion describes the elimination of drugs from the body. Question 9 Define Bioavailability. Bioavailability is the measure of the extent of drug absorption for a given drug and route (from 0%-100%). Question 10 Describe how a drug given enterally is absorbed into the body. In enteral administration the drug is absorbed into circulation via the stomach and/or intestines. They then go to the liver where hepatic enzymes metabolize the drug and then the remaining active ingredients are passed into general circulation. Question 11 Name a route of administration that is known for its inability to consistently enter the bloodstream leading to it being used locally. Topical Question 12 Where is the primary site of drug metabolism within the body? What is the name of the enzymes responsible for metabolism? The liver is the primary site of metabolism. There is a class of enzymes within the liver called the cytochrome P-450 enzymes that are responsible for the majority of drug metabolism. Question 13 What organ is primarily responsible for drug excretion? Kidney Question 14 Define the terms "half-life" and "steady state" including how they relate. The half-life of a drug is defined as the time it takes 50% of a given drug to be removed from the body. The most important thing to remember about a drug half-life is that after about five half-lives most drugs are considered to be effectively removed from the body. Steady state refers to the physiologic state in which the amount of drug removed via elimination is equal to the amount absorbed with each dose. The longer the half-life the longer it takes to reach steady state. Question 15 In terms of pharmacodynamics, name three ways that drugs can exert their action on the body. Acting on receptors, enzymes, and nonselective interactions. Question 16 What is the term that means "the study of what drugs do to the body"? Pharmacodynamics Question 17 List the different ways that drugs can interact with receptors. Agonist, partial agonist, antagonist, competitive antagonist, noncompetitive antagonist Question 18 List factors that affect how a person responds to drug therapy. age, weight, sex, genetics. Question 19 Where is the most common site of drug interactions? The most common drug interactions happen when there is competition between two drugs for metabolizing enzymes within the cytochrome P-450 enzymes Question 20 List the pregnancy drug classes and name the one that is considered most safe for use in pregnancy. Pregnancy Category A, B, C, D, X, NR. Pregnancy category A is considered most safe. Question 21 Define the terms Drug tolerance and Drug dependence. Drug tolerance is defined as a decreased effect that occurs after repeated administration. Drug dependence is a condition wherein reliance on the administration of a particular drug becomes extremely important to the well-being of the individual. This can be psychological and physical. Question 22 How many kg are in 1 pound? 2.2kg Question 23 Show how you would set up a proportion for a basic drug calculation. 10mg/kg = Xmg/50mg where you solve for “X”