PH 16 Drugs for Immunization and Immunomodulation PDF

15 Drugs for Immunization and Immunomodulation LEARNING OUTCOMES 1. Explain the differences between innate immunity and acquired immunity. 2. Describe the role of antibodies in providing true immunity. 3. Explain how vaccination affects acquired immunity. 4. Describe the proper technique for giving...

15 Drugs for Immunization and Immunomodulation LEARNING OUTCOMES 1. Explain the differences between innate immunity and acquired immunity. 2. Describe the role of antibodies in providing true immunity. 3. Explain how vaccination affects acquired immunity. 4. Describe the proper technique for giving drugs for routine immunization. 5. Describe the recommended schedules for vaccination for children, adults, and older adults. 6. List issues for vaccination during pregnancy. 7. List the names, actions, possible side effects, and adverse effects of selective immunosuppressant drugs. 8. Explain what to teach patients and families about selective immunosuppressant drugs. KEY TERMS acquired immunity (ă-KWĪRD ĭ-MYŪ-nĭ-tē, p. 281) A long-acting and “learned” protective response by lymphocyte production of antibodies that are directed against specific microorganisms. active immunity (ĂK-tĭv ĭ-MYŪ-nĭ-tē, p. 281) Acquired immunity in which your body makes specific antibodies to antigens. Can be natural or artificial. antibody (ĂN-tĭ-bŏ-dē, p. 281) A blood protein that is produced in response to and binds with any substance that the body's WBCs consider foreign such as bacteria, viruses, and foreign substances in the blood. antibody titer (TĪ-tĕr, p. 284) A test that detects and measures the amount of antibodies in the blood to help determine the strength of a person's immunity against a specific microorganism. antigen (ĂN-tĭ-jĕn, p. 281) Any substance your body's WBCs recognize as foreign that will cause lymphocytes to produce an antibody against it. antiproliferative drugs (ĂN-tĭ-prō-LĬF-ĕ-rāt-ĭv, p. 287) Drugs that slow the growth of those lymphocytes most responsible for autoimmune diseases and for transplant rejection. antirejection drugs (ĂN-tĭ-rĭ-JĔK-shĕn, p. 287) Drugs that suppress the cells and 513 factors of the immune system responsible for the receiving patient's rejection of transplanted tissues and organs. artificial acquired active immunity (ahr-tĭ-FĬ-shĕl ă-KWĪRD ĂK-tĭv ĭ-MYŪ-nĭ-tē, p. 282) The type of immunity that a person develops against a specific microorganism when a form of it is deliberately injected into his or her body as a “vaccination” or “immunization.” artificial acquired passive immunity (ahr-tĭ-FĬ-shĕl ă-KWĪRD PĂ-sĭv ĭ-MYŪ-nĭ-tē, p. 282) The type of immunity that is transferred as “premade” antibodies from one person or persons and even from animals into another person to provide immediate protection against a specific dangerous infection. attenuated vaccine (ĕ-TĔN-yū-wāt-ĕd văk-SĒN, p. 283) A vaccine containing live organisms that have been weakened and rendered harmless so that they are not capable of causing disease but are still able to produce an immune response. biosynthetic vaccine (BI-ō-sĭn-THĔ-tĭk văk-SĒN, p. 283) A vaccine composed of man-made substances that are very similar to the parts of a virus or bacterium that cause disease. calcineurin inhibitors (KĂL-sē-NYŪR-ĭn, p. 287) A class of drugs that works by forming a complex around the normal calcineurin present inside Tlymphocytes preventing the calcineurin from activating those cells. immunity (ĭ-MYŪ-nĭ-tē, p. 280) The body's physical resistance to becoming ill every time it comes into contact with pathogenic (disease-causing) microorganisms. immunization (Ĭ-myū-nī-ZĀ-shŭn, p. 282) The result of successful vaccination that causes a person to develop his or her own antibodies for immunity against the substance in the vaccine. Often used in the same way as the term vaccination. immunosuppressant drugs (Ĭ-myū-nō-sĕ-PRĔ-sănt, p. 287) Drugs that subdue or decrease the strength of the body's immune system. inactivated vaccine (ĭ-NĂK-tĕ-vāt-ĕd, p. 283) A vaccine in which the organisms have been killed or inactivated by heat, radiation, or chemicals to prevent them from reproducing and causing disease but that can still trigger antibody production and immunity. Also called a “killed” vaccine. innate immunity (ĭ-NĀT ĭ-MYŪ-nĭ-tē, p. 280) The body's intact protective barriers and the cellular responses of inflammation. natural acquired active immunity (NĂ-chĕ-rĕl ă-KWĪRD ĂK-tĭv ĭ-MYŪ-nĭ-tē, p. 281) The type of immunity a person develops to a microorganism that invades his or her body, usually making him or her sick, and triggering his or her immune system to make antibodies against it. natural acquired passive immunity (NĂ-chĕ-rĕl ă-KWĪRD PĂ-sĭv ĭ-MYŪ-nĭ-tē, p. 282) The immunity provided by the antibodies that a woman transfers to her fetus during pregnancy and to her infant during breastfeeding. passive immunity (PĂ-sĭv ĭ-MYŪ-nĭ-tē, p. 281) Acquired immunity in which antibodies made in another person or animal are given to you and your body 514 had no part in making them. Can be natural or artificial. toxoid (TŎK-sōĭd, p. 283) A pathogenic microorganism that is modified chemically so it is no longer toxic and can be used as a vaccine. vaccination (văk-sĭ-NĀ-shĕn, p. 282) An injection or ingestion of a harmless form of bacteria or virus to stimulate antibody production against a certain disease. vaccine (văk-SĒN, p. 282) A preparation of a synthetic, killed, or weakened form of a bacteria or virus that can be injected or ingested in order to stimulate antibody production against certain diseases. Overview of Immunity Immunity is your body's physical resistance to becoming ill every time you come into contact with pathogenic (disease-causing) microorganisms. It is provided by the immune system working together with the protective barriers of intact skin and mucous membranes along with the body's normal flora. The immune system has two main divisions, innate immunity (also known as nonspecific or general immunity), and acquired immunity (also known as specific or adaptive immunity). When all these protections are working well, we are healthy and well more often than we are sick, even when exposed to invading bacteria, viruses, and other organisms. Think of all the times someone in your family caught a cold, influenza, or some other contagious illness, but not everyone in the family got sick. Innate Immunity Innate immunity is the body's intact protective barriers and the cellular responses of inflammation. Inflammation is a predictable set of tissue and blood vessel actions caused by white blood cells (WBCs) and their products whenever the body is injured or invaded by microorganisms. Whenever microorganisms enter the body, many WBCs recognize them as “foreign” and take nonspecific actions against them to kill, neutralize, or eliminate them to prevent illness. WBCs can recognize invading organisms as foreign because all of your cells have a unique code on the surface that works like a universal product code for you (Fig. 15.1). Invaders have a different “code” on their cell surfaces than your cells do, and your WBCs recognize the difference (Fig. 15.2) and take actions against only the invader, not your own cells. These inflammatory responses and actions are general and can be overwhelmed, such as when you are heavily exposed to thousands of one type of streptococcal bacteria and develop a strep throat infection. If innate immunity were the only type of immunity you had, you would probably get another strep throat the next time the same type of streptococcal bacteria heavily invaded your body. This general part of innate immunity helps keep you well from day to day, but it does not provide you with the true immunity that acquired immunity does. 515 FIG. 15.1 Human cell with unique universal product code. (From Workman ML, LaCharity LA: Medical-surgical nursing: Patient-centered collaborative care, ed 2, St. Louis, 2016, Elsevier.) FIG. 15.2 Immune system cell recognizing an invading or foreign cell by differences in its universal product code. (Modified from Ignatavicius DD, Workman ML: Medical-surgical nursing: Patientcentered collaborative care, ed 8, St. Louis, 2016, Elsevier; and Workman ML, LaCharity LA: Medical-surgical nursing: Patient-centered collaborative care, ed 2, St. Louis, 2016, Elsevier.) Memory Jogger Innate immunity helps protect you from smaller day-to-day exposures to pathogenic organisms, but it cannot provide long-term immunity to any single specific disease-causing microorganism. Acquired Immunity Acquired immunity is a long-acting and “learned” protective response by lymphocyte production of antibodies that are directed against specific microorganisms, which are considered foreign substances known as antigens. Exposure to antigens is the trigger for lymphocytes to begin producing antibodies. (Thus an antigen is anything your WBCs recognize as foreign that will cause lymphocytes to produce an antibody against it.) These antibodies can be made in such high amounts that, when you are reinfected by the same microorganism, they attack and destroy it or rid the body of it before it can make you sick again. For example, if you are overwhelmingly infected with thousands of the 234 type of streptococcus (this is a made-up type) and developed a strep throat from the 516 infection, at the same time your lymphocytes would be learning how to make antibodies to streptococcus-234. Then the next time you were heavily exposed to streptococcus-234, you would make so many anti-streptococcus-234 antibodies that they would be killed or eliminated before you could get sick from them again. You would then be immune to streptococcus-234. (Unfortunately there are many different types of streptococcus and until you have had them all, you will not have antibodies to all of them.) Acquired immunity is specific, which means that antibodies to streptococcus-234 probably will not recognize and attack streptococcus-422. So until your body is exposed to type 422 and learns to make anti-streptococcus-422 antibodies, you could get sick from being infected with streptococcus-422. Acquired immunity has two major forms, natural and artificial, each of which can be active or passive. Both types involve the production of specific antibodies in response to exposure to an antigen. One difference between these two types is in how you are exposed to the antigen. Remember, your immune system cannot make an antibody against a specific antigen unless the antigen actually enters the body and the immune system is exposed to the antigen. Whether immunity is active or passive depends on who made the antibodies. When your body makes the antibodies, immunity is active. When the antibodies are made by another person or an animal, immunity is passive (because your body was not actively involved in making the antibody). Fig. 15.3 shows how the four different types of acquired immunity develop. FIG. 15.3 Examples demonstrating how different types of immunity develop. (From Applegate EJ: The anatomy and physiology learning system, ed 4, St. Louis, 2011, Saunders.) 517 Memory Jogger A person's immune system can make antibodies only to those antigens that have actually entered his or her body. Natural Acquired Active Immunity Natural acquired active immunity is the type of immunity you develop to a microorganism that invades your body naturally, usually making you sick and triggering your immune system to make antibodies against it. After your immune system learns to make these specific antibodies, every time you are reexposed to the microorganism, you make more and more antibodies against it. So you continually “self-boost” your immunity to it. This self-boosting part of natural acquired active immunity makes it the most long-lasting type of immunity to a specific microorganism. Therefore natural acquired active immunity is true immunity. Natural Acquired Passive Immunity Natural acquired passive immunity is composed of the antibodies that a woman transfers to her fetus during pregnancy and to her infant during breast-feeding. This immunity is short term but critically important in preventing young infants from developing illnesses during the first 6 months after birth. Artificial Acquired Active Immunity Artificial acquired active immunity is the type of immunity that you develop against a specific microorganism when a form of it is deliberately injected into you as a vaccination or immunization. It is still active immunity because your body has to work to learn how to make the antibodies, and it is artificial because you did not just “catch” the microorganisms, you were deliberately injected with them (or deliberately ingested them). Although this is a common type of immunity and usually works well, it wears off faster than natural acquired active immunity because you are injected with fewer microorganisms than the amount that entered your body naturally to make you sick. As a result, you will need periodic booster shots to help your immune system remember how to make the antibodies to these specific microorganisms. Artificial Acquired Passive Immunity Artificial acquired passive immunity is the type of immunity that is transferred as premade antibodies from one person or persons and even from animals to you. It is called passive because your body did not actively make these antibodies. This type of immunity is used only when a person is exposed to and highly likely infected with a microorganism that can cause serious disease and he or she has no immunity against it. The purpose of giving a person a lot of these specific antibodies is to have the antibodies rid the body of the dangerous microorganisms before the person becomes sick with the disease. Rabies is an example of when this type of immunity is needed. Most people have never received a rabies vaccination and have no antibodies to it. Once the disease occurs, it is almost always fatal. If a person is bitten by an animal with rabies, immediate passive immunity can help prevent him or her from developing rabies 518 and dying. As soon as possible the exposed person is given a series of injections of rabies antibodies that were made by other people or animals. These injected antibodies then attack and destroy the rabies virus before the disease can develop. This immunity is immediate but only temporary. Within a few weeks, the person's immune system will then destroy the “foreign” antibodies. Some other highly dangerous infections and disorders that can be managed with artificial acquired passive immunity include poisonous snakebites, tetanus, and Ebola. Memory Jogger Artificially acquired passive immunity through the transfer of premade antibodies from another person or animal provides only very short-term protection against a specific infectious disease. Vaccination Vaccinations work to prevent possible life-threatening infections. If a person acquires an infection naturally, he or she becomes immune to that microorganism; however, death or complications of the disease can occur. For instance, polio can cause paralysis, and measles can cause blindness. The first vaccine was for smallpox; it was created in 1796 by Dr. Edward Jenner. Today, more than 20 infectious diseases can be prevented with available vaccines. Vaccination is an injection or ingestion of a harmless form of bacteria or virus to stimulate antibody production by B lymphocytes (B cells) against a certain disease. (The B cells are the only type of WBC that can form antibodies in response to exposure to a specific antigen.) These antibodies provide immunity to the disease caused by the antigen. Although some vaccines, such as for polio, can be taken orally, most are injected. A vaccine is a preparation of a synthetic, killed, or a weakened form of a bacteria or virus that can be injected or ingested to stimulate antibody production against certain diseases. As a result of vaccination, the person's B cells start making the desired antibodies. However, vaccination is not as efficient in stimulating antibody-mediated immunity compared with when a person develops naturally acquired active immunity by actually becoming sick with the disease first. So for full immunity to develop from vaccination, more than one injection vaccination with the same vaccine over time may be needed. In addition, this immunity wears off eventually and the person requires a periodic booster shot with revaccination to ensure continued production of enough antibodies to maintain immune resistance against the organism. Many people use the terms vaccination and immunization interchangeably; however, immunization is the result of successful vaccination that causes a person to develop his or her own antibodies for immunity against the substance in the vaccine. Memory Jogger Successful vaccination causes immunization to develop with the production of antibodies against the organisms in the vaccine, leading to immunity. 519 Types of Vaccines Vaccines are prepared in different ways for different organisms. Often inactivated viruses or bacteria are used. Inactivated vaccines are composed of organisms that could cause diseases but have been killed or inactivated by heat, radiation, or chemicals that prevent the organisms from reproducing and causing disease. Diseases for which inactivated vaccines are commonly used include influenza, cholera, hepatitis A, and rabies. Attenuated vaccines (also called live virus vaccines) contain live organisms that have been weakened and rendered harmless so that they are not capable of causing disease but are still able to produce an immune response. Usually modifying the organisms through attenuation makes them noncontagious to people who have normal immune systems. Diseases for which attenuated vaccines are commonly used include measles, mumps, rubella, polio, and chickenpox. Toxoids are pathogenic microorganisms that are modified chemically so that they are no longer toxic and can be used as a vaccine. Disease for which toxoid vaccines are commonly used include tetanus, diphtheria, pertussis (whooping cough), human papilloma virus (HPV), and hepatitis B virus (HVB). Biosynthetic vaccines are those made by genetic engineering that contain a synthetic or natural extract of the virus or bacterium that causes disease. Many modern vaccines are produced this way. Memory Jogger The four types of vaccines that are currently available are: • inactivated vaccines • attenuated vaccines • toxoids • biosynthetic vaccines Vaccination and Boosting Schedules Vaccinations for artificial acquired active immunity usually require more than one injection to ensure that enough B cells are sufficient to the specific antigen and can begin making antibodies. As stated earlier, additional vaccinations (boosters) that contain smaller doses of the original antigens are needed to continue immunity. For example, “baby shots,” which are vaccinations that contain antigens for diphtheria, tetanus, and pertussis (DTaP) mixed into one injection, are given to infants three separate times, usually at ages 2, 4, and 6 months. Boosters of this vaccination are repeated once between the ages of 15 and 18 months, and once again between the ages of 4 and 6 years. Another booster with a different formulation of these same three antigens (known as Tdap [tetanus, diphtheria, acellular pertussis]) should be given once to children between the ages of 11 and 12 years and to women during each pregnancy. It is also recommended that all adults older than 19 years receive this booster vaccination every 10 years. Other common vaccinations recommended during childhood to prevent severe complications of contagious diseases include 520 HVB, Haemophilus influenza type B (Hib), pneumonia, polio, measles, mumps, rubella, hepatitis virus A (HVA), varicella, rotavirus, HPV, meningitis, and seasonal influenza. In addition to immunizing to prevent disease and complications of disease in individual persons, it is necessary to immunize to protect the population. When a significant portion of the public is immunized against a specific contagious disease, most people within that population are protected against that disease because an outbreak has little chance of occurring. People who cannot receive certain vaccines, such as pregnant women or those who are immunocompromised, are still protected because exposure to the disease is either limited or nonexistent. This is known as herd immunity and is the principle used to promote vaccination yearly for seasonal influenza. It is also the reason polio has been eradicated in the United States since 1979. The Centers for Disease Control and Prevention (CDC) website has free printable schedules for both regular and catch-up versions of immunizations to download so healthcare professionals can easily keep up to date and safely give vaccinations for both children and adults. You can access these schedules, as well as educational tools, at the CDC website. The website is published every year based on recommendations of the American Academy of Pediatrics, the CDC Advisory Committee, and the American Academy of Family Physicians. This website also features a phone app that is free to download and is available for both Android and iPhones for quick access to this information. Bookmark This! To access up-to-date immunization schedules for children: https://www.cdc.gov/vaccines/schedules/index.html. Fig. 15.4 shows a sample of what is available on the website. It is meant to simply be a sample and although current for the year 2017, it is not entirely complete. The CDC site includes a schedule for those who fall behind on vaccinations or who start late. There are also separate schedules for those who are immunosuppressed. Footnotes are included to provide further guidance on the use of all the vaccines that are available. 521 FIG. 15.4 Sample immunization schedule for children aged 0 to 18 years. Top Tip for Safety Tdap and DTaP have similar names but are used in different patients and different circumstances: DTaP is used for active immunization in infants and children, and Tdap is used as a booster vaccine for older children and adults. Vaccination and immunization are needed in adulthood, not just in childhood. Vaccines are recommended to stimulate protection for adults against common infectious diseases, especially for older adults and those who have chronic health problems. For these people, even less serious contagious disease, especially pneumonia and influenza, can have fatal consequences. Additional recommended vaccinations include those to prevent shingles (varicella), HVA, HVB, and pertussis. Recommendations for adults against other childhood disorders vary, depending on whether the person actually had these diseases as a child. See the CDC website for adult vaccination schedules. Bookmark This! To access immunizations schedules for adults: https://www.cdc.gov/vaccines/schedules/index.html. Additional vaccinations may be recommended for adults depending on the person's history, job, or travel. For example, the rabies vaccine is not part of a recommended set of vaccinations. However, for veterinarians and other animal 522 handlers, the vaccine is readily available. Military personnel and others who travel to areas of the world where contagious diseases are common may be vaccinated against diseases such as yellow fever, cholera, typhoid, malaria, anthrax, and many others, depending on which area of the world they enter. Many of these less common vaccinations require more than one injection on a specific schedule to ensure effective immunity. Vaccine guidelines and schedules for these contagious diseases can be found on the CDC website. Bookmark This! For vaccination guidelines and schedules for contagious diseases: https://www.cdc.gov/vaccines/hcp/acip-recs/index.html It is important to properly store, handle, and give vaccines so that potency and safety are maintained. Box 15.1 has important nursing responsibilities and actions for vaccine handling, storage, and administration. Box 15.1 Nursing Responsibilities and Actions for Vaccine Administration Storage • Immediately unpack vaccines as soon as received from the manufacturer and store in a designated area with a designated refrigerator that is separate from other drugs or food. • Ensure the refrigerator is labeled “DO NOT UNPLUG” and is plugged into an outlet that has emergency power. • Keep all opened and unopened vials in their original boxes. • Do not place vaccine vials on the door of the refrigerator or in the freezer. • Check the vials weekly for expiration dates, and discard those that are expired. Before Administration • Check the recommended schedule for whether the vaccination is appropriate for the patient. • Check the expiration date on the vaccine vial and, if a diluent is to be used, check the expiration date on the diluent's vial. • Read the package insert to determine all vaccine components (i.e., preservatives); the recommended dosage, techniques, and solutions for dilution; and any special instructions for administration. • Ask the patient (or parent) whether he or she has ever had a reaction to the 523 vaccine or its components. • Ask the patient (or parent) when he or she last received this or any other vaccine. • Ask the patient (or parent) about any known allergies. • Ask whether the patient is ill or has been ill within the previous 24 hours (some vaccines should not be given to a patient who has a fever or any type of infection). • Using aseptic technique and the recommended type of syringe, draw up the appropriate dose. Use an appropriate needle for the patient size and vaccine type. • Inject the drug using the recommended technique and site. After Administration • Document the following information in the patient's medical record or permanent vaccination log: • Name and age of the patient • Name of the vaccine • Manufacturer, lot number, and expiration date of the vaccine • Dosage of the vaccine • Site of vaccination • Condition of the site • Give the patient or parent a copy of the specific vaccine's Vaccine Information Statement (VIS). • Document which VIS was given to the patient or parent. • Observe the patient as recommended by the manufacturer for any immediate reaction. • Tell the patient what side effects to expect and which ones require immediate attention. Antibody Titer Does vaccination always result in successful immunization? A person's immunity to a specific organism can be assessed by performing a blood titer for that antibody. An antibody titer is a test that detects and measures the amount of specific antibody in the blood to help determine the strength of a person's immunity against a specific organism. This titer can be used to determine the effectiveness of vaccination, as well as to determine whether a person has retained immunity to a disease he or she once had. For example, a person who has a 0 titer for anti–chickenpox antibody (anti– varicella zoster virus [anti-VZV] or varicella) has no antibodies to the chickenpox virus and is highly likely to develop the disease if he or she is heavily exposed to the organism. A person who has a positive antibody titer of 32 has so much antibody that it is still detectable even when the blood has been diluted to a ratio of 1 part blood to 31 parts diluent. This result indicates good immunity to the chickenpox virus. Overall, this test can indicate whether you have ever had a specific infectious disease (or have been vaccinated against it) and how much immunity you had to it at 524 the time the test was performed. The interpretation of antibody titers is guided by laboratory reference values that are specific to the antibody of the disease. Seasonal Influenza Vaccination Many people wonder why adults and children are recommended to receive seasonal influenza vaccination every year. Doesn't the protection from an influenza vaccination last longer than a year? There are many strains of influenza. Each strain is somewhat different and has a different unique code. If you get sick with one specific strain this year, you will develop active immunity to it. However, each year different strains may come to your community. Last year's antibodies do not provide immunity to this year's strain and, if sufficiently infected, you will get sick with the new strain of influenza. The case with flu shots is the same. When you receive this year's seasonal flu shot, the vaccination contains antigens for the three or four viruses that are predicted by the CDC to be the most common ones prevalent this year. Receiving the vaccination helps you develop active immunity only to these three or four influenza strains, which then protects you against those strains for a long time. However, next year the predicted most common strains may not be the ones you were vaccinated against this year. So if you skip next year's vaccination, you may not have any immunity to the different strains of influenza and could become sick if you are heavily exposed to one or all of them. It is advisable for healthcare workers to receive the flu shot every year not only to prevent individual sickness, but also to prevent giving the flu to an already sick population, which could make them sicker and even lead to untimely death. It takes about 2 weeks to develop antibodies after being vaccinated. Memory Jogger Some infectious organisms have many strains with different codes. Immunity to each requires either becoming sick with each strain or being vaccinated against each strain. Lifespan Considerations Pediatric Vaccination For best effect, the recommended pediatric vaccination schedules must be followed closely. Most vaccinations given before 6 months of age require multiple doses over time because more time is needed for the infant's immature immune system to learn to make antibodies. Lifespan Considerations Vaccination and Pregnancy 525 Some, but not all, vaccinations can be safely given during pregnancy. Live virus vaccinations, such as for chickenpox, polio, measles, mumps, and rubella, are not recommended during pregnancy. Vaccinations that are recommended during pregnancy include seasonal influenza and Tdap. Lifespan Considerations Vaccinations and Older Adults As a person ages, previously acquired immunity slowly declines. As a result, older adults gradually lose immunologic protection, even natural active immunity. They need to receive scheduled booster shots to immunizations they have already received and need new immunizations to other organisms such as influenza, pneumonia, and the VZV (the same virus that causes chickenpox). Many older adults are not aware of their loss of immunologic protection and the need for additional vaccination. Urge all older adults to follow the recommended schedules for vaccination and revaccination. Expected Side Effects All vaccines can cause side effects, but they are generally minor. A sore arm and minor swelling and redness at the injection site or low-grade fever are common and go away within a few days. Fever can be relieved by keeping the child cool or with age-appropriate doses of acetaminophen or ibuprofen. Cool compresses to the injection area will relieve minor swelling and discomfort. Fever over 101°F should be reported to the healthcare provider because this may indicate an infection. Adverse Reactions Vaccines are constantly monitored for safety, but just like all other drugs they can cause adverse effects. The risk for rare complications from vaccines outweighs the risk for the serious problems that disease can cause for both the child and all others who come in contact with the child. The CDC lists all vaccines licensed in the United States. Expected side effects and any adverse reactions associated with each of them can be found on the CDC website. Bookmark This! For adverse side effects of individual vaccinations: https://www.cdc.gov/vaccines/vac-gen/side-effects.htm Nursing Implications and Patient Teaching Assessment. Obtain a medical history, in particular a history of any immune deficiency disease such as HIV, any specific congenital immunodeficiency disease, pregnancy, or plan 526 to become pregnant that will prohibit vaccination with a live virus. Some vaccines can be given during pregnancy, but other vaccines, such as the measles, mumps, rubella (MMR) vaccine, must be given a month or more before pregnancy occurs. Obtain a drug history, including immunosuppressant drugs, immune globulins, or blood products. Some drugs may interfere with the antibody response of vaccines. Intervals between live vaccines and blood product transfusions are recommended because live vaccines must replicate to initiate an immune response. Antibodies against injected live vaccine antigen in transfused blood may interfere with that replication. People who are immunocompromised are at increased risk for an adverse reaction after administration of live attenuated vaccines because they have less of an ability to build up an effective immune response. Ask if there is an immunocompromised person living with the person who is to be vaccinated. Before receiving a vaccination with a live vaccine, the household member's healthcare provider should be consulted because the patient with reduced immunity may be at increased risk for contracting the virus the vaccine is designed to prevent. A complete allergy history that includes drugs, foods, vaccines, and environmental allergens should be taken. An updated CDC recommendation for people with egg allergy can be found at https://www.cdc.gov/flu/protect/vaccine/egg-allergies.htm. Recent studies examining the use of injectable influenza vaccine in egg-allergic persons indicate that severe allergic reactions are highly unlikely. The only contraindication for allergic individuals is a previous severe allergic reaction to flu vaccine for any reason. Assess the patient for symptoms of illness with or without fever that may require a delay in giving the vaccination until symptoms have subsided. Take a complete immunization history so current vaccination needs can be determined. In addition, ask about family and household members who are immunocompromised or unvaccinated so their health and safety also can be assessed. Planning and implementation. Adhere to the vaccination storage (see Box 15.1 for nursing responsibilities and actions) to ensure the vaccination will be effective. Never mix vaccines in the same syringe. Keep epinephrine or an anaphylactic kit readily available for immediate use in case of an anaphylactic reaction. Evaluation. Observe the patient for any signs and symptoms of adverse reactions and provide the patient with a record of the vaccinations (see Box 15.1). Patient and family teaching • Teach the parent or patient that localized reactions to the injection can occur. The discomfort can be relieved with cool compresses to the site and age-appropriate acetaminophen or ibuprofen as directed by the healthcare provider. 527 • Advise the parents or patient to notify the healthcare provider of fever greater than 101°F, rash, itching, or shortness of breath. • Tell the parent or patient to keep a current record of the immunizations. It is advisable to keep two copies in case of loss. • Teach the parent or patient the risks of contracting the disease that the vaccine is preventing. • Tell female patients that they should not become pregnant for at least 1 month after receiving the MMR vaccine. • Remind the parent or patient to bring the immunization record with them to all visits. • Give the parent or patient information and an appointment date to return for the next vaccination. Immunomodulating Therapy Selective Immunosuppressants for Autoimmune Diseases Although the immune system is protective most of the time, for some people it can overreact in certain tissues as a result of autoimmune disorders, such as rheumatoid arthritis or psoriasis. In such disorders the immune system sees normal body tissue as “foreign” and attacks it. These problems can be chronic and destructive, requiring that the immune responses be selectively modified or suppressed. In addition, immune modification is needed after organ transplantation to prevent destruction of the transplanted organ by an immune system that sees this new organ as “foreign.” In both cases, management involves suppression of the immune response. Some immunosuppressant drugs are nonselective and cause such general immune suppression that the patient is at high risk for life-threatening infections. These general immunosuppressive drugs include corticosteroid anti-inflammatories and some types of cancer chemotherapy, such as methotrexate. Their use has decreased and, even when they are used today, the dosages are lower because they are used along with more selective immunosuppressants. The actions, effects, nursing implications, and other information specific for corticosteroids are detailed in Chapter 11. More recent drug therapy for autoimmune disorders uses selective immunosuppressants that confine their effects to those cells and products of the immune system most directly involved in tissue-damaging actions. The most common drug category of selective immunosuppressants for this use is the diseasemodifying antirheumatic drugs (DMARDs). The actions, effects, nursing 528 implications, and other information specific for DMARDs are detailed in Chapter 11. Selective Immunosuppressants to Prevent Transplant Rejection The immune system of a person who receives a transplanted organ (from anyone who is not an identical sibling) recognizes the transplanted organ as “foreign” and tries to attack it. For a transplanted organ to remain healthy in the recipient, the parts of his or her immune system that usually attack it must be suppressed forever. Drug therapy to prevent solid-organ rejection is lifelong and uses combination drug therapy. Antirejection drugs suppress the cells and factors of the immune system responsible for the receiving patient's rejection of transplanted tissues and organs. The dosages must be adjusted to the immune response of each patient because these drugs do cause some degree of general immunosuppression. In addition to corticosteroids and some DMARDs, the selective immunosuppressant drugs for this purpose are the antiproliferative drugs and calcineurin inhibitors. Action Antiproliferative drugs slow the growth of those lymphocytes most responsible for autoimmune diseases and for transplant rejection. A less selective drug in this class is azathioprine. It inhibits the metabolism of purines, which are important in DNA synthesis and cell division. This inhibition suppresses the actions of T lymphocytes that are toxic to transplanted organs and also are responsible for causing tissue damage in some autoimmune diseases. The names, usual adult dosages, and nursing implications of the antiproliferative drugs are listed in Table 15.1. Table 15.1 Examples of Selective Immunosuppressants for Transplant Rejection Antiproliferative drugs: reduce transplant rejection by slowing the growth of many immune system cells that are responsible for transplant rejection DRUG/ADULT DOSAGE RANGE NURSING IMPLICATIONS azathioprine (Azasan, Imuran) 1–5 mg/kg orally • Teach patients to look for signs of bleeding, such as bleeding gums, easy bruising, and nosebleeds, once daily or 1–1.5 g IV because these drugs can decrease platelet counts as well as WBC counts. mycophenolate (CellCept, Myfortic) 1.5 g orally • All patients should have BUN and creatinine levels checked as ordered and notify the healthcare twice daily or 1.5 g IV twice daily provider for signs of renal failure such as decreased urine output, fatigue, swelling, or shortness of sirolimus (Rapamune) 6 mg orally loading dose, breath. followed by 2 mg orally once daily for • Antiproliferative drugs commonly cause nausea and vomiting. Warn patients that if these maintenance symptoms are accompanied by fever and diarrhea, they should notify their healthcare provider. everolimus (Zortress) 0.75 mg orally every 12 • Teach patients not to take these drugs with grapefruit juice because it can cause increased toxicity. hours initially; dosages adjust according to • Allopurinol use with azathioprine can cause increased toxicity of the drug, leading to an extreme patient responses decrease in WBCs and bone marrow suppression, which can be life-threatening. • Mycophenolate is associated with congenital abnormalities if used in pregnancy. Remind female patients who are sexually active to use two forms of birth control while on this or any of these antiproliferative drugs. • Mycophenolate can cause hyperglycemia. Caution diabetic patients that it may be difficult to control sugar levels. • Sirolimus and cyclosporine doses must be separated by at least 4 hours to ensure the best effect. • Oral solutions of sirolimus must be mixed in a glass container with milk, orange, or apple juice and not water. Calcineurin drugs: reduce transplant rejection from T cell activation by binding to protein and forming a complex that inhibits calcineurin present in some immune system cells that is needed to allow these cells to function and reproduce DRUG/ADULT DOSAGE RANGE NURSING IMPLICATIONS cyclosporine (Neoral, Gengraf, Sandimmune) 4–8 • Both of these drugs can cause significant kidney and liver toxicity. Monitor serum electrolyte, BUN, mg/kg orally twice daily initially and creatinine levels closely along with liver enzymes. tacrolimus (Astagraf XL, HECORIA, Prograf) • All patients should have BUN and creatinine levels checked as ordered. Notify the healthcare Immediate-release capsules, 0.1 mg/kg orally provider for signs of renal failure such as decreased urine output, fatigue, swelling, or shortness of every 12 hours breath. Extended-release capsules, 0.2 mg/kg orally • Teach patients who are taking cyclosporine to monitor their blood pressure daily because this drug once daily causes hypertension. • Teach patients who are taking cyclosporine to practice good oral hygiene because it can cause gingival hyperplasia. • Neoral and Gengraf cannot be used interchangeably with Sandimmune because the absorption is 529 different between them. • These drugs should not be given with grapefruit juice because it can lead to toxicity. • Many drug interactions can occur, most commonly with St. John's wort and NSAIDs. Remind the patient to never take any over-the-counter drugs before checking first with the pharmacist or healthcare provider. • Do not crush or split the tablets or capsules because they are extended release and could cause toxicity. • Oral solutions of cyclosporine must be mixed in a glass container with milk, orange, or apple juice and not water. Mycophenolate is more selective in suppressing T and B lymphocyte activity by inhibiting an enzyme needed for lymphocyte reproduction. It also prevents T cell activation. As a result, the immune responses most associated with autoimmune tissue destruction and transplant rejection are selectively suppressed. Sirolimus selectively inhibits T cell activation and reproduction by blocking the mammalian target or rapamycin (mTOR) signal pathways that promote completion of cell division for T cells. If fewer T cells are present, then there is less tumor necrosis factor and other substances present to attack normal tissues and transplanted organs. Sirolimus also suppresses B cell growth and maturation (which makes antibodies against normal tissue and against transplanted organs), so there are fewer antibody attacks on these tissues. Everolimus is a drug that acts very similarly to sirolimus. It also inhibits the mTOR pathway, so lymphocyte cell division and growth are reduced. It is more specific against those immune system cells that attack normal self-cells and transplanted organs than are the general antiproliferative drugs. Calcineurin inhibitors work by forming a complex around the normal calcineurin present inside T lymphocytes preventing the calcineurin from activating those cells. With less ability to be activated, the T cells have less power to attack and damage transplanted tissues and organs. The two main calcineurin inhibitors are cyclosporine and tacrolimus. The names, usual adult dosages, and nursing implications of the antiproliferatives are listed in Table 15.1. Expected Side Effects All selective immunosuppressants reduce immunity to some extent and increase the patient's risk for infection. So these drugs are not to be used when a patient has a systemic infection. With reduced immunity and inflammation, the symptoms of infection may not be present even when the patient has a significant infection. Side effects of the selective immunosuppressants vary depending on the exact mechanism of action. All of these drugs cause GI problems and many skin rashes. Tacrolimus can cause diabetes mellitus. Sirolimus and everolimus increase blood cholesterol levels. The calcineurin inhibitors increase blood cholesterol levels, which leads to hypertension. They also increase blood glucose levels (hyperglycemia), making diabetes more difficult to control. Many patients who are taking cyclosporine develop gingival (gum) hyperplasia. Adverse Effects All selective immunosuppressants increase the risk for cancer development, especially skin cancers, because they reduce immunity. This problem is thought to be related to reduced immunosurveillance by loss of immune system early recognition of when normal cells transform into cancer cells. The risk is higher for the drugs that are taken long term, including the antiproliferatives and the 530 calcineurin inhibitors. Antiproliferative drugs given intravenously can cause phlebitis and thrombosis at the administration site. Liver toxicity and liver failure have occurred with all of the antiproliferative drugs and the calcineurin inhibitors. The risk is increased if the patient has other liver problems or is exposed to other substances that are liver toxic, such as alcohol and acetaminophen. Other adverse effects vary by the drug's mechanism of action. Most of these drugs can cause imbalances of potassium, phosphorus, and magnesium. Patients who are taking selective immunosuppressant drugs are advised to avoid vaccinations with live vaccines because their reduced immunity increases their risk for getting the disease the vaccine is designed to prevent. Drug Interactions All the selective immunosuppressants interact with numerous other drugs. Transplant patients usually need other drugs in addition to their lifetime immunosuppressant therapy, which increases their risk for drug interactions. Be sure to consult a drug reference book or pharmacist for more information about specific drug interactions with the antiproliferative drugs and the calcineurin inhibitors. Nursing Implications and Patient Teaching Assessment. A healthcare provider completes a detailed history and physical for each patient who will receive a transplant. Transplantation is a multifaceted medical and ethical issue, and the many healthcare team members include specialty healthcare providers, nurses, nurse practitioners, social services, psychologists, and a variety of other professionals involved in the care of a transplant patient and the patient's family. Your continued assessment after transplantation will be guided by the individual medical needs of the patient and are covered in the following subsection. Planning and implementation. The antiproliferative drugs can be absorbed through skin and mucous membranes, and they exert effects on whoever prepares them. So using personal protective equipment (PPE) of gowns, gloves, and masks is critical when preparing and giving these drugs to prevent accidental exposure of these drug to yourself. Be sure to obtain a list of all other drugs (prescribed and over-the-counter drugs) that the patient takes because most selective immunosuppressant drugs interact with many other agents. Be sure to consult a drug reference book or pharmacist for more information about specific drug interactions. If needed, consult with the prescriber about dosage or changing the patient's other drugs. All patients who are taking or receiving any selective immunosuppressant have baseline laboratory tests that include complete blood cell counts, electrolyte studies, platelet counts, kidney function tests, liver function tests, bilirubin levels, and ECGs. These tests, as well as assessment and documentation of signs and symptoms of infection and bleeding, are done at regular intervals throughout the patient's lifetime to prevent drug toxicities. Review the results of laboratory tests and notify the 531 healthcare provider for any abnormal results. For best effects, intravenous (IV) formulations of these drugs must be mixed with the manufacturer-recommended diluent. Do not mix or give selective immunosuppressants with other IV drugs, and do not give other drugs through the same IV line used for immunosuppressant therapy. Assess the site for irritation, phlebitis, and thrombosis. Monitor patients closely during infusions of any immunosuppressant drugs for signs of allergic (hypersensitivity) reactions and anaphylaxis. If these occur, stop the infusion immediately and follow your institution's protocol for an emergency situation. If you are in a clinic, make sure the crash cart or emergency drug box is close by. Be sure to document the reaction to the drug, flag the chart, and alert the patient that the drug should not be taken again. Assess the functioning of all patient organ systems. Assess vital signs and report abnormalities. Ask the patient about fever, chills, fatigue, lethargy, cough, or difficult breathing that may indicate infection. Look in the mouth for signs of gum hyperplasia (can be caused by cyclosporine) or evidence of fungal infection. Assess the patient for yellowing of the skin or whites of the eyes that may indicate liver dysfunction. Kidney function can be affected, especially with tacrolimus, so weigh the patient to assess for changes in fluid balance. A weight gain of 1 kg is equal to 1 L of fluid. In addition, check the blood urea nitrogen (BUN), creatinine, and electrolyte studies, and ask the patient about color, amount, and consistency of urine. Small amounts of dark yellow concentrated urine can indicate dehydration, infection, or a problem with the kidneys caused by drug toxicity. Patient and family teaching. Tell the patient and family the following: • Take your temperature daily and watch for the common signs and symptoms of infection because these drugs reduce your ability to fight infection. Common indications of infection include fever, foul-smelling drainage, pain or burning on urination, sore throat, and cough. • Immediately report any indication of infection to your healthcare provider. • Check with your healthcare provider for what types of vaccinations you should receive while on immunosuppressive therapy. • Keep all appointments for monitoring of blood counts and other laboratory tests. • Take your drugs exactly as prescribed to maintain the effectiveness in preventing transplant rejection. Even a 532 few missed doses can lead to tissue-damaging responses and transplant rejection episodes. • Notify your healthcare provider if you develop yellowing of the skin or eyes, darkening of the urine, or lightening of the stools. These problems are signs of liver toxicity, a serious adverse effect of these drugs. • Avoid drinking alcohol or using acetaminophen while taking these drugs because these substances also can cause liver damage. • If you are taking the oral suspensions of sirolimus or cyclosporine, mix the drug exactly as directed, using the recommended solution (e.g., milk, orange juice, or apple juice); do not mix with water. After drinking the suspension, rinse the container with the same solution and drink the rinse for better drug effectiveness. Remember that cyclosporine must be mixed in a glass container, not a plastic one. • If you are taking both sirolimus and cyclosporine, separate the drug dosages by at least 4 hours to ensure the best effect. • Do not take sirolimus or tacrolimus with grapefruit juice because it decreases the effectiveness of the enzyme that metabolizes these drugs, and their blood levels could become dangerously high, leading to toxic side effects. • Do not take other drugs or supplements without checking with your healthcare provider because the antiproliferatives and calcineurin inhibitors interact with so many other drugs. Lifespan Considerations Pregnancy and Selective Immunosuppressants Pregnancy is an absolute contraindication for the use of antiproliferative drugs 533 because these drugs are associated with birth defects and other severe problems. Tell sexually active women of childbearing age to use two reliable methods of contraception during this therapy and for at least 12 weeks after the therapy is discontinued. These drugs also enter breast milk and can have an adverse effect on the infant. Get Ready for the NCLEX® Examination! Key Points • Innate immunity helps protect a person from infection but does not provide true immunity to any specific infectious microorganism. • The immune system cannot make an antibody against a specific antigen unless it is exposed to that antigen. • Antibodies made by one person or animal can be transferred to another person for short-term passive immunity. • The four types of vaccines currently available are inactivated (“killed”) vaccines, attenuated (“live”) vaccines, toxoids, and biosynthetic vaccines. • Vaccinations usually require more than one dose and often must be “boosted” for best long-term immunity to a specific organism. • For some infectious microorganisms there are many different strains of the microorganisms, each of which requires vaccination for immunity. One example is seasonal influenza. • Pregnant women should receive seasonal influenza vaccination and the Tdap vaccination during every pregnancy. Most other vaccinations are avoided during pregnancy. • Vaccinations are used to help people develop immunity to a dangerous disease without the risk for becoming sick first. • Immunizing the majority of a community produces herd immunity, which prevents disease transmission to those persons who are unable to become vaccinated. • The immune systems of patients who receive transplanted organs (unless from an identical sibling) can attack and reject the new organ. They need to take immunosuppressive drugs daily to prevent transplant rejection. • All patients who are taking immunosuppressive drugs are at increased risk for infection and cancer development. • Ask patients about all other drugs or supplements they take before giving any selective immunosuppressant drug because these drugs have many interactions. • Use PPE when preparing or giving selective immunosuppressants to prevent accidental exposure of the drug to you. • The antiproliferative drugs are associated with poor pregnancy outcomes; therefore teach sexually active women of childbearing age who are taking these 534 drugs to use two reliable methods of contraception during therapy and for 12 weeks after antiproliferative drugs are discontinued. Review Questions for the NCLEX® Examination 1. Which condition is a contraindication for receiving a measles, mumps, rubella (MMR) vaccine? 1. Cold symptoms 2. Pregnancy 3. Urinary tract infection 4. Anemia 2. Which of the following symptoms are considered expected side effects of IM vaccinations? (Select all that apply.) 1. Rash 2. Fever less than 101°F 3. Redness and soreness of injection site 4. Shortness of breath 5. Earache 6. Sore throat 3. A patient asks what all the adverse reactions of a yellow fever vaccination are before consenting to the injection. Which response by the nurse is the most appropriate? 1. “There are side effects to every drug, but the side effects far outweigh getting yellow fever.” 2. “The expected side effects are redness and soreness at the injection site. A warm compress and some acetaminophen will take care of those symptoms.” 3. “You should ask the pharmacist or healthcare provider that question.” 4. “The CDC regularly monitors adverse side effects of all vaccinations. Let's pull up the CDC website so we can look up the adverse effects of the vaccine, as well as the dangers of getting yellow fever.” 4. Which type of immunity does an injection with rabies antibodies represent? 1. Natural acquired active immunity 2. Natural acquired passive immunity 3. Artificial acquired active immunity 4. Artificial acquired passive immunity 5. A mother brings her 9-month-old child to the clinic for his scheduled immunizations. Which statement by the mother would cause the nurse to question giving the child his immunization at this visit? 1. “Ethan's nose has been stuffy for a week.” 2. “Ethan's thigh was really sore and red the last time he was vaccinated.” 3. “Ethan was cranky, crying, and wouldn't eat his dinner the last time he was vaccinated.” 535 4. “Ethan had a fever last night, but it is back to normal since I gave him ibuprofen.” 6. A 45-year-old female patient is receiving cyclosporine (Neoral, Sandimmune) after a kidney transplant. The patient has a sore throat, fatigue, and a fever of 99°F. What should the nurse suspect at this time? 1. The patient's kidney has begun to fail. 2. The patient is rejecting the kidney. 3. The patient may have an infection. 4. The patient is beginning to have an adverse reaction to the cyclosporine. 7. Which laboratory test on a transplant patient is most important to monitor closely for an adverse effect of tacrolimus? 1. Liver enzymes 2. Electrolytes 3. Platelet count 4. Serum creatinine 8. Which of the following fruits should be avoided when a patient is taking cyclosporine? 1. Apples 2. Grapefruit 3. Apricots 4. Oranges 9. A patient on long-term immunosuppressants should adhere to which of the following behaviors? (Select all that apply.) 1. Staying away from persons who are sick 2. Using acetaminophen for minor discomfort 3. Routinely have a healthcare professional check for skin lesions 4. Receiving only inactivated or dead vaccines 5. Washing fruits and vegetables well before eating 6. Not straining while bearing down for a bowel movement 10. Order: cyclosporine (Sandimmune) 15 mg/kg orally as a single dose for a child who weighs 77 lb. Cyclosporine (Sandimmune) is available in a 100 mg/1 mL oral solution. A. How many mg of cyclosporine should be given? (35 kg × 15 mg = 525 mg) B. How many mL of oral solution will you give the child? (5.25 mL of oral solution) Case Study Jennifer Walden is a 32-year-old mother who presents to the clinic for vaccinations. She desires a hepatitis B vaccine for herself because she will be returning to work as a healthcare worker in the jail infirmary and must have the vaccinations up to date before she begins employment. She also requests immunizations for her 4-year-old 536