Drugs for Immune System Modulation

Immunomodulators

  • Affect the body's defenses.
  • May stimulate or suppress body defenses.

Innate (Nonspecific) Body Defenses and the Immune Response

  • First line of defense.
  • Barrier to microbes or environmental hazards.
  • Deny entrance of pathogens.
  • General responses that are not specific to a particular threat.
  • Examples:
    • Skin, phagocytes, natural killer cells.
    • Complement system, fever, interferons, inflammation.

Adaptive (Specific) Body Defenses

  • Second line of defense - specific activation and effectiveness.
  • Known as immune response.
  • Lymphocytes interact with antigens.
  • Two major divisions of immune system
    • Antibody-mediated (humoral)
    • Cell-mediated

Humoral (Antibody-Mediated) Immune Response and Antibodies

  • Initiated when antigen encounters B cell.
  • Activated B cell divides and becomes plasma cell that secretes antibodies.
  • Plasma cells secrete antibodies (immunoglobulins):
    • Neutralize foreign agent.
    • Mark it for destruction by other defense cells.
    • Peak production occurs in about 10 days.
  • Memory B cells can speed a future defense against a specific antigen (2–3 days).

Administration of Vaccines

  • Active Immunity:
    • Immune system stimulated to produce antibodies.
    • Exposure to antigens produces active immunity.
    • Vaccines boost antibody production; produce active immunity.
  • Passive Immunity:
    • Preformed antibodies transferred from one individual to another.
    • Maternal antibodies cross the placenta.
    • Immune globulin.
    • Treatment for botulism, tetanus, and rabies.
    • For people who are exposed or have high-risk exposure.
    • For immunosuppressed people.

Vaccine Schedules

  • Nurses play key role in vaccination process.
  • Diphtheria, tetanus, pertussis (DPT, Tri-Immunol, Tripedia, Acel-Imune, Infanrix, Certiva):
    • IM; at 2 months, 4 months, 6 months, and 12–15 months.
  • Haemophilus influenzae type B conjugate (Hiberix, ActHIB, PedvaxHIB):
    • IM; 2 months, 4 months, 6 months, and 12–15 months.
  • Hepatitis A (Havrix, VAQTA):
    • Children - IM; at age 12 months and 6–12 months later.
    • Adults - 1 dose and another 6–12 months later.
  • Hepatitis B (Recombivax HB, Engerix-B):
    • Given to children - at birth, at 1–2 months, and 9–18 months later.
  • Human papillomavirus (Cervarix, Gardasil):
    • Children - age 11–12 years, again 6-12 months later, a three-dose schedule is indicated for those who start the series at age 15 or older.
  • Influenza vaccine (Fluzone, Fluvirin, others):
    • Given to children - IM, 6 months; then annual dose.
    • Adults - IM, one or two doses annually.
  • Measles, mumps, and rubella:
    • Given subcutaneously; age 12–15 months and 4–6 years.
  • Meningococcal conjugate vaccine (Menactra, Menomune, Menveo):
    • IM; at age 11–12 years and 16 years.
  • Pneumococcal, polyvalent (Pneumovax 23, Pnu-Immune 23) or 7-valent (Prevnar):
    • Given to children (Prevnar) - IM, 4 doses at ages 2 months, 4 months, 6 months, and 12–15 months.
    • Adults (Pneumovax 23 or Pnu-Immune 23) - subcutaneously or IM; 0.5 mL as single dose.
  • Poliovirus, inactivated (IPOL):
    • Given subcutaneously; at ages 2 months, 4 months, 6–18 months, 4–6 years.
  • Varicella zoster/chickenpox (Varivax):
    • For children - at ages 12–15 months and 4–6 years.
    • Adults - single dose at age 50 or older.
  • Rotavirus (Rotarix, RotaTeq):
    • 3 doses at ages 2 months, 4 months, 6 months.
  • Tetanus toxoid:
    • 3 doses, at age 7 or older, second dose 4–8 weeks after first, third dose 6–12 months after second dose.

Cell-Mediated Immunity and Cytokines

  • Activation of specific T cells
    • Helper T cells (CD4 receptor)
      • Activate most other immune cells
    • Cytotoxic T cells (CD8 receptor)
      • Travel through body killing bacteria, parasites, viruses, cancer cells
  • Cytokines secreted by T cells
    • Hormone-like proteins that regulate intensity and duration of immune response
    • Mediate cell-to-cell communication
    • Examples - interferon, interleukins

Prototype Drug - Hepatitis B Vaccine (Engerix-B, Recombivax HB)

  • Therapeutic Class - Vaccine
  • Pharmacologic Class - Vaccine
  • Actions and Uses
    • Hepatitis B vaccine is a highly effective vaccine that provides active immunity for 99% to 100% of patients.
    • Indications include the following
      • All infants, with first dose given at birth.
      • All children younger than age 19 who have not been vaccinated.
      • Persons at risk for HBV infection by sexual exposure.
      • People at risk for infection by percutaneous or mucosal exposure to blood.
      • Patients with diabetes, chronic liver disease, or infected with hepatitis C or HIV.
      • Living or traveling to regions with high or intermediate rates of endemic HBV infection.
    • HBV vaccine does not provide protection against exposure to other (non-B) hepatitis viruses.
    • HBV vaccine is produced through recombinant DNA technology using yeast cells. It is not prepared from human blood.
    • HBV vaccination requires three intramuscular (IM) injections - the second dose is given 1 month after the first and the third dose, 6 months after the first dose.
    • The effectiveness of the vaccine declines with age and boosters may be needed.
  • Administration Alerts
    • In adults, use the deltoid muscle for the injection site, unless contraindicated.
    • Because none of the formulas of Recombivax HB contain a preservative, once the single-dose vial has been penetrated, the withdrawn vaccine should be used promptly, and the vial discarded.
    • Epinephrine (1 - 1000) should be immediately available to treat a possible anaphylactic reaction.
    • Human and animal reproduction studies have not shown an elevated risk of fetal harm.
  • Pharmacokinetics
    • Onset: Antibodies appear in 2 weeks
    • Peak: 6 months
    • Duration: Immunity lasts 5 to 7 years
  • Adverse Effects
    • The most common adverse effects from HBV vaccination are pain at the injection site and mild to moderate fever and chills.
    • Approximately 15% of patients will experience minor symptoms such as fatigue, dizziness, fever, and headache.
    • Hypersensitivity reactions such as urticaria or anaphylaxis are possible.
  • Contraindications
    • This vaccine is contraindicated in patients with hypersensitivity to yeast or HBV vaccine.
    • Patients who demonstrated severe hypersensitivity to the first dose of the vaccine should not receive subsequent doses.
    • The drug should be administered with caution in patients with fever or active infections, or those with compromised cardiopulmonary status.
    • The vaccine should be given to pregnant or lactating women only if clearly needed to protect the health of the mother or child.
  • Interactions
    • Drug–Drug - Immunosuppressants will decrease the effectiveness of the HBV vaccine.
    • Herbal/Food - Unknown
  • Treatment of Overdose - Overdoses have not been recorded.

Pharmacotherapy with Immunostimulants

  • Biologic response modifiers
    • Interferons (IFNs) and interleukins (ILs)
  • Boost patient's immune system
  • Used to treat certain viral infections, immunodeficiencies, and specific cancers.
  • Assessment of infections and cancer verifies need for these drugs.
  • Contraindicated for patients with renal or liver disease and those who are pregnant.
  • Obtain results of lab tests to provide baseline data.
  • Keep patient well hydrated.
  • Assess for changes in mental status, including suicidal ideation.
  • Interferons
    • Secreted by lymphocytes and macrophages that have been infected with a virus.
    • Slow spread of viral infections and enhance activity of leukocytes.
    • Two major classes
      • Interferon alpha - used to treat leukemia, AIDS, and hepatitis B or C.
      • Interferon beta - used to treat multiple sclerosis, granulomatous disease, and severe osteoporosis.

Prototype Drug - Interferon Alfa-2b (Intron-A)

  • Therapeutic Class - Immunostimulant
  • Pharmacologic Class - Interferon, biologic response modifier
  • Actions and Uses
    • Interferon alfa-2b is a biologic response modifier prepared by recombinant DNA technology that is approved to treat cancers (hairy cell leukemia, malignant melanoma, non-Hodgkin lymphoma, AIDS- related Kaposi sarcoma) as well as viral infections (human papillomavirus, chronic hepatitis virus B and C).
    • Off-label indications may include chronic myelogenous leukemia, bladder cancer, herpes simplex virus, renal cell cancer, varicella-zoster virus, and West Nile virus.
    • It is available for IV, IM, and subcutaneous administration.
    • For treating condylomata acuminata (genital warts) the drug is injected directly into the lesion 3 times a week for 3 weeks. Peginterferon alfa-2b (PegIntron) is a newer formulation approved to treat melanoma.
  • Administration Alerts
    • Subcutaneous administration is recommended for patients at risk for bleeding (platelet count less than
    • In pregnant laboratory animals, this drug impaired fertility and increased spontaneous abortions. Combination therapy with ribavirin is contraindicated in pregnant patients and in the male partners of women who are pregnant. This drug should be used during pregnancy only if the potential benefit to the patient justifies the potential risk to the fetus.
  • Pharmacokinetics
    • Onset: 3 h (IM); immediate (IV)
    • Peak: 3–12 h (IM); end of infusion (IV)
    • Duration: 2–3 h
  • Adverse Effects
    • A flulike syndrome of fever, chills, dizziness, and fatigue occurs in 50% of patients, although this usually diminishes as therapy progresses.
    • Headache, nausea, vomiting, diarrhea, and anorexia are relatively common.
    • Depression and suicidal ideation have been reported and may be severe enough to require discontinuation of the drug. With prolonged therapy, serious toxicity such as immunosuppression, hepatotoxicity, and neurotoxicity may be observed.
  • Black Box Warning
    • IFNs may cause or aggravate fatal or life- threatening neuropsychiatric, autoimmune, ischemic, or infectious disorders.
  • Contraindications
    • Contraindications include hypersensitivity to IFNs, autoimmune hepatitis, and hepatic decompensation.
    • Neonates and infants should not receive this drug because it contains benzyl alcohol, which is associated with an increased incidence of neurologic and other serious complications in these age groups.
  • Interactions
    • Drug–Drug - Use with ethanol may cause excessive drowsiness and dehydration. There is additive myelosuppression with antineoplastics. Zidovudine may increase hematologic toxicity.
    • Herbal/Food - Unknown
  • Treatment of Overdose - Overdose may cause lethargy and coma. Treatment is by general supportive measures.

Interleukins (ILs)

  • Cytokines synthesized primarily by lymphocytes, monocytes, and macrophages in response to an antigen challenge.
  • Used to treat metastatic renal carcinoma.
  • Stimulate platelet production in immunosuppressed patients.
  • Enhance capabilities of immune system.
  • Stimulate cytotoxic T cells.
  • Aldesleukin therapy
    • limited by its high cost and by the risk of capillary leak syndrome
    • plasma proteins and other substances leave the blood and enter the interstitial spaces because of “leaky” capillaries.

Immunosuppressants

  • Inhibit patient's immune system.
  • Used to treat severe autoimmune disease.
  • Prevent tissue rejection following organ transplantation
    • Would be impossible without immunosuppressants

Indications for Immunosuppressants

  • Transplantation
    • Transplanted organs have antigens that trigger immune response
      • Called rejection
      • Often humoral response (acute rejection)
      • Antibodies destroy transplanted tissue within days
    • Cell-mediated response is slower, about 2 weeks after surgery.
    • Chronic rejection can occur months to years later.
  • Inflammatory and Autoimmune Disorders
    • Autoimmune disorders
      • the body creates antibodies against normal tissues
      • characterized by symptomatic periods alternating with remissions
  • Cancer Therapies
    • Drugs are administered to suppress rapidly dividing cancer cells.
    • Cells have developed mechanisms to evade normal body defenses and travel to distant sites have developed mechanisms to evade normal body defenses and travel to distant sites.

Immunosuppressant Medications for Preventing Transplant Rejection and Inflammatory Disorders

  • Corticosteroids
    • Inhibit inflammation
      • Used for short-term therapy for severe inflammation
      • Intervene at multiple steps
        • Antigen presentation
        • Production of cytokines
        • Proliferation of lymphocytes
  • Calcineurin Inhibitors
    • Tells T cells to begin synthesizing IL-2
  • Cytotoxic and Antimetabolites
    • Inhibit aspects of lymphocyte replication
      • Kill B and T cells
      • Similar indications and adverse effects as calcineurin inhibitors
  • Biologic Response Modifiers (BRMs)
    • modulate the inflammatory and immune responses
      • Ulcerative colitis
      • Crohn’s disease
      • RA
      • Ankylosing spondylitis
      • Psoriasis
      • Juvenile idiopathic arthritis

Nursing Clinical Judgement - Pharmacotherapy with Immunostimulants

  • Recognize and Analyze Cues
    • Obtain a complete health and drug history, especially the use of immunosuppressants or corticosteroids.
    • Obtain an immunization history and any unusual reactions or responses that occurred.
    • Obtain baseline vital signs, especially temperature. Evaluate appropriate laboratory findings (e.g., complete blood count [CBC], platelets, electrolytes, titers, liver and kidney laboratory tests).
  • Prioritize and Generate Solutions
    • Goals and Outcomes
      • Specific to interferons, when administering the medication, instruct the patient or caregiver in the proper self-administration of the drug. Proper administration will increase the effectiveness of the drug.
      • Teach parents the importance of vaccinating their children in accordance with the Advisory Committee on Immunization Practices (ACIP).
  • Take Action
    • Use opportunities during administration of medications and during assessments to provide patient education. Using time during nursing care helps to optimize and reinforce key teaching areas.
    • For patients traveling overseas, obtain immunization recommendations for the destination country. Current recommendations may be found on the CDC Travelers’ Health website.
    • Avoid or defer immunizations in any patient with a fever or autoimmune disease or in those who are taking corticosteroids as recommended by the provider. Fever may make it more difficult to discern drug reaction versus an infection. Immune response to vaccine may be under therapeutic, and an increased risk of adverse effects may result.
    • Ensure that caregivers, healthcare providers involved in patient care and others at high risk for preventable viral diseases (i.e., HBV) are appropriately immunized in accordance with ACIP.
  • Take Action Patient Teaching - Medication Adverse Effects
    • Continue to monitor vital signs, especially temperature and neurologic status. Immunizations and immunostimulants may cause dermatologic, cardiovascular, and neurologic adverse effects. An increase in temperature, localized ulcerations or signs of infection at the injection site, tachycardia or palpitations, dizziness, or changes in level of consciousness may indicate significant adverse effects. Immunostimulants may cause hypotension. Lifespan - Be particularly cautious with older adults who are at increased risk for hypotension and at greater risk for falls.
    • Report all significant adverse effects to the healthcare provider for reporting to VAERS.
    • Treat minor side effects symptomatically. Minor adverse effects may be treated with acetaminophen or as ordered by the healthcare provider for low-grade fevers less than
    • Monitor for signs of opportunistic and superinfections or an increase in bruising or bleeding in patients receiving interferon therapy. Myelosuppression may occur, increasing the risk of infections and bleeding.
    • Continue to monitor neurologic and mental status in the patient who is receiving interferon therapy. Psychosis, depression, and suicidal ideations are potential adverse effects of interferon use.
  • Patient Teaching - Lifestyle Considerations
    • Lifespan - Assess for the possibility of pregnancy, previous history of organ transplantation, and home environment, including significantly immunocompromised patients at home (e.g., from chemotherapy), before giving live virus immunizations. Some live vaccinations continue to be shed from the patient in the postvaccination period and may be transmitted to immunocompromised patients in the home environment. Pregnancy is a contraindication for vaccination with the live viruses, and women who become pregnant within 3 months of immunization with a live vaccine should consult their healthcare provider. For religious or other reasons, some patients may refuse to accept administration of any component derived from human blood or serum, including Rh0[D] immune globulin.
    • Teach the patient to immediately report any fever over as instructed by the healthcare provider, changes in consciousness such as drowsiness or disorientation, dyspnea, or tachycardia or palpitations.
    • Safety - Instruct the patient taking immunostimulants to rise from lying to sitting or standing slowly to avoid dizziness or falls. If dizziness occurs, the patient should sit or lie down and not attempt to stand or walk until the sensation passes.
    • Encourage the patient with concerns about vaccination, including those with components derived from human blood or serum, to consult with the healthcare provider in order to make an educated choice about accepting or refusing the drug.
  • Evaluate Outcomes Medication Effectiveness
    • Assess for patient adherence to recommended immunization schedule (e.g., need for repeated immunizations, boosters in adults). The patient should adhere to the recommended immunization schedule. Periodic titers may be needed to confirm immunity, especially in individuals who are over age 60 or those who are immunosuppressed.
    • Continue periodic monitoring of CBC and liver and kidney function studies as appropriate.
    • Assess vital signs, especially temperature.
    • Assess for and immediately report adverse effects - fever, dizziness, confusion, muscle weakness, tachycardia, hypotension, syncope, dyspnea, pulmonary congestion, skin rashes, bruising or bleeding, or anaphylactic reactions.
  • Evaluate Outcomes Patient Understanding
    • The patient should be able to state the reason for the drug; appropriate dose and scheduling; and what adverse effects to observe for and when to report them.
    • Teach the patient to take the medication as follows
      • Reconstitute the powder (if applicable) with the supplied diluent and gently rotate the vial between the palms; do not shake. Check the solution to be sure it is clear and has no particles.
      • Discard the solution as instructed by the healthcare provider (some vials remain available for use up to 30 days; others are for single use only). Single-use syringes should be discarded after use, even if solution remains.
      • Do not change manufacturer brands without consulting with the healthcare provider.
      • Have the patient or caregiver teach-back the injection technique until comfortable with administering the drug.