Ch 34 Drugs for immune system modulation

Immunomodulator

• Any drug or therapy that affects body defenses.

• May stimulate or suppress body defenses

Innate (Nonspecific) Body Defenses

• First line of defense

• General barrier to microbes or environmental hazards

• Deny entrance of pathogens

  • General responses that are not specific to a particular threat = same response to all pathogens

• i.e:

  • Skin, phagocytes, natural killer cells, Complement system, fever, interferons, inflammation

Adaptive (Specific) Body Defenses

• Second line of defense, specific activation to particular pathogens

• “immune response”

• primary cell = Lymphocytes

  • interact with antigens

• Two major divisions

  • 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, Helper T cells release cytokines to stimulate B cells

• 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 form to remember specific antigen-antibody interactions for future exposure of faster response time

Cell-Mediated Immunity and Cytokines

• Activation of specific T cells binding antigens of defective, infective, & cancer cells & transplants, releasing proteins destroying them

  • 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

Attenuated (live) vaccines

• contain microbes that are alive but weakened (attenuated) = unable to produce disease unless the patient is immunocompromised.

• Some cause a mild or subclinical case of the disease.

• i.e. measles, mumps, and rubella (MMR) vaccine.

Inactivated (killed) vaccines

• contain microbes that have been inactivated by heat or chemicals & are unable to replicate or cause disease.

• Some contain only a subunit of the microbe (pieces of the foreign plasma membrane or modified microbial proteins.)

• Boosters may be necessary to prolong immunity.

• i.e. influenza and hepatitis A vaccines.

Toxoid vaccines

• contain bacterial toxins that have been chemically modified to be incapable of causing disease.

• Induce the formation of antibodies that are capable of neutralizing the real toxins.

• i.e. diphtheria and tetanus toxoids.

Recombinant technology vaccines

• contain partial viral subunits or bacterial proteins that are generated in the laboratory using biotechnology.

• do not contain viral genetic material = not infectious.

• i.e. hepatitis B and human papillomavirus vaccines.

Coronavirus-19 (COVID-19) vaccines

• 2 types:

  • messenger RNA (mRNA)

    • introduce a small piece of RNA that codes for the spike protein

    • The body takes this RNA & makes antibodies.

  • viral vector

    • uses a harmless virus to carry a piece of the spike protein.

    • Once in the muscle, the body produces antibodies to the spike protein.

• None of these ingredients cause infection!!!

Active immunity

• induced by the real pathogen, or its vaccine

• body produces its own antibodies in response to exposure.

• closely resembles that caused by natural exposure to the antigen, including the generation of memory cells

Passive immunity

• occurs when preformed antibodies are transferred or donated from one person to another.

  • i.e. mothers antibodies crosses through placenta for the fetus

• For people who are exposed or have high-risk exposure& no time to immunize

• For immunosuppressed people

• do not stimulate the patient’s immune system = memory cells not produced

  • the protective effects will disappear w/in several weeks to several months after infusions dc.

Pharmacotherapy with Immunostimulants

• Primary indication: medications that fight infection and disease by increasing the actions of the immune system

  • primary uses of these drugs are to treat cancer and viral infections

• 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

• Biologic response modifiers

  • Interferons (IFNs) and interleukins (ILs)

Interferons (IFNs)

• cytokines secreted by lymphocytes and macrophages that have been infected with a virus

• Warn surrounding cells of occurring viral infection = Slow spread & enhance activity of leukocytes

• Actions: modulation of immune functions, (increasing phagocytosis & enhancing the cytotoxic activity of T cells.)

• Two major classes

  • alpha: used to treat leukemia, AIDS, and hepatitis B or C

  • beta: used to treat multiple sclerosis, granulomatous disease, and severe osteoporosis

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

• 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

• drugs that inhibit patient's immune system

• Used to treat severe autoimmune disease

• prevent tissue rejection in patients receiving transplanted tissues or organs, to treat severe inflammatory disorders, & cancer therapies

  • Transplant rejection

    • Acute, antibodies can destroy transplanted tissue within a few days

    • Chronic, may occur months or even years after surgery.

  • Inflammatory & autoimmune disorders

    • Given for brief periods in high doses to control relapses

  • Cancer therapies

    • Suppress rapidly diving cancer cells that have developed mechanisms to evade normal body defenses & travel to distant sites

Corticosteroids

• nonselective immunosuppressant mechanism

• Inhibit inflammation

  • Used for short-term therapy for severe inflammation

  • Intervene at multiple steps

    • Antigen presentation

    • Production of cytokines

    • Proliferation of lymphocytes

Calcineurin Inhibitors

• second class of immunosuppressants essential to transplant medicine

• Inhibiting the release of IL-2 suppresses the immune response.

  • (IL-2 is an important chemical mediator in promoting the proliferation of B cells, T cells, macrophages, and NK cells)

mTOR inhibitors

• Drugs inhibit mTOR to prevent transplant rejection

Cytotoxic and Antimetabolites

• medications used to kill B and T cells.

• Most are nonspecific, affecting many different cells of the immune response.

• They have similar indications and adverse effects as the calcineurin inhibitors.

• i.e. azathioprine and methotrexate.

Biologic Response Modifiers (BRMs)

• Target specific cytokines to modulate the inflammatory and immune responses used in autoimmune disease

  • Ulcerative colitis, Crohn’s disease, RA, Ankylosing spondylitis, Psoriasis, Juvenile idiopathic arthritis

Recognize & 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 lab findings

Prioritize & generate solutions

• develop goals  and outcomes based on the nursing diagnoses.

  • 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

• For patients traveling overseas, obtain immunization recommendations for the destination country.

• 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.

• 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. 

Evaluate outcomes

• Assess for patient adherence to 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 AE - fever, dizziness, confusion, muscle weakness, tachycardia, hypotension, syncope, dyspnea, pulmonary congestion, skin rashes, bruising or bleeding, or anaphylactic reactions.

Mechanisms of action of immunosuppressants

• All mechanisms differ BUT all suppress some aspect of T cell function

  • Nonselective

    • Corticosteroids

  • Calcineurin inhibitors 

  • mTOR inhibitors

  • Cytotoxic and Antimetabolites

  • Biologic Response Modifiers (BRMs):

Vaccination

• vaccine: biologic agents used to stimulate the immune system

• process of introducing foreign proteins or inactive cells (vaccines) into the body to trigger immune activation before exposure to real pathogen, forming memory B cells.

  • Boosters: provide sustained protection

  • Effectiveness: assessed by measuring the amount of antibody produced after the vaccine has been administered, titer

• goal: induce long-lasting immunity to a pathogen without producing an illness in an otherwise healthy person