Immunomodulators & Immunosuppressives [NCLEX Review 2019]

Immunomodulators & Immunosuppressives [NCLEX Review 2019]

Welcome to this video tutorial on immunomodulators
and immunosuppressive agents. The body’s immune system is a normally occurring
protective mechanism that helps the body defend itself against potentially harmful agents. However, sometimes the immune system perceives
normally harmless substances, such as allergens or the person’s own body tissues, as harmful
invaders and tries to eliminate them. This inappropriate activation of the immune
response is a major factor in allergic and autoimmune disorders. Let’s start with some definitions… Immunomodulators are natural or synthetic
substances that modulate or modify the immune response. They help regulate or normalize the immune
system by either stimulating or suppressing the immune system. Immunostimulants, such as vaccines and interferons,
enhance the body’s resistance against infections. Immunosuppressive agents are drugs that suppress
the immune system to reduce the risk of rejection of foreign bodies with organ transplant or
in autoimmune diseases. Immunosuppressant drugs are used to decrease
the immune response by interfering with the production or function of immune cells and
cytokines. When foreign tissue or an organ is transplanted
into the body, the body has an appropriate but undesirable immune response. If the immune response is not suppressed,
the body reacts by attempting to destroy the foreign tissue. Immunosuppressant drugs are used to decrease
this undesirable immune response with transplants and autoimmune disorders. Drug induced immunosuppression is a major
factor in tissue and organ transplantation. There is a fine balance to adequate immunosuppression
for the body to accept the transplant, without suppressing the immune system too much where
the patient develops serious infections and other adverse effects. Immunosuppressant drugs are also given for
autoimmune disorders to decrease the undesirable immune response of the body. Autoimmune disorders occur when a person’s
immune system attacks the healthy cells in the body by mistake – the body has lost its
ability to differentiate between antigens on its own cells (self-antigens) and antigens
on foreign cells. Generally, all autoimmune disorders share
inflammation as a major mechanism of tissue damage. There are many autoimmune diseases; we’ll
take a look at a few common ones. In multiple sclerosis (MS), the immune system
attacks nerve cells, causing symptoms that can include muscle spasms, weakness, poor
coordination, pain, and blindness. Rheumatoid arthritis occurs when the immune
system produces antibodies that attach to the linings of joints, which get attacked
by immune system cells, causing inflammation, swelling, and pain. In lupus (SLE), autoimmune antibodies attach
to tissues throughout the body, affecting the lungs, nerves, blood cells, joints, and
kidneys. Type 1 diabetes mellitus occurs when the immune
system antibodies attack and destroy insulin-producing cells in the pancreas. Inflammatory bowel disease (IBD) occurs when
the immune system attacks the lining of the intestines, causing episodes of abdominal
pain, diarrhea, urgent bowel movements, fever, and weight loss. There are two forms of IBD – Crohn’s disease
and ulcerative colitis. In psoriasis, overactive immune system T-cells
collect in the skin, stimulating the skin cells to reproduce rapidly, forming scaly
plaques on the skin. In myasthenia gravis, antibodies bind to nerves
and make them unable to stimulate muscles properly, seen as weakness that gets worse
with activity. Graves’ disease occurs when the immune system
produces antibodies that stimulate the thyroid gland to release excess amounts of thyroid
hormone, causing hyperthyroidism. Hashimoto’s thyroiditis occurs when antibodies
produced by the immune system attack the thyroid gland, slowly destroying the cells that produce
thyroid hormone, leading to hypothyroidism. Immunosuppressant drugs are diverse agents
with often overlapping mechanisms and sites of action. Older drugs are generally nonspecific and
depress the entire immune response to all antigens, greatly increasing the risk of serious
infections and other side effects. Immunosuppressants include… Corticosteroids
Cytotoxic, antiproliferative agents Conventional antirejection agents Corticosteroids are strong anti-inflammatory
drugs that suppress the immune response at multiple levels. They do have numerous side effects, so the
duration of therapy should be as short as possible. Examples include prednisone, dexamethasone,
hydrocortisone, betamethasone, and methylprednisolone. Cytotoxic, antiproliferative drugs damage
or kill cells that are able to reproduce, and are primarily used in cancer chemotherapy. However, in small doses, some are also used
to treat autoimmune disorders and to prevent organ transplant rejection. Examples include methotrexate and azathioprine. Conventional antirejection agents include
drugs such as cyclosporine, tacrolimus, and sirolimus, which are fungal metabolites with
strong immunosuppressive effects, used to prevent rejection reactions after organ transplants. Extensive research has been done to develop
drugs with a more specific immunosuppressive action, causing fewer or less severe adverse
effects than older immunosuppressants. They are often referred to as biologic response
modifiers or biologics. Biologics are antibodies made from biological
proteins (human or animal based) that stop certain proteins in the body from causing
inflammation. Biological products include a wide range of
products such as blood and blood components, vaccines, allergenics, gene therapy, and recombinant
therapeutic proteins. The biologics we will be discussing here are
immunosuppressive drugs that have had a profound impact on the treatment of many diseases,
which in most cases have had no effective therapies available. Biologics target overactive cells in the body,
and are designed to block diseases in the immune system rather than waiting to treat
the symptoms of the disease. Biologic therapies offer a distinct advantage
in treatment of diseases because their mechanisms of action are more precisely targeted to the
factors responsible for the disease, instead of affecting the whole body, as some immunosuppressants
do. Biologics are used to treat many autoimmune
diseases, however, their cost is significantly higher than other conventional medications. Some of the newer biologic agents used for
immunosuppression include – Antibody preparations, which include polyclonal
antibodies and monoclonal antibodies Cytokine inhibitors, which include interleukin-blocking
agent & tumor necrosis factor (TNF)- alpha blocking agents Antibody preparations are produced in the
laboratory or derived from animals injected with human lymphoid tissue to stimulate an
immune response. These drugs are used in inflammatory autoimmune
disorders, transplant rejection reactions, and cancer. Monoclonal antibody drugs end in “mab,” such
as basiliximab and daclizumab. Cytokine inhibitors are biologic agents that
inhibit cytokines that cause chronic, inflammatory autoimmune disorders, such as rheumatoid arthritis
(RA), Crohn’s disease, and psoriasis. They suppress inflammation and promote tissue
repair; however, they also increase the risks of serious infections, such as TB, pneumococcal
infections, necrotizing fasciitis, and others. An example of an interleukin-blocking agent
is anakinra (Kineret), used to treat moderate to severe RA. Some examples of TNF-alpha blocking agents
include adalimumab (Humira), infliximab (Remicade), and etanercept (Enbrel). These drugs are used to treat autoimmune diseases
such as RA, Crohn’s disease, ulcerative colitis, psoriasis, and psoriatic arthritis. Other immunosuppressants used to treat RA
include a biologic, abatacept (brand name Orencia), leflunomide (Arava), which is in
a drug class called disease-modifying antirheumatic drugs (DMARDs). This class of drugs can decrease joint damage
and disability caused by RA. The general side effects of all immunosuppressive
agents include increased risk of infection and cancer. Immunosuppressant drugs are used to treat
serious illnesses, but thorough assessment must be done to verify that the benefits outweigh
the risks. Let’s go over some general patient teaching
guidelines for patients taking immunosuppressant drugs: Wash hands often & thoroughly and practice
meticulous personal hygiene – this applies to patients and others around the patient. Avoid contact with infectious people. To enhance immune defenses, practice healthy
lifestyle habits, such as a nutritious diet, adequate sleep, and avoiding tobacco and alcohol. Keep a list of drugs taken, dosage, provider’s
information, and emergency instructions with you in case of emergency. Report adverse drug effects to a health care
provider, including signs/symptoms of infection, such as sore throat or fever, easy bruising
or bleeding if taking methotrexate, or decreased urine output if taking cyclosporine. See the doctor regularly, for evaluation of
drug responses, dosage changes, adverse drug reactions, and blood monitoring tests that
may be needed. Notify doctor if other drugs need to be taken
– immunosuppressant drugs may interact with other medications, decreasing therapeutic
effects or increasing adverse effects. Some vaccines should also be avoided while
taking immunosuppressants. Patients of reproductive age should practice
effective contraception during immunosuppressive therapy, due to the adverse effects of some
of the drugs on the fetus and mother. Protect skin from sunlight, as some drugs
increase the risk of sensitivity to the sun, sunburn, and skin cancer.


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