WEEK 04: DRUGS ACTING ON THE IMMUNE

SYSTEM
NCM 106: PHARMACOLOGY | LECTURER: EDGAR M. CHAN
Introduction to the Immune Response and
Inflammation
Lymphoid Tissues
The body has many defense systems in
place to keep it intact and to protect it from  Lymphoid tissues that play an important
external stressors. These stressors can include part in the cellular defense system include
bacteria, viruses, other foreign pathogens or the:
nonselfcells, trauma, and exposure to extremes of  Lymph nodes
environmental conditions.  Spleen
 Thymus gland (a bipolar gland
The body’s defenses include: located in the middle of the chest,
1. Barrier Defenses which becomes smaller with age)
2. Cellular Defenses  Bone marrow
3. The Inflammatory Response  Lymphoid tissue throughout the
4. The Immune Response respiratory and GI tracts.
 The bone marrow and the thymus gland
are important for creation of the cellular
components of the MPS.
1. Barrier Defenses
 The lymph nodes and lymphoid tissue
Certain anatomical barriers exist to
store concentrated populations of
prevent the entry of foreign pathogens and to
neutrophils, basophils, eosinophils, and
serve as important lines of defense in protecting
lymphocytes in areas of the body that
the body. These barriers include:
facilitate their surveillance for and
a) Skin destruction of foreign proteins.
b) Mucous Membranes  Other cells travel through the
c) Gastric Acid cardiovascular and lymph systems to
d) Major Histocompatibility Complex search for foreign proteins or to reach the
(MHC) sites of injury or pathogen invasion.

3. Inflammatory Response
The inflammatory response is the local
2. Cellular Defenses reaction of the body to invasion or injury. Any insult
Any foreign pathogen that manages to get to the body that injures cells or tissues sets off a
past the barrier defenses will encounter the human series of events and chemical reactions.
inflammatory and immune systems, or the
mononuclear phagocyte system (MPS). Previously Cell injury causes the activation of a
called the reticuloendothelial system the MPS is chemical in the plasma called factor XII or
composed primarily of: Hageman factor.

 Leukocytes Hageman factor

 Lymphocytes
 is responsible for activating at least three
 Lymphoid muscles
systems in the body: The kinin system,
 Numerous chemical mediators
which is discussed here; the clotting
Stem cells in the bone marrow produce cascade, which initiates blood clotting; and
two types of white blood cells or leukocytes: the plasminogen system, which initiates
the dissolution of blood clots.
1) Lymphocytes – are the key components
of the immune system and consist of t Kinin System
cells, b cells, and natural killer cells.
2) Myelocytes – can develop into a number  Hageman factor activates kallikrein a
of different cell types that are important in substance found in the local tissues, which
both the basic inflammatory response and causes the precursor substance kininogen
the immune response. Myelocytes include: to be converted to bradykinin and other
kinins.
 Neutrophils
 Bradykinin causes local vasodilation,
 Basophils
which brings more blood to the injured
 Eosinophils
area and allows white blood cells to
 Monocytes/Macrophages
escape into the tissues. It also stimulates
 nerve endings to cause pain, which alerts  Suppressor T Cells
the body to the injury. B. B Cells
 Bradykinin also causes the release of C. Complement Proteins
arachidonic acid from the cell membrane. D. Antibody Formation
Arachidonic acid is the precursor to many E. Other Mediators
substances called autocoids. These  Interferons
substances act like local hormones – they  Interleukins
are released from cells, cause an effect in
A. T CELLS
the immediate area.
T cells are programmed in the thymus gland and
Histamine Release
provide what is called cell-mediated immunity. T
 Histamine cause vasodilation, which cells develop into at least three different cell types:
brings more blood and blood components
1) Effector or cytotoxic T cells
to the area. It also alters capillary
 are found throughout the body.
permeability, making it easier for
These T cells are aggressive
neutrophils and blood chemicals to leave
against nonself-cells, releasing
the bloodstream and enter the injured
cytokines, or chemicals, that can
area. In addition, histamine stimulates pain
either directly destroy a foreign
perception. The vasodilation and changes
cell or mark it for aggressive
in capillary permeability bring neutrophils
destruction by phagocytes in the
to the area to engulf and get rid of the
area via an inflammatory
invader or to remove the cell that has been
response.
injured.
2) Helper T Cells
Chemotaxis  also called CD4 cells, respond to
the chemical indicators of immune
 is the ability to attract neutrophils and to activity and stimulate other
stimulate them and other macrophages in lymphocytes, including B cells, to
the area to be very aggressive. be more aggressive and
 Activation of the neutrophils and release of responsive.
other chemicals into the area can lead to 3) Suppressor T Cells
cell injury and destruction. When  also called CD8 cells, respond to
destroyed the cell releases various rising levels of chemicals
lysosomal enzymes that dissolve or associated with an immune
destroy cell membranes and cellular response to suppress or slow the
proteins. reaction.
Clinical Presentation B. B CELLS
 Activation of the inflammatory response  B cells are found throughout the MPS in
produces a characteristic clinical picture. groups called clones. B cells are
The Latin words calor, tumor, rubor, and programmed to identify specific proteins,
dolor describe a typical inflammatory or antigens. They provide what is called
reaction. Calor, or heat, occurs because of humoral immunity
the increased blood flow to the area.
Tumor, or swelling, occurs because of the C. Complement Proteins
fluid that leaks into the tissues as a result
 Complement proteins react in a cascade
of the change in capillary permeability.
fashion to form a ring around the antigen–
Rubor, or redness, is related again to the
antibody complex. The complement can
increase in blood flow caused by the
destroy the antigen by altering the
vasodilation. Dolor, or pain, comes from
membrane, allowing an osmotic inflow of
the activation of pain fibers by histamine
fluid that causes the cell to burst. They
and the kinin system. These signs and
also induce chemotaxis (attraction of
symptoms occur any time a cell is injured.
phagocytic cells to the area), increase the
4. The Immune Response activity of phagocytes, and release
A. T CELLS histamine.
 Effector or Cytotoxic T Cells
 Helper T Cells
 Chickenpox eruptions are an example of  Interleukin 1 (IL-1) stimulates T and B cells
an antigen–antibody–complement complex that to initiate an immune response.
deposits in the skin and causes a local  IL-2 is released from active T cells to
inflammatory reaction. stimulate the production of more T cells
and to increase the activity of B cells,
cytotoxic cells, and natural killer cells.

Interleukins also cause fever, arthralgia,

D. Antibody Formation myalgia, and slow-wave sleep induction—all things
that help the body to conserve energy for use in
 The initial formation of antibodies, or fighting off the invader.
primary response, takes several days.
Once activated the B cells form memory Interrelationship of the Immune and the
cells that will produce antibodies for Inflammatory Response
immediate release in the future if the
The immune and the inflammatory response
antigen is encountered. The antibodies are
released in the form of immunoglobulins.
work together to protect the body and
maintain the homeostasis within the body
Five different types of immunoglobulins have
been identified: - Helper T cells stimulates the B cell and
effector T cells
1) The first immunoglobulin released is M - Suppressor T cells monitor the
(IgM), which contains the antibodies
chemical activity in the body and act to
produced at first exposure to the antigen.
suppress B cells and T cells activity
2) IgG, another form of immunoglobulin,
contains antibodies made by the memory when the foreign antigen is under
cells that circulate and enter the tissue; control.
most of the immunoglobulin found in the - Both B cells and T cells ultimately
serum is IgG. depend on an inflammatory reaction to
3) IgA is found in tears, saliva, sweat, achieve the end goal of the destruction
mucus, and bile. It is secreted by plasma of the foreign protein or cell.
cells in the GI and respiratory tracts and in
epithelial cells. These antibodies react with
specific pathogens that are encountered in
Pathophysiology Involving the Immune
exposed areas of the body.
System
4) IgE is present in small amounts and
1) Neoplasms
seems to be related to allergic responses
2) Viral Invasion of Cells
and to the activation of mast cells.
3) Autoimmune Disease
5) IgD is another identified immunoglobulin
4) Transplant Rejection
whose role has not been determined.

This process of antibody formation,

called acquired or active immunity, is a lifelong 1.) Neoplasms
reaction. o Neoplasms occur when mutant cells
escape the normal surveillance of the
E. Other Mediators
immune system and begin to grow and
 Several other factors also play an multiply.
important role in the immune reaction.
Interferons are chemicals that are
secreted by cells that have been invaded 2.) Viral Invasion of Cells
by viruses and possibly by other stimuli. o Viruses are parasites that can survive only
The interferons prevent viral replication by invading a host cell that provides the
and also suppress malignant cell nourishment necessary for viral
replication and tumor growth. replication. Invasion of a cell alters the cell
membrane and the antigenic presentation
Interleukins are chemicals secreted by of the cell (the MHC). This change can
active leukocytes to influence other leukocytes. activate cellular immunity, or it can be so
subtle that the immune system’s response
to the cell is mild or absent.
 who are unresponsive to
conventional therapy, and
3.) Autoimmune Disease can be very toxic
o Autoimmune disease occurs when the Inflammatory the body’s nonspecific
body responds to specific self-antigens to response response to cell injury,
produce antibodies or cell-mediated resulting in pain, swelling,
immune responses against its own cells. heat, and redness in the
o The cause of autoimmune disease is not affected area
known, but theories speculate that: Nonsteroidal anti- drugs that block
1. It could be a result of response to inflammatory prostaglandin synthesis
a cell that was invaded by a virus, drugs (NSAIDs) and act as anti-
inflammatory, antipyretic,
leading to antibody production to
and analgesic agents
similar cells;
2. Production of autoantibodies is a
Salicylates salicylic acid compounds,
normal process that goes on all used as anti-inflammatory,
the time, but in a state of antipyretic, and analgesic
immunosuppression, the agents; they block the
suppressor T cells do not prostaglandin system
suppress autoantibody production;
3. There is a genetic predisposition Salicylism syndrome associated with
to develop autoantibodies. high levels of salicylates—
dizziness, ringing in the
4.) Transplant Rejection ears, difficulty hearing,
o Self-transplantation, or auto nausea, vomiting, diarrhea,
transplantation, results in no immune mental confusion, and
response. All other transplants produce an lassitude
immune reaction. DRUG LISTS
o Therefore, matching a donor’s HLA
markers as closely as possible to those of a) Salicylates
the recipient for histocompatibility is b) Nonsteroidal anti-inflammatory related
essential. The more closely the foreign Agents
cells can be matched the less aggressive c) Nonsteroidal anti-arthritis
the immune reaction to the donated tissue. SALICYLATES

 Aspirin
Anti-inflammatory, Antiarthritis, and Related  Balsalazide
Agents  Choline magnesium trisalicylate
Glossary of Terms:  Diflunisal
 Mesalamine
Terms Definition  Olsalazine
Analgesic compounds with pain-
 Salsalate
blocking properties,
capable of producing Nonsteroidal Anti-Inflammatory and Related
analgesia Agents

Anti-inflammatory drugs that block the effects Nonsteroidal anti-inflammatory agents (NSAIDS)
agents of the inflammatory
response Propionic acids

 Fenoprofen
Antipyretic blocking fever, often by  Flurbiprofen
direct effects on the
 Ibuprofen
thermoregulatory center in
 Ketoprofen
the hypothalamus or by
blockade of prostaglandin  Naproxen
mediators  Oxaprozin
Chrysotherapy treatment with gold salts;
Acetic acids
gold is taken up by
macrophages, which then  Diclofenac
inhibit phagocytosis; it is  Etodolac
reserved for use in patients
  Indomethacin  Block or alter the reactions associated with
 Ketorolac the inflammatory response to stop the
 Nabumetone signs of symptoms of inflammation.
 Sulindac
 Tolmetin

Fenamates Several different types of drugs are used as

anti-inflammatory agents:
 Meclofenamate
 Mefenamic acid Corticosteroids

 Used systemically to block the

inflammatory and immune systems.
Oxicam derivatives Blocking these important protective
 Meloxicam processes may produce many adverse
 Piroxicam effects, including decreased resistance to
infection and neoplasms.
Cyclooxygenase-2- inhibitor  Used topically to produce a local anti-
inflammatory effect without as many
 celecoxib
adverse effects.
 related agent
 acetaminophen Antihistamines
ANTIARTHRITIS AGENTS  are used to block the release of histamine
in the initiation of the inflammatory
GOLD COMPOUNDS
response.
 Auranofin
Drug Therapy Across the Lifespan
 Gold sodium thiomalate
Children
TUMOR NECROSIS FACTOR BLOCKER
 Children are more susceptible to the GI
 Adalimumab and CNS effects of these drugs.
 Certolizumab  Aspirin and Choline – only salicylates
 Etanercept recommended for children.
 Golimumab  Ibuprofen, naproxen, tolmetin, meloxicam,
 Infliximab indomethacin – nonsteroidal anti-
inflammatory drugs (NSAIDs) approved for
Other anti-arthritis drugs the use of children.
 Anakinra  Acetaminophen – most common used
 Etanercept anti-inflammatory for children
 Hyaluronidase derivatives Adults
 Leflunomide
 Penicillamine  They should also be cautioned to report
 Sodium hyaluronate OTC drug use to their health care provider
 Tofacitinib when they are receiving any other
prescription drug to avoid possible drug–
Inflammatory Response
drug interactions and the masking of signs
 Designed to protect the body from injury and symptoms of disease.
and pathogens  Pregnant and nursing women should not
 Employs a variety of potent chemical use these drugs unless the benefit clearly
mediators to produce the reaction that outweighs the potential risk to the fetus or
helps to destroy pathogens and promote neonate.
healing Older Adults
 Body produces signs and symptoms of
disease (swelling, fever, aches, and  Older patients may be more susceptible to
pains). the CNS and GI effects of some of these
drugs.
Anti-inflammatory Agents
 Geriatric warnings have been associated
with naproxen, ketorolac, and ketoprofen
 because of reports of increased toxicity other nonsteroidal anti-inflammatory drugs
when they are used by older patients. (NSAIDs) or tartrazine because of the risk
 Gold salts, used to treat arthritis, which is of allergic reaction; bleeding abnormalities
more common in older patients, are because of the changes in platelet
particularly toxic for geriatric patients. aggregation associated with these drugs;
impaired renal function because the drug
SALICYLATES is excreted in the urine; chickenpox or
 Oldest and popular inflammatory response influenza because of the risk of Reye
because of their antipyretic (fever- syndrome in children and teenagers;
blocking) and analgesic (pain-blocking surgery or other invasive procedures
properties) scheduled within 1 week because of the
 Available without prescription and risk of increased bleeding; and pregnancy
relatively non-toxic when used as directed. or lactation because of the potential
adverse effects on the neonate or mother.

Therapeutic Actions and Indications

 Salicylates inhibit the synthesis of Adverse Effects
prostaglandin, an important mediator of  The adverse effects associated with
the inflammatory reaction. salicylates may be the result of direct drug
 The antipyretic effect of salicylates may be effects on the stomach (nausea,
related to blocking of a prostaglandin dyspepsia, heartburn, epigastric
mediator of pyrogens (chemicals that discomfort) and on clotting systems (blood
cause an increase in body temperature loss, bleeding abnormalities).
and that are released by active white  Salicylism can occur with high levels of
blood cells) at the thermoregulatory center aspirin; dizziness, ringing in the ears,
of the hypothalamus. difficulty hearing, nausea, vomiting,
 At low levels, aspirin also affects platelet diarrhea, mental confusion, and lassitude
aggregation by inhibiting the synthesis of can occur.
thromboxane A2, a potent vasoconstrictor
that normally increases platelet
aggregation and blood clot formation.
Nursing Considerations for Patients
 At higher levels, aspirin inhibits the Receiving Salicylates
synthesis of prostacyclin, a vasodilator  Assess for contraindications or cautions
that inhibits platelet aggregation.  Perform physical assessment to establish
 Salicylates are indicated for the treatment baseline status before beginning therapy
of mild to moderate pain, fever, and and to monitor for any potential adverse
numerous inflammatory conditions, effects.
including rheumatoid arthritis and  Assess for the presence of any skin
osteoarthritis.
 Monitor
Pharmakocinetics  Evaluate CNS status
 Are readily absorbed directly from the  Evaluate respirations and adventitious
stomach, reaching peak levels within 5 to sounds to detect hypersensitivity
30 minutes. reactions.
 They are metabolized in the liver and  Perform a liver evaluation and monitor
excreted in the urine, with a half-life of 15 bowel
minutes to 12 hours, depending on the  Monitor laboratory tests for complete blood
salicylate. count (CBC), liver and renal function tests,
 Salicylates cross the placenta and enter urinalysis, stool guaiac, and clotting times.
breast milk; they are not indicated for use
NONSTEROIDAL ANTI-INFLAMMATORY
during pregnancy or lactation because of
AND RELATED AGENTS
the potential adverse effects on the
Nonsteroidal anti-inflammatory drugs
neonate and associated bleeding risks for
(NSAIDs) provide strong anti-inflammatory and
the mother.
analgesic effects without the adverse effects
Contraindication and Caution associated with the corticosteroids
 Salicylates are contraindicated in the
Therapeutic Actions and Indications
presence of known allergy to salicylates,
  The anti-inflammatory, analgesic, and Pharmacokinetics
antipyretic effects of the NSAIDs are  The NSAIDs are rapidly absorbed from the
largely related to inhibition of GI tract, reaching peak levels in 1 to 3
prostaglandin synthesis. hours. They are metabolized in the liver
 The NSAIDs block two enzymes, known and excreted in the urine. NSAIDs cross
as CYCLOOXYGENASE-1 (COX-1) and the placenta and cross into breast milk.
(COX-2)
Contraindications and Cautions
CYCLOOXYGENASE-1  The NSAIDs are contraindicated in the
presence of allergy to any NSAID or
COX-1 is present in all tissues and seems to be salicylate, and celecoxib is also
involved in many body functions, including blood contraindicated in the presence of allergy
clotting, protecting the stomach lining, and to sulfonamides.
maintaining sodium and water balance in the
kidney. Adverse Effects
 Patients receiving NSAIDs often
experience nausea, dyspepsia, GI pain,
constipation, diarrhea, or flatulence
caused by direct GI effects of the drug.
CYCLOOXYGENASE-2 The potential for GI bleeding often is a
cause of discontinuation of the drug.
COX-2 is active at sites of trauma or injury when Headache, dizziness, somnolence, and
more prostaglandins are needed, but it does not fatigue also occur frequently and could be
seem to be involved in the other tissue functions. related to prostaglandin activity in the
CNS.
Comparison of Cyclooxygenase (COX)
Receptors ACETAMINOPHEN
COX-1 COX-2  It is the most frequently used drug for
Site of Action managing pain and fever in children. It is
Found in many tissues, Induced by widely available OTC and is found in many
important for inflammatory stimuli
combination products. It can be extremely
homeostasis at the site of
toxic. It causes severe liver toxicity that
inflammation
Effects can lead to death when taken in high
-Converts arachidonic -Increases pain, doses.
acid to inflammatory inflammation Therapeutic Actions and Indications
prostaglandins -Vasodilates
 Acetaminophen acts directly on the
-Maintains renal -Blocks platelet
thermoregulatory cells in the
function clumping
-Provides for gastric hypothalamus to cause sweating and
mucosa integrity vasodilation; this in turn causes the
-Promotes vascular release of heat and lowers fever. The
homeostasis, mechanism of action related to the
increases bleeding analgesic effects of acetaminophen has
-Autocrine effects not been identified. It is indicated for the
causing fever treatment of pain and fever associated
Effects of blocking with a variety of conditions.
-Decreases swelling, -Decreases pain,
pain, inflammation inflammation Pharmacokinetics
-Sodium retention, -Prevents protective  Acetaminophen is rapidly absorbed from
edema, increased vasodilation, allows the GI tract, reaching peak levels in 0.5 to
blood pressure platelet clumping, 2 hours. It is extensively metabolized in
-Gastrointestinal which can lead to the liver and excreted in the urine, with a
erosion, bleeding myocardial infarction, half-life of about 2 hours.
-Decreases fever cerebrovascular
accident Contraindications and Cautions
-Myriad of skin  Acetaminophen is contraindicated in the
reactions, including presence of allergy to acetaminophen
Stevens-Johnson because of the risk of hypersensitivity
Syndrome reactions. It should be used cautiously in
pregnancy or lactation because of the
 potential for adverse effects on the fetus or Adverse Effects
baby and in hepatic dysfunction or chronic  A variety of adverse effects is common
alcoholism because of associated toxic with the use of gold salts, and they are
effects on the liver. probably related to their deposition in the
tissues and effects at that local level
Adverse Effects
 Adverse effects associated with Disease-Modifying Antirheumatic Drugs
acetaminophen use include headache, Other anti-arthritis drugs, called disease-
hemolytic anemia, renal dysfunction, skin modifying antirheumatic drugs (DMARDs), are
rash, and fever. Hepatotoxicity is a available for treating arthritis and aggressively
potentially fatal adverse effect that is affect the process of inflammation.
usually associated with chronic use and
Two types of DMARDs includes:
overdose and is related to direct toxic
effects on the liver. When overdose 1) Tumor Necrosis Factor (TNF) blockers
occurs, acetylcysteine can be used as an 2) Other disease-modifying antirheumatic
antidote. Life support measures may also drugs
be necessary.
Tumor Necrosis Factor Blockers
 Tumor necrosis factor (TNF) blockers are
often the first class used with progressing
arthritis.

ANTIARTHRITIS AGENTS
Gold Compounds Therapeutic Actions and Indications

 Some patients with rheumatic  Tumor necrosis factor (TNF) blockers are
inflammatory conditions do not respond to often the first class used with progressing
the unusual anti-inflammatory therapies, arthritis.
and their conditions worsen despite weeks Pharmacokinetics
or months of standard pharmacological
treatment.  TNF blockers must be given
subcutaneously, with the exception of
Therapeutic Actions and Indications infliximab which is given IV. They have a
 Chrysotherapy (treatment (as of slow onset, usually peaking in 48–72
rheumatoid arthritis) by injection of gold hours. They are primarily excreted in the
salts) results in inhibition of phagocytosis. tissues and have very long half-lives
Because phagocytosis is blocked the ranging from 115 hours to 2 weeks. They
release of lysosomal enzymes is inhibited cross the placenta and may enter breast
and tissue destruction is decreased. milk, so use in pregnancy and
Pharmacokinetics breastfeeding should be discouraged.
 The gold salts are absorbed at varying Contraindications and Cautions
rates, depending on their route of
administration. They are widely distributed  These drugs cannot be used in anyone
throughout the body but seem to with an acute infection, cancer, sepsis,
concentrate in the hypothalamic–pituitary– tuberculosis, hepatitis, myelosuppression,
adrenocortical system and in the adrenal or demyelinating disorders because they
and renal cortices. block the body’s immune/inflammatory
response and serious reactions could
Contraindications and Cautions
occur.
 Gold salts can be quite toxic and are
 Etanercept cannot be used with a history
contraindicated in the presence of any
of allergy to Chinese hamster ovary
known allergy to gold, severe diabetes,
products because it is made from these
congestive heart failure, severe
products.
debilitation, renal or hepatic impairment,
 They should not be used in pregnancy or
hypertension, blood dyscrasias, recent
breastfeeding because of the potential
radiation treatment, history of toxic levels
effects on the fetus or neonate. Caution
of heavy metals, and pregnancy or
should be used with renal or hepatic
lactation.
 disorders, heart failure, and latex allergies and is reserved for patients who have not
to prevent adverse reactions. responded to traditional therapies.

Adverse Effects Pharmacokinetics

 TNF blockers come with black box  Anakinra is slowly absorbed from the
warnings about the risk of serious to fatal subcutaneous tissue, reaching peak levels
infections and the development of in 3 to 7 hours. It is metabolized in the
lymphomas and other cancers. Patients tissues and excreted in the urine. It has a
need to be screened and monitored half-life of 4 to 6 hours. The hyaluronidase
accordingly. Demyelinating disorders have derivatives are not absorbed systemically.
occurred, including multiple sclerosis and  Leflunomide is slowly absorbed from the
various neuritis conditions. Myocardial GI tract, reaching peak levels in 6 to 12
infarction (MI), heart failure, and hours. It undergoes hepatic metabolism
hypotension are also reported with the use and excretion in the urine. The half-life of
of these drugs. Irritation at the injection leflunomide is 14 to 18 days.
site can also occur.  Penicillamine is an oral drug that reaches
peak levels in 1 to 3 hours after
Other Disease-Modifying Antirheumatic
administration. It is extensively
Drugs
metabolized in the liver and excreted in
Therapeutic Actions and Indications the urine with a half-life of 2 to 3 hours.
 Tofacitinib is absorbed quickly, reaching
 Anakinra is one of the newest of the anti- peak levels in 0.5 to 1 hour, it is
arthritis drugs. This drug is an interleukin-1 metabolized in the liver and excreted in
receptor antagonist. It blocks the the urine with a half-life of 3 hours.
increased interleukin-1, which is
responsible for the degradation of cartilage Contraindications and Cautions
in rheumatoid arthritis. This drug must be
 These drugs are contraindicated in the
given each day by subcutaneous injection
presence of allergy to the drugs or to the
and is often used in combination with other
animal products from which they were
anti-arthritis drugs.
derived to avoid hypersensitivity reactions.
 Hyaluronidase derivatives, such as hylan
G-F 20 and sodium hyaluronate, have Adverse Effects
elastic and viscous properties. These
drugs are injected directly into the joints of  A variety of adverse effects are common
patients with severe rheumatoid arthritis of with the use of these drugs, including local
the knee. They seem to cushion and irritation at injection sites (anakinra,
lubricate the joint and relieve the pain etanercept, hyaluronidase derivatives, and
associated with degenerative arthritis. sodium hyaluronate), pain with injection,
They are given weekly for 3 to 5 weeks. and increased risk of infection.
 Leflunomide directly inhibits an enzyme,
IMMUNE STIMULANTS
dihydroorotate dehydrogenase, that is
 Are naturally compounds that “modulate
active in the autoimmune process that
the immune system by increasing the
leads to rheumatoid arthritis, relieving
host’s resistance to disease”
signs and symptoms of inflammation and
 Used to recognize the immune system
blocking the structural damage this
when it is exhausted from fighting
inflammation can cause, slowing disease
prolonged invasion or when the immune
progression.
system needs help fighting a specific
 Penicillamine lowers the immunoglobulin
pathogen or cancer cell.
M rheumatoid factor levels in patients with
 It include the interferons, which are
acute rheumatoid arthritis, relieving the
naturally released from human cells in
signs and symptoms of inflammation. It
response to viral invasion; interleukins,
may take 2 to 3 months of therapy before
which are chemicals produced by T cells
a response is noted.
to communicate between leukocytes; and
 Tofacitinib is a kinase inhibitor that blocks
the colony-stimulating factors that are
signaling pathways within immune cells to
used to stimulate the bone marrow to
prevent their activity. It is an oral agent
produce more white blood cells in
situations where the levels of these cells
 are very low and the patient is at serious may further suppress the bone marrow,
risk for infection. and with central nervous system (CNS)
dysfunction of any kind because of the
INTERFERONS potential for CNS depression and
 Interferons are substances naturally personality changes that have been
produced and released by human cells reported.
that have been invaded by viruses. They
may also be released from cells in Adverse Effects
response to other stimuli, such as  The adverse effects associated with the
cytotoxic T cell activity. use of interferons are related to the
immune or inflammatory reaction that is
Therapeutic actions and indications being stimulated (stimulating the immune
 Interferons act to prevent virus particles and inflammatory response causes a flu-
from replicating inside cells. like syndrome with lethargy, myalgia,
 They also stimulate interferon receptor arthralgia, anorexia, nausea).
sites on noninvaded cells to produce
antiviral proteins, which prevent viruses Other commonly seem adverse effects include:
from entering the cell.
 Headache
 In addition, interferons have been found to
 Dizziness
inhibit tumor growth and replication, to
 Photosensitivity
stimulate cytotoxic T cell activity and to
 Bone marrow depression
enhance the inflammatory response.
 Depression and suicidal ideation
 Interferon gamma-1b also acts like an
 Liver impairment
interleukin, stimulating phagocytes to be
more aggressive

Pharmacokinetics
 The interferons are generally well INTERLEUKINS
absorbed after subcutaneous or  A group that naturally occurring proteins
intramuscular injection. that mediate communication between cells
 They have a rapid onset of action and  This are synthetic compounds much like
peak within 3 to 8 hours, with a half-life the interleukins, they communicate
ranging from 3 to 8 hours between lymphocytes, which stimulate
 Exception of interferon beta-1a, which has cellular immunity and inhibit tumor growth.
an onset of action of 12 hours and reaches  Interleukin-2 stimulates cellular immunity
peak levels in 48 hours, with a half-life of by increasing the activity of natural killer
10 hours. cells, platelets, and cytokines.
 They are broken down in the liver and Two interleukin preparations are available for
kidneys and seem to be excreted primarily use:
through the kidneys.
o Aldesleukin (proleukin) – is a human
Contraindications and Cautions
interleukin produced by recombinant DNA
 Many of the interferons are teratogenic in
technology using E.Coli bacteria.
animals and therefore should not be used
o Oprelvekin (neumega) – is a newer agent
during pregnancy. Use of barrier
that is also produced by DNA technology
contraceptives is advised for women of
childbearing age. Therapeutic Actions and Indications
 It is not known whether these drugs cross  Natural interleukin-2 is produced by
into breast milk, but because of the various lymphocytes to activate cellular
potential adverse effects on the baby, it is immunity and inhibit tumor growth by
advised that the drugs not be used during increasing lymphocyte numbers and their
lactation unless the benefits to the mother activity.
clearly outweigh any risks to the baby.  When interleukins are administered, there
 Caution should be used in the presence of are increases in the numbers of natural
known cardiac disease because killer cells and lymphocytes, in cytokine
hypertension and arrhythmias have been activity, and in the number of circulating
reported with the use of these drugs, with platelets.
myelosuppression because these drugs
 Pharmacokinetics  The colony-stimulating factors are
 The interleukins are rapidly distributed produced by recombinant DNA
after injection. technology.
 Aldesleukin, given IV, reaches peak  Are used to stimulate the bone marrow to
levels in 13 minutes and has a half-life of produce more white blood cells in
85 minutes. situations where the levels of these cells
 Oprelvekin, which is given are very low and the patient is at serious
subcutaneously, reaches peak levels in 3 risk for infection.
to 5 hours and has a half-life of 7 to 8  Filgrastim (Neupogen) and
hours. They are primarily cleared from the pegfilgrastim (Neulasta) increase the
body by the kidneys. production of neutrophils in the bone
marrow with little effect on other
Contraindications and Cautions
hematopoietic cells.
 Interleukins are contraindicated in the
 Sargramostim (Leukine) increases the
presence of any allergy to an interleukin or
proliferation and differentiation of
Escherichia coli–produced product to
hematopoietic progenitor cells and can
prevent hypersensitivity reactions.
activate mature granulocytes and
Because they were shown to be
monocytes.
embryocidal and teratogenic in animal
studies, they should not be used during Therapeutic Actions and Indications
pregnancy.  Increasing the production of white cells
 Use of barrier contraceptives is  Used to reduce the incidence of infection
recommended for women of childbearing in patients with bone marrow suppression
age who require one of these drugs. It is  Decrease the neutropenia associated with
not clear whether the drugs cross into bone marrow transplants and
breast milk, but it is recommended that chemotherapy
they not be used during lactation  Help in the treatment of various blood-
 Caution should be used with renal, liver, or related cancers.
cardiovascular impairment because of the
adverse effects of the drugs. Pharmacokinetics
 Filgrastim can be given IV or by
Adverse Effects subcutaneous injection, reaching peak
 Their effect on the body during levels in 2 hours IV or 8 hours
inflammation (flu-like effects: lethargy, subcutaneously
myalgia, arthralgia, fatigue, fever).  Half-life of about 220 minutes and a
 Respiratory difficulties, CNS changes, and duration of 4 days
cardiac arrhythmias also have been  Metabolism and excretion are not known.
reported, and the patient should be  Pegfilgrastim is only given by
monitored for these effects and the drug subcutaneous injection with similar onset
stopped if they do occur. but has a much longer half-life, 15 to 80
 Oprelvekin has been associated with hours, than filgrastim.
severe hypersensitivity reactions, and  Sargramostim can be given IV or
patients should be closely watched when subcutaneously with a duration of 6 hours
beginning therapy and encouraged to (IV) or 12 hours subcutaneously.
report any difficulty breathing or  It has a half-life of 1 to 3 hours; its
swallowing, chest tightness, or swelling. metabolism and excretion are not known.
 Patients receiving these drugs are at
increased risk for infection and for the Contraindications and Cautions
development of neoplasms due to their  Interleukins are contraindicated in the
blocking effect on the immune system. presence of any allergy to any component
Patients may experience headache, of the drug or to E.coli–produced products
tremors, secondary infections such as to prevent hypersensitivity reactions.
Acne, Gl upset, diarrhea, and  Sargramostim is contraindicated in
hypertension. neonates because of benzyl alcohol in the
solution and with excessive leukemic
COLONY-STIMULATING FACTORS myeloid blasts in the bone marrow or
peripheral blood, which could be worsened
by the drug.
  Sargramostim should also be used with  Monoclonal antibodies – antibodies
caution in hepatic or renal failure which produced by a single clone of B cells that
could alter the pharmacokinetics of the react with specific antigens.
drug, during or immediately after radiation  There is a new drug, belatecept (nulojix),
or chemotherapy because of a potential that was approved for the prevention of
loss of effectiveness. acute transplant rejection in adults with
 These drugs should be used with caution kidney transplants.
in pregnancy and lactation because the
potential effects on the fetus or neonate IMMUNE MODULATORS
are not known  The immune modulators block the release
of various cytokines involved in the
Adverse effects inflammatory response and activation of
The adverse effects associated with lymphocytes, decreasing immune activity.
colony-stimulation factors are gastrointestinal (GI) The immune modulators are a relatively
effects: new class of drugs and include fingolimod
(Gilenya), lenalidomide (Revlimid), and
 Nausea
thalidomide (Thalomid), an old drug with
 Constipation
new uses
 Fatigue
 Vomiting Therapeutic Actions and Indications
 Anorexia  Lenalidomide and thalidomide inhibit the
 Generalized weakness secretion of proinflammatory cytokines
 Diarrhea and increase the secretion of anti-
 Headache inflammatory cytokines from monocytes
 Alopecia and dermatitis and have varying effects on cell
 Generalized pain and bone pain proliferation.
 Fingolimod inhibits the release of
The effects are thought to be associated
lymphocytes from lymph nodes into the
with the drug effects on the bone marrow cells and
peripheral blood
their increased activity.
Pharmacokinetics
 Fingolimod is slowly absorbed from the GI
tract, reaching peak levels in 12 to 16
hours. It is metabolized in the liver and
IMMUNE SUPPRESSANTS excreted through the kidneys with a half-
 Immune suppressants often are used in life of 6 to 9 days.
conjunction with corticosteroids, which  Lenalidomide is absorbed quickly from the
block the inflammatory reaction and GI tract, reaching peak levels in 30 to 90
decrease initial damage to cells. minutes. It is excreted unchanged in the
 Are used to block the normal effects of the urine with a half-life of 3 hours.
immune system in cases of organ  Thalidomide is very slowly absorbed from
transplantation (in which non-self-cells are the GI tract, reaching peak levels in 3 to 6
transplanted into the body and destroyed hours. The metabolism of thalidomide is
by the immune reaction) and in not known; it is excreted in the urine with a
autoimmune disorders (in which the body’s half-life of 12 to 24 hours.
defenses recognize self-cells as foreign
and work to destroy them) in some Contraindications and Cautions
cancers. Each group acts at various sites  All of these drugs are contraindicated
within the immune response. during pregnancy because their effects on
 They are especially beneficial in cases of cells can cause serious fetal harm; women
organ transplantation and in the treatment of childbearing age should be advised to
of autoimmune diseases. use barrier contraceptives when using this
 They are especially beneficial in cases drug, and proof that the patient is not
of organ transplantation and in the pregnant needs to be documented in the
treatment of autoimmune diseases. chart before beginning therapy and
 The immune suppressant include the periodically during therapy.
immune modulators; T and B-cell T AND B CELLS SUPPRESSORS
suppressors, Interleukin receptor
antagonist.
 Several T and B cell immune suppressors development of neoplasms due to their
are available for use. Of the numerous blocking effect on the immune system.
agents available, cyclosporine is the most  Other potentially dangerous adverse
commonly used immune suppressant. effects include hepatotoxicity, renal
Additional agents include abatacept toxicity, renal dysfunction, and pulmonary
(Orencia), alefacept (Amevive), edema.
azathioprine (Imuran), cyclosporine  Patients may experience headache,
(Sandimmune, Neoral), glatiramer tremors, secondary infections such as
(Copaxone), mycophenolate (CellCept), acne, GI upset, diarrhea, and
pimecrolimus (Elidel), sirolimus hypertension.
(Rapamune), and tacrolimus (Prograf).
 T-CELL SUPPRESSOR – A type of INTERLEUKIN RECEPTOR ANTAGONISTS
An interleukin receptor antagonist works to
immune cell that blocks the actions of
block the activity of the interleukins that are
some other types of lymphocytes, to keep
released in an inflammatory or immune response.
the immune system from becoming over-
The only available interleukin receptor antagonist
active.
is Anakinra (Kineret).
 B – CELL SUPPRESOR – Inhibit immune
responses through the release of specific Therapeutic Actions and Indications
 Anakinra specifically antagonizes human
Therapeutic Actions and Indications
interleukin-1 receptors, blocking the
 The exact mechanism of action of the T
activity of interleukin-1. Interleukin-1 levels
and B cell suppressors is not clearly
are elevated in response to inflammation
understood. It has been shown that they
or immune reactions and are thought to be
block antibody production by B cells,
responsible for the degradation of cartilage
inhibit suppressor and helper T cells, and
that occurs in rheumatoid arthritis.
modify the release of interleukins and of T
 Anakinra is used to reduce the signs and
cell growth factor. The T and B cell
symptoms of moderately to severely active
suppressors are indicated for the
rheumatoid arthritis in patients 18 years of
prevention and treatment of specific
age and older who have not responded to
transplant rejections.
the traditional antirheumatic drugs.
Pharmacokinetics
Pharmacokinetics
 Cyclosporine is well absorbed from the
 The recommended dosage is 100 mg/d by
GI tract, reaching peak levels in 1 to 2
subcutaneous injection.
hours. It is extensively metabolized in the
liver by the cytochrome P450 system and  Anakinra is administered by subcutaneous
is primarily excreted in the bile. injection and is absorbed slowly, reaching
peak effects in 3 to 7 hours.
 The half-life of the drug is about 19 hours
for sand immune  It is metabolized in the tissues with a 4- to
6-hour half-life and is excreted in the urine.
 8.4 hours for Neoral. It is available as an
oral solution that can be mixed with milk, Contraindications and Cautions
chocolate milk, or orange juice for ease of  It should be used with caution during
administration. pregnancy and lactation
Contraindications and Cautions  It is also used cautiously in patients with
 Prevent hypersensitivity reactions renal impairment, immunosuppression, or
any active infection
 Usage during pregnancy and lactation
because of the potential serious adverse  There is an increased risk of infection
effects on the fetus or neonate whenever this drug is used, and the
patient needs to be protected from
 Caution should be used with renal or
exposure to infections and monitored
hepatic impairment, which could interfere
closely after any invasive procedures.
with the metabolism or excretion of the
drug, and in the presence of known  Immunizations cannot be given while the
neoplasms, which potentially could spread patient is on this drug.
with immune system suppression. Adverse Effects
Adverse Effects  Headache, sinusitis, nausea, diarrhea,
 Patients receiving these drugs are at upper respiratory and other infections, and
increased risk for infection and for the
 injection site reactions are among the  Vaccines and immune sera, including
most common adverse effects. antivenins and antitoxins, are usually
referred to as biologicals. They are used to
MONOCLONAL ANTIBODIES
stimulate the production of antibodies, to
 Can have monovalent affinity, binding only
provide preformed antibodies to facilitate
the same epitope
an immune reaction, or to react specifically
Therapeutic Actions and Indications with the toxins produced by an invading
 Muromonab-CD3, a T cell–specific pathogen or venins injected by poisonous
antibody that was available as an IV snakes or spiders.
agent. It reacted as an antibody to human
Immunity
T cells, disabling the T cells and acting as
an immune suppressor  Immunity is a state of relative resistance to
 Muromonab is indicated for the treatment a disease that develops after exposure to
of acute allograft rejection in patients the specific disease-causing agent.
undergoing renal transplantation.
 Adalimumab, certolizumab, golimumab, 2 types of Immunity
and infliximab are antibodies specific for
human tumor necrosis factor. It keeps the 1. Active Immunity
inflammatory reaction in check by reacting,
with and deactivating the free-floating  Occurs when the body recognizes a
tumor necrosis factor released by active foreign protein and begins producing
leukocytes. antibodies to react with that specific
protein or antigen.
Pharmacokinetics  After plasma cells are formed to produce
 With the exception of erlotinib (an oral antibodies, specific memory cells that
agent), all of the monoclonal antibodies produce the same antibodies are created.
have to be injected. They can be given IV, If the specific foreign protein is introduced
IM, or subcutaneously. into the body again, these memory cells
Contraindications and Cautions react immediately to release antibodies.
 Prevent hypersensitivity reactions and in  This type of immunity was always thought
the presence of fluid overload, which could to be lifelong, but it was discovered that
be exacerbated. They should be used patients who had been immunized against
cautiously with fever (treat the fever before smallpox often had no antibodies to
beginning therapy) and in patients who smallpox after many years. It is thought
have had previous administration of the that the eradication of the disease has
monoclonal antibody (serious resulted in no stimulation of the memory
hypersensitivity reactions can occur with cells, and after a prolonged period with no
repeat administration). stimulation, perhaps the memory cells no
longer produce antibodies.
Adverse Effects
The most serious adverse effects 2. Passive Immunity
associated with the use of monoclonal antibodies
 Occurs when preformed antibodies are
are:
injected into the system and react with a
 Acute pulmonary edema (dyspnea, chest specific antigen. These antibodies come
pain, wheezing), which is associated with from animals that have been infected with
severe fluid retention the disease or from humans who have had
 Cytokine release syndrome (flu-like the disease and have developed
symptoms that can progress to third- antibodies.
spacing of fluids and shocks)  It is limited. It lasts only as long as the
 Other adverse effects that can be circulating antibodies last because the
anticipated include fever, chills, malaise, body does not produce its own antibodies.
myalgia, nausea, diarrhea, vomiting, and
IMMUNIZATION
increased susceptibility to infection and
cancer development  It lasts only as long as the circulating
antibodies last because the body does not
VACCINES AND SERA
produce its own antibodies.
  The proteins could be a weakened the initial dose to further stimulate
bacterial cell membrane, the protein coat antibody production.
of a virus, or a virus (protein coat with the
Contraindications and Cautions of Vaccines
genetic fragment that makes up the virus)
 Presence of immune deficiency
that has been chemically weakened so
because the vaccine could cause disease
that it cannot cause disease.
and the body would not be able to respond
 The goal is to cause an immune response
as anticipated if it is in an immunodeficient
without having the patient suffer the full
state
course of a disease. Adults may require
 During pregnancy because of potential
immunizations in certain situations:
effects on the fetus and on the success of
Exposure, travel to an area endemic for a
the pregnancy
disease they have not had and have not
been immunized against, and occupations  Patients with known allergies to any of
that are considered high risk. Children are the components of the vaccine (refer to
routinely immunized against many each individual vaccine for specifics,
infections that were once quite sometimes including eggs, where some
devastating. pathogens are cultured)
 Patients who are receiving immune
VACCINES globulin or who have received blood or
blood products within the last 3 months
 Comes from the Latin word for smallpox, because a serious immune reaction could
vaccinia. occur.
 Vaccines are immunizations containing  Caution should be used any time a
weakened or altered protein antigens that vaccine is given to a child with a history of
stimulate the formation of antibodies febrile convulsions or cerebral injury, or in
against a specific disease. any condition in which a potential fever
 They are used to promote active immunity would be dangerous.
 Made from chemically inactivated  Caution also should be used in the
microorganisms or from live, weakened presence of any acute infection.
viruses or bacteria.
 Toxoids are vaccines that are made from Adverse Effects
the toxins produced by the microorganism.  Adverse effects of vaccines are associated
The toxins are altered so that they are no with the immune or inflammatory reaction
longer poisonous but still have the that is being stimulated: Moderate fever,
recognizable protein antigen that will rash, malaise, chills, fretfulness,
stimulate antibody production. drowsiness, anorexia, vomiting, and
irritability.
 Pain, redness, swelling, and even nodule
formation at the injection site are also
common. In rare instances, severe
hypersensitivity reactions have been
reported.

Clinically Important Drug-Drug Interactions

 Rash
 Anorexia
 Drowsiness
 Chills
 Malaise
 Vomiting
USE OF VACCINE DEPENDS ON
Vaccines should not be given with any
 The possible exposure a person will have immunosuppressant drugs, including
to a particular disease corticosteroids, which could alter the body’s
 The age of the person. Some vaccines are response to the vaccine.
used only in children, and some cannot be
used in infants. IMMUNE SERA
 Some vaccines require booster doses –
Therapeutic Actions and Indications
doses that are given a few months after
  Used to provide passive immunity globulins or to the components of the drug
 May be used as prophylaxis being used
 May also be used to lessen severity of a  Administer the drug as indicated.
disease Preparation varies with each product;
always check the manufacturer's
Pharmacokinetics guidelines.
 No available data for these biologicals  Monitor for severe reactions and have
Contraindications and Cautions emergency equipment
 Patient with history of severe reaction to  Arrange for supportive care and comfort
immune sera should be used with caution measures for flu-like symptoms (rest,
during pregnancy environmental control, acetaminophen)
 In patient with coagulation defects or and for the local reaction (heat to injection
thrombocytopenia patient with a known site, anti-inflammatories)
history of previous exposure to immune  Provide thorough patient teaching,
sera including measures
 Provide a written record of immune sera
Adverse Effects use and encourage the patient or family to
 Adverse effects can be attributed either to keep that information
the effect of immune sera on the immune
system (rash, nausea, vomiting, chills, Evaluation
fever) or to allergic reactions
 Monitor the patient’s response to the drug
 Local reactions  Monitor for adverse
Clinically Important Drug-Drug Interactions  Evaluate the effectiveness of the teaching
 Caution should be used if these drugs are plan
combined with any immune suppressant  Monitor the effectiveness of comfort
drugs measures and compliance with the
regimen.
Nursing Considerations for Patients
Receiving Immune Sera

Assessment: History and Examination

o Assess for contraindications or cautions

o Previous exposure to the serum being
used
o Evidence of thrombocytopenia or
coagulation disorders
o Immunization therapy
o Perform a physical assessment
o Inspect for the presence of any skin
lesions
o Check temperature, monitor pulse,
respiration, and blood pressure
o Auscultate lungs for adventitious sounds
o Assess level of orientation

Nursing Diagnoses

 Acute pain related to local, GI, and flu-like

effects
 Ineffective tissue perfusion related to
possible severe reactions
 Deficient knowledge regarding drug
therapy

Implementation

 Do not administer to any patient with a

history of severe reaction to immune