Drugs Affecting the Immune
System
NSAIDs

Large and chemically diverse group of
drugs with the following properties:




Analgesic
Anti-inflammatory
Antipyretic
Antirheumatic
NSAIDs: Indications

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Analgesia (mild to moderate)
Antigout effects
Anti-inflammatory effects
Antipyretic effects
Relief of vascular headaches
Platelet inhibition (ASA)
Various bone, joint, and muscle pain
Osteoarthritis
Rheumatoid arthritis
Dysmenorrhea
NSAIDs: Mechanism of
Action
Analgesia—treatment of headaches,
mild to moderate pain, and
inflammation
Antipyretic: reduce fever



Inhibit prostaglandin E2 within the area of the
brain that controls temperature
Salicylates also have antiplatelet activity

Inhibit platelet aggregation
Figure 43-1 Arachidonic acid pathway.
NSAIDS: Mechanism of action
• Inflammation: response to tissue injury and infection
• Cardinal signs of inflammation
• Chemical Mediators
– Prostaglandins
• Vasodilation, relaxation of smooth muscles, increased capillary
permeability & sensitization of nerve cells to pain
– Cyclooxygenase (COX)
• COX-1 & COX-2
• Enzyme responsible for conversion of arachidonic acid into
prostaglandins

-Leukotrienes
Chemical Categories of
NSAIDs
Seven structurally related groups
1.
2.
Acetic acids
Carboxylic acids (salicylates)
Acetylated and nonacetylated
3.
4.
5.
6.
7.
Propionic acids
COX-2 inhibitors
Fenamic acids
Napthylalkanones (nonacidic)
Oxicams
NSAIDs: Acetic Acid

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diclofenac sodium, Voltaren
Indomethacin, indocin
Sulindac, Clinoril
tolmetin
NSAIDs: Carboxylic Acids
Acetylated


acetylsalicytic acid
diflunisal , Dolobid
Nonacetylated


Ketorolac, Toradol
sodium salicylate
NSAIDs: Propionic Acids


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Flurbiprofen, Ansaid
Ibuprofen, (Advil, Motrin)
Ketoprofen(Orudis)
Naproxen(Aleve, Anaprox, Naprosyn)
NSAIDs: Other Agents
COX-2 inhibitors


Celebrex
Vioxx (removed in 2004)
NSAIDs: Other Agents (cont’d)
Oxicams


Meloxicam, Mobic
piroxicam
Fenamic acids

mefenamic acid
Nonacidic compounds

nabumetone
NSAIDs: Salicylates
salicylates (aspirin)


More potent effect on platelet aggregation
and thermal regulatory centre in the brain
 Analgesic
 Antipyretic
 Anti-inflammatory
Antithrombotic effect: used in the treatment
of MI and other thromboembolic disorders
NSAIDs: Antigout Agents

Gout: condition that results from
inappropriate uric acid metabolism



Underexcretion of uric acid
Overproduction of uric acid
Uric acid crystals are deposited in
tissues and joints, resulting in pain
NSAIDs: Antigout Agents
(cont’d)
allopurinol

Used to reduce production of uric acid
colchicine

Reduces inflammatory response to the deposits of
urate crystals
probenecid, sulfinpyrazone

Increase excretion of uric acid in the urine
NSAIDs: Side Effects
Gastrointestinal

Dyspepsia, heartburn, epigastric distress, nausea
 GI bleeding*
 Mucosal lesions* (erosions or ulcerations)
*misoprostol (Cytotec) can be used to reduce these dangerous effects
Renal


Reductions in creatinine clearance
Acute tubular necrosis with renal failure
NSAIDs
Salicylate Toxicity


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Adults: tinnitus and hearing loss
Children: hyperventilation and CNS
effects
Effects arise when serum levels exceed
300 mcg/mL
Metabolic acidosis and respiratory
alkalosis may be present
NSAIDs:
Nursing Implications

Before beginning therapy, assess for
conditions that may be contraindications to
therapy, especially:
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GI lesions or peptic ulcer disease
Bleeding disorders
Assess also for conditions that require
cautious use
Perform laboratory studies as indicated
(cardiac, renal, liver studies, CBC, platelet
count)
Nursing Implications


Perform a medication history to assess for
potential drug interactions.
Several serious drug interactions exist

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Alcohol
Heparin
Phenytoin
Oral anticoagulants
Steroids
Sulfonamides
Nursing Implications (cont’d)


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Salicylates are NOT to be given to children
under age 12 because of the risk of Reye’s
syndrome
Because these agents generally cause GI
distress, they are often better tolerated if
taken with food, milk, or an antacid to avoid
irritation
Explain to clients that therapeutic effects may
not be seen for 3 to 4 weeks
Nursing Implications (cont’d)


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Educate clients about the various side effects
of NSAIDs, and to notify their physician if
these effects become severe or if bleeding or
GI pain occurs
Clients should watch closely for the
occurrence of any unusual bleeding, such as
in the stool
Enteric-coated tablets should not be
crushed or chewed
Nursing Implications (cont’d)

Monitor for therapeutic effects, which
vary according to the condition being
treated
 Decrease in swelling, pain, stiffness,
and tenderness of a joint or muscle
area
Case Study: NSAIDS
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Mrs Jones is 78 years old and has been
discharged from hospital following an open
reduction internal fixation of her Right
tib/fibula.
She has a remote history of GI bleed in her
60’s
Her orthopedic surgeon prescribes:
Cytotec,
ASA 81 mg
Celebrex
Your discharge instructions
will be:

ASA:

Celebrex:

Cytotec:
Client teaching about NSAIDS:

Take with food/milk
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Check stools for blood
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Report stomach pain
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Report to other health care providers
(ie dentist)
Immune System

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
Defends the body against invading
pathogens, foreign antigens, and its
own cells that become cancerous
Can also sometimes attack itself,
causing “autoimmune diseases” or
immune-mediated diseases
Participates in analphylaxis &
tissue/organ rejection
Immunosuppressants

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Agents that decrease or prevent an
immune response, thus suppressing the
immune system
Used to prevent or treat rejection of
transplanted organs
Immunosuppressants (cont’d)


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All suppress certain T-lymphocyte cells
lines, preventing their involvement in
the immune response
Result: a pharmacologically
immunocompromised state
Mechanisms of action vary according to
agent
Immunosuppressants (cont’d)

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Corticosteroids
azathioprine
muromonab-CD3
daclizumab
sirolimus

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cyclophosphamide
cyclosporine
tacrolimus
basiliximab
glatiramer acetate
Immunosuppressants (cont’d)



Indications vary from agent to agent
Primarily indicated for the prevention of
organ rejection
Some also used for immunological
diseases such as rheumatoid arthritis
and multiple sclerosis
Immunosuppressants (cont’d)

azathioprine


Used as an adjunct medication to prevent
rejection of kidney transplants
Also used in the treatment of rheumatoid
arthritis
Immunosuppressants (cont’d)

cyclosporine



Primary agent used in the prevention of
kidney, liver, heart, and bone marrow
transplant rejection
May be used for other autoimmune
disorders
tacrolimus

Used for the prevention of liver and kidney
transplant rejection
Immunosuppressants (cont’d)

glatiramer acetate


The only immunosuppressant agent used
for the treatment of multiple sclerosis (MS)
Used to reduce the frequency of MS
relapses (exacerbations) in relapsingremitting multiple sclerosis (RRMS)
Immunosuppressants (cont’d)

Side effects vary according to agents,
and may be devastating
**All immunosuppressed clients have a
heightened susceptibility to
opportunistic infections**
Nursing Implications

Thorough assessment should be
performed before administering these
agents
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Renal, liver, and cardiovascular function
Respiratory assessment
Baseline vital signs
Baseline laboratory studies, including
hemoglobin, hematocrit, WBC, and platelet
counts
Nursing Implications (cont’d)


Assess for contraindications, drug
allergies
Monitor WBC counts throughout
therapy; if the count drops below 3.0 x
109/L the drug should be discontinued,
but only after contacting the physician
Nursing Implications (cont’d)
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Oral immunosuppressants should be taken
with food to minimize GI upset
Oral forms are used when possible to
decrease the risk of infection that may occur
with parenteral injections
Oral antifungal agents are usually given with
these agents to treat oral candidiasis that
may occur
Observe the oral cavity often for white
patches on the tongue, mucous membranes,
and oral pharynx
Nursing Implications (cont’d)


Follow guidelines for parenteral
administration carefully
Clients need to be told that lifelong
therapy with immunosuppressants is
indicated with organ transplantation
Nursing Implications (cont’d)

Clients taking immunosuppressants should be
encouraged to take measures to reduce the
risk of infection
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Avoiding crowds
Avoiding people with colds or other infections
Clients should be told to report any fever,
sore throat, chills, joint pain, fatigue, or other
signs of a severe infection immediately
Immunity

Immune response

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Antigens
Antibodies
Active immunization
Passive immunization
Table 45-1 Active versus passive immunity
Immunizing Biologicals

Biological antimicrobial agents
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Also called biologicals
Antitoxins
Serum
Toxoids
Vaccines
Used to prevent, treat, or cure infectious
diseases
Toxoids
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Antigenic (foreign) preparations or bacterial
exotoxins
Detoxified with chemicals or heat
Cannot revert back to a toxic form
Stimulate one’s immune system to produce a
specific antibody
The production of these antibodies protect
against future exposures to the antigen
Ex. Tetanus
Vaccines


Suspensions of live, attenuated
(weakened) or killed (inactivated)
micro-organisms
The weakened form prevents the
person from contracting the disease
Vaccines (cont’d)



Also stimulate the production of
antigens against a specific antibody
Vaccinations with live bacteria or virus
provide lifelong immunity
Vaccinations with killed bacteria or virus
provide partial immunity, and booster
shots are needed periodically
Active Immunization

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The body is exposed to a relatively
harmless form of an antigen
The immune system is stimulated, and
“remembers” this antigen if subsequent
exposures occur
The immunizations do not cause a fullblown infection
Examples of
Active Immunizing Agents
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BCG vaccine (tuberculosis)
Diphtheria,tetanus, and pertussis toxoids,
several forms
Cholera vaccine
Haemophilus influenzae type b conjugate
vaccine
Hepatitis A and B virus vaccines
Measles, mumps, and rubella virus vaccine,
live—several forms
Poliovirus vaccine, several forms
Examples of Active
Immunizing Agents (cont’d)
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Rabies virus vaccine
Smallpox virus vaccine
Tetanus toxoid
Varicella virus vaccine (chicken pox)
Yellow fever virus vaccine
Indications

Active immunization

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Prevents infection caused by bacterial
toxins or viruses
Provides long-lasting or permanent
immunity
“Herd immunity”
Passive Immunization

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Serum or concentrated immune globulins
from humans or animals are injected into a
person
The substances needed to fight off invading
micro-organisms are given directly to a
person
The immune system is bypassed
Short-lived compared with active
immunization, but works faster
Passive Immunization (cont’d)

Naturally acquired passive immunity

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From mother to fetus through the placenta
From mother to infant through breast milk
Artificially acquired passive immunity

Acquired from an external source, such as
injection of antibodies or immunoglobulins
Examples of
Passive Immunizing Agents
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Antivenins
Diphtheria antitoxin
Hepatitis B immune globulin
Immune globulin, various forms
Rabies immune globulin (human)
Rh0(D) immune globulin (RhoGAM)
Tetanus immune globulin
Varicella zoster immune globulin (chicken
pox/shingles)
Indications (cont’d)

Passive immunization

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Antitoxins, antivenins, immune globulins
Minimizes effects of poisoning by the
venoms of spiders and certain snakes
Provides quick immunity before a person’s
own immune system has a chance to make
antibodies (such as in cases of exposure to
hepatitis B or rabies viruses)
Indications (cont’d)

National Advisory Committee on
Immunization recommendations for
adult and pediatric immunizations
(Canada)

Provide specific dosages and intervals for
immunizations
Mechanism of action:vaccines
Anitgens: foreign substances
Anitbodies: immunoglobulins
Once the vaccine is administered the body
produces immunoglobulins: IgG, IgA, IgE,
IgD, IgM to attack and kill the foreign invader
Anitbody titre: the amount of immunoglobulin in
the body that must be present to protect the
body against the pathogen
Booster shot: given when antibody titre reveals
low levels
Side Effects


Range from mild and transient to very
serious or life threatening
Minor effects


Fever, minor rash, soreness at injection
site, itching
Severe effects

Fever >38° C, encephalitis, convulsions,
anaphylactic reaction, dyspnea, others
Immunization schedule
Side Effects (cont’d)

Minor reactions


Treated with acetaminophen and rest
Serious or unusual reactions


Serum sickness
Report serious or unusual reactions to the
Canadian Adverse Events Following
Immunization Surveillance System
Nursing Implications



Assess client’s health history,
medication history, allergies, pregnancy
status
Assess previous reactions and
responses to immunizations
Assess for contraindications, including
immunosuppression
Nursing Implications (cont’d)


Before giving any agent, recheck the
specific protocols for administration and
schedules for administration
Follow manufacturer’s guidelines for
drug storage, administration, routes,
and site of administration
Nursing Implications (cont’d)


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If discomfort occurs at the injection
site, apply warm compresses and give
acetaminophen
Do not give acetylsalicylate acid to
children
Monitor for therapeutic responses and
adverse reactions
Cancer




Cellular transformation
Uncontrolled and rapid cellular growth
Invasion into surrounding tissue
Metastasis to other tissues or organs
Cancer (cont’d)

Cancerous cells do not have:



Growth control mechanisms
Positive physiological function
Cancer cells either:


Grow and invade adjacent tissues
Break away from original tumour mass and
travel by means of blood or lymphatic
system to distant sites
Cancer (cont’d)

Metastasis


Neoplasm


Uncontrolled cell growth
Mass of new cells; tumour
Tumour


Benign
Malignant (cancer)
Table 46-2 Tumour classification based on specific tissue of origin
Etiology of Cancer

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Age- and sex-related differences
Genetic factors
Ethnic factors
Oncogenic factors (viruses)
Occupational and environmental carcinogens
Radiation
Immunological factors
Chemotherapy



Pharmacological treatment of cancer
Antineoplastic agents
Divided into two groups based on
where in the cellular life cycle they work


Cell cycle nonspecific (CCNS)
Cell cycle specific (CCS)
Chemotherapy (cont’d)




Drugs have a narrow therapeutic index
Combination of agents is usually more
effective than single-agent therapy
Nearly all agents cause side effects and
adverse effects
Dose-limiting side effects
Chemotherapy (cont’d)

Harmful to all rapidly growing cells


Harmful cancer cells
Healthy, normal human cells

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
Hair follicles
GI cells
Bone marrow cells
Chemotherapy:
Contraindications

Few given the fatal outcome of cancer

Low wbc

Infectious process
Extravasation



Leaking of an antineoplastic drug into
surrounding tissues during IV administration
Can result in permanent damage to nerves,
tendons, muscles, loss of limbs
Skin grafting or amputations may be
necessary
Prevention is essential, Continuous monitoring
of the IV site is essential
Extravasation (cont’d)




If suspected, stop the IV infusion immediately
but do not remove the IV tube
If possible, aspirate remaining drug or blood
from the tube
Follow instructions for giving the appropriate
antidote (if one exists) through the existing
IV tube, then remove the catheter
Some antidotes are not given through the IV
catheter
Extravasation (cont’d)



Cover area with sterile, occlusive
dressing
Apply warm or cold compresses,
depending on the extravasated agent
Elevate the limb
Nursing Implications



Assess baseline blood counts before giving
any antineoplastic agents
Follow specific administration guidelines for
each antineoplastic agent
Remember that all rapidly dividing cells (both
normal and cancer cells) are affected



Mucous membranes
Hair follicles
Bone marrow component
Nursing Implications (cont’d)

Monitor for complications

GI mucous membranes: stomatitis, altered
bowel function with high risk for poor
appetite, nausea, vomiting, diarrhea, and
inflammation and possible ulcerations of GI
mucosa
Nursing Implications (cont’d)

Monitor for complications

Hair follicles: loss of hair (alopecia)

Bone marrow components: dangerously
low (life-threatening) blood cell counts
Nursing Implications (cont’d)



Implement measures to monitor for and
prevent infection in clients with
neutropenia
Implement measures to monitor for and
prevent bleeding in clients with
thrombocytopenia and anemia
Keep in mind that anemia may result in
severe fatigue
Nursing Implications (cont’d)



Monitor for stomatitis (oral inflammation and
ulcerations) and implement measures to
reduce the effects if it occurs
Anticipate nausea and vomiting and
implement measures to reduce these effects
Women of childbearing age will need to use a
nondrug form of contraception during therapy
Nursing Implications (cont’d)


In addition to physical measures, keep
in mind the need for emotional support
during this time for both the client and
family
Monitor for therapeutic responses to
antineoplastic therapies and the many
possible side/adverse effects