Transcript Pharmacology Nursing 3704 Corticosteroids, Immunizing,Hematopoietic, and Immunosuppressant Agents By Linda Self Immunity     Last line of defense against infection Has characteristics of specificity, memory and inducibility to provide long-term.

Pharmacology
Nursing 3704
Corticosteroids,
Immunizing,Hematopoietic, and
Immunosuppressant Agents
By Linda Self
Immunity
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Last line of defense against infection
Has characteristics of specificity, memory and
inducibility to provide long-term protection
against specific antigens
Must have ability to distinguish self from nonself
Normal immunity can do this by recognizing
epitopes (distinctive molecules on non-self
antigens)
Immunity cont.
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Hyperactive system will create
autoimmune diseases such as
rheumatoid arthritis, lupus
erythematosus, others
When system is underactive,
immunodeficiency diseases occur
Types of Immunity
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Natural immunity-general protective
mechanisms that protect an individual from
infectious agents that cause disease in other
species
Acquired immunity—active or passive. Active
immunity is caused by own immune systems,
passive immunity is where antibodies are
“transferred” to the host. Active immunity
tends to be longer lasting than passive.
Types of Immunity
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Cellular—involving activated T
lymphocytes in body tissues
Humoral immunity involves B
lymphocytes and antibodies.
Interplay between two types of
immunity; virtually all antigens elicit
both cellular and humoral responses
Immunizations
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Involves administration of an antigen to
induce antibody formation (for active
immunity) or serum from immune
people (for passive immunity)
Immunizations are biologic agents
Are regulated by the U.S. FDA
Specific recommendations
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Only use the inactivated form of polio
vaccine in US; unfortunately is injectible
only
Hepatitis B recommended now
recommended for all newborns and for
non-immunized children before starting
school
Specific Recommendations
cont.
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Everyone should be immunized against
diphtheria and tetanus every 7 to 10
years for life
Combining vaccinations to prompt
greater compliance include: IPV with
DTaP with hepatitis B (Pediarix),
Haemophilus b (Hib) with hepatitis B
(Comvax), and hepatitis A&B=Twinrix.
Agents for Active Immunity
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Vaccines and toxoids
Vaccines are suspensions of microorganisms
or their antigenic products that have been
killed or attenuated; may have lifelong effects
Toxoids are bacterial toxins or products that
have been modified to destroy toxicity while
retaining antigenic properties; not permanent
effects
Agents for Active Immunity
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For maximum effectiveness, must be
given before actual exposure
Indications for Use
1.
Routine immunization of all children
against diphtheria, Haemophilus
influenza, hepatitis B, mumps,
pertussis, pneumococcal infection,
poliomyelitis, rubella (German
measles), rubeola (red measles) and
varicella
Indications for Use cont.
2. Immunizations of adolescents and adults
against diphtheria and tetanus
3. Immunization of prepubertal girls or women
of childbearing age against rubella.
4. Immunization of adults and children at high
risk for exposure to a particular disease such
as yellow fever, malaria, etc.
Contraindications to Use of
agents for active immunity
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Febrile illnesses
If receiving immunosuppressive therapy
In immunodeficiency states
Leukemia
Lymphoma
In pregnancy
If generalized malignancy is present
Agents for Passive Immunity
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Immune serums are the biologic
products used for passive immunity
Only create temporary immunity
Goal is to prevent or modify the disease
process
Are made from the serum of individuals
with high concentrations of the specific
antibody or immunoglobulin required
Agents for Passive Immunity
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Cytomegalovirus
Hepatitis B
Rabies
Rubella
Tetanus
Varicella zoster
Respiratory syncytial virus infections
Reporting of Vaccine
preventable diseases
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Report to the local or state health
department
Information is then sent to the CDC
www.cdc.gov/nip/acip is authoritative
site
Reporting of Adverse
Reactions
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All health care providers must report
any serious adverse reactions to the
Department of Health and Human
Services
Website is:
www.fda.gov/cber/vaers.html.
Storage of Vaccines
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Most products require refrigeration at 2
to 8 degrees celsius (35.6 to 46.4
degrees Fahrenheit)
Protect from light
Vaccines and Toxoids for
Active Acquired Immunity
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*Haemophilus Influenza (Hib)—age 2-5
mos. Then q2mos x 3 doses; then at
12-15 mos.
Vaccines and Toxoids for
Active Immunity
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*Hepatitis B—children at birth, repeat in
one month then again six months later;
different preparations such as
Recombivax and Engerix
*Measles, Mumps and Rubella—12-15
months; 2nd dose at 4-6 years.
Immunizations cont.
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*Poliomyelitis—sub Q injection. Give at 2, 4,
6-18 mos then at 4-6 years
Influenza—may start at greater than 6
months. Give one dose then follow by 2nd
dose in one month. If 9 years or older,
require only one dose.
Meningococcal—effective against Neisseria
meningitidis. Type A should only be given to
infants and children <2years
Immunizations
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*Pneumococcal 7 valent conjugate
(Prevnar) give at 2, 4, and 6 mos. then
again at 12-15 months.
*Varicella—12 months or older, follow
by a second dose 4-8 weeks after the
first dose; booster at age 12 years
Immunizations using toxoids
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*DTaP—at 2, 4, 6 months, at 15-18
mos. then a booster of Td at age 4-6
years.
Immune Serums for Passive
Immunity
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Cytomegalovirus
Hepatitis B
Immune globulin in case of hepatitis A,
measles, varicella, rubella, bacterial
infections
Rabies immune globulin
RSV immune globulin
RhoGAM
New vaccines
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HPV—bivalent and quadravalent
vaccines
Herpes Zoster
HIV
Immunizing the unborn eg RSV
Malaria vaccinate the infected to
prevent passage to others
Key points in Immunizations
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Determine whether patient has any
conditions that contraindicate
administration of immunizing agents
For children with chronic illnesses such
as asthma, heart disease, diabetes and
others, flu vaccine is recommended
annually after 6 months of age
Key Points in Immunizations
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For children with HIV, live viral and
bacterial vaccines are contraindicated
as they can cause disease (MMR,
varicella, bacillus Calmetter-Guerin).
Annual influenza vaccine and one time
pneumococcal vaccine at 65 years
recommended for healthy older adults
and those with chronic conditions.
Key Points in Immunizations
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To avoid rubella induced abnormalities in
fetal development, women of childbearing
age must avoid becoming pregnant for 3
months following being immunized
Likewise for Varicella
After receiving Varicella vaccine, aboid close
contact with newborns, pregnant women and
anyone who is immunocompromised
Key Points in Immunizations
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After receiving a vaccine, stay in the
area for approx. 30 minutes
Give DTP in lateral thigh muscle of
infant
Aspirate carefully before IM or Sub-q
injection of any immunizing agent
With varicella vaccine, salicylates my
increase risk of Reye’s
Hematopoietic and
Immunostimulant Drugs
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Cytokines or biologic response modifiers
are given to restore normal function or
to increase the ability of the immune
system to eliminate potentially harmful
invaders
Examples are colony-stimulating
factors, several interferons and two
interleukins
Definitions
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Interferons are glycoproteins with
antiviral activity
Interleukins are cytokines that enable
communication among leukocytes and
other cells active in inflammation or the
cell-mediated immune response.
Result—a maximized response to a
microorganism or other foreign antigen.
Cytokines
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Are substances produced by bone marrow cells,
activated helper T cells, activated macrophages and
other cells.
Regulate cellular activities by acting as chemical
messengers among cells.
Helper T cells and macrophages are the main
producers of cytokines
Act by binding to receptors on the membranes of
numerous types of target cells.
Are the key components in producing hematopoietic
and immunostimulant drugs
Hematopoietic and
Immunostimulant Drugs
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Most hematopoietic and immunostimulant
drugs are facsimiles of cytokines
The endogenous cytokines control the
reproduction, growth and differentiation of
stem cells and colony forming units; these
agents are simulated.
The manufactured cytokines involve
inserting the identified genes that are
involved in their production into yeasts or
bacteria; thus producing the substances
exogenously.
General Characteristics cont.
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Very powerful biologic response modifiers
May be difficult to maintain an effective dose
levels for prolonged treatment periods
Can have untoward and unanticipated side
effects
Can act as antiproliferative and
immunoregulatory agents; can augment the
activity of natural killer cells and/or enhance
activities of immune cells
General Characteristics cont.
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Cannot be take orally
May have substantial side effects
decreasing patient compliance
Hematopoietic Agents
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Epogen or Procrit (Darbepoetin alfa and
epoetin alfa)==drug preparations of
erythropoietin
Use to treat anemias
Dosage is adjusted according to
response; should be adjusted with
when hematocrit approaches 36%;
check HCT 2x/weekly
Colony Stimulating Factors
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Neupogen (filgrastim),Neulasta
(pegfilgrastim) are used to stimulate blood
cell production by the bone marrow in
patients with bone marrow transplantation or
chemotherapy-induced neutropenia
Leukine (sargramostim) GM-CSF used as
above but also useful as angiogenetic in
ischemic heart disease
Interleukins
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Proleukin (aldesleukin) is a recombinant
DNA version of interleukin 2. Function is
to activate cellular immunity; produces
tumor necrosis factor and inhibits tumor
growth
Used to treat metastatic renal cell CA
and melanoma; others under
investigation.
Interleukins cont.
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Proleukin is contraindicated in recent
organ transplantation or with serious
cardiopulmonary disease
Proleukin may cause renal and/or
hepatic impairment
Toxicity of this agent can cause: GI
bleed, CNS coma, cardiac dysrhythmias
or respiratory embarrassment
Interleukins cont.
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If toxicity occurs, dosage reduction is
not the recommendation. Either DC the
drug or withhold one or two doses.
Neumega (oprelvekin) is recombinant
IL-11. Used to prevent severe
thrombocytopinia and to reduce the
need for platelet tranfusions in patients
receiving cancer chemotherapy.
Interferons
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Interferon alfa-2a and 2b are used to treat
hairy cell leukemia and Kaposi’s sarcoma
Interferon alfa-2b useful also for tx of chronic
hepatitis and condyloma acuminata
Interferon alfa-n1 approved for tx of chronic
hepatitis C
Interferon beta for multiple sclerosis
Other uses under investigation
Main SE are flu-like S/S
Bacillus Calmette-Guerin
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Suspension of attenuated
Mycobacterium bovis
Stimulates cell-mediated immunity
Used as a topical agent for superficial
cancers of the urinary bladder with an
80% response rate
Contraindicated in immunosuppression
as can cause TB in high risk populations
Corticosteroids and
Immunosuppressants
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These drugs are used to decrease an
inappropriate or undesirable immune
response for certain conditions.
Examples include RA, SLE, asthma or
suppression of transplant rejection
Corticosteroids
Glucocorticoids
 Reduce immune response and reduce
inflammation
 Used as anti-inflammatory,
immunosuppressive, antiallergic and
antistress
 SE include infection, decreased wound
healing, HPA axis suppression, osteoporosis,
hyperglycemia, and muscle wasting
Corticosteroid effects on the
body
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Increase production and decrease utilization of
glucose in the blood
Catabolic—protein depletion
Decrease inflammatory response by stabilizing
lysosomal membranes
Decrease immune response by decreasing antibody
production, lymphocytes, eosinophils, macrophages
and lymphoid tissue.
More neutrophils leave marrow but fewer are
involved in inflammatory processes
Corticosteroids cont.
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Stabilize mast cells thus the release of
histamine
Affect stomach mucous contributing to
the development of peptic ulcers
Muscle atrophy
Adrenal cortex suppression
Corticosteroids
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Prednisone is the prototype
Celestone (betamethasone)
Decadron (dexamethasone)
Solucortef (methylprednisolone)
Kenalog (triamcinolone)
Indications for Steroids
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Asthma, COPD, arthritis
Adrenal insufficiency
Cancer—inhibit cell reproduction and
are cytotoxic to lymphocytes; excellent
for tx of cerebral edema, GVHD after
bone marrow transplantation
Chemotherapy-induced emesis
Immunosuppressant Drugs
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Used in conjunction with steroids
Used in autoimmune disorders
Used to reduce the immune response when
foreign tissue is transplanted into the body
Older drugs depressed immune system; had
unfortunate SE. Infections, cancer,
hypertension and metabolic bone disease.
Immunosuppressants
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Have developed new agents that modify
the immune response
Newer agents target specific
components of the immune response so
will have less global effect on patient’s
total immunity, susceptibility to
infection
Immunosuppressants—Cytotoxic,
Antiproliferative Agents
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Damage or kill cells that are able to
reproduce
Used primarily in cancer
Imuran (azathioprine) is an
antimetabolite that interferes with the
production of DNA and RNA so blocks
cellular reproduction, growth and
development
Cytotoxic Agents cont.
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Imuran targets rapidly proliferating cells
including T and B lymphocytes
Well abosorbed orally
Used mainly to prevent organ graft
rejection but has little effect on acute
rejection
Lifelong administration
Dosage depends on WBC count
Cytotoxic Agents
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Rheumatrex (methotrexate) is a folate
antagonist. Inhibits biosynthesis of DNA
and cell reproduction of immune cells,
especially T cells. Used both for cancer
and for autoimmune or inflammatory
disorders (psoriasis and arthritis).
Also used to prevent graft-versus-host
disease.
Conventional Antirejection
Agents
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Sandimmune (cyclosporine) and Prograf
(tacrolimus) are fungal metabolites with
strong immunosuppressive effects. Action is
to inhibit synthesis of a cytokine, IL-2,
necessary for activation of T cells and B cells.
Rapamune (sirolimus) affects T cell activation
and proliferation secondary to several
interleukins.
Antirejection Agents cont.
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Sandimmune is used to prevent
rejection reactions and prolong graft
survival after solid organ
transplantation, or to treat chronic
rejection
Water insoluble so prepared in etoh or
olive oil for oral admin. And in castor oil
or etoh for IV admin.
Antirejection Drugs cont.
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Prograf (tacrolimus) prevents rejection of
transplanted organs by inhibiting growth and
proliferation of T lymphocytes
Multiple drug interaction as metabolized by
cytochrome p450
Is a macrolide
Showing promise in preventing liver and
intestinal transplantations
Antibody Preparations
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Prepared in lab or in animals injected with
human lymphoid tissue to stimulate an
immune response
May be monoclonal or polyclonal mixtures of
antibodies (eg IgA, IgD, IgE, IgG, or IgM)
Designed to suppress the specific
components of the immune system that are
causing the damage
Antibody Preparations
Monoclonal antibodies
 Remicade (infliximab) humanized IgG
monoclonal antibody used to treat RA
and Crohn’s. Inhibits cytokine, TNF-alfa,
from binding to its receptors.
 Can cause hypersensitivity reactions
 Can cause infections and
hypersensitivity reactions
Miscellaneous
Immunosuppressants
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Enbrel (etanercept) is a manufactured
TNF receptor binder that prevents it
from binding with normal receptors.
TNF is a cytokine that enhances
leukocyte migration into areas of tissue
injury and induces the production of
other cytokines.
Used to treat RA
Misc. Immunosuppressants
cont.
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Arava (leflunomide) has both
antiproliferative and antiinflammatory
activities
Inhibits the synthesis of pyrimidines,
essential for RNA and DNA synthesis.
Used to treat RA.
Immunosuppressants cont.
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Imuran—be aware of bone marrow
depression
With Sandimmune—closely monitor for s/s of
renal or hepatic compromise, hypertension,
anaphylaxis or CNS toxicity (seizures,
tremors)
Methotrexate—bone marrow depression,
hepatotoxicity and GI disorders
Remicade—infusion reactions, GI upset and
resp. s/s