week 5: Ch. 42 [ Immunostimulants & suppressants] Flashcards
Immunomodulators either enhance or suppress body’s ability to :
fight infection and disease.
Immunostimulants VS Immunosuppressants
–Immunostimulants
▪Increase immune system’s ability to __________________________________
▪Usually used to treat patients with ___________
–Immunosuppressants
▪Diminish immune system’s ability to _____________________
▪Usually used to prevent ________________________ and dampen hyperactive immune responses (e.g., SLE or RA)
–Immunostimulants
▪Increase immune system’s ability to fight infection and disease
▪Usually used to treat patients with cancer
–Immunosuppressants
▪Diminish immune system’s ability to fight infection and disease
▪Usually used to prevent transplant rejection and dampen hyperactive immune responses (e.g., SLE or RA)
Cytokines are substances that help the body mediate and intensify:
the immune response
*Biologic response modifiers
–Agents to boost specific functions of the immune system
–Natural _____________ made in enough quantity to treat certain disorders
cytokines
*Interferons (IFNs)
–Have antineoplastic and anti-inflammatory properties
–Unable to protect infected cell
–Warn surrounding cells that a viral infection has occurred
They attach to nearby uninfected cells and induce production of :
protective antiviral proteins
*Pegylation
–Polyethylene glycol (PEG) bonds to IFN.
–Extends ___________ of the drug for once-weekly dosing
half-life
- Prototype drug: Interferon Alfa-2b (Intron A)
– Therapeutic classification ?
– Pharmacologic classification ?
– Therapeutic classification
▪Immunostimulant
– Pharmacologic classification
▪Interferon
▪Biologic response modifier
Interferon Alfa-2b (Intron A)
Therapeutic effects and uses:
▪____________ conditions
▪______ infections
▪Intralesional treatment of condylomata acuminate
▪Chronic myelogenous leukemia
▪Bladder and renal cell cancer
▪Herpes simplex virus
▪Multiple myeloma
▪Human immunodeficiency virus (HIV)
▪Varicella-zoster virus (VZV)
▪West Nile virus
▪Neoplastic conditions
▪Viral infections
▪Intralesional treatment of condylomata acuminate
▪Chronic myelogenous leukemia
▪Bladder and renal cell cancer
▪Herpes simplex virus
▪Multiple myeloma
▪Human immunodeficiency virus (HIV)
▪Varicella-zoster virus (VZV)
▪West Nile virus
Mechanism of action of Interferon Alfa-2b (Intron A)
▪Increases _______________________ of macrophages andmonocytes
▪Suppresses growth of _________________
▪Increases phagocytic activity of macrophages and monocytes
▪Suppresses growth of cancer cells
Adverse effects of Interferon Alfa-2b (Intron A)
– Adverse effects
▪Flulike syndrome of fever, chills, dizziness, weight
loss, and fatigue
▪Headache, nausea, vomiting, diarrhea, and anorexia
▪Hair loss
▪Depression and suicidal ideation
– Serious adverse effects
▪Immunosuppression
▪Hepatotoxicity
▪Neurotoxicity
Black box warning for Interferon Alfa-2b (Intron A)
▪IFNs may cause or aggravate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, or infectious disorders
Contraindications/precautions for Interferon Alfa-2b (Intron A)
▪Hypersensitivity to IFNs
▪Autoimmune hepatitis or hepatic decompensation
▪Neonates or infants
▪Cardiac disease
▪Herpes zoster
▪Recent exposure to chickenpox
Drug interactions for Interferon Alfa-2b (Intron A)
▪With Theophylline, levels may increase.
▪May increase hematologic toxicity and cause
immunosuppression
Interferon Alfa-2b (Intron A) – Treatment of overdose
▪Supportive for lethargy, coma
[reduce lethargy to combat coma]
Interleukins (ILs) are ___________ synthesized by lymphocytes, monocytes, macrophages, and other cells in response to antigen exposure
cytokines
Interleukins (ILs) mechanisms of action:
A
▪Stimulate ________________ activity
▪Activate increased production of ____ cells
▪Increase B-cell and_________ production
▪Increase neutrophil chemotaxis
▪Promote inflammation
▪Stimulate cytotoxic T-cell activity
▪Activate increased production of NK cells
▪Increase B-cell and plasma production
▪Increase neutrophil chemotaxis
▪Promote inflammation
Colony-stimulating factors promote production of:
white blood cells.
For immunostimulants, prototype drug:
Aldesleukin (Proleukin)
Aldesleukin (Proleukin)
– Therapeutic classification ?
– Pharmacologic classification ?
– Therapeutic classification
▪Immunostimulant
– Pharmacologic classification
▪Interleukin
▪Biologic response modifier
Aldesleukin (Proleukin)
Therapeutic effects and uses:
▪Metastatic renal cell carcinoma
▪Metastatic malignant melanoma
▪Chemotherapy of non-Hodgkin’s lymphoma and
acute myelogenous leukemia
▪Off-label use for leprosy
Aldesleukin (Proleukin)
– Mechanism of action
▪Activates :
▪Promotes proliferation of :
▪Activates IFNs, TNF, and other ILs
▪Promotes proliferation of B cells, T cells,
macrophages, NK cells
Aldesleukin (Proleukin)
Adverse effects
Many effects caused by Capillary Leak Syndrome
▪Flulike symptoms occur frequently
▪Diarrhea, nausea, or vomiting
▪Confusion, drowsiness, oliguria, stomatitis,
anorexia, hyperbilirubinemia, and hypothyroidism
▪Hepatic enzymes
▪Weight gain
▪Dyspnea
▪Pulmonary congestion
▪Common changes in the blood values
– Thrombocytopenia, anemia & leukopenia
– Serious adverse effects
▪Hypotension
▪Tachycardia and other dysrhythmias
Contraindications/precautions with Aldesleukin (Proleukin)
▪Significant cardiac, central nervous system
(CNS), pulmonary, renal, or hepatic impairment
▪Seizures in epileptic patients
▪May worsen autoimmune disease, including
scleroderma, RA, diabetes mellitus, and thyroiditis
Drug interactions with Aldesleukin (Proleukin)
▪Mood disturbances/drowsiness with antianxiety drugs, opioids, sedatives, or antipsychotic meds
▪Additive organ damage with hepatotoxic or
nephrotoxic drugs
▪Increased risk of bleeding w/ drugs that modify
coagulation & platelet inhibitors
▪Additive hypotension with concurrent use with
antihypertensive drugs
Treatment of overdose with Aldesleukin (Proleukin)
Dexamethasone
Immunosuppressants Inhibit :
Prevent:
Treat:
inhibit immune response
prevent transplant rejection
and autoimmune disorder treatment
An immunosuppressant is used to prevent Transplant rejection- a response wherein ___________ destroy transplanted tissue within
48 hours after a transplant
antibodies
Sometimes, chronic transplant rejection may occur ___________________ after surgery.
months or years
Autoimmune disorders: body creates ____________ against normal tissue and the body attacks own cells as if they are foreign > this results in tissue injury
antibodies
Autoimmune disorder examples:
Hashimoto’s thyroiditis, RA, SLE, and myasthenia gravis
Immunosuppressed patients are susceptible to __________ from viral, bacterial, fungal, and protozoan pathogens.
infection
Classification of immunosuppressant drugs:
[4]
▪Calcineurin inhibitors
▪Cytotoxic drugs & antimetabolites
▪Antibodies
▪Corticosteroids (glucocorticoids)
Calcineurin: enzyme that acts as an :
intracellular messenger
- Tell T cells to synthesize IL-2
–Suppresses immune response
Calcineurin Inhibitors are preferred drugs for prophylaxis of :
transplant rejection
Cyclosporine and tacrolimus are ___________ inhibitors.
calcineurin
Prototype drug: Cyclosporine (Gengraf, Neoral, Sandimmune)
– Therapeutic classification ?
– Pharmacologic classification ?
– Therapeutic classification
▪Immunosuppressant
– Pharmacologic classification
▪Calcineurin inhibitor
Therapeutic effects and uses of Cyclosporine (Gengraf, Neoral, Sandimmune)
▪____________ of kidney, heart, and liver transplant rejection
▪Psoriasis
▪Xerophthalmia
▪___________ uses include a number of autoimmune and inflammatory conditions.
▪Prophylaxis of kidney, heart, and liver transplant rejection
▪Psoriasis
▪Xerophthalmia
▪Off-label uses include a number of autoimmune and inflammatory conditions.
Mechanism of action of Cyclosporine (Gengraf, Neoral, Sandimmune)
▪Inhibits function of _____________
▪Diminishes activity of ___________________ and suppresses immune response
▪Inhibits function of calcineurin
▪Diminishes activity of T cells and B cells and suppresses immune response
Adverse effects of Cyclosporine (Gengraf, Neoral, Sandimmune)
▪Nephrotoxicity –Reduced urine flow
▪HTN
▪Tremor
▪Hirsutism [excessive facial hair growth]
▪Elevated hepatic enzymes, headache, and
gingival hyperplasia
▪Decreased leukocytes
– Black box warnings [take at hospital only]
▪May result in serious infections
▪Kidney damage may occur.
Contraindications/precautions with Cyclosporine (Gengraf, Neoral, Sandimmune)
▪Preexisting _____
▪______________ or lactation
▪Avoid direct exposure to the ______
▪Chronic kidney disease
▪Hepatic or biliary impairment
▪Preexisting HTN
▪Pregnancy or lactation
▪Avoid direct exposure to the sun
▪Chronic kidney disease
▪Hepatic or biliary impairment
Drug interactions with Cyclosporine (Gengraf, Neoral, Sandimmune)
▪Phenytoin, phenobarbital, carbamazepine, and
rifampin may decrease drug level.
▪May interact with drugs that inhibit or induce
CYP3A4
▪Increased drug level with macrolide antibiotics
▪Adjustment of doses of antihypertensives
▪Avoid potassium-sparing diuretics = causes
hyperkalemia
▪Give with caution with other nephrotoxic drugs
▪Myopathy or rhabdomyolysis can occur with concurrent use with statins.
▪Herbal/food
–Grapefruit juice can raise drug level by 50%-200%.
–Astragalus and echinacea may interfere with drug
action
Cyclosporine (Gengraf, Neoral, Sandimmune): overdose treatment
Supportive for nephrotoxicity, hepatotoxicity
Cytotoxic drugs and antimetabolites work by various mechanisms
▪Some block replication of DNA, others inhibit:
protein synthesis
Cytotoxic drugs and antimetabolites have same general indications and adverse effects as:
calcineurin inhibitors
Prototype drug: Azathioprine (Azasan, Imuran)
– Therapeutic classification ?
– Pharmacologic classification ?
– Therapeutic classification
▪Immunosuppressant
– Pharmacologic classification
▪Cytotoxic drug
Therapeutic effects and uses of Azathioprine (Azasan, Imuran)
▪Prophylaxis of kidney transplant rejection
▪Treatment of severe RA
▪Off-label: other inflammatory disorders such as UC, Crohn’s disease, autoimmune hepatiti, myasthenia gravis, SLE
Mechanism of action of Azathioprine (Azasan, Imuran)
▪Inhibits DNA synthesis
–DNA damage and chromosome breakage
▪Metabolized in liver to mercaptopurine
Adverse effects of Azathioprine (Azasan, Imuran)
▪Bone marrow suppression
▪Serious infections
▪Hepatotoxicity
▪Skin and lymphoid malignancies
– Black box warning
▪May result in serious or fatal infections and
possible malignancies
▪Complete blood counts (CBCs) monitored during
therapy
Contraindications/precautions with Azathioprine (Azasan, Imuran)
▪Pregnancy and lactation
▪Preexisting hematologic disease or hepatic
impairment
Drug interactions with Azathioprine (Azasan, Imuran)
▪Other immunosuppressants (additive effect)
▪Concurrent use with allopurinol can lead to
hematologic toxicity.
▪Concurrent use with angiotensin-converting
enzyme (ACE) inhibitors can lead to anemia and
severe leukopenia
Treatment of overdose with Azathioprine (Azasan, Imuran)
Hemodialysis
Polyclonal antibodies VS Monoclonal antibodies (MABs)
–Polyclonal antibodies
▪Contain a wide mixture of different __________
▪Used to prevent transplant rejection, ______________
disorders, malignancies
–Monoclonal antibodies (MABs)
▪Harvested from antibodies produced by a _____________ cell
▪Very specific, targeting a single type of target __________________
–Polyclonal antibodies
▪Contain a wide mixture of different antibodies
▪Used to prevent transplant rejection, autoimmune
disorders, malignancies
–Monoclonal antibodies (MABs)
▪Harvested from antibodies produced by a single B
cell
▪Very specific, targeting a single type of target cell
or receptor
Prototype drug: Basiliximab (Simulect)
– Therapeutic classification ?
– Pharmacologic classification ?
– Therapeutic classification
▪Immunosuppressant
– Pharmacologic classification
▪Monoclonal antibody
Therapeutic effects and uses of Basiliximab (Simulect)
Prophylaxis of acute kidney transplant rejection
Mechanism of action of Basiliximab (Simulect)
Prevents binding of IL-2 to CD25 on surface of activated T cells
Adverse effects of Basiliximab (Simulect)
– Adverse effects
▪Nausea
▪Vomiting
▪Abdominal pain
▪Diarrhea
– Serious adverse effects
▪Anaphylaxis
– Black box warning
▪should only be used by healthcare providers experienced in immunosuppressive therapy.
Basiliximab (Simulect)
– Contraindications/precautions
– Drug interactions
- overdose?
– Contraindications/precautions
▪Hypersensitivity
– Drug interactions
▪Does not interact significantly with major drugs
used in transplant medicine
▪Caution when administering multiple drugs that
suppress immune function
[overdose rare, only 2 doses]
Corticosteroids: used as immunosuppressants but have significant __________ __________ effects
longterm adverse
Corticosteroids
▪Lymphocte effect ?
▪Monocyte effect ?
▪Neutrophil effect ?
▪Other effects ?
▪Lymphocyte effect –Reduces circulating lymphocytes
▪Monocyte effect –Depletes body of monocytes and macrophages
▪Neutrophil effect –Causes neutrophils to move from bone marrow to general circulation
▪Other effects –Blocks production of prostaglandins and ILs
Corticosteroids: Preferred drugs for _____________ therapy of severe inflammation
short-term
Corticosteroids- Common drugs:
▪Prednisone
▪Methylprednisolone
Long-term adverse effects of Corticosteroids
▪Osteoporosis
▪Cataract formation
▪Mental status changes
▪Fluid and salt retention
▪HTN
▪Hyperglycemia
▪Obesity
▪Adrenal atrophy
