week 5: Ch. 42 [ Immunostimulants & suppressants] Flashcards by Sasha K.

Immunomodulators either enhance or suppress body’s ability to :

fight infection and disease.

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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)

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Cytokines are substances that help the body mediate and intensify:

the immune response

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*Biologic response modifiers

–Agents to boost specific functions of the immune system
–Natural _____________ made in enough quantity to treat certain disorders

cytokines

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*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

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*Pegylation

–Polyethylene glycol (PEG) bonds to IFN.
–Extends ___________ of the drug for once-weekly dosing

half-life

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Prototype drug: Interferon Alfa-2b (Intron A)

– Therapeutic classification ?
– Pharmacologic classification ?

– Therapeutic classification
▪Immunostimulant

– Pharmacologic classification
▪Interferon
▪Biologic response modifier

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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

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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

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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

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Black box warning for Interferon Alfa-2b (Intron A)

▪IFNs may cause or aggravate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, or infectious disorders

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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

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Drug interactions for Interferon Alfa-2b (Intron A)

▪With Theophylline, levels may increase.
▪May increase hematologic toxicity and cause
immunosuppression

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Interferon Alfa-2b (Intron A) – Treatment of overdose

▪Supportive for lethargy, coma

[reduce lethargy to combat coma]

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Interleukins (ILs) are ___________ synthesized by lymphocytes, monocytes, macrophages, and other cells in response to antigen exposure

cytokines

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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

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Colony-stimulating factors promote production of:

white blood cells.

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For immunostimulants, prototype drug:

Aldesleukin (Proleukin)

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Aldesleukin (Proleukin)

– Therapeutic classification ?
– Pharmacologic classification ?

– Therapeutic classification
▪Immunostimulant

– Pharmacologic classification
▪Interleukin
▪Biologic response modifier

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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

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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

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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

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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

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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

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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

week 5: Ch. 42 [ Immunostimulants & suppressants] Flashcards

(62 cards)