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

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

1
Q

Immunomodulators either enhance or suppress body’s ability to :

A

fight infection and disease.

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2
Q

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)

A

–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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3
Q

Cytokines are substances that help the body mediate and intensify:

A

the immune response

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4
Q

*Biologic response modifiers

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

A

cytokines

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5
Q

*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 :

A

protective antiviral proteins

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6
Q

*Pegylation

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

A

half-life

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7
Q
  • Prototype drug: Interferon Alfa-2b (Intron A)

– Therapeutic classification ?
– Pharmacologic classification ?

A

– Therapeutic classification
▪Immunostimulant

– Pharmacologic classification
▪Interferon
▪Biologic response modifier

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8
Q

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

A

▪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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9
Q

Mechanism of action of Interferon Alfa-2b (Intron A)

▪Increases _______________________ of macrophages andmonocytes

▪Suppresses growth of _________________

A

▪Increases phagocytic activity of macrophages and monocytes

▪Suppresses growth of cancer cells

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10
Q

Adverse effects of Interferon Alfa-2b (Intron A)

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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11
Q

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

A

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

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12
Q

Contraindications/precautions for Interferon Alfa-2b (Intron A)

A

▪Hypersensitivity to IFNs
▪Autoimmune hepatitis or hepatic decompensation
▪Neonates or infants
▪Cardiac disease
▪Herpes zoster
▪Recent exposure to chickenpox

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13
Q

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

A

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

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14
Q

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

A

▪Supportive for lethargy, coma

[reduce lethargy to combat coma]

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15
Q

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

A

cytokines

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16
Q

Interleukins (ILs) mechanisms of action:

A
▪Stimulate ________________ activity
▪Activate increased production of ____ cells
▪Increase B-cell and_________ production
▪Increase neutrophil chemotaxis
▪Promote inflammation

A

▪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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17
Q

Colony-stimulating factors promote production of:

A

white blood cells.

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18
Q

For immunostimulants, prototype drug:

A

Aldesleukin (Proleukin)

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19
Q

Aldesleukin (Proleukin)

– Therapeutic classification ?
– Pharmacologic classification ?

A

– Therapeutic classification
▪Immunostimulant

– Pharmacologic classification
▪Interleukin
▪Biologic response modifier

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20
Q

Aldesleukin (Proleukin)
Therapeutic effects and uses:

A

▪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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21
Q

Aldesleukin (Proleukin)
– Mechanism of action
▪Activates :
▪Promotes proliferation of :

A

▪Activates IFNs, TNF, and other ILs
▪Promotes proliferation of B cells, T cells,
macrophages, NK cells

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22
Q

Aldesleukin (Proleukin)

Adverse effects

A

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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23
Q

Contraindications/precautions with Aldesleukin (Proleukin)

A

▪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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24
Q

Drug interactions with Aldesleukin (Proleukin)

A

▪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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25
Q

Treatment of overdose with Aldesleukin (Proleukin)

A

Dexamethasone

26
Q

Immunosuppressants Inhibit :
Prevent:
Treat:

A

inhibit immune response
prevent transplant rejection
and autoimmune disorder treatment

27
Q

An immunosuppressant is used to prevent Transplant rejection- a response wherein ___________ destroy transplanted tissue within
48 hours after a transplant

A

antibodies

28
Q

Sometimes, chronic transplant rejection may occur ___________________ after surgery.

A

months or years

29
Q

Autoimmune disorders: body creates ____________ against normal tissue and the body attacks own cells as if they are foreign > this results in tissue injury

A

antibodies

30
Q

Autoimmune disorder examples:

A

Hashimoto’s thyroiditis, RA, SLE, and myasthenia gravis

31
Q

Immunosuppressed patients are susceptible to __________ from viral, bacterial, fungal, and protozoan pathogens.

A

infection

32
Q

Classification of immunosuppressant drugs:
[4]

A

▪Calcineurin inhibitors
▪Cytotoxic drugs & antimetabolites
▪Antibodies
▪Corticosteroids (glucocorticoids)

33
Q

Calcineurin: enzyme that acts as an :

A

intracellular messenger

  • Tell T cells to synthesize IL-2
    –Suppresses immune response
34
Q

Calcineurin Inhibitors are preferred drugs for prophylaxis of :

A

transplant rejection

35
Q

Cyclosporine and tacrolimus are ___________ inhibitors.

A

calcineurin

36
Q

Prototype drug: Cyclosporine (Gengraf, Neoral, Sandimmune)

– Therapeutic classification ?
– Pharmacologic classification ?

A

– Therapeutic classification
▪Immunosuppressant

– Pharmacologic classification
▪Calcineurin inhibitor

37
Q

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.

A

▪Prophylaxis of kidney, heart, and liver transplant rejection
▪Psoriasis
▪Xerophthalmia
▪Off-label uses include a number of autoimmune and inflammatory conditions.

38
Q

Mechanism of action of Cyclosporine (Gengraf, Neoral, Sandimmune)

▪Inhibits function of _____________

▪Diminishes activity of ___________________ and suppresses immune response

A

▪Inhibits function of calcineurin

▪Diminishes activity of T cells and B cells and suppresses immune response

39
Q

Adverse effects of Cyclosporine (Gengraf, Neoral, Sandimmune)

A

▪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.

40
Q

Contraindications/precautions with Cyclosporine (Gengraf, Neoral, Sandimmune)

▪Preexisting _____
▪______________ or lactation
▪Avoid direct exposure to the ______
▪Chronic kidney disease
▪Hepatic or biliary impairment

A

▪Preexisting HTN
▪Pregnancy or lactation
▪Avoid direct exposure to the sun
▪Chronic kidney disease
▪Hepatic or biliary impairment

41
Q

Drug interactions with Cyclosporine (Gengraf, Neoral, Sandimmune)

A

▪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

42
Q

Cyclosporine (Gengraf, Neoral, Sandimmune): overdose treatment

A

Supportive for nephrotoxicity, hepatotoxicity

43
Q

Cytotoxic drugs and antimetabolites work by various mechanisms

▪Some block replication of DNA, others inhibit:

A

protein synthesis

44
Q

Cytotoxic drugs and antimetabolites have same general indications and adverse effects as:

A

calcineurin inhibitors

45
Q

Prototype drug: Azathioprine (Azasan, Imuran)

– Therapeutic classification ?
– Pharmacologic classification ?

A

– Therapeutic classification
▪Immunosuppressant

– Pharmacologic classification
▪Cytotoxic drug

46
Q

Therapeutic effects and uses of Azathioprine (Azasan, Imuran)

A

▪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

47
Q

Mechanism of action of Azathioprine (Azasan, Imuran)

A

▪Inhibits DNA synthesis
–DNA damage and chromosome breakage

▪Metabolized in liver to mercaptopurine

48
Q

Adverse effects of Azathioprine (Azasan, Imuran)

A

▪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

49
Q

Contraindications/precautions with Azathioprine (Azasan, Imuran)

A

▪Pregnancy and lactation
▪Preexisting hematologic disease or hepatic
impairment

50
Q

Drug interactions with Azathioprine (Azasan, Imuran)

A

▪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

51
Q

Treatment of overdose with Azathioprine (Azasan, Imuran)

A

Hemodialysis

52
Q

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 __________________

A

–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

53
Q

Prototype drug: Basiliximab (Simulect)

– Therapeutic classification ?
– Pharmacologic classification ?

A

– Therapeutic classification
▪Immunosuppressant

– Pharmacologic classification
▪Monoclonal antibody

54
Q

Therapeutic effects and uses of Basiliximab (Simulect)

A

Prophylaxis of acute kidney transplant rejection

55
Q

Mechanism of action of Basiliximab (Simulect)

A

Prevents binding of IL-2 to CD25 on surface of activated T cells

56
Q

Adverse effects of Basiliximab (Simulect)

A

– 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.

57
Q

Basiliximab (Simulect)
– Contraindications/precautions
– Drug interactions
- overdose?

A

– 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]

58
Q

Corticosteroids: used as immunosuppressants but have significant __________ __________ effects

A

longterm adverse

59
Q

Corticosteroids
▪Lymphocte effect ?
▪Monocyte effect ?
▪Neutrophil effect ?
▪Other effects ?

A

▪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

60
Q

Corticosteroids: Preferred drugs for _____________ therapy of severe inflammation

A

short-term

61
Q

Corticosteroids- Common drugs:

A

▪Prednisone
▪Methylprednisolone

62
Q

Long-term adverse effects of Corticosteroids

A

▪Osteoporosis
▪Cataract formation
▪Mental status changes
▪Fluid and salt retention
▪HTN
▪Hyperglycemia
▪Obesity
▪Adrenal atrophy

Pharmacology (18 decks)

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