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Pharmacology S1 Exam 5 > Immunomodulation Therapy; L2 (11-11-15) > Flashcards

Immunomodulation Therapy; L2 (11-11-15) Flashcards

1
Q

Glucocorticoids (Prednisone, Prednisolone) - Indications

  • __
  • To prevent __ rejection
  • To prevent __
  • Tx of __-release syndrome
  • Tx of a wide variety of ___ and __ diseases, e.g., RA, SLE, asthma, etc.
A

Glucocorticoids (Prednisone, Prednisolone) - Indications

  • Immunosuppression
  • To prevent graft rejection
  • To prevent GvHD
  • Tx of cytokine-release syndrome
  • Tx of a wide variety of autoimmune and inflammatory diseases, e.g., RA, SLE, asthma, etc.
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2
Q

Glucocorticoids (Prednisone, Prednisolone) - MOA

  • Activates the __ receptor transcription factor
  • Modifies expression of __ and other __regulatory genes
  • Suppresses active __ responses
A

Glucocorticoids (Prednisone, Prednisolone) - MOA

  • Activates the glucocorticoid receptor transcription factor
  • Modifies expression of cytokine and other immunoregulatory genes
  • Suppresses active immune responses
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3
Q

Glucocorticoids (Prednisone, Prednisolone) - Adverse Effects

  • MANY adverse effects
  • __glycemia
  • __tension
  • __lipidemia
  • Obesity
  • Diabetes
  • Poor __ healing
  • Mania and psychosis
  • Increased risk of __
A

Glucocorticoids (Prednisone, Prednisolone) - Adverse Effects

  • MANY adverse effects
  • Hyperglycemia
  • Hypertension
  • Hyperlipidemia
  • Obesity
  • Diabetes
  • Poor wound healing
  • Mania and psychosis
  • Increased risk of infections
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4
Q

Glucocorticoids (Prednisone, Prednisolone) - Misc

  • Glucocorticoid dose should be __ reduced to minimize adverse effects
  • Glucocorticoids should NOT be __ __
A

Glucocorticoids (Prednisone, Prednisolone) - Misc

  • Glucocorticoid dose should be gradually reduced to minimize adverse effects
  • Glucocorticoids should NOT be withdrawn abruptly
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5
Q

Azathioprine - Indications

  • __
  • To prevent __ rejection
  • To prevent __
  • Tx of __ diseases
A

Azathioprine - Indications

  • Immunosuppression
  • To prevent graft rejection
  • To prevent GvHD
  • Tx of autoimmune diseases
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6
Q

Azathioprine - MOA

  • __
  • Converted to _-__ by __
  • Inhibits de novo __ synthesis
  • Incorporated into DNA and causes __ base mispairing -> apoptosis
  • Inhibits __ co-stimulation
A

Azathioprine - MOA

  • Prodrug
  • Converted to 6-MP by HGPRT
  • Inhibits de novo purine synthesis
  • Incorporated into DNA and causes SS base mispairing -> apoptosis
  • Inhibits CD28 co-stimulation
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7
Q

Azathioprine - Adverse Effects

  • __penia/__penia
  • __toxicity
  • Increased risk of __
  • Increased risk of __
A

Azathioprine - Adverse Effects

  • Leukopenia/thrombocytopenia
  • Hepatotoxicity
  • Increased risk of infections
  • Increased risk of malignancy
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8
Q

Azathioprine - Misc

-Interacts with __-__ drugs (__ and __) -> __ [azathioprine] -> increased __

A

Azathioprine - Misc

-Interacts with anti-gout drugs (allopurinol and febuxostat) -> increased [azathioprine] -> increased toxicity

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9
Q

Mycophenolate Mofetil - Indications

  • __
  • To prevent __ rejection
  • To prevent __
  • Tx of __ diseases
A

Mycophenolate Mofetil - Indications

  • Immunosuppression
  • To prevent graft rejection
  • To prevent GvHD
  • Tx of autoimmune diseases
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10
Q

Mycophenolate Mofetil - MOA

  • __
  • Converted to __ __
  • Inhibits __ __ (IMPDH) type II (selectively expressed in __) -> inhibition of __ nucleotide synthesis - no __ pathway in lymphocytes
A

Mycophenolate Mofetil - MOA

  • Prodrug
  • Converted to mycophenolic acid
  • Inhibits inosine monophosphatedehydrogenase (IMPDH) type II (selectively expressed in lymphocytes) -> inhibition of purine nucleotide synthesis - no salvage pathway in lymphocytes
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11
Q

Mycophenolate Mofetil - Adverse Effects

  • __penia/anemia
  • __ (male/female)
  • Increased risk of __
  • Increased risk of __

-RARE - __ __ __ __ __ (PML) - fatal viral disease caused by reactivation of JC virus

A

Mycophenolate Mofetil - Adverse Effects

  • Leukopenia/anemia
  • Teratogenic (male/female)
  • Increased risk of infections
  • Increased risk of malignancy

-RARE - Risk of Progressive Multifocal Leukoencephalopathy (PML) - fatal viral disease caused by reactivation of JC virus

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12
Q

Mycophenolate Mofetil - Misc

-Contraindicated in __, women who wish to __ __, and men who wish to __ __

A

Mycophenolate Mofetil - Misc

-Contraindicated in pregnancy, women who wish to become pregnant, and men who wish to become fathers

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13
Q

Calcineurin Inhibitors (Cyclosporine, Tacrolimus) - Indications

  • __
  • To prevent __ rejection
  • To prevent __
  • Tx of __ diseases
A

Calcineurin Inhibitors (Cyclosporine, Tacrolimus) - Indications

  • Immunosuppression
  • To prevent graft rejection
  • To prevent GvHD
  • Tx of autoimmune diseases
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14
Q

Calcineurin Inhibitors (Cyclosporin, Tacrolimus) - MOA

  • Cyclosporin and tacrolimus bind __ and __, respectively, to form inhibitory complexes
  • __/cyclosporin and __/tacrolimus complexes inhibit the Ca2+-regulated phosphatase, __
  • Inhibition of __ inhibits the activation of the __ transcription factor, which is involved in regulating the expression of IL-__ and multiple other immunoregulatory genes
  • Potently inhibit the T-cell immune response by inhibiting signal __
A

Calcineurin Inhibitors (Cyclosporin, Tacrolimus) - MOA

  • Cyclosporin and tacrolimus bind cyclophilin and FKBP, respectively, to form inhibitory complexes
  • Cyclophilin/cyclosporin and FKBP/tacrolimus complexes inhibit the Ca2+-regulated phosphatase, calcineurin
  • Inhibition of calcineurin inhibits the activation of the NFAT transcription factor, which is involved in regulating the expression of IL-2 and multiple other immunoregulatory genes
  • Potently inhibit the T-cell immune response by inhibiting signal 1
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15
Q

Calcineurin Inhibitors (Cyclosporine, Tacrolimus) - Adverse Effects

  • **__**
  • __tension
  • __toxicity/tremor
  • Glucose intolerance ( __ > __ )
  • Hyperlipidemia ( __ > __ )
  • Hypertrichosis (__)
  • Alopecia (__)
  • Increased risk of __
  • Increased risk of __
A

Calcineurin Inhibitors (Cyclosporine, Tacrolimus) - Adverse Effects

  • **Nephrotoxicity**
  • Hypertension
  • Neurotoxicity/tremor
  • Glucose intolerance ( T > C )
  • Hyperlipidemia ( C > T )
  • Hypertrichosis (C)
  • Alopecia (T)
  • Increased risk of infections
  • Increased risk of malignancy
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16
Q

Calcineurin Inhibitors (Cyclosporine, Tacrolimus) - Misc

  • Metabolized by CYP3A4 -> MANY drug interactions
  • 3A4 inhibitors promote __ drug levels -> increased risk of __
  • 3A4 inducers promote __ drug levels -> increased risk of __ rejection
A

Calcineurin Inhibitors (Cyclosporine, Tacrolimus) - Misc

  • Metabolized by CYP3A4 -> MANY drug interactions
  • 3A4 inhibitors promote increased drug levels -> increased risk of toxicity
  • 3A4 inducers promote decreased drug levels -> increased risk of graft rejection
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17
Q

mTor Inhibitors (Sirolimus, Everolimus) - Indications

  • __
  • To prevent __ rejection (but NOT __, NOT __)
  • To prevent __
  • Included in __ stents to inhibit re__
A

mTor Inhibitors (Sirolimus, Everolimus) - Indications

  • Immunosuppression
  • To prevent graft rejection (NOT lung, NOT liver)
  • To prevent GvHD
  • Included in arterial stents to inhibit restenosis
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18
Q

mTor Inhibitors (Sirolimus, Everolimus) - MOA

  • Drugs form complex with __
  • __/drug complex inhibits IL-__ mediated activation of mTor kinase (T-cell signal __)
  • Inhibits IL-__ stimulated protein synthesis, cell proliferation, and survival
A

mTor Inhibitors (Sirolimus, Everolimus) - MOA

  • Drugs form complex with FKBP
  • FKBP/drug complex inhibits IL-2 mediated activation of mTor kinase (T-cell signal 2)
  • Inhibits IL-2 stimulated protein synthesis, cell proliferation, and survival
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19
Q

mTor Inhibitors (Sirolimus, Everolimus) - Adverse Effects

  • __triglyceridemia
  • __cholesterolemia
  • Increased __ disease
  • Increased risk of __
  • Anemia, thrombocytopenia, and leukopenia
  • Decreased __ healing
  • Teratogenic
  • Increased risk of __
  • Increased risk of __
A

mTor Inhibitors (Sirolimus, Everolimus) - Adverse Effects

  • Hypertriglyceridemia
  • Hypercholesterolemia
  • Increased lung disease
  • Increased risk of diabetes
  • Anemia, thrombocytopenia, and leukopenia
  • Decreased wound healing
  • Teratogenic
  • Increased risk of infections
  • Increased risk of malignancy
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20
Q

mTor Inhibitors (Sirolimus, Everolimus) - Misc

  • Metabolized by __
  • Many drug interactions
  • Contraindicated in __
  • NOT RECOMMENDED in __ transplantation (risk anastomotic dehiscence), __ transplantation (risk __ artery thrombosis)
A

mTor Inhibitors (Sirolimus, Everolimus) - Misc

  • Metabolized by CYP3A4
  • Many drug interactions
  • Contraindicated in pregnancy
  • NOT RECOMMENDED in lung transplantation (risk anastomotic dehiscence), liver transplantation (risk hepatic artery thrombosis)
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21
Q

Rabbit anti-thymocyte globulin - Indications

-Induction __therapy

A

Rabbit anti-thymocyte globulin - Indications

-Induction immunotherapy

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22
Q

Rabbit anti-thymocyte globulin - MOA

  • Rabbit __clonal antibodies specific for human __
  • Depletes __ from the blood
A

Rabbit anti-thymocyte globulin - MOA

  • Rabbit polyclonal antibodies specific for human lymphocytes
  • Depletes lymphocytes from the blood
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23
Q

Rabbit anti-thymocyte globulin - Adverse Effects

  • __ release syndrome
  • __penia
A

Rabbit anti-thymocyte globulin - Adverse Effects

  • Cytokine release syndrome
  • Leukopenia
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24
Q

Alemtuzumab - Indications

-Induction __therapy

A

Alemtuzumab - Indications

-Induction immunotherapy

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25
Q

Alemtuzumab - MOA

  • Binds to CD__ expressed on t-cells, b-cells, macrophages, NK cells, and granulocytes
  • Depletes cells from the blood by __-__ lysis
A

Alemtuzumab - MOA

  • Binds to CD52 expressed on t-cells, b-cells, macrophages, NK cells, and granulocytes
  • Depletes cells from the blood by Ab-mediated lysis
26
Q

Alemtuzumab - Adverse Effects

  • __ release syndrome
  • __penia
  • Can take over ____ for immune system to recover
A

Alemtuzumab - Adverse Effects

  • Cytokine release syndrome
  • Leukopenia
  • Can take over 1 yr for immune system to recover
27
Q

Basiliximab - Indications

-Induction __therapy

A

Basiliximab - Indications

-Induction immunotherapy

28
Q

Basiliximab - MOA

  • Antagonist of the IL-__
  • Blocks __ proliferation
A

Basiliximab - MOA

  • Antagonist of the IL-2R
  • Blocks t-cell proliferation
29
Q

IVIG - Indications

-Provide short-lived __ immunity to patients with deficiency in __ immune system (e.g., hypogammaglobinemia)

A

IVIG - Indications

-Provide short-lived humoral immunity to patients with deficiency in humoral immune system (e.g., hypogammaglobinemia)

30
Q

IVIG - MOA

  • Pooled __ from healthy individuals
  • Provides patient with __ from healthy immunized donors to provide immunity to common pathogens
A

IVIG - MOA

  • Pooled Ig from healthy individuals
  • Provides patient with Ig from healthy immunized donors to provide immunity to common pathogens
31
Q

Rho (D) - Indications

-Prevention of __ disease of the newborn in newborns born to __ females

A

Rho (D) - Indications

-Prevention of hemolytic disease of the newborn in newborns born to Rh- females

32
Q

Rho (D) - MOA

  • Purified Ig to ____ antigen
  • Given to __ mother at 28 weeks and 72 hours post-pregnancy to deplete any fetal __ in maternal blood, to prevent the mother from generating an __ response to fetal __
A

Rho (D) - MOA

  • Purified Ig to Rh (D) antigen
  • Given to Rh- mother at 28 weeks and 72 hours post-pregnancy to deplete any fetal RBC in maternal blood, to prevent the mother from generating an immune response to fetal RBC
33
Q

Hyperimmune Ig - Indications

-To provide rapid specific __ immunity to specific viruses and/or toxins

A

Hyperimmune Ig - Indications

-To provide rapid specific antibody immunity to specific viruses and/or toxins

34
Q

Hyperimmune Ig - MOA

  • Purified __ to specific antigens purified from healthy volunteers
  • Given __ to patients in order to promote clearance of virus/toxin
A

Hyperimmune Ig - MOA

  • Purified Ig to specific antigens purified from healthy volunteers
  • Given IV to patients in order to promote clearance of virus/toxin
35
Q

Ipilimumab - Indications

-Tx of late-stage __

A

Ipilimumab - Indications

-Tx of late-stage melanoma

36
Q

Ipilimumab - MOA

  • Antibody specific for __
  • Antagonizes the negative regulatory __ protein responsible for down-regulating activated __
  • Enhances __ response
A

Ipilimumab - MOA

  • Antibody specific for CTLA4
  • Antagonizes the negative regulatory CTLA4 protein responsible for down-regulating activated T-cells
  • Enhances T-cell response
37
Q

Ipilimumab - Adverse Effects

-Potential for __ autoimmune response (can be fatal)

A

Ipilimumab - Adverse Effects

-Potential for RARE autoimmune response (can be fatal)

38
Q

Pembrolizumab/Nivolumab - Indications

-Tx of late-stage __

A

Pembrolizumab/Nivolumab - Indications

-Tx of late-stage melanoma

39
Q

Pembrolizumab/Nivolumab - MOA

  • Antibody specific for the __ protein, which is a __ regulatory receptor expressed on activated __ that is responsible for down-regulating __ responses
  • The __ ligand __ is expressed on __ cells - this is a mechanism for __ cells to avoid the immune response
  • These antibody drugs block __/__ interactions, blocking the inhibitory signal and leading to enhanced __ immune responses
A

Pembrolizumab/Nivolumab - MOA

  • Antibody specific for the PD1 protein, which is a negative regulatory receptor expressed on activated t-cells that is responsible for down-regulating t-cell responses
  • The PD1 ligand PD-L1 is expressed on tumor cells - this is a mechanism for tumor cells to avoid the immune response
  • These antibody drugs block PD1/PD1-L1 interactions, blocking the inhibitory signal and leading to enhanced tumor immune responses
40
Q

Methotrexate - Indications

-Tx of autoimmune diseases - especially __ __

A

Methotrexate - Indications

-Tx of autoimmune diseases - especially rheumatoid arthritis

41
Q

Methotrexate - MOA

  • Inhibition of __ __ to inhibit __ proliferation
  • __ mechanism of immunosuppression
A

Methotrexate - MOA

  • Inhibition of dihydrofolate reductase to inhibit lymphocyte proliferation
  • Indirect mechanism of immunosuppression
42
Q

Methotrexate - Adverse Effects

  • __ toxicity
  • __ toxicity
  • __ toxicity
  • __ disease
  • __ suppression
  • __toxicity
  • __genic
A

Methotrexate - Adverse Effects

  • Renal toxicity
  • Hepatic toxicity
  • GI toxicity
  • Lung disease
  • BM suppression
  • Neurotoxicity
  • Teratogenic
43
Q

Methotrexate - Misc

-Contraindicated in __

A

Methotrexate - Misc

-Contraindicated in pregnancy

44
Q

Cyclophophamide - Indications

  • To prevent __ rejection
  • To prevent __
  • Tx of __ cases of autoimmune disease
A

Cyclophophamide - Indications

  • To prevent graft rejection
  • To prevent GvHD
  • Tx of severe cases of autoimmune disease
45
Q

Cyclophophamide - MOA

  • __ chemotherapeutic agent
  • ____ DNA, RNA, and proteins
  • Inhibits __ proliferation
  • Promotes __
A

Cyclophophamide - MOA

  • Alkylation chemotherapeutic agent
  • Cross-links DNA, RNA, and proteins
  • Inhibits cell proliferation
  • Promotes apoptosis
46
Q

Cyclophophamide - Adverse Effects

  • __ suppression
  • __ toxicity
  • Increased risk of __
  • Increased risk of __
  • __genic (male/female)
A

Cyclophophamide - Adverse Effects

  • BM suppression
  • GI toxicity
  • Increased risk of infections
  • Increased risk of malignancy
  • Teratogenic (male/female)
47
Q

Cyclophophamide - Misc

-Contraindicated in __, women who wish to __ __, and men who wish to __ __

A

Cyclophophamide - Misc

-Contraindicated in pregnancy, women who wish to become pregnant, and men who wish to become fathers

48
Q

Chlorambucil - Indications

-Sometimes used in the tx of __ diseases

A

Chlorambucil - Indications

-Sometimes used in the tx of autoimmune diseases

49
Q

Chlorambucil - MOA

  • __ chemotherapeutic agent
  • ____ DNA, RNA, and proteins
  • Inhibits __ proliferation
  • Promotes __
A

Chlorambucil - MOA

  • Alkylation chemotherapeutic agent
  • Cross-links DNA, RNA, and proteins
  • Inhibits cell proliferation
  • Promotes apoptosis
50
Q

Chlorambucil - Adverse Effects

  • __ suppression
  • __ toxicity
  • Increased risk of __
  • Increased risk of __
  • __genic (male/female)
A

Chlorambucil - Adverse Effects

  • BM suppression
  • GI toxicity
  • Increased risk of infections
  • Increased risk of malignancy
  • Teratogenic (male/female)
51
Q

Chlorambucil - Misc

-Contraindicated in __, women who wish to __ __, and men who wish to __ __

A

Chlorambucil - Misc

-Contraindicated in pregnancy, women who wish to become pregnant, and men who wish to become fathers

52
Q

Fingolimod - Indications

-Tx of relapsing-remitting __ __

A

Fingolimod - Indications

-Tx of relapsing-remitting multiple sclerosis

53
Q

Fingolimod - MOA

  • __ analog
  • Binds to 51P receptor to promote sequestration of __ in the lymph node, thereby preventing __ entry to CNS
A

Fingolimod - MOA

  • Sphingosine analog
  • Binds to 51P receptor to promote sequestration of lymphocytes in the lymph node, thereby preventing lymphocyte entry to CNS
54
Q

Fingolimod - Adverse Effects

  • __arrhythmia
  • __ __
  • Increased risk of __ __ __ infection (potentially fatal)
  • Increased risk of __
A

Fingolimod - Adverse Effects

  • Bradyarrhythmia
  • AV block
  • Increased risk of varicella zoster virus infection (potentially fatal)
  • Increased risk of malignancy
55
Q

Natalizumab - Indications

-Tx of relapsing-remitting __ __

A

Natalizumab - Indications

-Tx of relapsing-remitting multiple sclerosis

56
Q

Natalizumab - MOA

  • Binds __ __ adhesion molecule
  • Prevents entry of __ into the CNS
A

Natalizumab - MOA

  • Binds alpha4 integrin adhesion molecule
  • Prevents entry of lymphocytes into the CNS
57
Q

Natalizumab - Adverse Effects

-Increased risk of __ - especially if: a) prior use of immunosuppression, b) seropositive for __ virus, c) chronic treatment

A

Natalizumab - Adverse Effects

-Increased risk of PML - especially if: a) prior use of immunosuppression, b) seropositive for JC virus, c) chronic treatment

58
Q

Interferon beta - Indications

-Tx of relapsing-remitting __ __

A

Interferon beta - Indications

-Tx of relapsing-remitting multiple sclerosis

59
Q

Interferon beta - MOA

  • Activates __ beta receptors
  • Alters expression of __ gene expression
  • Inhibits entry of __ cells into CNS
A

Interferon beta - MOA

  • Activates IFN beta receptors
  • Alters expression of pro-inflammatory gene expression
  • Inhibits entry of inflammatory cells into CNS
60
Q

Glatiramer acetate - Indications

-Tx of relapsing-remitting __ __

A

Glatiramer acetate - Indications

-Tx of relapsing-remitting multiple sclerosis

61
Q

Glatiramer acetate - MOA

  • Polymer of 4 amino acids found in __ __ __ (MBP)
  • Production of specific suppressor __ that suppress inflammation in the __
A

Glatiramer acetate - MOA

  • Polymer of 4 amino acids found in myelin basic protein (MBP)
  • Production of specific suppressor T-cells that suppress inflammation in the CNS
62
Q

Drugs covered in this lecture

  • Glucocorticoids/steroids: __/__
  • Proliferation inhibitors and anti-metabolites: __, __ __
  • Immunophilin-binding drugs - inhibitors of t-cell signaling pathways: calcineurin inhibitors (__, __), mTOR inhibitors (__, __)
  • Other anti-proliferative drugs used for immunosuppression: __, __, __

-Antibodies for induction immunosuppression: __ __ __-__ __, __, __

  • Misc immunosuppressive drugs used in the tx of RR-multiple sclerosis: __, __, __, __
  • Passive immunization IG: __, __, __
  • Immune checkpoint inhibitors: __, __ and __
A

Drugs covered in this lecture

  • Glucocorticoids/steroids: prednisone/prednisolone
  • Proliferation inhibitors and anti-metabolites: azathioprine, mycophenolate mofetil
  • Immunophilin-binding drugs - inhibitors of t-cell signaling pathways: calcineurin inhibitors (cyclosporin, tacrolimus), mTOR inhibitors (sirolimus, everolimus)
  • Other anti-proliferative drugs used for immunosuppression: methotrexate, cyclophosphamide, chlorambucil

-Antibodies for induction immunosuppression: rabbit polyclonal anti-thymocyte globulin, alemetzumab, basiliximab

  • Misc immunosuppressive drugs used in the tx of RR-multiple sclerosis: fingolimod, natalizumab, interferon, glatiramer
  • Passive immunization IG: IVIG, Rho(D) Ig, Hyperimmune Ig
  • Immune checkpoint inhibitors: ipilimumab, nivolumab and pembrozilmab

Pharmacology S1 Exam 5 (5 decks)

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