Lecture 1 and 2: Immunopharmacology Flashcards by Katlyn Heneghan

What are three possible long-term effects that are associated with corticosteroids (prednisone, methylprednisolone, dexamethasone)?

1) Iatrogenic Cushing’s Syndrome
2) Osteoporosis Infections
3) Ulcers

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How do corticosteroids affect the concentration of neutrophils (PMN’s)?

How do corticosteroids affect the concentration of lymphocytes (T and B cells), monocytes, eosinophils, and basophils?

Corticosteroids
- Increase concentration of PMN’s

Decrease concentration of lymphocytes (T and B cells), monocytes, eosinophils, and basophils in peripheral blood

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How do corticosteroids affect the functions of leukocytes and tissue macrophages?

1) Reduce response to antigens and mitogens
2) Reduce production of IL-1, IL-2, and TNF-a

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Corticosteroids inhibit which two enzymes?

PLA2 (inhibition results in lower prostaglandin and leukotriene synthesis)

and

COX-2 (inhibition results in lower prostaglandin formation)

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How do corticosteroids affect vasoconstriction, complement effects, and antibody production?

Vasoconstriction: Increase, thereby reducing capillary permeability

Complement: Inhibit

Ab production: Reduce

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True or False: The adverse effects associated with glucocorticoid therapy include: adrenal suppression, dyslipidemia, glucose intolerance, and increased bacterial and mycotic infections

True

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Which four conditions can be treated with corticosteroids?

1) Allergic disorders
2) Hematological disorders
3) Hepatic and renal disorders
4) Collagen disorders

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Which of the following corticosteroids are long-acting and can be administered orally, IV, or IM?
A. Prednisone
B. Dexamethasone
C. Methylprednisolone

B. Dexamethasone

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Which four drugs are cytotoxic and anti-proliferative agents (T and B cells)?

1) Cyclophosphamide
2) Azathioprine
3) Methotrexate
4) Mycophenolate Mofetil

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True or False: Methotrexate is nitrogen gas while Mycophenolate Mofetil is a purine analog

False - Cyclophosphamide is nitrogen gas while Azathioprine is a purine analog

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Which four drugs are Signal 3 Inhibitors?

Cyclophosphamide
Mycophenolate Mofetil
Methotrexate
Azathioprine

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Which of the following cytotoxic and anti-proliferative agents preferentially inhibits T cells over B cells?
A. Cyclophosphamide
B. Methotrexate
C. Mycophenolate Mofetil
D. Azathioprine

D. Azathioprine

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Which of the following cytotoxic and anti-proliferative agents is used to treat cancers (malignant diseases) as well as RA and RA-like conditions?
A. Cyclophosphamide
B. Methotrexate
C. Mycophenolate Mofetil
D. Azathioprine

A. Cyclophosphamide

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____ is a cell cycle-nonspecific alkylating agent that inhibits nucleotide synthesis while ____ is a cell cycle specific (s phase!) anti-metabolite that inhibits nucleotide synthesis

Cyclophosphamide ; Azathioprine

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Which of the following requires metabolic activation by cytochrome P450, where it is activated to alkylating metabolites?
A. Cyclophosphamide
B. Methotrexate
C. Mycophenolate Mofetil
D. Azathioprine

A. Cyclophosphamide

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True or False: Azathioprine inhibits adenosine deaminase, thereby inhibiting the production of adenosine MP

True

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Which of the following can be used to treat RA, Renal Homotransplantation, or Chron’s Disease (low dose)?
A. Cyclophosphamide
B. Methotrexate
C. Mycophenolate Mofetil
D. Azathioprine

D. Azathioprine

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True or False: Methotrexate can cause fetal harm, has a risk of carcinogenesis, and can temporarily decreased spermatogenesis (!!!)

False - Azathioprine

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____ competitively inhibits dihydrofolic acid reductase, thereby interfering with DNA synthesis, repair, and cellular replication

Methotrexate

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Delayed ___ ____ is one of the major factors responsible for toxicity of methotrexate

Delayed drug clearance

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How can you decrease the potential for toxicity associated with methotrexate?

Leucovorin calcium

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Alopecia is an AE associated with ____ use

Cyclophosphamide

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True or False: Leukopenia and Thrombocytopenia are AE associated with Cyclophosphamide and Azathioprine

True

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Which of the following is associated with hepato/nephrotoxicity, leukopenia, and COPD?
A. Cyclophosphamide
B. Methotrexate
C. Mycophenolate Mofetil
D. Azathioprine

B. Methotrexate

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Black box warning: periodic monitoring of toxicity (including: CBC w/dif and platelet count) is associated with: A. Cyclophosphamide B. Methotrexate C. Mycophenolate Mofetil D. Azathioprine

B. Methotrexate

Which three conditions can be treated by Methotrexate?

Cancers (neoplasms) Juvenile RA Adult RA

What primary causes nephrotoxicity in methotrexate use?

Precipitation of methotrexate in the renal tubules

How does Cyclosporine inhibit Signal 1?

By inhibiting calcineurin phosphatases

Cyclosporine inhibits the release of IL__ and activation of ___ cells

IL-2; T cells

Cyclosporine suppresses some ___ immunity and, to a greater extent, _____ immune reactions

humoral immunity; cell-mediated

How does cyclosporine cause anti-inflammatory and immunosuppressive effects?

Reversibly inhibits immunocompetent lymphocytes in G0 or G1 phase of cell cycle

Cyclosporine preferentially inhibits which type of lymphocytes?

T Lymphocytes (T helper)

Which drug is metabolized by Cytochrome P450 3A?

Cyclosporine

Which of the following crosses the placenta and is embryo and fetotoxic? A. Cyclophosphamide B. Methotrexate C. Mycophenolate Mofetil D. Cyclosporine

D. Cyclosporine

Mouth sores and HTN are AE associated with ____

Cyclosporine

Mild or chronic nephrotoxicity, as well as chronic-progressive type, is associated with use of which drug?

Cyclosporine note: renal biopsies reveal interstitial fibrosis and peritubular capillary congestion

What are three clinical uses for cyclosporine?

1. Allogenic transplants (kidney, liver, heart) 2. RA 3. Psoriasis

Cyclosporine is ALWAYS to be taken in conjunction with ____. It has also been used in combination with ____ and ____.

adrenal corticosteroids; azathioprine, corticosteroids

Mycophenolate Mofetil (MMF) is hydrolyzed to form ___, a potent and reversible inhibitor of ____, which inhibits the synthesis of _____

MPA (mycophenolic acid); IMP dehydrogenase; guanosine nucleotide synthesis

Which of the following drugs prolongs survival of allogenic transplants in animals and reverse ongoing acute rejection? A. MMF B. Cyclosporine C. Azathioprine D. Cyclophosphamide

A. MMF (Mycophenolate Mofetil)

True or False: MPA has potent cytostatic effects on lymphocytes. In particular, it inhibits proliferative responses of T and B lymphocytes.

True

Which of the following suppresses antibody formation by B-Lymphocytes and prevents glycosylation of lymphocyte and monocyte glycoproteins involved in intracellular adhesion? A. Cyclophosphamide B. Methotrexate C. Mycophenolate Mofetil D. Cyclosporine

C. Mycophenolate Mofetil

Black box warning for development of lymphoma and embryo-fetal toxicity is associated with which drug?

Mycophenolate Mofetil (MMF)

Infections such as endocarditis, Tb, meningitis, and those of the myobacterial sort are AE associated with _____

MMF

True or False: Sepsis, infections, vomiting, diarrhea, and leukopenia are the principal AE associated with Mycophenolate

True

Bone marrow suppression is associated with all of the cytotoxic and anti-proliferative agents except ____

MMF

Which three drugs are T cell suppressants?

Cyclosporine MMF Lymphocyte Immune Globulin

Which three drugs are Ab Immunosppressives?

1) Rh Immune Globulin 2) Bevacizumab 3) Ranibizumab

______ is a lymphocyte immune globulin that is obtained from serum Ig of horses immunized from lymphocytes from human thymus tissues A. Ranibizumab B. Bevacizumab C. Rh Immune Globulin D. Lymphocyte Immune Globulin

D. Lymphocyte Immune Globulin

True or False: Lymphocyte Immune Globulin is associated with Signal 3

False - Signal 1

______ reduces the number of thymus-dependent lymphocytes (T-cells) in the blood, as well as thymus-dependent areas of the spleen and lymph nodes

Lymphocyte Immune Globulin

Fevers, chills, vertigo, as well as systemic infections are associated with use of ___. Therefore, as a precaution, a skin test for sensitivity for equine serum should be done prior to first infusion.

Lymphocyte Immune Globulin

True or False: Lymphocyte Immune Globulin does not have any adverse effects on the fetus

False - Lymphocyte Immune Globulin DOES have an adverse effects on the fetus

True or False: Lymphocyte Immune Globulin can be used to minimize allograft rejection in RENAL transplant patients

True

Lymphocyte Immune Globulin is used in combination with ___ and ____

antimetabolites; corticosteroids

______ is a sterile, concentrated solution of immune globulin. Further, it is a cold alcohol fractionation of human plasma obtained from donors immunized to produce high levels of Rh0 antibodies.

Rh0 Immune Globulin

Rh0 Immune Globulin is contraindicated in ___ patients and ____ patients who have already developed Rh0 antibodies

Rh0-positive patients Rh0-negative patients

_____is used to prevent Rh0 hemolytic disease of the newborn (Erythroblastosis fetalis) in a subsequent pregnancy

Rh0 Immune Globulin

True or False: Rh0 Immune Globulin suppresses the specific immune response of Rh0-negative individuals to Rh-0 positive blood cells

True

When should Rh0 Immune Globulin be administered to a Rh0 negative mother?

Within 72 hours after either birth of Rh0 (+) infant, miscarriage, abortion, etc.

True or False: RhoGam (Rh Immune Globulin) can prevent sensitization to Rh0 factor in pregnant Rh- negative women

True

_____ is a recombinant, humanized mab that binds to and NEUTRALIZES VEGF _____ is a recombinant, humanized mab fragment that binds and INHIBITS VEGF

Bevacizumab: a recombinant, humanized mab that binds to and neutralizes VEGF Ranibizumab: is a recombinant, humanized mab fragment that binds and inhibits VEGF

True or False: Blurred vision is associated with use of Ranibizumab

False - Bevacizumab

Intravitreal Bevacizumab can be used for age-related ___ edema

macula

____ inhibits VEGF binding to its receptors, thereby suppressing neovascularization and slowing LOSS OF vision

Ranibizumab

What are four AE associated with Ranibizumab?

1) Conjunctival bleeding 2) Corneal edema 3) Cataracts 4) Eyelid pain

True or False: Bevacizumab can be used to treat diabetic macular edema and diabetic retinopathy

False - Ranibizumab

___ ____ is an agent for replacement therapy and is associated with Signal 1

Immune Globulin

___ ___ is made of IgG and IgM from human plasma and passively supplies broad spectrum IgG ab against many antigens (bacterial, viral, parasitic, and mycoplasmic)

Immune Globulin

True or False: Immune Globulin inhibits pathogenic autoantibodies

False - neutralizes

True or False: Immune Globulin can bind to IL-1a, IL-6, TNF-a, and TCR, suppressing pathogenic cytokines and phagocytes

True

The Ab in Immune Globulin can interfere with pathogenic effect of products of ___ activation

complement

Clinical uses of Immune Globulin?

1) Hypogammaglobulinemia 2) HIV-infected peds patients 3) Idiopathic thrombocytopenic pupura 4) Guillian-Barre Syndrome

Black box warning of thrombosis, renal dysfunction, and acute renal failure are associated with ____ ____

Immune Globulin

Why can the risk of infectious agents not totally be eliminated w/r/t Immune Globulin?

Made from human plasma, which may allow for transmission of BBP

Interferon _____ is a recombinant amino acid protein. Binding to its receptor initiates a complex cascade of intracellular events. A. Interferon Beta-1b B. Interferon Alpha-2A

A. Interferon Beta-1b

Interferon beta has ___ and ____ activities

antiproliferative and immunoregulatory activities

What are the three most serious AE associated with Interferon Beta 1B?

1) Depression 2) SI 3) Injection Site Reactions

True or False: Interferon Gamma is used to treat relapsing-remitting MS

False - Inteferon Beta

Which two drugs are given Intravitreal?

Mab drugs

True or False: Flu-like symptoms are associated with Interferon Gamma

True

Which interferon has phagocyte-activating effects that are not seen with other inteferon preparations, including generation of toxic oxygen metabolites within phagocytes?

Interferon Gamma 1B

What is Interferon Gamma-1B used to treat?

Chronic granulomatous disease

True or False: Interferon Gamma 1b can enhance phagocyte function, leading to elevated superoxide levels and improved killing of Staph a.

True

Gingivitis, inflammation of nares, and granuloma formation in the neck of symptoms of _____

chronic granulomatous

Anaphylaxis is a ____ drug allergy while urticaria (cutaneous) and glomerulonephritis (renal) are _____

generalized; organ-specific

True or False: women are more likely to have cutaneous reactions and children are less likely to have allergic reactions

True

In Type 1 hypersensitivity reactions, initial exposure to drugs result in production of ___ antibodies, which binds to ___ cells and blood ___

IgE; mast cells; blood basophils

___ and ___ are mediators of Type 1 Hypersensitivity Reactions

Histamine and Leukotrienes - note: these are release from mast cells /basophils

Which four drugs can treat Type 1 hypersensitivity reactions?

1) Prednisone 2) Isoproterenol 3) Epi 4) Theophylline

___ is a sympathomimetic catecholamine that is the most potent alpha receptor activator ____ will cause bronchodilation by inhibition of PDE III and IV

Epinephrine Theophylline

In Type 1 Hypersensitivity Reactions, re-exposure to allergen leads to cross-linking of membrane bound ___

IgE

True or False: Theophylline decreases leakage from endothelial cells and decreases cytokine release from T Lymphocytes and Macrophages + decreases mediators released

True

Clinical manifestations of Type ___ Hypersensitivity reaction include: Rh0 hemolytic disease in newborn, agranulocytosis, and autoimmune hemolytic anemia

Type 2 Hypersensitivity

Type II hypersensitivity reactions involve __ and __ antibodies

IgG and IgM - note: these are the mediators!

How do you treat Type II and III Hypersensitivity Reactions?

Drug withdrawl and corticosteroids

Which two Ab are involved in Type III Hypersensitivity Reactions?

IgM and IgG (note: these Ab generate drug-antibody complexes that often deposit in b. vessel walls, result in complement activation)

Serum sickness is associated with which hypersensitivity?

Type III

What results due to complement activation in Type III Hypersensitivity Reactions?

1) Increased vascular permeability 2) Aggregation of neutrophils 3) Hemorrhagic vasculitic lesion

What is the major difference between type 2 and 3 hypersensitivity reactions?

Type 2 involves cells in circulatory system while Type 3 involves lysis of cells that line b. vessels

Which type of hypersensitivity reaction is mediated by T lymphocytes and macrophages? How is this type treated?

Type 4 (cell mediated/delayed) - Treatment: corticosteroids

True or False: Both Interferons can be administered SC

True