Lecture 1 and 2: Immunopharmacology Flashcards
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
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
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
Corticosteroids inhibit which two enzymes?
PLA2 (inhibition results in lower prostaglandin and leukotriene synthesis)
and
COX-2 (inhibition results in lower prostaglandin formation)
How do corticosteroids affect vasoconstriction, complement effects, and antibody production?
Vasoconstriction: Increase, thereby reducing capillary permeability
Complement: Inhibit
Ab production: Reduce
True or False: The adverse effects associated with glucocorticoid therapy include: adrenal suppression, dyslipidemia, glucose intolerance, and increased bacterial and mycotic infections
True
Which four conditions can be treated with corticosteroids?
1) Allergic disorders
2) Hematological disorders
3) Hepatic and renal disorders
4) Collagen disorders
Which of the following corticosteroids are long-acting and can be administered orally, IV, or IM?
A. Prednisone
B. Dexamethasone
C. Methylprednisolone
B. Dexamethasone
Which four drugs are cytotoxic and anti-proliferative agents (T and B cells)?
1) Cyclophosphamide
2) Azathioprine
3) Methotrexate
4) Mycophenolate Mofetil
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
Which four drugs are Signal 3 Inhibitors?
Cyclophosphamide
Mycophenolate Mofetil
Methotrexate
Azathioprine
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
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
____ 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
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
True or False: Azathioprine inhibits adenosine deaminase, thereby inhibiting the production of adenosine MP
True
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
True or False: Methotrexate can cause fetal harm, has a risk of carcinogenesis, and can temporarily decreased spermatogenesis (!!!)
False - Azathioprine
____ competitively inhibits dihydrofolic acid reductase, thereby interfering with DNA synthesis, repair, and cellular replication
Methotrexate
Delayed ___ ____ is one of the major factors responsible for toxicity of methotrexate
Delayed drug clearance
How can you decrease the potential for toxicity associated with methotrexate?
Leucovorin calcium
Alopecia is an AE associated with ____ use
Cyclophosphamide
True or False: Leukopenia and Thrombocytopenia are AE associated with Cyclophosphamide and Azathioprine
True
Which of the following is associated with hepato/nephrotoxicity, leukopenia, and COPD?
A. Cyclophosphamide
B. Methotrexate
C. Mycophenolate Mofetil
D. Azathioprine
B. Methotrexate
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?
- Allogenic transplants (kidney, liver, heart)
- RA
- 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