Immunosuppressive Drugs Pha 430
- 1.
Which statement is incorrect regarding cyclosporine?
- A.
It is lipophilic
- B.
It binds to cyclophilins in the cytoplasm to form a complex
- C.
It inhibits IL-2 synthesis as well as secretion
- D.
The attenuation of IL-2 is achieved through decreased expression of transforming growth factor beta
Correct Answer
D. The attenuation of IL-2 is achieved through decreased expression of transforming growth factor betaExplanation
Increased expression of growth factorRate this question:
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- 2.
The cyclosporine-cyclophilin complex serves as an inhibitor on what component in the cytoplasm:
- A.
Calcineurin
- B.
Neuricalcin
- C.
MTOR
- D.
None of the above
Correct Answer
A. CalcineurinExplanation
The correct answer is Calcineurin. The cyclosporine-cyclophilin complex acts as an inhibitor on calcineurin, a phosphatase enzyme found in the cytoplasm. By inhibiting calcineurin, the complex prevents the activation of transcription factors like NFAT, which are involved in the immune response. This inhibition helps to suppress the immune system and is used in the treatment of autoimmune diseases and to prevent rejection in organ transplantation. Neuricalcin and mTOR are not components inhibited by the cyclosporine-cyclophilin complex.Rate this question:
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- 3.
Phosphorylated NF-ATc binding with NF-ATn is what normally stimulates the release of IL-2
- A.
True
- B.
False
Correct Answer
B. FalseExplanation
NF-ATc must be dephosphorylated before binding with NF-ATnRate this question:
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- 4.
Which statement is the most correct regarding cyclosporine and cellular effects?
- A.
Causes lymphocyte death / does not cause apoptosis
- B.
Does not cause lymphocyte death / does not cause apoptosis
- C.
Causes lymphocyte death / causes apoptosis
- D.
Does not cause lymphocyte death / causes apoptosis
Correct Answer
B. Does not cause lympHocyte death / does not cause apoptosisExplanation
Cyclosporine does not cause lymphocyte death or apoptosis. Cyclosporine is an immunosuppressant drug commonly used in organ transplantation to prevent rejection. It works by inhibiting the activation of T-lymphocytes, which are an important component of the immune system. By suppressing T-cell activation, cyclosporine helps to prevent the immune system from attacking and rejecting the transplanted organ. However, it does not directly cause lymphocyte death or apoptosis.Rate this question:
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- 5.
To prevent hemolytic disease of the newborn in Rh- mothers with Rh+ fetuses, RhoGAM needs to be administered when?
- A.
Within 72 hours before birth of the first child
- B.
Within 72 hours of birth of the first child
- C.
Within 72 hours of birth of every child after the first
- D.
Within 72 hours of birth of every child including the first
Correct Answer
B. Within 72 hours of birth of the first childExplanation
RhoGAM needs to be administered within 72 hours of birth of the first child to prevent hemolytic disease of the newborn in Rh- mothers with Rh+ fetuses. This is because during childbirth, there is a possibility of fetal-maternal blood mixing, which can lead to the Rh- mother developing antibodies against the Rh+ blood of the fetus. By administering RhoGAM within 72 hours of birth, the medication can prevent the mother from developing these antibodies and reduce the risk of hemolytic disease in subsequent pregnancies.Rate this question:
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- 6.
Cyclosporine is poorly orally bioavailable, with an oral F of 20-50%.
- A.
True
- B.
False
Correct Answer
A. TrueExplanation
The statement is true because it states that Cyclosporine has a poor oral bioavailability, with an oral F (fraction absorbed) of 20-50%. This means that when Cyclosporine is taken orally, only a small percentage of the drug is actually absorbed into the bloodstream, resulting in low bioavailability.Rate this question:
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- 7.
Cyclosporine metabolism primarily takes place how?
- A.
Renally
- B.
Hepatically
- C.
Fecally
- D.
Unknown
Correct Answer
B. HepaticallyExplanation
Cyclosporine metabolism primarily takes place hepatically, meaning it is mainly metabolized in the liver. This suggests that the liver plays a crucial role in breaking down and eliminating cyclosporine from the body.Rate this question:
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- 8.
Which of these are toxicities associated with cyclosporine? [Select all that apply]
- A.
Nephrotoxicity
- B.
Hypertension
- C.
Neurological effects
- D.
Substantially decreased liver enzymes
- E.
Alopecia
- F.
Gingival hyperplasia
Correct Answer(s)
A. NepHrotoxicity
B. Hypertension
C. Neurological effects
F. Gingival hyperplasiaExplanation
Cyclosporine can increase transaminase and bilirubin levels, and can cause hirsutismRate this question:
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- 9.
Cyclosporine is used for heart, kidney, and lung transplants, as well as GVHD, but not autoimmune disorders
- A.
True
- B.
False
Correct Answer
B. FalseExplanation
Cyclosporine is a medication commonly used to prevent organ rejection in heart, kidney, and lung transplant patients, as well as to treat graft-versus-host disease (GVHD). However, it is also used to manage various autoimmune disorders such as rheumatoid arthritis, psoriasis, and Crohn's disease. Therefore, the statement that Cyclosporine is not used for autoimmune disorders is incorrect.Rate this question:
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- 10.
Tacrolimus is a macrolide antibiotic
- A.
True
- B.
False
Correct Answer
A. TrueExplanation
This is what he has in the slides, although other sources on the internet suggest it is simply a macrolide, of which some are antibiotics.Rate this question:
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- 11.
Tacrolimus is roughly 50-100x more potent than cyclosporine
- A.
True
- B.
False
Correct Answer
A. TrueExplanation
Tacrolimus is a medication that is used to suppress the immune system and prevent organ rejection in transplant patients. It is considered to be roughly 50-100 times more potent than cyclosporine, another immunosuppressive drug. This means that tacrolimus requires a lower dose to achieve the same therapeutic effect as cyclosporine. The higher potency of tacrolimus can be advantageous as it may lead to fewer side effects and better patient outcomes. Therefore, the statement "Tacrolimus is roughly 50-100x more potent than cyclosporine" is true.Rate this question:
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- 12.
The MOA of tacrolimus is identical to cyclosporine, with no deviations
- A.
True
- B.
False
Correct Answer
B. FalseExplanation
The statement is false because the MOA (mechanism of action) of tacrolimus is not identical to cyclosporine. While both drugs are immunosuppressants used in organ transplantation, they have different mechanisms of action. Tacrolimus inhibits the production of cytokines, which are involved in the immune response, while cyclosporine inhibits the production of interleukin-2, a key cytokine for T-cell activation. Therefore, there are deviations in their MOA.Rate this question:
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- 13.
What step of the MOA of tacrolimus is different from cyclosporine?
- A.
Ca2+ influx does not occur
- B.
Substrate complex; does not inhibit calcineurin
- C.
Substrate Complex; Tac binds and forms Tac-FK06 complex
- D.
NFATc/NFATn complex does not form
Correct Answer
C. Substrate Complex; Tac binds and forms Tac-FK06 complexExplanation
The step of the MOA of tacrolimus that is different from cyclosporine is the formation of the substrate complex. Tacrolimus binds and forms a complex with FK06, while cyclosporine does not inhibit calcineurin. This difference in the formation of the substrate complex is what sets tacrolimus apart from cyclosporine in their mechanisms of action.Rate this question:
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- 14.
Tacrolimus is less orally bioavailable than cyclosporine
- A.
True
- B.
False
Correct Answer
A. TrueExplanation
Only ~25% oral F with tacRate this question:
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- 15.
Nephrotoxicity associated with tac is equal to or worse than cyclosporine
- A.
True
- B.
False
Correct Answer
B. FalseExplanation
The statement is false because nephrotoxicity associated with tac (tacrolimus) is actually less than cyclosporine. Nephrotoxicity refers to the potential for causing damage to the kidneys. Tacrolimus is a medication commonly used in organ transplantation to prevent rejection, and while it can still have some nephrotoxic effects, it is generally considered to be less nephrotoxic compared to cyclosporine, another immunosuppressive drug.Rate this question:
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- 16.
Rarely, tacrolimus is associated with:
- A.
B-cell cancers
- B.
T-cell cancers
- C.
Both B- and T-cell cancers
- D.
None of the above
Correct Answer
B. T-cell cancersExplanation
Tacrolimus, an immunosuppressive drug, is rarely associated with T-cell cancers. T-cell cancers refer to malignancies that arise from the T-cells of the immune system. These cancers can include T-cell lymphomas or leukemias. While tacrolimus is generally effective in preventing organ transplant rejection, it can also suppress the immune system, potentially leading to the development of T-cell cancers in rare cases.Rate this question:
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- 17.
Rapamycin is similar to tacrolimus in that it is a macrolide, binds to FK in the cytoplasm, and inhibits calcineurin activation
- A.
True
- B.
False
Correct Answer
B. FalseExplanation
The statement is false because rapamycin is not similar to tacrolimus in inhibiting calcineurin activation. While both rapamycin and tacrolimus are macrolides and bind to FK in the cytoplasm, rapamycin inhibits the mammalian target of rapamycin (mTOR) pathway, while tacrolimus inhibits calcineurin. Therefore, they have different mechanisms of action and do not inhibit calcineurin activation in the same way.Rate this question:
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- 18.
The inhibition of mTOR by rapamycin has which downstream effect? Pick the most correct statement
- A.
Cell does not proceed to G2 phase of cell cycle
- B.
Cell does not proceed to S phase of cell cycle
- C.
Cell does not enter G1 phase of cell cycle
- D.
Cell undergoes spontaneous apoptosis unrelated to cell cycle
Correct Answer
B. Cell does not proceed to S pHase of cell cycleExplanation
Does not proceed to S phase > Cell Cycle blocked > apoptosis may occurRate this question:
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- 19.
Rapamycin inhibits IL-2 receptor dependent cell cycling
- A.
True
- B.
False
Correct Answer
A. TrueExplanation
Rapamycin is known to inhibit the IL-2 receptor-dependent cell cycling. This means that it prevents the activation and proliferation of immune cells, specifically T cells, which rely on the IL-2 receptor signaling pathway for their growth and division. By inhibiting this pathway, rapamycin can effectively suppress the immune response, making it useful in certain medical applications such as preventing organ transplant rejection or treating autoimmune diseases. Therefore, the statement "Rapamycin inhibits IL-2 receptor dependent cell cycling" is true.Rate this question:
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- 20.
Because rapamycin is associated with _____________, it should be started _________ a transplant
- A.
Impaired wound healing; after
- B.
Accelerated wound repair; before
- C.
Impaired wound healing; either before or after
- D.
None of the above - contraindicated in transplant surgeries
Correct Answer
A. Impaired wound healing; afterExplanation
Rapamycin is associated with impaired wound healing, which means it can slow down the process of healing wounds. Therefore, it should be started after a transplant surgery to avoid further complications in wound healing. Starting rapamycin before the surgery may hinder the healing process and delay the recovery.Rate this question:
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- 21.
Select the correct statement(s) regarding rapamycin:
- A.
May be used with cyclosporine
- B.
Is not used in B-cell lymphoma
- C.
DDIs are similar to cyclosporine
- D.
Does not have a significant nephrotoxicity risk
Correct Answer(s)
A. May be used with cyclosporine
C. DDIs are similar to cyclosporine
D. Does not have a significant nepHrotoxicity riskExplanation
Rapamycin may be used with cyclosporine in certain cases, as they have similar drug-drug interactions (DDIs). Additionally, rapamycin does not pose a significant risk of nephrotoxicity. However, it is not used in B-cell lymphoma.Rate this question:
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- 22.
Everolimus is similar to rapamycin except that it is used after tissue transplantation for the prevention of graft rejection
- A.
True
- B.
False
Correct Answer
A. TrueExplanation
Everolimus is indeed similar to rapamycin. Both drugs belong to a class of medications called mTOR inhibitors, and they work by suppressing the immune system. However, the key difference is that everolimus is specifically used after tissue transplantation to prevent graft rejection. This means that the statement "Everolimus is similar to rapamycin except that it is used after tissue transplantation for the prevention of graft rejection" is true.Rate this question:
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- 23.
Everolimus is indicated for which of the following according to Dr. Khan's slides? Select all that apply
- A.
Cardiac allograft vasculopathy
- B.
Cardiac autograft vasculopathy
- C.
Post-transplant lymphosuppressive disorders
- D.
Post-transplant lymphoproliferative disorders
- E.
Breast cancers
- F.
Treatment of heart failure
- G.
Treatment of MS
- H.
Treatment of Parkinson's Disease
Correct Answer(s)
A. Cardiac allograft vasculopathy
D. Post-transplant lympHoproliferative disorders
E. Breast cancers
F. Treatment of heart failure
G. Treatment of MSExplanation
Everolimus is indicated for the treatment of cardiac allograft vasculopathy, post-transplant lymphoproliferative disorders, breast cancers, treatment of heart failure, and treatment of multiple sclerosis (MS). It is not indicated for the treatment of cardiac autograft vasculopathy, post-transplant lymphosuppressive disorders, or Parkinson's Disease.Rate this question:
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- 24.
Fingolimod is a prodrug requiring dephosphorylation to work properly
- A.
True
- B.
False
Correct Answer
B. FalseExplanation
Needs to be phosphorylated for activationRate this question:
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- 25.
Which is the most correct statement regarding the MOA of fingolimod
- A.
Increases peripheral blood lymphocyte count
- B.
Cells are hypersensitized to the presence of sphingosine-1 phosphate and respond overtly to its signal
- C.
It is associated with little to no adverse events
- D.
An internalization of G-protein linked receptors on thymocytes/lymphocytes
Correct Answer
D. An internalization of G-protein linked receptors on thymocytes/lympHocytesExplanation
Fingolimod acts by causing an internalization of G-protein linked receptors on thymocytes/lymphocytes. This means that the drug binds to these receptors and causes them to be taken inside the cells, resulting in a decrease in the number of receptors available on the cell surface. This leads to a reduction in the migration of lymphocytes from lymph nodes into the bloodstream, which helps to decrease inflammation in conditions such as multiple sclerosis. This mechanism of action is well-established and supported by scientific evidence.Rate this question:
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- 26.
Which of these are adverse events associated with fingolimod (per Dr. Khan's slides)? Select all that apply.
- A.
Fatal infection
- B.
Tachycardia
- C.
Bradycardia
- D.
DIC
- E.
Hemorrhage
- F.
Hypercapnia
Correct Answer(s)
A. Fatal infection
C. Bradycardia
E. HemorrhageExplanation
Fingolimod is an immunosuppressant medication used to treat multiple sclerosis. According to Dr. Khan's slides, adverse events associated with fingolimod include fatal infection, bradycardia, and hemorrhage. Fatal infection can occur due to the medication's immunosuppressive effects. Bradycardia refers to a slow heart rate, which can be a side effect of fingolimod. Hemorrhage, or excessive bleeding, is another potential adverse event. Tachycardia, DIC (disseminated intravascular coagulation), and hypercapnia (elevated carbon dioxide levels in the blood) are not listed as adverse events associated with fingolimod.Rate this question:
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- 27.
Belatacept is a drug generated by recombinant DNA technology, by fusing the Fc region of IgG1 to the extracellular domain of CTLA-4
- A.
True
- B.
False
Correct Answer
A. TrueExplanation
Belatacept is a drug that is indeed generated using recombinant DNA technology. This technology involves combining genetic material from different sources to create a new DNA sequence. In the case of Belatacept, the Fc region of IgG1 (a type of antibody) is fused with the extracellular domain of CTLA-4 (a protein involved in regulating immune responses). This fusion creates a novel molecule that can modulate the immune system and is used as an immunosuppressive drug in certain transplant procedures. Therefore, the statement is true.Rate this question:
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- 28.
CTLA-4 is also known as which of these?
- A.
CD152
- B.
CD86
- C.
CD80
- D.
CD28
Correct Answer
A. CD152Explanation
CTLA-4 is also known as CD152.Rate this question:
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- 29.
CTLA-4 indiscriminately blocks the process of T-cell activation
- A.
True
- B.
False
Correct Answer
B. FalseExplanation
Stated as a "selective blocking"Rate this question:
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- 30.
Which of the following transplant types is belatacept approved for?
- A.
Bone marrow
- B.
Liver
- C.
Stomach/Kidney/Pancreas
- D.
Kidney
Correct Answer
D. KidneyExplanation
Belatacept is a medication that is used to prevent organ rejection in kidney transplant patients. Therefore, it is specifically approved for kidney transplants. It is not approved for bone marrow, liver, or stomach/kidney/pancreas transplants.Rate this question:
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- 31.
Belatacept should only be given to patients who are seronegative for EBV
- A.
True
- B.
False
Correct Answer
B. FalseExplanation
The statement is false because Belatacept should only be given to patients who are seropositive for EBV, not seronegative. This is because Belatacept can increase the risk of developing EBV-related complications, such as post-transplant lymphoproliferative disorder (PTLD). Therefore, it is important to determine the EBV status of patients before considering Belatacept treatment.Rate this question:
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- 32.
Belatacept is associated with B-cell cancers in the CNS (e.g. PTLD), as well as increased risk of infection from bacterial/viral/fungal/protozoal sources
- A.
True
- B.
False
Correct Answer
A. TrueExplanation
Belatacept is a medication that is used to prevent organ rejection in transplant patients. However, it has been found to be associated with an increased risk of certain types of cancer, specifically B-cell cancers in the central nervous system (CNS), such as post-transplant lymphoproliferative disorder (PTLD). Additionally, belatacept can weaken the immune system, making individuals more susceptible to infections caused by bacteria, viruses, fungi, and protozoa. Therefore, the statement that belatacept is associated with B-cell cancers in the CNS and increased risk of infection is true.Rate this question:
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- 33.
Abatacept and belatacept differ by only ________ amino acids. (Use only the number in numeric form)
Correct Answer
2Explanation
Abatacept and belatacept differ by only 2 amino acids.Rate this question:
- 34.
Select the correct use(s) of abatacept
- A.
In rheumatoid arthritis across the lifespan
- B.
In rheumatoid arthritis in individuals 6+ years of age as first line therapy
- C.
In rheumatoid arthritis in individuals 6+ years of age when other DMARDs fail
- D.
With kineret to enhance its effect(s)
- E.
Not in combination with any TNF-alpha targeting agents
Correct Answer(s)
C. In rheumatoid arthritis in individuals 6+ years of age when other DMARDs fail
E. Not in combination with any TNF-alpHa targeting agentsExplanation
Should never be used with kineretRate this question:
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- 35.
The side effects are significant with abatacept and typically prompt discontinuation of the drug
- A.
True
- B.
False
Correct Answer
B. FalseExplanation
The statement suggests that the side effects of abatacept are significant and usually lead to the discontinuation of the drug. However, the correct answer is false, indicating that the statement is incorrect. This implies that the side effects of abatacept may not be significant enough to warrant discontinuation of the drug, or that they can be managed effectively without stopping the medication.Rate this question:
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