Immunosuppressive Drugs Pha 430

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.

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.

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.

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.

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.

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.

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.

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.

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.

Abatacept and belatacept differ by only 2 amino acids.

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.

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.

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.

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.

Only ~25% oral F with tac

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.

Increased expression of growth factor

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.

Does not proceed to S phase > Cell Cycle blocked > apoptosis may occur

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.

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.

NF-ATc must be dephosphorylated before binding with NF-ATn

CTLA-4 is also known as CD152.

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.

Needs to be phosphorylated for activation

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.

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.

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.

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.

Stated as a "selective blocking"

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.

Should never be used with kineret

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.

Cyclosporine can increase transaminase and bilirubin levels, and can cause hirsutism

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.