Immunosuppressive Drugs

Question 1

Calcineurin inhibitors 1.) Individual Drugs 2.) Mechanism of Action 3.) Uses 4.) Adverse Effects

Answer 1

1.) Cyclosporine (CsA), Tacrolimus (FK506)
2.) Bind to and inhibit calineurin -> no de-P of NF-AT -> can’t enter nucleus and promote transcription of IL-2
3) Prevention and treatment of transplant rejection; AI disorders
4.) Interacts w/ drugs, grapefruit that affect CYP P450 – sirolimus
Renal toxicity
HTN, diabetes
↑ risk malignancies, infections

Question 2

mTOR inhibitors 1.) Individual Drugs 2.) Mechanism of Action 3.) Uses 4.) Adverse Effects

Answer 2

1.) Sirolimus (Rapamycin), Everolimus
2.) Blocks IL-2-induced T cell proliferation and differentiation
3.) Transplant pts (esp those w/ calcineurin toxicity); anti-CA for renal CA; AI disorder
4.) Dose-dep ↑ in serum cholesterol and TAGs
Can enhance calcineurin inhibitors nephrotoxicity by extending drug ½ life
Anemia, leukopenia, infections

Question 3

Azthioprine 1.) Drug Group 2.) Mechanism of Action 3.) Uses 4.) Adverse Effects

Answer 3

1.) Cytotoxic Drugs
2.) Inhibits de novo purine synthesis and DNA replication
3.) Adjunct for preventing kidney rejection; RA
4.) BM suppression
↑ risks of neoplasia, infections
Interacts w/ Allopurinol

Question 4

Mycophenolate mofetil 1.) Drug Group 2.) Mechanism of Action 3.) Uses 4.) Adverse Effects

Answer 4

1. ) Cytotoxic drugs
2. )Inhibits IMPDH -> inhibits de novo purine synthesis (GMP) -> suppresses B and T lymphocyte proliferation
3. ) Can be used w. calcineurin inhibitors and corticosteroids in transplant patients
4. ) Mild – GI disturbances, myelosuppression, headache, HTN

Question 5

Anti-lymphocyte/thymocyte Abs 1.) Drug Group 2.) Mechanism of Action 3.) Uses 4.) Adverse Effects

Answer 5

1. ) Immunosuppressive Abs
2. ) Acts 1°ly on circulating lymphocytes; will also deplete thymus-dep lymphocytes
3. ) Induction therapy in organ/BM transplant
4. ) General immunosuppressive side effects

Question 6

Daclizumab 1.) Drug Group 2.) Mechanism of Action 3.) Uses 4.) Adverse Effects

Answer 6

1. ) Immunosuppressive Abs
2. ) Competitive antagonism CD 25 - IL-2R -> prevents induction of T cell proliferation
3. ) Against acute rejection in renal transplant recipients
4. ) General immunosuppressive side effects

Question 7

Muromonab-CD3 Ab 1.) Drug Group 2.) Mechanism of Action 3.) Uses 4.) Adverse Effects

Answer 7

1.) Immunosuppressive Abs
2.) Causes destruction of CD3 bearing T cells
3.) Prevent acute transplant rejection; deplete T-cells from donor BM prior to BMT
4.) Cytokine release syndrome
Acute hypersensitivity rxns
↑ infections

Question 8

Glucocorticoids Calcineurin inhibitors 1.) Individual Drugs 2.) Mechanism of Action 3.) Uses 4.) Adverse Effects

Answer 8

1. ) Cortisone, Dexamethasone, Prednisone
2. ) Inhibit expression of cytokine genes and T-cell prolif and T-cell dep immunity
3. ) Prevention of organ transplant rejection; AI disorders, asthma, Shock, Adrenocortical dysfxn
4. ) Growth retardation in kids, Osteoporosis, ↑ risk infections, Obesity, Hyperglycemia, HTN, Muscle wasting, Moon face