Pharm: Immunomodulating Drugs Flashcards
What class of drugs regulates gene expression (BY INHBITING SYNTHESIS OF EICOSANOIDS) and interferes with cellular immunity?
Corticosteroids
Prednisone, Dexamethasone, and FLUDROCORTISONE (as well as Cortisone, Triamcinolone and Betamethasone) belong to what class of immune-modulating drugs?
Corticosteroids
What drugs are used as FIRST LINE immunosuppression for solid organ transplant and hematopoietic stem cell transplant?
Corticosteroids
What effect does corticosteroids have on glucose?
Causes hyperglycemia –> STEROID DIABETES
What are two major side effects of corticosteroids associated with long term use?
Osteoporosis and Glaucoma
What 2 drugs belong to the “Calcineurin inhibitor” Class?
Cyclosporine, Tacrolimus
What drug binds to cyclophilin?
Cyclosporine
What happens after cyclosporine binds to cyclophilin?
Inhibits T-cell activation –> Decreases IL-2, IL-3, IFN-gamma
Inhibits Calcineurin
What organ transplants is Cyclosporine used for?
Cadaveric –> Kidneys, Liver, Pancreas, Cardiac
What is the role of Cyclosprine in Graft-vs-Host disease?
Tx of G-vs-H disease AFTER hematopoietic stem cell transplant. Combined with methotrexate.
STANDARD PROPHYLAXIS TO PREVENT G-VS-H DISEASE AFTER ALLOGENIC STEM CELL TRANSPLANT
What 4 Autoimmune disorders is cyclosporine indicated for? (one bolded)
UVEITIS, RA, psoriasis, asthma
What should you know about the metabolism of cyclosporine?
Metabolized by the P450 3A enzyme in the liver –> resultant multidrug interactions.
What is the role of inducers on the P450 system?
Inducers DECREASE the half-life and blood levels of the drug.
What are the most important (bolded) toxicities of cyclosporine? (4)
Induces TGF-Beta;
Promotes tumor invasion and metastasis;
Increases incidence of lymphomas;
Kaposi’s Sarcoma
Tacrolimus belongs to what drug class?
Calcineurin inhibitor
What is the MOA for Tacrolimus?
Binds to immunophilin FK-binding protein (FKBP)
Clinical indications, metabolism, and toxicity of tacrolimus are similar to what other drug? What is the difference between the 2 drugs?
Cyclosporine –> Tacrolimus is more potent than cyclosporine
Sirolimus belongs to what drug class?
Proliferation signal inhibitors
What is the MOA of sirolimus?
- Binds to Immunophilin (FKBP-12) but does NOT inhibit calcineurine.
- BLOCKS mTOR (mammalian target of rapamycin) –> BLOCKS THE RESPONSE OF T CELL TO CYTOKINES
- A potent inhibitor of B-cell proliferation and immunoglobulin production
What is the most important toxicity associated with Sirolimus?
PROFOUND MYELOSUPPRESSION, especially thrombocytopenia
RH0 Immune Globulin Micro-Dose is used in the prevention of what disease?
Hemolytic disease of newborns
What are the indications for Hyperimmune Immunoglobulins?
Respiratory syncytial virus; CMV; Varicella zoster, Human Herpes virus-3; Hep B; Rabies; Tetanus; Digoxin overdose
What drugs classification does Alemtuzumab, Bevacizumab, Cetuximab, Gemtuzumab, Rituximab, and Trastuzumab fit into?
Monoclonal Antibodes - which are Immunosuppressive antibodies
MOA of Alemtuzumab?
Humanized IgG1 that binds to CD52 on normal and malignant B and T lymphocytes, NK cells, monocytes, and macrophages
What is Alemtuzumab used for?
Tx of REFRACTORY B CELL LYMPHOCYTIC LEUKEMIA in patients treated with alkylating agents who have failed fludarabine therapy
What is the MOA of Bevacizumab?
- Humanized IgG1 monoclonal antibody that BINDS TO VASCULAR ENDOTHELIAL GROWTH FACTOR (VEGF) and inhibits VEGF from binding to its receptor, especially endothelial cells.
- An ANTI-ANGIOGENIC DRUG that inhibits growth of blood vessels (angiogenesis) in tumors
Clinical indications for Bevacizumab?
FIRST-LINE TREATMENT OF PATIENTS WITH METASTATIC COLORECTAL CANCER alone or in combo with 5-FU chemo
What is important to remember about giving Bevacizumab to patients?
- Contraindicated around surgery 28 days before or after the surgery due to increased risk of hemorrhage.
- Contraindicated in patients with HTN (Systolic >160)
MOA of Cetuximab
- Human-mouse chimeric
- TARGETS EPIDERMAL GORWTH FACTOR RECEPTOR (EGFR)
- Binds EGFR and inhibits tumor cell growth via: Decrease in kinase activity; Matrix metalloproteinase activity; and increased apoptosis
Clinical use of Cetuximab?
In patients with METASTATIC COLORECTAL cancer (tumor over-expression of EGFR)
MOA of Gemtuzumab?
Humanized IgG4 with a kappa light chain specific for CD33 FOUND ON LEUKEMIC BLAST CELLS IN 80-90% OF PATIETNS WITH AML
Clinical use of Gemtuzumab?
Approved for RELAPSED CD33 ACUTE MYELOID LEUKEMIA
MOA of Rituximab?
- Chimeric murine-human IgG1 that binds to CD20 molecule on Malignant B lymphocytes
- Causes: Induction of apoptosis; complement-mediated lysis; Antibody-dependent cellular cytotoxicity
Clinical use of Rituximab?
Approved for the therapy of PATIENTS WITH RELAPSED OR REFRACTORY low-grade or follicular, B-CELL NON-HODGKIN’S LYMPHOMA
MOA of Trastuzumab?
A recombinant DNA-derived, human monoclonal antibody that binds to the extracellular domain of the HUMAN EPIDERMAL GROWTH FACTOR receptor HER-2/neu
Clinical use of Trastuzumab?
Treatment of METASTATIC BREAST CANCER in patients whose tumors over-express HER-2/neu
What disease causes rapid destruction of the kindeys and bleeding into the lung?
Goodpasture’s Disease
What is the treatment of Goodpasture’s Disease
Prednisolone, Cyclophosphamide, Plasma exchange
What hypersensitivity reaction is SLE?
Type II
What test is positive in SLE?
ANA
What is the treatment for SLE?
Steroids (Prednisolone tabs, methylprednisolone IV), Cyclophosphamide, Azathioprine
What is the standard first-line prophylaxis to prevent Graft-vs-Host disease after allogeneic stem cell transplant?
Cyclosporine combined with Methotrexate
Tx or Vasculitis
Steroids, cyclophosphamide, Azathioprine, Plasma exchange
Tx of sjogren’s syndrome:
Hydroxychloroquine
Tx of Dermatomyositis:
Prednisone, Methotrexate, Azathioprine, Mycophenolate, Hydroxychloroquine, Chloroquine
Tx of Psoriasis:
Betamethasone, Cyclosprine
MOA of Mycophenolate Mofetil:
INOSINE MONOPHOSPHATE DEHYDROGENASE (IMPDH) INHIBITOR
- Hydrolyzed to MYCOPHENOLIC ACID - the active immunosuppressive moiety
3 Clinical uses of Mycophenolate Mofetil:
- Used for solid organ transplants for REFRACTORY REJECTION (second line to cyclosporine)
- AN ALTERNATIVE TO CYCLOSPORINE OR TACROLIMUS
- For PROPHYLAXIS to prevent G-vs-H disease
(aside: used in combo with prednisone)
Which hypersensitivity is this:
Allergy to certain drugs when the drug is not capable of inducing an immune response by covalently binding to a host-carrier protein (hapten)?
Type I
Immune response to Type I hypersensitivity:
Immune system detects the drug-hapten conjugate and responds by generating IgE ANTIBODIES SPECIFIC FOR DRUG-HAPTEN COMPLEX.
Tx for Type I hypersensitivity:
Prednisone or desensitization to drugs
Auto immune disease with IgG antibodies binding to drug-modified tissues followed by complement system activation and destruction of the cells or by phagocytic cells with Fc receptors = what type of hypersensitivity?
Type II
Tx for Type II sensitivity?
Immunosuppressive therapy used for severe cases
Serum sickness and Vasculitic Reactions are what type of hypersensitivy?
Type III
Which type of Hypersensitivity is this?
Urticarial and erythematous skin eruptions, arthralgia, arthritis, lymphadenopathy, glomerulonephritis, peripheral edema, and fever.
Type III
Immune vasculitis can be induced by what drugs?
Sulfonamides, penicillin, thiouracil, anti-convulsants, iodides
Type III Hyper-sensitivity reactions involve what antibodies?
IgM and IgG
Tx for Type III hyper-sensitivity?
Glucocorticoids.
Severe cases: Plasmapheresis to remove offending drug from circulation
