Immunopharmacology Flashcards
overall effect of glucocorticoid administration
anti inflammatory and immunosuppressive
mechanism of glucocorticoids in term of anti inflammatory actions
inhibit prostaglandin synthesis by
- induction of annex I –> inhibits phospholipase A2α
- induction of MAPK phosphatase I
- inhibition of NF-kB -> reducing expression of COX-2
uses of glucocorticoids
- prevent and treat transplant rejection
- treat autoimmune disorders
- alleviate pain, nausea, fatigue, anorexia, malaise, and improve quality of life
name some glucocorticoids
Dexamethasone
Prednisone
Prednisolone
Methylprednisolone
adverse effects of glucocorticoids
- short term: hypertension, hyperglycemia, immunosuppression, psychotic reactions, cognitive impairment
- long term: osteoporosis, weight gain, poor wound healing, increased risk of infections, adrenal suprresion
what are the immunosuppressive agents
glucocorticoids calcineurin inhibitors proliferation signal inhibitors angiogenesis inhibitors cytotoxic drugs other agents
what are the calcineurin inhibitors
Cyclosporine
Tacrolimus
mechanism of cyclosporine
binds to cyclophilin and forms a complex that inhibits cytoplasmic phosphatase, calcineurin which is needed for activation of T cell transcription factors –> IL-2, IL-3, TNFα etc
uses of cyclosporine
organ transplantation
uveitis
RA
psoriasis
adverse effects of cyclosporine
Nephrotoxicity
Osteoporosis
Hirsutism
Gum Hyperplasia
mechanism of tacrolimus
binds to FK binding protein and then the complex inhibits calcineurin needed for T cell transcription factor
uses of tacrolimus
- prevention of rejection of kidneys, liver, or heart
- atopic dermatitis and psoriasis (topical use)
adverse effects of tacrolimus
similar to cyclosporine
Nephrotoxicity Neurotoxicity Hyperglycemia Hypertension Hyperkalemia GI symptoms
what is the proliferation signal inhibitor
Sirolimus
mechanism of Sirolimus
binds to FK binding protein then the complex binds and inhibits serine threonine kinase mTOR –> leading to blockage of IL-2 driven T cell proliferation
uses of Sirolimus
renal transplantation
inhibition of re-stenosis of BV in CAD
adverse effects of Sirolimus
Myelosuppression
Hepatotoxicity
Hypertriglyceridemia
Pneumonitis
inhibitor of angiogenesis and its mechanism
Thalidomide
inhibits synthesis of TNFα and inhibits angiogenesis
uses of thalidomide
Erythema nodosum leprosum
Multiple Myeloma
adverse effects of thalidomide
Teratogenesis
Increased risk of DVT
Peripheral Neuropathy, constipation, rash, fatigue, hypothyroidism
what are the cytotoxic drugs
CLAMM
Cyclophosphamide Leflunomide Azathioprine Methotrexate Mycophenolate Mofetil
mechanism of azathioprine
converted to 6-mercaptopurine –> inhibits de novo purine synthesis –> suppression of B and T cells function, immunoglobin production, IL-2 secretion
uses and drug interaction of azathioprine
- used for organ transplant rejection and RA
- with allopurinol, should be reduced dose of azathioprine (since its effect relies on interaction with xanthine oxidase) to prevent excessive toxicity
mechanism of methotrexate
inhibits AICAR transformylase –> increased AICAR –> inhibits AMP deaminase –> increased AMP –> converted to adenosine –> suppresses NF-kB and inhibits inflammation
