immunotherapy Flashcards
MOA of glucocorticoids
substitute for cortisol -> inhibits production of inflammatory mediators and MF release of inflammatory cytokines
ADR of glucocorticoids
Cushing syndrome, including DM, reduced resistance to infection, osteoporosis, cataracts, inc appetite -> wt gain, HTN
*abrupt cessation -> adrenal insufficiency = must taper!
azathioprine MOA and use
prodrug of 6-MP
inhibits lymphocyte proliferation by blocking nucleotide synthesis
first drug for post-transplant immunosuppression
methotrexate MOA and use
folate analog, irreversibly binds and inhibits DHF reductase, halting purine and pyrimidine synthesis in rapidly proliferating cells
used to treat malignancies, among other conditions
ADR methotrexate
oral and GI ulcers, pancytopenia, alopecia, hepatotoxicity (inc fibrosis, cirrhosis, hepatitis), pulmonary fibrosis, infection
mycophenolic acid MOA
inhibits inosine monophosphate dehydrogenase (IMPDH) (rate limiting step in guanosine synth)
acts 1’ on lymphocytes (dependent on de novo purine synth)
*better efficacy vs AZA
leflunomide MOA and use
prodrug of teriflunomide, blocks synthesis of UMP by inhibiting dihydroorotate dehydrogenase (DHOD), preventing DNA/RNA synth for proliferation and cytokine production in lymphocytes
used for RA
cyclophosphamide MOA, use, ADR
alkylating agent, cross-links DNA at guanine N7
used in SLE, Wegener’s; often combined with corticosteroids
ADR: hemorrhagic cystitis, prevented with mesna (mercapto-ethane sulfonate, neutralizes toxic metabolites)
MOA cyclosporine
complexes with cyclophilin, binds calcineurin and inhibits Ca-stimulated de-P of cytosolic part of NFAT, blocking T-cell activation by preventing IL-2 transcription
uses of cyclosporine
kidney, liver, heart, other organ transplants
RA
psoriasis
GVHD: cyclosporine + MTX
ADRs of cyclosporine
renal dysfunction/ nephrotoxicity
tremor - neurotoxicity
hirsutism, HTN, hyperlipidemia, gum hyperplasia
*little BM suppression
cyclosporine drug interactions
CYP 3A4 metabolism, so interacts with both CYP inhibitors (macrolides, azoles, grapefruit juice) and inducers (phenytoin, carbamazepine, abx, rifampin)
MOA tacrolimus
complexes with FKBP-12, binds calcineurin and inhibits Ca-stimulated de-P of cytosolic part of NFAT, blocking T-cell activation by preventing IL-2 transcription
uses of tacrolimus
prophylaxis of solid-organ allograft rejection
eczematous conditions
GVHD: tacrolimus + MTX
ADR of tacrolimus
same as cyclosporine but no gum hyperplasia or hirsutism
*hyperglycemia, diabetes
MOA sirolimus and everolimus
inhibits T-lymph activation and proliferation downstream of IL-2
complexes with FKBP-12 and inhibits mTOR, blocking cell-cycle progression at G1->S phase transition
uses of sirolimus
prophylaxis of organ transplant rejection in combination with calcineurin inhibitor and glucocorticoids
ADRs of sirolimus
dose-dependent inc in serum cholesterol and TGs
anemia, leukopenia, thrombocytopenia
*no nephrotoxicity
specific ADR everolimus
hypersensitivity pneumonitis
role of TNF-a
cytokine secreted by MFs, mast cells, activated Th cells
stimulates MFs to produce cytotoxic metabolites and inc phagocytic killing activity
a/w autoimmune dz like RA, psoriasis, Crohn’s dz
etanercept
TNF-a blocker
fusion protein of Fc portion of IgG1 and TNF-R2
infliximab
TNF-a blocker
partially humanized mouse mab
adalimumab
TNF-a blocker
fully human IgG1 mab
uses of TNF-a blockers
RA, juvenile idiopathic arthritis
Crohn’s dz, ulcerative colitis
