Immunosupressive Drugs Flashcards
(34 cards)
Uses of immunosuppressive drugs (4)
- prevent rejection following organ transplant: life long treatment
- tx acute rejection episodes: short term treatment
- tx various autoimmune d/os: long-term tx
- tx allergies & asthma
Corticosteroids (prednisone) affect immune system : short term? long term? how?
SHORT TERM: ANTI-INFLAMMATORY effects occur rapidly (hours-days)
IMMUNOSPRESSIVE effects take time (SEVERAL WEEKS) to develop
affect most aspects of immune response
- DEPRESS MACROPHAGE FXN
- MODIFY fxn of T HELPER cells by inhibiting expression of genes for IL-1, IL-2, IL-6, interferon alpha and TNF-alpha
- INHIBIT RESPONSE of cytotoxic T cells & NKI cells to IL2 & other cytokines
- INHIBIT T CELL PROLIFERATION
- frequently used short term (2-3 mos) POST-TRANSPLANT to decrease likelihood of rejection
Corticosteroid uses (3)
- w/other immunosuprressives in transplant pts to prevent rejection
- minimize allergic response to antilymphocytic globulin or monoclonal antibodies
- AUTOIMMUNE DZs
Corticosteroids (SEs w/chronic use)
- HYPERGLYCEMIA -OSTEOPOROSIS
- suppression of HPA axis
- truncal obesity, moon face, buffalo hump, salt retention
T cell suppressants: name the 3 approved drugs
and what do they do
Cyclosporine (Sandimmune)
Tacrolimus (FK506; Prograf)
Sirolimus (Rapamune)
selectively inhibit fxn of T-lymphocytes
precent cell-mediated immunological rxns, such as rejection
Cyclosporine (Sandimmune; Neoral)
- inhibits T-cell activation w/out causing bone marrow suppression
- binds to cyclophilin, inhibiting fxn of CALCINEURIN, needed for ACTIVATION of T-cells
- used to prevent rejection in organ transplant pts
Cyclosporine: drug interactions, therapeutic range
drug intrxns are COMMON
1. pentobarbital, PHENYTOIN & RIFAMPIN induce CYP3A4 & DECREASE CNCTRN (PR decreases cyclosporine concentration)
- ERYTHROMYCIN, KETOCONAZOLE, GRAPEFRUIT JUICE & VERAPAMIL inhibit CYP3A4 & INCREASE CNCNTRTN (K-Veg increases cyclosporine concentration)
therapeutic range: NARROW
-monitor blood levels [rejection if dose too low, toxicity if dose to high]
Cyclosporine uses (4)
- prevent rejection in organ transplant patients (heart, kidney, liver, lung)
- may be combined w/other immunosuppressive drugs
- BONE MARROW transplants
- tx of various AUTOIMMUNE d/os (psoriasis, DM type 2, RA, IBD, severe asthma, etc)
Cyclosporine toxicity
potentially serious
GINGIVAL HYPERPLASIA,
HTN (in 30% of renal, almost all hrt transplant pts)
RENAL TOXICITY (very common, maintain fluid intake
HYPERGLYCEMIA
hirsuitism, hyperlipidemia, gallstomes
D, N/C, anorexia, abdominal pain
Tacrolimus; FK506 (Prograf): how does it work (2)
T cell suppressor
- INHIBITS FXN OF CALCINEURIN through binding FK506
- INHIBITS T-Cell activation & decreases IL-2 & IL-4
Tacrolimus; FK506 (Prograf): indications, administration, therapeutic range, spec instructions?
used more commonly than cyclosporine; (U) better tolerated
- DOC to PREVENT REJECTION
- “RESCUE” DURING A REJECTION EPISODE
- uses same as cyclosporine
IV, oral, topical for atopic dermatitis
narrow therapeutic range
FOOD DECREASES ABSORPTION BY >80%; BEST TAKEN ON AN EMPTY STOMACH
Tacrolimus; FK506 (Prograf): side effects
nephrotoxicity & HTN are dose limiting SEs, kidney fxn & BP are monitored frequently
HYPERGLYCEMIA is common, may require use of insulin
increase in OPPORTUNISTIC INFECTIONS & NEOPLASMA, ESP SKIN CA
Tacrolimus; FK506 drug intrxns
-metabolized by CYP3A4 (like cyclosporine)
NO GRAPEFRUIT JUICE WHEN TAKIN TACROLIMUS
narrow therapeutic range, BLOOD LEVELS MONITORED REGULARLY
-nephrotoxicity additive if given w/cyclosporine
Pimecrolimus (Elidel): use, administration, side effects, mechanism
CREAM used TOPICALLY for TX of ATOPIC DERMATITIS
- less likely to cause skin atrophy than corticosteroid creams
- burning & SKIN IRRITATION may occur initially
- mechanisms of action is similar to Tacrolimus
Sirolimus (Rapamune): what does it do, administration, absorption, metabolism, positive effects, negative effects
BLOCKS RESPONSE OF T-CELLS to IL2, inhibits B cell proliferation
- reduces rejection after kidney & heart transplants
- long-lasting effect
- NO renal damage (so starting to replace cyclosporine & tacrolimus)
oral absorption reduced significantly by food; metabolized by CYP3A4
may cause anemia, leucopenia, impair wound healing, increase cholesterol & TRIGLYCERIDES
Mycophenolate Mofetil (CellCept); Mycophenolate (Myfortic)
what does it do?
how is it administered? absorbed? excreted?
decrease proliferation
-inhibit inosine monophosphate dehydrogenase, needed for DE NOVO purine synthesis in T & B lymphocytes (specific for these cells, others don’t use this pathway
SELECTICLEY SUPPRESSES LYMPHOCYTE PROLIFERATION & ANTIBODY FORMATION by B cells
- inhibits recruitment of leukocytes to inflammatory sites
- given orally, rapidly absorbed, 90% excreted in urine
Mycophenolate Mofetil (CellCept); Mycophenolate (Myfortic): uses, side effects
Uses: combined w/cyclosporine or tacrolimus & glucocorticoids TO PREVENT REJECTION
-used in rejection episodes refractory to other drugs, or where other drugs aren’t tolerated
SEs:
GI most common: N/V, diarrhea, abdominal pain, constipation, dyspepsia, anorexia
-increased incidence of INFECTIONS & sepsis
-SKIN RASH; leucopenia possible
Azathioprine (Imuran): how does this think work
converted in vivo to 6-mercaptupurine, which inhibits de novo purine synthesis->blocks gene translation, inhibits cell proliferation, lymphocyte fxn, delayed hypersensitivity rxn & cellular cytotoxicity after transplant
Azathioprine (Imuran): Uses, SEs, interactions
adjunct to PREVENT REJECTION in organ transplant pts
tx of SEVER REHEUMATOID ARTHRITIS
SE: BONE MARROW SUPPRESSION: (C) leukopenia, thrombocytopenia, anemia
-increased risk of INFECTIONS, esp herpes
-N/V/D/pancreatitis/alopecia
-skin rashes, drug fever, (P) hepatotoxicity
FETAL TOXICITY: don’t use in pregao
AZATHIOPRINE IS METABOLIZED BY XANTHINE OXIDASE, in pts tx w/allopurinol (Xylorpim, the does of azathioprine must be reduces significantly)
Cyclophasphamide (Cytoxan): effects
direct effect on T and B lymphocytes, esp those that have undergone antigenic differentiation & division
CAN INHIBIT ESTABLISHED IMMUNE RESPONSE
Cyclophasphamide (Cytoxan): uses, side effects
ORGAN TRANSPLANT RESCUE & BONE MARROW transplants
tx of severe MS, RA, lupus
ANTINEOPLASTIC
SEs: HEMORRHAGIVE CYSTITIS: prevent w/hydration & MESNA
n/v
BONE MARROW SUPPRESSION
aspermia after 3-6 mos therapy, ovulation impairment, infertility
BLADDER fibrosis & carcinoma
alopecia
Methotrexate (Folex): mech of action, uses, SEs
inhibits DIHYDROFOLATE REDUCTASE: disrupts folate-dependent steps in purine synthesis, well absorbed orally, excreted by kidneys
uses: IMMUNOSUPPRESSION in organ transplant recipients
psoriasis
RHEUMATOID ARTHRITIS
SEs: BONE MARROW SUPPRESSION, alopecia, hepatotoxicity, FETAL DEATH-DO NOT USE IN PREGNANCY
Thalidomide (Thalomid)
SUPPRESSES TNF-alpha
USED FOR PRECENTION OF GRAFT-VS HOST
USES:
HIV-related wasting syndrome decrease ulcers
causes weight gain
SEs: PREGNANCY CATEGORY X-TERATOGENIC, drowsiness, dizziness, HA, neutropenia in up to 20% of HIV pts, constipation & peripheral neuropathy
Name 3 category X drugs (not all from immunosuppression lecture)
Thalidomide
Ribavirin
Efavirenz
