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34 Cards in this Set
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Immunosuppressants
listed |
Corticosteroids
Cyclosporine, tacrolimus Mycophenolate Azathioprine -Cyclophosphamide Methotrexate Thalidomide Etanercept Immune Globulins Anti-thymocyte Rho(D) Immune globulin -Monoclonals Murononab-CD3 Infliximab |
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Corticosteroids
as immunosuppressants named moA adv. Rxs indications |
Mechanism of action-gold standard
Lyse and promote redistribution of lymphocytes from blood Increased apoptosis of lymphocytes Anti-inflammatory-******* suppress all cytokines and mediators of inflamm---- here large doses Adverse effects Adrenal suppression—anytime systemic –inhale not much Increased risk of infections*****----huge factor Formation of ulcers Increased risk of osteoporosis----also cataracs Don’t forget growth retardaTION******* Indications Organ transplant----cornerstone….common Autoimmune |
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Cyclosporine, Tacrolimus & Sirolimus
moA |
Mechanism of action
all three Interfere with T cell function*****(only) by binding to immunophilins inhibiting calcineurin that stimulates cytokine production underlying T-cell Receptor activation. (thus not total increase in infection) Cyclo-THIS DRUG CHANGED THE WORLD |
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Cyclosporine binds
thus |
cyclophilin
Both (Tacrolimus)disrupt calcineurin activity to inhibit activation of cytosolic nuclear factor of activated T cells (NF-AT) that promotes interleukin-2 production Both inhibit production of cytokines********key mechamism—by slight dif mech……theoretically may use superadditive |
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Tacrolimus binds
thus |
FK-binding protein 12
Both (cyclosporin also)disrupt calcineurin activity to inhibit activation of cytosolic nuclear factor of activated T cells (NF-AT) that promotes interleukin-2 production Both inhibit production of cytokines********key mechamism—by slight dif mech……theoretically may use superadditive |
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Sirolimus binds
thus |
FK-binding protein that complexes with mammalian target of Rapamycin
Blocks activation of T-Cells in cell cycle to disrupt proliferation of the cells Inhibits the response to interleukin-2************ but does not alter production ****Interleukin-2 can be antagonist to all three (theory) |
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Cyclosporine, Tacrolimus, and Sirolimus
Adverse effects |
Adverse effects---can be nasty
Renal failure—problem used AS renal (is it toxic or reject)---so do we inc or dec Dose?---if reject important to incr dose (or test by doing it) Hypertension Neurotoxicity Hyperglycemia**** These inhibit use of sirolimus Hyperlipidemia*** (especially sirolimus) Hepatoxicity*** (especially sirolimus) Myelosuppression** (especially sirolimus) |
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Cyclosporine, Tacrolimus, and Sirolimus
p-kinetics-scenes indications |
Pharmacokinetics
Orally active (all) or injectable (cyclosporine and tacrolimus) Cyclosporine***** has variable bioavailability and required careful adherence to dosing procedures (ritualize effective dose when found)***** Elimination is by biotransformation(complex) with high potential for interactions—dose allready at edge of toxic** We should predict response Indications Organ transplants----prevent initiation (THEY STOP BEGINNING)*******others used to stop rejection |
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Cyclosporine as Restasis
? |
Indicated for inflammation-associated ocular dryness (only in inflammation)
Ophthalmic drops (topical) Should not be used during ocular infections (depress eye immune response) Relatively low systemic side effects Common side effects are ocular irritation |
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Azathioprine
moA indications |
(Azasan, Imuran)
Mechanism of action (anti cancer-ish) drug is liked Converted first to mercaptopurine (anticancer drug) and then to false nucleotides that inhibit purine pathways (incorporates) Inhibits T cell function more than B cell function (but both so inc infect) Powerful anti-inflammatory action Indications Autoimmune disorders Organ transplants |
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Azathioprine
Ad. RXs p-kinetics |
--Pharmacokinetics
Orally absorbed Biotransformed*******careful with allopurinal increases azathioprine(like mercaptopurine)****** Adverse effects---typical anticancer Bone marrow depression Increased risk of infections Gastrointestinal upset and ulcers Hepatotoxicity Carcinogenicity-all inc. sec. cancer |
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Mycophenolate Mofetil
Mechanism of action Indications |
(CellCept)
Mechanism of action-not really a cancer drug but sim mech Converted to mycophenolic acid, inhibits purine synthesis Suppresses both T and B cell activation T and B cells are very sensitive to purine synthesis inhibition (both so incr. infection) Indications Organ transplants |
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Mycophenolate Mofetil
Adv rxs |
(purine inhibitor)
Gastrointestinal upset and ulceration Bone marrow suppression Increased risk of infection |
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Cyclophosphamide
moA indications |
Converted to alkylating agent that irreversibly complexes with DNA
Toxic to most proliferating cells Greatest effect on B cells (but both = ^ infections) Indications Autoimmune diseases Organ and tissue transplants |
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Cyclophosphamide
adv Rx |
(an alkylator)
Adverse effects---typical cancer Bone marrow depression Increased risk of infections Gastrointestinal upset and ulcers Hepatotoxicity ****Bladder cystitis******* (may become hemorrhagic) ------hydrate*****---though lower than conc. Of chemo but used chronically not in cycles) Sterility |
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Methotrexate
moA indic. |
(Rheumatrex Dose Pack)
Inhibitor of dihydrofolate reductase****** Inhibition leads to depletion of reduced folates and inhibits purine synthesis*** Toxic to most proliferating cells Greatest effect on B cells (both thus incr infection) Indications Popular in RA-- Autoimmune diseases Organ and tissue transplants |
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Methotrexate
adv Rx |
Adverse effects ( give reduced folate to avoid many of the SEs (low dose in RA) here used low doses but chronically
Bone marrow depression Increased risk of infections Gastrointestinal upset and ulcers Hepatotoxicity |
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Thalidomide
moA indic |
Mechanism of action-
(bad history---was sedative in morning sickness guy----teratogenic bigtime---now back) Suppresses tumor necrosis factor-α production***** Anti-angiogenic action*****may explain some SEs Indications---powerful inti inflam Leprosy Cancer Immune disorders Wasting syndrome in AIDS |
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Thalidomide
adv. Rx |
Adverse effects
Teratogenic ******(Pregnancy category X)*************** Limited access in US (MUST USE TWO FORMS BC)has been succesful Anti-angiogenic action may be mechanism of terato Sedation (was used as sleep aid) Bone marrow depression Peripheral neuropathy Hypertension---historical was original thought for not passing FDA |
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Etanercept
moA indic |
(Enbrel)
Mechanism of action Recombinant human tumor necrosis factor receptor****(just binding domain but considered R) Binds the inflammatory TNF-α Blocks the inflammatory response Decreased interleukin release Indications Rheumatoid arthritis Limited access |
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Etanercept
advRx |
Adverse effects—increases with every use it is a PROtein –tnf-a pretty broad based action
Increased risk of infections Rash Urinary tract complications Injection site reactions |
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Infliximab
moA indic |
Chimeric IgG1 antibody
Human constant regions Mouse variable regions (careful in mouse allergy) Binds Tumor Necrosis Factor-α Suppresses cytokine synthesis and release Indications Crohn’s disease Rheumatoid arthritis |
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Infliximab
adv rx |
Adverse effects
Hypersensitivity Common effects Fever, chills, aches, flu-like symptoms Serious effects Increased risk of infections Hypersensitivity reactions Congestive heart failure exacerbation(as with Ab) Activation of latent tuberculosis (important concern)***********pretest for TB*****and tough to treat cause we are hurting the immune sytem- |
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Anti-thymocyte Globulin
moA indic |
(ATG, Thymoglobulin)
Derived from rabbit, horses or sheep immunized with human T-lymphocytes There are some horse-derived forms also available (may have sens. To one animal) Cytotoxic antibodies to surface T-cell antigens Direct cytotoxicity (complement and cell-mediated) and blockade of remaining lymphocytic function (take out the proliferating T-CELLS)*********not discriminatory Indications ******Acute transplant rejection*****************, usually with other agents---a rescue agent (one of only two) When you stop Tx the whole LINE is gone (not like steroids-comes back) |
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Anti-thymocyte Globulin
adv Rx |
Adverse effects----not pleasant
Hypersensitivity---can be serious Fever and chills Hypotension******** Minimize above by pretreatment with corticosteroids, acetaminophen, or antihistamines (STANDARD process with multifold) |
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Rh0(D)
moA indic adv Rx |
(MICRhoGAM, RhoGAM)
Human IgG preparation of antibodies to human red blood cell Rh0(D) antigens Indications Prevention of Rh hemolytic disease in newborns Inhibition of Rh+ antibody production in women Feedback immunosuppression Feto-maternal reactions related to Rh events (this to avoid rejection in the SECOND preg) Adverse effects Generally well tolerated |
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Muromonab-CD3
moA indic |
(Orthoclone Okt3)
Obtained from mouse (murine) watch sensitive Anti-CD3 Monoclonal Antibodies Antibody directed at the CD3 antigen on the surface of T-lymphocytes Blocks antigen recognition site that triggers cell signaling and proliferation Indications Acute organ transplantation rejection*********** |
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Muromonab-CD3
adv RXs |
Adverse effects--nasty
Hypersensitivity ( tends to be more of the severe) (often second-line to ATG) Cytokine release syndrome ***************(t-cell lysis) High fever, chills/rigor, headache, nausea and vomiting, diarrhea, abdominal pain, muscle/joint aches and pain, and generalized weakness Minimized by pretreatment with corticosteroids (standard)—stabalize things anti-inflam Severe reactions can include seizures, pulmonary edema, respiratory distress and cardiovascular collapse. |
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Immunoenhancers
listed |
cytokines-Aldesleukin (rIL-2),Epoetin alfa (Epogen, Procrit),Sargramostim (GM-CSF, Leukine)
Bacille Calmette-Guérin (adjuvant) |
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Aldesleukin (rIL-2)
moA |
a cytokine-
Recombinant interleukin-2 (rIL-2)--preferred Lymphokine that stimulates production of T cells and activates killer cells Indications Adjunctive therapy for renal carcinoma HIV?---(experimentally) also theory antidote of the others( not really very effective or used) Adverse reactions Cardiovascular toxicity (capillary leak syndrome)(blood leak) |
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Epoetin alfa
moA adverse |
(Epogen, Procrit)
Erythropoietin---now ass. With cardiovascular probs (now used more testosterone) Stimulates red blood cell production |
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Sargramostim
moA adverse |
(GM-CSF, Leukine)
Granulocyte-macrophage colony stimulating factor Stimulates granulocyte and macrophage production Commonly used to stimulate bone marrow activation after transplantation (and in chemo to shorten cycle time) May include donor (actually more used here) as well as recipient (too high dose can have pain) |
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Cytokines
adverse reaction |
Aldesleukin (rIL-2),Epoetin alfa (Epogen, Procrit),Sargramostim (GM-CSF, Leukine)
Adverse effects Flu-like symptoms Hypertension----high dose Renal abnormalities Stroke, seizures and myocardial infarctions (esp epo) |
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Bacille Calmette-Guérin
all about |
BCG-
Mycobacterium bovis (viable attenuated strain) used in some countries as a immunization for tuberculosis (similar enough) Activates macrophages with subsequent increase in immune function (trick us into) Indicated for treatment of some bladder cancers Instilled into bladder and held for 2 hours ( hard) Adverse effects Hypersensitivity Flu-like symptoms Renal complications-rare Note, patients treated with BCG may test positive for tuberculosis on skin tests (use chest X-ray to be sure) |
