Immunopharmacology Flashcards
What are the categories of immunosupressive drugs?
- Glucocorticoids
- Calcineurin Inhibitors
- Proliferation Signal Inhibitors
- Inhibitors of Angiogenesis
- Cytotoxic Agents
- Other Agents
- Immunosuppressive Antibodies
What is the anti-inflammatory MOA of glucocorticoids?
- Inhibition of PLA2
- Reduction of transcription of COX-2
What are the short term and long term AE of glucocorticoids?
Short term: HTN, hyperglycemia, immunosuppression, psychotic reactions, and cognitive impairment
Long term: myopathy, Cushing’s syndrome, and osteoporosis
Cyclosporine MOA, Uses, AE, DI
Calcineurin Inhibitor
MOA: binds cyclopihllin to inhibit calcineurin which prevents activation of NFAT which would regulate IL-2 gene expression
Uses: organ transplantation, Uveitis, RA, Psoriasis
AE: nephrotoxicity, tremor, HTN, hyperglycemia, hyperlipidemia, osteoporosis, hirsutism, gum hyperplasia, little bone marrow toxicity
DI: metabolized by CYP3A4
Tacrolimus MOA, Uses, AE
Calineurin Inhibitor
MOA: binds FK-binding protein (FKBP) to inhibit calineurin
Uses: prevention of rejection of transplanted kidney/liver/hear, topical for atopic dermatitis, and psoriasis
AE: less severe nephrotoxicity, neurotoxicity, hyperglycemia, HTN, hyperkalemia, GI complaints
Sirolimus MOA, Uses, AE
Proliferation Signal Inhibitors
MOA: binds FKBP which binds and inhibits mTOR to prevent to block IL-2 driven T-cell proliferation
Uses: renal transplantation, sirolimus-eluting coronary stents
AE: myelosuppresion, hepatotoxicty (less than calcineurin inhibitors), diarrhea, hypertriglyceridemia, pneumonitis, HZ
Thalidomide MOA, uses
Inhibitor of angiogenesis
MOA: unclear but inhibits synthesis of TNF-alpha and angiogenesis
Uses: erythemia nodosum leprosum and multiple myeloma
What are the antimetabolites?
- Azathioprine
- Methotrexate
- Mycophenolate mofetil
- Leflunomide
Azathioprine MOA, uses, AE, DI
MOA: purine antimetabolite converted to 6-MP to inhibit de novo purine nucleotide synthesis > supression of B and T cell function and production of IL-2
Uses: prevention of organ transplant rejection, severe RA
AE: bone marrow suppression, GI disturbances, increase risk of infection/malignancies
DI: Allopurinol will increase Azathioprine
Methotrexate MOA, Uses, AE
MOA: inhibition of aminoimidazolecarboxamide ribonucleotide (AICAR) transformylase which catalyzes the final step of de novo purine syntheis leading to IMP > accumulation of AMP > broken down to adenosine a potent inhibitor of inflammation
Uses: RA, psoriasis, psoriatic arthritis, anklylosing spondylitis, SLP
AE: nausea, mucosal ulcers, leukopenia, anemia, GI ulcers, hepatotoxicity, cirrhosis (rare), hypersensitivity pneumonitis; reduced with leucovorin or folic acid but CI in pregnancy
Mycophenolate Mofetil MOA, Uses, AE
MOA: converted to mycophenolic acid which inhibits inosine monophosphate dehydrogenase in the de novo pathway of GTP synthesis
Uses: prophylaxis of transplant rejection, SLE
AE: N/V/D, abd pain, HA, HTN, reversible myelosuppression
Leflunomide MOA, uses, AE
MOA: prodrug of teriflunomide which inhibits dihydroorate dehydrogenase to derease levels of UMP essential for synthesis of pyrimidines
Uses: RA, SLE, Myasthenia gravis
AE: diarrhea, reversible alopecia, rash, myelosuppression, increase aminotransferase activity; CI in pregnancy and CBC and LFT monitored
Cyclophosphamide MOA, Uses, AE
MOA: alkylates DNA and other molecules in resting cells > destroy proliferating lymphoid cells
Uses: SLE and other autoimmune diseases
AE: infertility, bone marrow suppresion, hemorrhagic cystitis, bladder CA, acrolein metabolite can cause urine toxicity, long term use increases risk of infection/malignacy
Hydroxychloroquine MOA, Uses, AE
MOA: anti-inflammatory action is unclear
Uses: mild RA, lupus erythemaous but takes 3-6 months
AE: side effects rare, hemolysis pts with G6PD, and retinal damage
Sulfasalazine MOA, Uses, AE
MOA: metabolized by bacteria in colon to constituent moieties
Uses: UC, RA, Chorhn’s disease, ankylosing spondylitis
AE: N/V, HA, rash, neutropenia, thrombocytopenia, drug induced lupus, hemolysis in pts with G6PD
Antilymphocyte & Antithymocyte Antibodies Uses
Uses: stem cell transplantation, solid organ transplant
RHo(D) Immune Globulin Uses
Uses: prevention of Rh hemolytic disease in newborn
TNF-alpha Inhibitors MOA, Use, AE
-
Adalimumab - fully human IgG1 monoclonal
- Uses: RA, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, UC
-
Infliximab - chimeric monoclonal
- RA, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, UC
-
Etanercept - not true Mab with ligand binding portion of human TNF-a fused to Fc of human IgG1
- RA, ankylosing spondylitis, psoriatic arthritis
MOA: bind TNF-alpha to prevent its interaction with its receptor
AE: cytopenias (monitor CBC), increase infection/malignacy risk, not given with active infection or live vaccination, pts screened for TB/HBV, GI ulcer, exacerbate HF
Omalizumab MOA, Uses
MOA: binds IgE to prevent binding to mast cell
Uses: asthma refratory to ICS and evidence of allergic sensitization, chornic uticaria
Basilizimab MOA, uses
MOA: IL-2 receptor antagonist; chimeric human-mouse IgG
Uses: prevent renal transplant rejection
Anakinra MOA, Uses
MOA: IL-1 receptor antagonist
Uses: moderate-severe RA
Abatacept MOA, Uses
MOA: fusion protein that interferes with T cell activation
Uses: moderate-severe RA
What are the immunostimulants?
- Aldesleukin
- Interferons
- Bacillus Calmette-Guerin (BCG)
Aldesleukin MOA, uses
MOA: recombinant IL-2
Uses: renal cell carcinoma, malignant melanoma
Interferon-a/b/g uses
- Interferon-a: hairy cell leukemia, chornic myelogenous leukemia, malignant melanoma, Kaposi’s sarcoma, hepatitis B/C
- Interferon-b: relapsing multiple sclerosis
- Interferon-g: chronic granulomatous disease
Bacillus Calmette-Guerin (BCG) MOA, uses, AE
MOA: live attenuated mycobacterium bovis which is active against tumors
Uses: tx/prophylaxis of carcinoma of urinary bladder
AE: hypersensitivity, shock, chills, fever, malaise, immune complex disease
