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Flashcards in Immune suppressing drugs Deck (36):

TNF alpha

Tumor necrosis factor-alpha is a cytokine which mediates immune response by increasing the transport of white blood cells to sites of inflammation and through additional molecular mechanisms which initiate and amplify inflammation


Etanercept/ Enbrel

TNF alpha blocker
Class: DMARD, recombinant-DNA drug
• Indication: Moderate to severe rheumatoid
arthritis, moderate to severe polyarticular juvenile arthritis, psoriatic arthritis, ankylosing spondylitis and moderate to severe plaque psoriasis.
• MOA: Reduction of inflammatory response via anti-TNF alpha therapy.
• Char: **SQ**, dosed once or twice weekly. Supplied in powder or pre-mixed solution. injected subcutaneously, typically by the patient at home.


Etanercept/ Enbrel SE

• Side effects: Very broad side effect profile with notable decreased resistance to infection. Increasing number of reports of potential for increased risk for **leukemia**, **lymphoma** and solid tumors, as well as increasing number of reports of serious liver injury, congestive heart failure and demyelinating central nervous system disorders.
• Cost: $12,000 to 16,000+ per year


Infliximab/ Remicade

• Class: DMARD, recombinant-DNA drug
• Indication: RA, Crohn’s disease, U.C.
• MOA: According to product labeling,
Infliximab neutralizes the biological activity of TNFα by binding with high affinity to the soluble (free floating in the blood) TNFα and the trans-membrane (located on the outer membranes of T cells and similar immune cells) forms of TNFα, thus preventing the effective binding of TNFα with its receptors.
**Anti-TNF antibody! along with humira

Char: Infliximab is administered by intravenous infusion, typically at 6-8 week intervals. It cannot be administered orally, because the digestive system would destroy the drug.


infliximab treats:

psoriasis, Crohn's disease, ankylosing spondylitis, psoriatic arthritis, rheumatoid arthritis and ulcerative colitis.

"mab" suffix =antibody, recombinant


Infliximab/ Remicade vs Etanercept/Enbrel MOA

• Infliximab causes programmed cell death of TNFα expressing activated T cells but Enbrel does not have this activity.
• It is generally assumed that the effect on activated T cells by Infliximab explains its efficacy in Crohn's disease and U.C. **whereas Etanercept has shown no efficacy in treating inflammatory bowel disease.**


Hydroxychloroquine/ Plaquenil uses

• Hydroxychloroquine is a drug that was discussed in our review of anti-malarial agent.
• Hydroxychloroquine is also useful in treating rheumatoid arthritis, systemic lupus erythematosus and Sjögren's Syndrome.
• Hydroxychloroquine is also widely used in the treatment of post-Lyme arthritis that can be induced by Lyme disease.


Hydroxychloroquine/ Plaqueni MO

• While Hydroxychloroquine has been known for some time to increase lysosomal pH in antigen presenting cells, its mechanism of action in inflammatory conditions has been clarified further.
• It is now known that Hydroxychloroquine blocks the activation of toll-like receptors on plasmacytoid dendritic cells (PDCs).

• Toll-like receptor 9 (TLR 9), which recognizes DNA-containing immune complexes, leads to the production of interferon and causes the dendritic cells to mature and present antigen to T cells.

• By decreasing TLR 9 signaling, Hydroxy- chloroquine reduces the activation of dendritic cells which acts to limit the inflammatory process.


Hydroxychloroquine/ Plaquenil class/char/indications

• Class: Immunosuppressant and anti- malarial.
• Indication: RA, SLE, and Sjögren's Syndrome as well as malaria in area of the world ion which there is low risk for hydroxychloroquine resistant malaria.
• MOA: As noted. The action of the drug may involve an anti-spirochete activity as well as an anti-inflammatory activity.
char: oral


Hydroxychloroquine/ Plaquenil and eyes

need to do frequent dilated eye exams! corneas can become opaque.

Because of the possibility of corneal and macular damage, yearly dilated eye exams are indicated for all patients on chronic therapy even when they have no vision or ocular symptoms.


Hydroxychloroquine/ Plaquenil sx of overdose

Symptoms of overdose can occur within a half-hour of taking the medication. Overdose symptoms include drowsiness, headache, vision problems, shortness of breath, and convulsions.

Children are more sensitive to hydroxychloroquine than adults are, and small doses can be potentially fatal.


Hydroxychloroquine/ Plaquenil SE

• Side effects: ** GI** and retina***Abdominal cramps, diarrhea, reduced appetite, headache, nausea and vomiting, vision difficulties, tinnitus, hearing loss diminished reflexes, hives, itching, rash, loss of hair, weakness and anemia.
• **Patients with G6PD enzyme deficiency who take Hydroxychloroquine can develop a severe anemia and should be closely monitored if the drug is not stopped.Lysis of RBCs.


Gold salts

• Gold salt compounds act to reduce inflammation, especially related to RA, inflammatory bowel disease, psoriatic arthritis, membranous nephritis, lupus erythematosus and infrequently, juvenile rheumatoid arthritis.

• Gold salts are sometimes used for children with progressive poly-arthritis who are unresponsive to NSAIDs, Methotrexate, and other medications such as DMARDs.


Gold Salts MOA

MOA: The mechanism by which gold drugs operate to treat arthritis is a matter of scientific debate.
• Of the various mechanisms that have been suggested, gold is proposed as having anti-mitochondrial activity as well as potentially inducing cell apoptosis.


Gold salts char

• Gold drugs can be administered orally or by intramuscular injection, in which case it is administered weekly for ~three to five months before less-frequent doses begin.
• Auranofin (Ridaura) is the capsule form for oral administration that is marketed in the US.
• Orally administered gold has fewer side effects than intramuscular injections.


Gold salt types

Gold sodium thiomalate (Aurolateor or Myochrysine in the U.S.) and Aurothioglucose (Solganal in U.S.) are administered by injection. Regular urine tests to check for protein (indicating kidney damage) and blood tests are needed.
Cost = $500 to $700 per month


Immunosuppression indication

• Organ transplantation
• Treatment of autoimmune disorders and
various rheumatologic conditions esp. rheumatoid arthritis, in order to:
► Induce or maintain a remission
► Reduce the frequency of flare or relapse ► Allow tapering of glucocorticoids while
maintaining disease control


The major risk involved in the use of DMARD

he patient becomes more vulnerable to infections and malignancy.


Immunosuppression via corticosteroids MOA

Corticosteroids inhibit several populations of white cells and multiple cell mediators.
• Corticosteroids can inhibit the expression of genes encoding for cytokines such as IL-1, IL-2, IL-6, interferon alpha, and TNF-alpha.
• Corticosteroids also inhibit the proliferation of T-cells and diminish T-cell dependent immunity.


corticosteroid SE

Side effects include but are not limited to increased susceptibility to infection, poor wound healing, hyperglycemia, increased risk for osteoporosis, Cushing's syndrome, and potential adrenal suppression.


non-steroidal cytotoxic immunosupressors

Cyclophosphamide, Chlorambucil, Methotrexate, and Azathioprine.

prevent clonal expansion of both B and T lymphocytes.


Cyclosporine and Tacrolimus MOA

specifically target calcineurin and thereby inhibit the production of interleukin-2 by activated T-lymphocytes.
suppress the immune system by inhibiting the proliferation or function of lymphocytes.


Methotrexate/ MTX

Methotrexate/ MTX
• In the 1940's, Methotrexate was initially developed for leukemia therapy.
Methotrexate used in combination with another cytotoxic drug (i.e. Imuran, Cytoxan) or in combination with Enbrel (Etanercept), may be more beneficial than Methotrexate used alone for some people.
given earlier in the course of treatment may provide better results.


Methotrexate/ MTX

• Class: Anti-metabolite and anti-folate immunosuppressant and chemotherapeutic
• Indication: Cancer, autoimmune diseases, including rheumatoid arthritis, psoriasis, psoriatic arthritis, lupus and Crohn's disease as well as an abortifacient. MTX has also been used for multiple sclerosis but is not yet FDA approved for this indication.


Methotrexate/ MTX moa, char

• MOA: Anti-metabolite and anti-folate drug • Char: PO, IM, IV, SQ and IT (intra-thecal).
Oral doses are taken on a weekly not a daily. Routine monitoring of the CBC, LFTs, and creatinine are recommended. Assessment of creatinine levels are recommended at least every 2 months.


Methotrexate/ MTX SE

myelopathies, leukoencephalopathies-esp. intrathecally
• Side effects: The most common adverse effects include: nausea, abdominal pain, fatigue, fever, dizziness, ulcerative stomatitis, low white blood cell count and thus predisposition to infection. Other adverse effects include acute pneumonitis and rarely, pulmonary fibrosis.

folate can reduce SE


Methotrexate/ MTX labeling

CATEGORY X-abortefacient
• Methotrexate is a highly teratogenic drug and is considered category X by the FDA. Women must not take the drug during pregnancy, if there is a risk of becoming pregnant, or if they are breastfeeding. To engage in any of these activities (after discontinuing the drug), women must wait until the end of a full ovulation cycle.


Azathioprine/ Imuran

• Class: Purine anti-metabolite immuno- suppressant
• Indication: Prevention of transplant rejection, inflammatory bowel disease, SLE and rheumatoid arthritis.
• MOA: Metabolic breakdown products of Azathioprine act to inhibit purine synthesis which will block protein synthesis, particularly in cells that experience rapid turnover.
• Char: PO, IV. Imuran and its metabolites excreted primarily in the urine.


Azathioprine/ Imuran SE

• Side effects: Rapidly growing cells are most readily affected, leading to hair loss, bone marrow suppression, GI toxicity, leukopenia, and thrombocytopenia. Decreased ability to fight infection. Can cause pancreatitis. Known to cause birth defects.


Cyclosporine/ Sandimmune

• Class: An immunosuppressant drug derived from a soil fungus.
• Indication: Prevent rejection of kidney, liver and heart transplants as well as for treatment of RA and other autoimmune diseases such as severe psoriasis.
• MOA: T-cell inhibition. Blocks the signal to lymphocytes to produce IL-1, IL-2, IL-3, IL-4, and interferon gamma
• Char: PO, IV. Blood levels of Cyclosporine must be carefully monitored.


Cyclosporine/ Sandimmune SE

• Side effects: Nausea, vomiting, diarrhea, loss of appetite, high blood pressure, kidney damage, tremors, headaches, seizures, excessive hair growth, excessive gum growth, confusion, coma, and gout.
• As is the case with all immunosuppressive drugs, there is increased risk for infection leading to sepsis for any patient taking Cyclosporine.


Cyclosporine/ Sandimmune fun facts

• Blood levels of Cyclosporine are increased when patients drink grapefruit juice.
• Cyclosporine is metabolized by the P450 3A4 enzyme system (primarily found in the liver and small intestine).
• The effects of grapefruit juice on blood levels of Cyclosporine blood and on blood levels of other medications metabolized by this enzyme results from the inhibition of intestinal P450 3A4 by flavanoids (esp. bergamottin) found in grapefruit juice.


Tacrolimus/ Prograf

• Class: An immunosuppressant drug related to the macrolide class of antibiotics extracted from soil microorganism.
• Indication: Protection against rejection of organ transplantation. Topical treatment for severe eczema.
• MOA: T-cell inhibition similar to that of Cyclosporine. Tacrolimus is approximately 100x more potent in its immunosuppressive effects then an equal volume of Cyclosporine.
Char: PO, IV, topical. Very similar to Cyclosporine. Also metabolized by the P450 enzyme system so grapefruit juice need to be avoided to prevent accidental increased blood levels of the drug.


Tacrolimus/ Prograf SE

• Side effects: Also very similar to Cyclosporine in side effect profile with nausea, vomiting, diarrhea, loss of appetite, high blood pressure, kidney damage and increased risk for infection.



• Disease-modifying anti-rheumatic drugs (DMARDs) is a category of drugs used in many autoimmune disorders to slow down disease progression.
• The use of these drugs was first propagated in rheumatoid arthritis (hence the name) but has come to include many other diseases, such as Crohn's disease, lupus erythematosus (SLE), idiopathic thrombocytopenic purpura (ITP), myasthenia gravis and other conditions.



• Etanercept (Enbrel)
• Adalimumab (Humira)
• Infliximab (Remicade)
• Azathioprine (Imuran)
• Cyclosporine/ Sandimmune