Exam 3: Anti-Inflammatory Drugs

Front 1

NSAIDs

Back 1

inhibit COX enzymes but have no inhibitory activity on the lipoxygenase. have analgesic, antipyretic & antiinflammatory activities. anti-inflammatory effects is higher (about twice) of the analgesic/antipyretic dose.

Front 2

Aspirin

Back 2

its inhibition is irreversible (serine active site). The COX enzyme more affected by this reaction is the one present in platelets and mediates platelet aggregation. Aspirin increases acid secretion and decreases mucus protection.

Front 3

Non-Acetylated Salicylates (Choline salicylate, Na-salicylate, Methyl salicylate, Salsalate)

Back 3

Non-acetylated salicylates inhibit COX1 and COX2 (reversible). they cause little or no inhibition of platelet aggregation. Salsalate (a prodrug) releases two molecules of salicylate in an alkaline environment (small intestine) => Safe for gastric mucosa.

Front 4

Propionic Acid Derivatives (Ibuprofen, Naproxen, others)

Back 4

Ibuprofen causes less gastric bleeding and less inhibition of platelet aggregation. Ibuprofen may reduce the anti-platelet aggregation effects of aspirin. Because naproxen is COX1 selective the risk for MI and strokes is lower.

Front 5

Propionic Acid Derivatives Naproxen + Esomeprazole (Vimovo)

Back 5

esomeprazole, a proton pump inhibitor (PPI). treating osteoarthritis (OA), rheumatoid arthritis (RA) and ankylosing spondylitis (AS) while lowering the risk of developing NSAID-associated gastric ulcers.

Front 6

Propionic Acid Derivatives Naproxen + Lansoprazole (Prevacid Naprapac)

Back 6

lansoprazole (Prevacid), a proton pump inhibitor (PPI). treating osteoarthritis (OA), rheumatoid arthritis (RA) and ankylosing spondylitis (AS) while lowering the risk of developing NSAID-associated gastric ulcers.

Front 7

Diclofenac + Misoprostol (Arthrotec)

Back 7

misoprostol (Cytotec), a prostaglandin analog. Misoprostol can protect against NSAID-associated gastric ulcers. Misoprostol may precipitate diarrhea and uterine contractions (leading to pregnancy loss).

Front 8

Second Generation NSAIDs (COXIBs) COX2 inhibitors (Celecoxib (Celebrex), Rofecoxib (Vioxx),
Valdecoxib (Bextra), others.)

Back 8

can also induce gastric ulcers, are as effective as 1st generation NSAIDs, NSAIDs, can cause renal failure, increase the risk of MI and stroke, do not, or poorly, inhibit platelet aggregation

Front 9

Celecoxib (Celebrex)

Back 9

At therapeutic levels it selectively inhibits COX2 but not COX1. Drug-drug interactions: Celecoxib contains sulfur => it can precipitate an allergic reaction in patients allergic to sulfonamides. Celecoxib may increase the anticoagulant effects of warfarin.

Front 10

Steroidal Anti-Inflammatory Drugs (SAIDs) Glucorticoids (GC)

Back 10

Glucorticoids block both branches of the eicosanoid synthetic pathway. They alter gene expression. They inhibit cellular processes that mediate inflammation. They suppress phagocyte infiltration to the site of inflammation and reduce lymphocyte proliferation.

Front 11

Acetaminophen (Tylenol)

Back 11

Preferentially inhibits COXs located in the brain and other CNS tissues (COX3). relieves pain and fever by its CNS action without causing GI damage or anti-inflammatory action. Unlike aspirin, for fever and minor pain in children

Front 12

Phenacetin (Saridon)

Back 12

Phenacetin is a pro-drug that is rapidly transformed into acetaminophen. This process can be saturated and excess of phenacetin is converted to nephrotoxic products. no longer used in the U.S.

Front 13

Glucocorticoids
Prednisone (Deltasone)
Prednisolone (Hydeltasol)

Back 13

inhibition of antigen presenting cells and lymphocyte function. Block interleukin-1 (IL-1) production. Block lymphocyte proliferation.

Front 14

Cyclosporine (Sandimune, Neoral) & Tacrolimus (FK506, Prograf)
Inhibitors of the signaling pathway coupling T/B-cell receptor activation to IL-2 gene transcription (IL-2 signals clonal expansion of T-cells and B-cells).

Back 14

Drug targets are immunophilin binding proteins that regulate the Ca++-dependent protein phosphatase“Calcineurin”
=> Cyclosporine binds cyclophilin
=> Tacrolimus binds FKBP-12

Front 15

Sirolimus (Rapamycin, Rapamune)
IL-2 receptor signaling blocker

Back 15

It blocks IL-2 receptor signaling required for Tcell activation and proliferation. It forms a complex with the immunophilin FKBP-12, it inhibits the mTOR kinase, (and consequently PHAS-1 & p70 S6) blocking cell cycle progression at G1 > S.

Front 16

Azathioprine (AZA, Imuran)

Back 16

Cleaved to 6-mercaptopurine by nucleophiles (glutathione).
Inhibits de novo purine synthesis and can be converted to thio-GTP causing DNA damage upon incorporation.

Front 17

Mycophenolate Mofetil (MMF, Cellcep)

Back 17

MMF is a prodrug. Desterification produces mycophenolic acid (MPA) MPA is a potent inhibitor of inosine monophosphate dehydrogenase (IMPDH) which is critical for de novo purine synthesis. Interaction with drugs for tubular secretion in renally-impaired patients.

Front 18

Methotrexate (MTX, Rheumatrex)

Back 18

Inhibits dehydrofolate reductase, an enzyme required for thymidylate synthesis. Second-line drug for autoimmune disease (continuous low dose). Not used for transplantation. Effective in inducing abortions (e.g., ectopic pregnancies).

Front 19

Cyclophosphamide (Cytoxan, Neosar)
Nitrogen mustard class of alkylating agent

Back 19

Prodrug activated by p450 system. Alkylates DNA leading to inhibition of DNA replication and transcription. Second-line drug for autoimmune disease (continuous low dose). Only used for bone marrow transplantation.

Front 20

Leflunomide
Approved for rheumatoid arthritis
Solid organ transplantation

Back 20

Prodrug
Inhibitor of pyrimidine synthesis

Front 21

Hydroxychloroquine
Antimalarial (a quinoline)
Rheumatoid arthritis and systemic lupus
Used to treat/prevent graft-host disease

Back 21

Suppresses intracellular antigen processing, and increases pH within lysosomes and endosomes in T-cells
Must be administered with caution in patients with G-6-PD deficiency

Front 22

Etanercept & Infliximab
TNF-α inhibitors have shown therapeutic efficacy in the treatment of numerous autoimmune diseases including, rheumatoid arthritis, psorasis, Crohn’s disease, etc.

Back 22

Etanercept & infliximab (and also adalimumab, certolizumab & golimumab) bind to tumor necrosis factor-α (TNF-α), preventing it from activating TNF receptors. Etanercept may also bind TNF-β. Before treatment, patients must undergo TB screening

Front 23

Golimumab (Simponi)
Golimumab is a fully human mAb directed against TNF-α

Back 23

Golimumab (Simponi) (alone or in combination with methotrexate), is used for the treatment of moderate to severe rheumatoid arthritis and active psoriatic arthritis. Golimunab is also used for active ankylosing spondylitis (subQ injections).

Front 24

Thalidomide (Thalomid)
TNF-α Inhibitor

Back 24

originally developed for treating morning sickness during pregnancy.
for treating severe complication from leprosy, multiple myeloma and as an immunosuppressive drug.

Front 25

Anakinra (Kineret)
IL-1 Inhibitor and used for rheumatoid arthritis
Biological Response Modifier (BRM) because it is able to selectively target pathologic elements of the disease.

Back 25

Anakinra acts similarly to endogenous IL-1RA). Subcutaneous injection. It can be applied alone or in combination with disease-modifying antirheumatic drugs (DMARDs) except for TNF-α inhibitors.

Front 26

Ustekinumab (Stelara)
Humanized mAb directed against the p40 subunit shared by IL-12 and IL-23
Psoriasis & multiple sclerosis

Back 26

binds the p40 subunit of IL-12 inhibiting natural killer cell activation, CD4+ cell differentiation and activation.
binds the p40 subunit of IL-23 inhibiting the differentiation of ‘naïve’ T-cells blocking the secretion of IL-17 and IL-22.

Front 27

Tocilizumab (Actemra)
Cytokine receptor antagonists
Humanized mAb directed against IL-6 receptors
Rheumathoid arthritis

Back 27

binds IL-6 receptors producing (pure) antagonistic effects

Front 28

Anti-thymocyte globulin (Atgam)
used in transplantation, in the treatment of moderate to severe aplastic anemia in patients who are unsuitable for bone marrow transplantation, help reduce graft versus host disease (GvHD)

Back 28

Rapidly lowers numbers of circulating lymphoid cells. Impairs lymphocyte action. Available in solution for IV administration. May be recognized as a foreign protein.

Front 29

Muromonab-CD3 (Anti-CD3, Orthoclone, OKT-3)
used in solid organ transplantation, in cancer detection and therapy
Mouse mAb directed against T-cell CD3 surface proteins.

Back 29

Blocks formation of antigen recognition complex and activation of T-cell receptors (CD3).
Rapid inactivation and elimination of T-cells. Available in solution for IV administration.
May be recognized as a foreign protein.

Front 30

Rh0(D) Immunoglobulin (Rhogam, Gammulin)
Prevention of hemolytic disease in newborns. Rh0(D)(-) mother carrying Rh0(D)(+) fetus.

Back 30

Administration in advance of anti-Rh0(D) antibodies block primary immune response to exposure to the Rh0(D) antigen. Available in solution for IV administration.