Exam One; Therapeutic Use, MOA, AE. ; inflammatory mediators, nsaid, immunosuppressants, RA, gout Flashcards
- Therapeutic use: Antipyretic, analgesic. Given in 325mg doses.
- MOA: Inhibits COX. Peroxides inhibit function; antioxidants stimulate.
- AE: Liver toxicity
- Notes: Treat toxicity with N-acetylcysteine.
- Toxicity: Liver in large doses (10g); GSH inactivates with P450
Acetaminophen
• Therapeutic Use: RA! antipyretic, Antiplatelet, analgesia, anti-inflammatory, prevents MI prophylactically.
• MOA: irreversibly Acetylates COX; salicyclate competitively inhibits. Inhibits thromboxane A2 synthesis.
o Nonimmunologic – defect in mast cell histamine storage and shunting of arachidonic acid Lipox pathways.
• AE: Everything imaginable!
• Notes: Do not give to pregnant chick in labor. Can cause a gout flare up. Large doses can stimulate glucocorticoid secretion. Epinephrine release => hyperglyemia
• Toxicity: 50-80 = respiratory alkalosis; 80-110 = metabolic acidosis; >160 = respiratory acidosis/ death.
Aspirin
- Therapeutic Use: used in acute gouty attacks.
* MOA: an NSAID that inhibits PG synthase and urate crystal phagocytosis.
Indomethacin
- Therapeutic Use: Hormonal agent/ Adrenocorticosteroid. part of MOPP and CVPP
- MOA: glucocorticoid receptor; regulates transcription of specific proteins involved in the metabolism and inflammatory response.
- AE: Cushing’s and immunosuppression
Prednisone
• MOA: binds cortisol-receptor complex and directly affects DNA to decrease cytokines, and impair macrophage, T cell and B cell function.
• AE: Affect renal secretion and need to do a withdrawal process.
o Toxicity: Cushings can develop with long term use.
• Notes: Vasoconstricts, and decreases capillary permeability.
Dexamethasone
• Therapeutic Use: Calcineurin inhibitor. Transplant rejection, autoimmune diseases (RA), ophthalmic emulsion.
• MOA:
o Cyclosporin: Binds cyclophilin C to decrease cytokine production and lower T cell response. Met by CYP3A4. Inhibits synthesis of IL-1 and IL-2.
o Tacrolimus: binds FK506 to inhibit calcineurin => lower cytokine production and T cell response. Much more potent than cyclosporine.
• AE: Serious but reversible nephrotoxicity (dose limiting), stimulates TGF-B which may lead to cancer
Notes: eryhthromycin, ketoconazole, amphotericin B, and grapefruit juice inhibit metabolism. Phenobarbital and rifampin increase clearance. Metabolized by CYP450 3A.
Cyclosporin A
Tacrolimus (FK506)
• Therapeutic Use: Antiproliferative agent. Oral, transplant rejection
• MOA: Binds FKBP-12 but doesn’t inhibit calcineurin, inhibits mTOR to inhibit T cell activation
• AE: Thromboytopenia, leucopenia, hyperlipidemia.
• Notes: No effect on cytokines.
o Rap(e) is Sirious! Unless you yell surprise.
Sirolimus (Rapamycin, Rapamune)
- Therapeutic Use: oral and IV combine with corticosteroids to inhibit transplant rejection and RA.
- MOA: Prodrug; inhibits purine and inosinic acid synthesis. Cytotoxic agent; anti prolif
- AE: Bone marrow suppression, GI toxicity, mild hepatotoxicity. Carcinogenic and mutagenic.
- Notes: Co-administeration with allopurinol may increase toxicity.
Azathioprine
- Therapeutic Use: Oral and IV, Combine with cyclosporine (calcineurin inhibitor) and corticosteroids to prevent transplant rejection.
- MOA: inhibits inosine monophosphate DH => lower purine synthesis and T/B lymphocytes.; anti prolif
- AE: Diarrhea, leukopenia, cytomegalovirus.
Mycophenoate mofetil
- Therapeutic Use: SIP-R agonist; oral; Multiple sclerosis
- MOA: Lymphocyte homing
- AE: lowers HR, infection, macular edema… Fetal risk
- Notes: Additive effect w/ beta blockers to heart. Met by CYP4F2. Avoid live attenuated vaccines.
Fingolimod
S1P-R Agonist
- Therapeutic Use: depletes T lymphocytes. Can be used with corticosteroids.
- MOA: purified equine Ig against human thymus thymocytes.
- AE: Hypersensitivity, Nephritis and anaphylaxis
Antithymocyte globulin
- Therapeutic Use: acute kidney, hepatic, cardiac transplant rejection
- MOA: binds CD3 glycoprotein on T lymphocytes (T cells cant recognize foreign Ag).
- AE: Flu-like symptoms
Muromonab-CD3
- Therapeutic Use: prevents renal transplant rejection.
- MOA: Block IL-2 receptor on T lymphocytes.
- AE:
- Notes: Give with cyclosporine and orticosteroids.
Basiliximab
Daclizumab
- Therapeutic Use: RA, Crohns
- MOA: IV infused. anti-TNF-a mab (Chimeric IgG1).
- AE: infusion reaction, Upper res and UTIs, rarely a SLE like symptom.
- Notes: function improves with methotrexate or other DMARDs.
Infliximab
- Therapeutic Use: RA, psoriatic arthritis, ankylosing spondylitis.
- MOA: Given SC. contains ligand binding sequence of human TNF-a receptor fused to IgG1.
- AE:
- Notes: fully human IgG1 and anti-TNF –mab. Down regulates macrophage and T cell function.
Etanercept
- Therapeutic Use: RA DMARD.
- MOA: Inhibits AICAR and decreases PMN chemotaxis, lowers lymphocyte and macrophage function.
- AE: Don’t use if PREGGERS. Nausea and mucosal ulcers. Must check for TB (macrophage dependent infection).
- Notes: absorbed and hydroxylated in GI. Good for juvenile RA also. Should do a folic acid supplementation. Give with leucovorine.
Methotrexate
- Therapeutic Use: RA and juvenile chronic arthritis.
- MOA: met by intestinal bacteria to a derivative of salicyclic acid. Decreases production of IgA and IgM
- AE: Serious side effects.
Sulfasalazine
• Therapeutic Use: Gout
• MOA: PO; competitive inhibition of xanthine oxidase. Metabolized to oxipurinol.
o Minor: depletes 5’-phosphoribosyl pyrophosphate and inhibits 5’-PRPP aminotransferase to reduce de novo purine synthesis.
• AE: Renal insufficiency hypersensitivity, GI, peripheral neuritis, necrotizing vasculitis, hepatic toxicity
• Notes: Not antagonized by salicyclates. Cyclophosphamide will increase toxicity. 1 tablet per day
Allopurinol
Inhibitors of Uric Acid Synthesis
- Therapeutic Use: Gout
- MOA: PO; non-purine like, potent and selective inhibitor of xanthine oxidase.
- AE:
- Notes: Good for chronic gout or pt who cant take allopurinol. Liver metabolized and urine excreted. Use with colchicine or NSAIDs initially. No dosage adjustments required.
Febuxostat
Inhibitors of Uric Acid Synthesis
- Therapeutic Use: Uricosuric against gout.
- MOA: PO; decrease renal active secretion of other compounds. Increase renal excretion of oxipurinol
- AE: GI intolerance, dermatitis, nephrotic syndrome.
- Notes: use for pt with allergic rxn to allopurinol with normal renal function. Can be given with colchicine prophylactically.
Probenecid
Uricosuric Agents
- Therapeutic Use: prophylactic, adjunct therapy to uricosurics and inhibitors of uric acid synthesis.
- MOA: PO every 2 hours or IV. Prevents leukocyte migration and urate crystal phagocytosis. Liver deacetlyated.
- AE:
- Notes:
Colchicine
• Therapeutic Use: use in hyperuricemia in peds cancer pt.
• MOA: IV; Catalyzes uric acid conversion to allantoin.
• AE: limited by SE; Ab production, acute renal failure, anaphylaxis, GI abnormalities.
Notes: produced by saccharomyces cerevisiae strain. Lowers urate levels better than allopurinol
Rasburicase
