Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
60 Cards in this Set
- Front
- Back
|
immune responses become harmful if they lead to |
chronic inflammation without resolution of the underlying injurious process; chronic inflammation involves the release of multiple cytokines and chemokines plus a very complex interplay of immunoactive cells; the whole range of autoimmune diseases (e.g. RA, vasculitis, SLE) and inflammatory conditions (e.g. gout) derive from abnormalities in this cascade |
|
|
what happens in cell damage associated with inflammation |
acts on cell membranes to release leukocyte lysosomal enzymes; arachidonic acid is then liberated form precursor compounds; lipoxygenase pathway of arachidonate metabolism yields leukotrienes which have a powerful chemotactic effect on eosinophils, neutrophils, and macrophages and promote bronchoconstriction and alterations in vascular permeability; during inflammation stimulation of the neutrophil membranes produces oxygen derived free radicals and other reactive molecules such as hydrogen peroxide and hydroxyl radicals; interaction of these substances with arachidonic acid results int he generation of chemotactic substances perpetuating the inflammatory process |
|
|
what are the 2 goals of treatment of pts with inflammatory disorders |
Relief of symptoms and the maintenance of function, which are usually the major continuing complaints of the patient= NONSTEROIDAL ANTI INFLAMMATORY DRUGS (NSAIDS), ASPIRIN, AND ACETAMINOPHEN, GLUCOCORTICOIDS; Slowing or arrest of the tissue-damaging process= DISEASE MODIFYING ANTIRHEUMATIC DRUGS (DMARDS) |
|
|
name the glucocorticoids |
Betamethasone, dexamethasone, methylprednisolone, prednisolone, PREDNISONE, triamcinolone (just know predisone, dexamethasone, and prednisolone) |
|
|
name the traditional DMARDS |
Methotrexate,azathioprine, cyclophosphamide, hydroxychloroquine, leflunomide, mycophenolate mofetil, sulfasalazine, cyclosporine; tofacitinib (marketed as a biologic) is actually anonbiologic DMARD |
|
|
name the biologic DMARDS |
Abatacept, adalimumab, ANAKINRA, certolizumab pegol, ETANERCEPT, golimumab, INFLIXIMAB, rituximab, tocilizumab |
|
|
glucocorticoids: sides effects |
significant toxicity associated with high doses and long term therapy; low dose corticosteroids have disease modifying properties, their toxicity makes them less favored than other medications; continue to have a significant role in the long term treatment of arthritis |
|
|
glucocorticoids: important effects on intermediary metabolism and immune function |
Most likely due to their ability to modify cellular functions; Cellular immunity is more affected than humoral immunity; Increases catabolic rate of IgG, lowering effective concentration of specific antibodies; Mineralocorticoids= principally salt-retaining activity; Corticoids with androgenic or estrogenic activity |
|
|
glucocorticoids: mechanisms of action |
Effects mediated by glucocorticoid receptors widely distributed in body= Physiologic effects (insulin and glucagon, catecholamine responses), Metabolic effects (carbohydrate, protein, fat metabolism), Catabolic and antianabolic effects in lymphoid tissues, connective tissue, muscle, peripheral fat, andskin; responsible for thinning of skin, osteoporosis reduced growth in children during long-term administration, ANTIINFLAMMATORY AND IMMUNOSUPPRESSIVE EFFECTS |
|
|
glucocorticoids: antiinflammatory and immunosuppresive effects= leukocytes, cytokines, chemokines |
Profound effects on concentration, distribution, and function of peripheral leukocytes= CONCENTRATION OF PMN IN CIRCULATION INCREASE (increased movement from bone marrow to blood and decreased migration from blood vessels), CONCENTRATION OF LYMPHOCYTES, MONOCYTES, EOSINOPHILS, AND BASOPHILS DECREASE (movementfrom vascular bed to lymphoid tissue), Restricts accumulation of PMNs and Mφ in tissue; Suppressive effectson inflammatory cytokines and chemokines and other mediators of inflammation |
|
|
glucocorticoids: antiinflammatory and immunosuppresive effects= macrophages, lymphocytes, phospholipase A2, COX-2 |
Effectson MACROPHAGES,other APCs= Reduces ability to respond to antigens and mitogens , Limitsability to phagocytose and kill microbes, Reduces ability to produce TNF-α, IL-1, metalloproteinases and plasminogen activator in the innate response and IL-12 for the Th1 response; Effect on LYMPHOCYTES= Reduces ability to produce INF-γ, reduced activation of macrophages in Th1 response; Inhibition of PHOSPHOLIPASE A2= Reduced synthesis of arachadonic acid (precurosor for prostaglandins, leukotrienes), Reduced synthesis of, platelet-activating factor; REDUCED EXPRESSION OF COX-2 (inducible) in inflammatory cells so reduced ability to produce prostaglandins |
|
|
glucocorticoids: antiinflammatory and immunosuppresive effects= effect on skin, effect on complement system, effect on antibodies |
Cause vasoconstriction when applied directly to the skin= Suppress mast cell degranulation, Decrease capillary permeability by reducing the amount of histamine released by basophils and mastcells; No effect on complement activation, but its effects are inhibited; Large doses reduce antibody production |
|
|
glucocorticoids: naturally occurring glucocorticoids |
Naturally-occurring glucocorticoids (cortisol)= Very sensitive to negative feedback by circulating cortisol and exogenous (synthetic) glucocorticoids, Short acting, cortisone metabolized to hydrocortisone, 90%PROTEIN BOUND (corticosteroid-binding globulin [tightly] and albumin [loosely]), METABOLIZED IN TISSUES AND LIVER, EXCRETED IN URINE; CORTISONE (PO/topical)/ HYDROCORTISONE (PO/IM/IV/topical/combos) |
|
|
glucocorticoids: synthetic glucocorticoids |
Similar pharmacokinetics except bind albumin rather than CBG so more available; Short to medium-acting; in order of longevity= PREDNISONE (PO)/ PRESDNISOLONE (PO/ophth) / METHYLPREDNISOLONE (PO/IV/IM), Prednisone metabolized to prednisolone ; Intermediate= TRIAMCINOLONE (IM/ topical/ inhaled/ intranasal/ intravitreal/ intralesional); Long-acting= DEXAMETHSONE (IM/IV/PO/ophth), BETAMETHASONE (IM/PO/IL) |
|
|
glucocorticoids: indications, dosing |
Indications= RA(60-70%), slowing the appearance of new bone erosions, during periods of exacerbation, GOUT, VASCULITIS including granulomatosis with polyangiitis, microscopic polyangiitis, giant cell arteritis, SLE, MCTD, polymyalgia rheumatica, sarcoidosis, MECHANICAL JOINT AND TISSUE INJURIES like osteoarthritis, bursitis, tendinitis, carpal tunnel; KEEP DOSAGE AS LOW AS POSSIBLE (below 7.5 mg/d)= Even 3-5 mg/d can cause adverse effects in susceptible individuals when used overprolonged periods; USE INTERMITTENT ADMINISTRATION if therapeutic results can be obtained; INTRA-ARTICULAR CORTICOSTEROIDS are often helpful to alleviate painful symptoms and, when successful, arepreferable to increasing the dosage of systemic medication |
|
|
glucocorticoids: contraindications, cautions, drug interactions |
Contraindications= similar for all, Untreated serious infections; Cautions= similar for all , Pre-existing conditions: cirrhosis, ocular herpes simplex, hypertension, diverticulitis,thyroid disease, seizure disorders, hypothyroidism, myasthenia gravis, pepticulcer disease, osteoporosis, ulcerative colitis, psychotic tendencies,untreated systemic infections, renal insufficiency, pregnancy, Monitor anyone with positive PPD, Delayed wound healing is possible, Risk of cleft palate if used during pregnancy; Drug interactions depend on specific glucocorticoid, Prednisolone: contraindicated 1, serious 73, significant 224, minor 127, Dexamethasone: contraindicated 17, serious 110, significant 281, minor 136 |
|
|
glucocorticoids: adverse effects, monitor carefully for the development of what |
Adverse effects are MANY, type depends on use and specific glucocorticoid= Short-termuse: sleeping difficulties, dyspepsia, increased appetite, tremulouness, anxiety/psychosis, Long-term use: Cushing syndrome, obesity, diabetes, osteoporosis, immune suppression leading to infections, cataracts, depression, hirsutism, myopathy, thromboembolism, weight gain, Withdrawal symptoms: severe fatigue, weakness, body aches, joint pain; Monitor carefully for the development of= Hyperglycemia, glycosuria, Sodium retention with edema or hypertension, hypokalemia, Pepticulcer, Osteoporosis, Hidden infections |
|
|
approach to treatment of rheumatic disorders |
Slowing or arrest of the tissue-damaging process= Disease modifying antirheumatic drugs (DMARDS)= Slow-acting compared with NSAIDS and glucocorticoids:2 weeks to 6 weeks to 6 months, Decrease inflammation, improve symptoms, and slow the bone damage associated with RA, They affect more basic inflammatory mechanisms than do glucocorticoids or the NSAIDs, They may also be more toxic than those alternative medications; Biologic (large molecule, often produced by recombinant DNA technology) and non-biologic (small molecule) |
|
|
name the non biologic DMARDs |
Methotrexate, Leflunomide, Hydroxychloroquine, Sulfasalazine, Cyclophosphamide, Azathioprine, Mycophenolatemofetil, Cyclosporine, Tofacitinib= NEW, may not have been discussed |
|
|
methotrexate: MOA, pharmcokinetics |
Mechanism of action= antimetabolite, Inhibition of amino-imidazole carboxamide ribonucleotide (AICAR) transformylase (AICAR accumulates intracellularly and competitively inhibits AMP deaminase --> increased AMP, Released AMP --> adenosine so inhibits inflammation, Suppresses inflammatory functions of PMN, Mφ, DC, lymphocytes), Secondary effect on PMN chemotaxis, Direct inhibitory effect on proliferation of and stimulates apoptosis in immune-inflammatory cells, Inhibits proinflammatory cytokines linked to rheumatoid synovitis; Pharmcokinetics= LOW doses, Oral 70% absorbed, Metabolized to less active hydroxylated product, Serum half-life 6-9 h polyglutamated metabolite and parent compound remain in cells for long periods |
|
|
methotrexate: principle uses, adverse effects |
Principle uses= RHEUMATOID ARTHRITIS, juvenile chronic arthritis (decreases the rate of appearance of new erosions), Psoriaticarthritis, ankylosing spondylitis, polymyositis, dermatomyositis, granulomatosiswith polyangiitis, giant cellarteritis, other vasculitides, and systemic lupus erythematosus; Adverse effects= Mucosal ulcers and nausea |
|
|
leflunomide: MOA, pharmacokinetics, principle use, adverse effects |
Mechanism of action= Undergoes rapid conversion to A77-1726, its active metabolite, Inhibits dihydroorotate dihydrogenase --> decreases ribonucleotide synthesis --> arrest of stimulated cells in G1 phase of growth, Inhibits T cell proliferation, reduces autoantibody production by B cells; Pharmacokinetics= A77-1726 has plasma half-life of 19 days, Subject to enterohepatic recirculation; Principle use= RA (inhibits bony damage), especially with methotrexate; Adverse effects= Diarrheain 25%, Elevation in liver enzymes |
|
|
hydroxychloroquine (antimalarial): MOA, indications, adverse effects |
Mechanism of action= Thought to suppress intracellular antigen processing and loading of peptides onto MCH class II molecules by increasing the pH of lysosomal and endosomal compartments, Thus, decreases T cell activation; Indications= SLE: skin manifestations, serositis, andjoint pain; Adverse effects= Ocular toxicity, although not usually at lower doses used for SLE, Ophthalmologic monitoring every 12 months advised |
|
|
salfasalazine: MOA, pharmacokinetics, principle uses, adverse effects |
Mechanism of action= Metabolized to SULFAPYRIDINE (probableactive moiety for RA) and 5-aminosalicylic acid (probable active moiety forIBD), Decreases IgA and IgM rheumatoid factor production, In vitro, inhibition of inflammatory cytokine production, T cell responses to mitogen, and B-cell proliferation; Pharmacokinetics= Oral administration, 10-20% absorbed, Active sulfapyridine well-absorbed; 5-aminosalicylic acid unabsorbed, Sulfapyridine excreted after modification in liver; Principle uses= RA (reduces radiologic disease progression), Juvenile chronic arthritis, ankylosing spondylitis, psoriatic arthritis, inflammatory bowel disease; Adverse effects= 30% discontinue use because of toxicity, Nausea, vomiting, headache, rash, Neutropenia in 1-5%, Reversible infertility occurs in men, but not in women |
|
|
cyclophosphamide: MOA, pharmacokinetics, principle uses, adverse effects |
Mechanism of action= Active metabolite phosphoramide mustard cross-links DNA, Suppresses T- and B-cell function by 30-40%, Tcell suppression correlates with clinical response in rheumatic diseases; Pharmacokinetics= low doses, 2-3mg/kg/day or 500 mg every 2 weeks (for vasculitis) compared with 60-120 mg/kd/day or 1000 mg in 5 days (for cancer), Bioavailability 75%; metabolized by liver; excreted in urine; Principle uses= Vasculitis (eg, granulomatosis with polyangiitis), SLE; Adverse effects= Hemorrhagic cystitis (prevent with mesna) at higher doses, lengthy administration |
|
|
azathioprine: MOA, pharmacokinetics, principle uses, adverse effects |
Mechanism of action= Purine antimetabolite 6-thioguanine suppresses inosinic acid synthesis, B-celland T-cell function, Ig production, IL-2 secretion; Pharmacokinetics= Rapid metabolizers (active thiopurine methyltransferase [TPMT]) clear drug four times faster than slow metabolizers, Persons with low or absent TPMT (0.3% population) are at high risk of myelosuppression if dosage is not adjusted; Principle uses= Maintenance of remission in vasculitis, RA; Adverse effects= Bone marrow suppression, GI disturbances |
|
|
mycophenolate mofetil: MOA, principle uses, adverse effects |
Mechanism of action= Converted to mycophenolic acid, Inhibits inosine monophosphate dehydrogenase, Suppresses T- and B-cell proliferation, Interferes with leukocyte adhesion to endothelial cells by inhibition of E-selectin, P-selectin, and ICAM-1; Principle uses= SLE: RENAL DISEASE (nephritis), possibly in vasculitis; Adverse effects= Nausea,dyspepsia, abdominal pain |
|
|
cyclosporine (peptide antibiotic): MOA, pharmacokinetics, principle use, adverse effects |
Mechanism of action= Regulates gene transcription by inhibiting calcineurin, Inhibits IL-1 and IL-2 receptor production, Secondarily inhibits Mφ-T-cell interaction, T-cell-dependent B-cell function; Pharmacokinetics= Microemulsion formulation improves bioavailability (20-30%), Grapefruit juice increases bioavailability by 62%, Metabolized by CYP3A, large number of drug interactions; Principle uses= RA (retards appearance of new bony erosions), psoriasis; Adverse effects = Leukopenia, thrombocytopenia, lesser extent anemia |
|
|
tofacitinib: MOA, pharmacokinetics, indications, adverse effects |
Mechanism of action= Selectively inhibits all members of the Janus kinase family, primarily JAK3 and JAK1, which inhibits signal transduction from the common γ-chain receptor (IL-2RG) for IL-2, -4, -7, -9, -15, and -21, Prevents differentiation, proliferation, and function of NK cells and T and B cells, loss of signal transduction from IL-6 and interferon receptors; Pharmacokinetics= Oral, targeted DMARD with 74% bioavailability, Metabolized in liver by CYP3A4; Indications= PTS WITH SEVERELY ACTIVE who have failed or are intolerant of methotrexate [Testing for IBD, SA, and other diseases, not licensed]; Adverse effects = INCREASED RISK FOR INFECTION, LYMPHOMA AND OTHER MALIGNANCIES, Neutropenia and anemia require discontinuation of drug |
|
|
name the biologic DMARDs |
1 T-cell-modulating biologic = abatacept; 1 B-cell cytotoxic agent = rituximab; 1 anti-IL-6 receptor antibody = tocilizumab; 3 IL-1-inhibiting agents = anakinra, rilonacept, canakinumab ; 5 TNF-α-blocking agents = etanercept,infliximab, adalimumab, certolizumab pegol, golimumab; NEW– B cell stimulator antagonist |
|
|
human antimouse antibodies (HAMAs): how do you make them, what are the types, how do you name them |
Murine antibodies administered as such to human patients elicit production of HAMAs = Clear the original murine proteins very rapidly, And can result in serum sickness (type III hypersensitivity); HUMANIZATION involves replacing most of the murine antibody with equivalent human regions while keeping only the variable, antigen-specific regions intact (“-Umab” or“-ZUmab” for humanized antibodies); CHIMERIC MOUSE-HUMAN ANTIBODIES have similar properties with less complete replacement of the murine components (“-Omab” or“-XImab” for chimeric products (human/foreign)) |
|
|
abatacept (T cell): MOA, pharmacokinetics, principle uses, adverse effects |
Mechanism of action= COSTIMULATION MODULATOR, CTLA-4, binds to CD80/86 inhibiting its binding to CD28, PREVENTS ACTIVATION OF T CELLS; Pharmacokinetics= Given IV at 0, 2, 4 weeks (induction) then monthly, Used as monotherapy or with methotrexate or other DMARDS; Principle uses= Moderate to severe RA, JIA; Adverse effects= Increased risk of infections (URTI), anti-abacept antibodies in <5%, increased risk of lymphoma (unclear), Screen patients for latent tb and viral hepatitis |
|
|
rituximan (B cell): MOA, pharmacokinetics, principle uses, adverse effects |
Mechanism of action= CHIMERIC anti-CD20 binds to B cells and induces cell-mediated and complement-mediated cytolysis; stimulates cell apoptosis, Decrease in B cells decreases presentation of antigen to T cells, inhibiting secretion of proinflammatory cytokines; Pharmacokinetics= IV infusions 2 week apart then repeated every 6-9 months as needed; Principle uses= With methotrexate for moderate to severe active RA in those who have inadequate response to one or more TNF-a antagonists, With glucocorticoids for granulomatosis with polyangiitis and microscopic polyangiitis; Adverse effects= 30%develop rash with 1st infusion, decreases with each course of therapy, Serious,sometimes fatal, bacterial, fungal, and viral infections reported for up to one year of last dose, Associated with reactivation of HBV (test before therapy) |
|
|
tocilizumab (anti-IL06 receptor): MOA, pharmacokinetics, principle uses, adverse effects |
Mechanism of action= Humanized antibody that binds to soluble and membrane-bound IL-6 receptors inhibiting IL-6-mediated signaling (antagonist), Inhibits T-cell activation, hepatic acute-phase protein synthesis, and stimulation of inflammatory processes involved in rheumatologic diseases; Pharmacokinetics= Given IV, half-life is 11 days or 13 days depending on dose, Inhibits IL-6, which mayrestore CYP450 activities to higher levels, may necessitate dosage adjustment of drugs like warfarin or cyclosporine; Principle uses= Adults with moderate to severe RA, who have inadequate response to one or more DMARDs; Adverse effects= Serious infections (tb, fungal, viral, other opportunistic; URTI), Headache, hypertension, elevated liver enzymes, Anti-to cilizumab antibodies in 2%, hypersensitivity requiring discontinuation |
|
|
anakinra (recombinant ILL-1RA): MOA, pharmacokinetics, principle uses, adverse effects |
Mechanism of action= IL-1RA binds to IL-1 receptors but does not initiate the intracellular signaling pathway, Competitive inhibitor of IL-1α andIL-1β, thereal ligands of IL-1Rs; Pharmacokinetics= Given daily subcutaneously, 95% bioavailability, 4 to 6-h terminal half-life; Principle uses= Oldest of the three drugs in the family, use in CAPS (familial cold auto inflammatory syndrome), particularly in neonates, USE IN GOUT; Adverse effects (common to all)= Injection site reactions (up to 40%), URTI |
|
|
other IL-1 antagonists: canakinumab and rilonacept: MOA, pharmacokinetics, indications |
canakinumab: Mechanism of action= HumanIgG1/K against IL-1b, Prevents its binding to IL-1R; Pharmacokinetics= Subcutaneous injections, 66% bioavailability, 26-day mean terminal half-life; Indications= CAPS, gout; rilonacept: Mechanismof action= Ligand-binding domain of IL-1R–BindsIL-1b neutralizing it; Pharmacokinetics= Subcutaneous, Steady-state plasma concentration after 6 weeks; Indications= CAPS, gout |
|
|
why in gout? |
IL-1 |
|
|
TNF-alpha blocking agents: MOA in general |
TNF-α appears to be particularly important in the inflammatory process, especially in RA ; TNF-α affects cellular function via activation of specific membrane-bound TNF receptors (TNFR1, TNFR2) |
|
|
adverse effects of TNF-alpha-blocking agents |
Risk of bacterial infections and macrophage-dependent infection (including tuberculosis, fungal, and other opportunistic infections) is increased; Activation of latent tuberculosis is lower with etanercept than with other TNF-α-blocking agents;but screen all patients for latent tb; Associated withincreased risk of HBV reactivation; screen for HBV before starting the treatment; Increase the risk of skin cancers—including melanoma—which necessitates periodic skin examination, especially in high-risk patients; Anti-drug antibodies in about 17% of cases= May interfere with drug efficacy and correlate with infusion site reaction, Injection site reactions occur in 20–40% of patients, although they rarely result in discontinuation of therapy |
|
|
infliximab: MOA, pharmacokinetics, principle uses |
Mechanism of action= Chimeric (25%mouse, 75% human) IgG1 monoclonal antibody that binds with high affinity to soluble and possibly membrane-bound TNF-α --> down regulation of Mφ andT-cell function; Pharmacokinetics= IV at0, 2, and 6 weeks (induction) and maintenance every 8 weeks after, Elicits human antichimeric antibodies in up to 62% of patients; Formation of humananti-monoclonal antibody isdecreased when given with methotrexate; Principle uses= RA, psoriasis, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, ulcerative colitis, pediatric IBD |
|
|
etanercept: MOA, pharmacokinetics, principle uses |
Mechanism of action= Recombinant fusion protein consisting of 2 soluble TNF p75 receptors moieties linked to Fc portion of human IgG1, Binds TNF-α and TNF-β (lymphotoxin); Pharmacokinetics= Given subcutaneously once or twice weekly, Slowly absorbed, peak-concentration 72 hours post administration, Serume limination half-life of 4.5 days, Monotherapy or with methotrexate; Principle uses= RA, juvenile chronic arthritis, psoriasis, psoriatic arthritis, and ankylosing spondylitis, Also scleroderma, granulomatosis with polyangiitis, giant cell arteritis, uveitis, sarcoidosis, Behçet’s disease |
|
|
adalimumab: MOA, pharmacokinetics, principle uses |
Mechanism of action= Fully-human IgG1 anti-TNF monoclonal antibody, Complexes with soluble TNF-α prevents interaction with p55 and p75 cell surface receptors --> down regulation of Mφ and T-cell function; Pharmacokinetics= Given subcutaneously every other week, Clearance is decreased by 40% when given with methotrexate, Formation of human anti-monoclonal antibody decreased with methotrexate; Principleuses= RA, ankylosing spondylitis, psoriatic arthritis, JIA, plaque psoriasis, Crohn’s disease, ulcerative colitis; decreases the rate of formation of new erosions |
|
|
certolizumab: MOA, pharmacokinetics, principle uses |
Mechanism of action= Recombinant humanized Fab conjugated to polyethylene glycol (PEG) with specificity for human TNF-α, Neutralizes soluble and membrane-bound TNF-α --> down regulation of Mφ andT-cell function; Pharmacokinetics= Given subcutaneously and has a half-life of 14 days, Concomitant methotrexate decreases the appearance of anti-certolizumab antibodies; Principle uses= Adults with moderately to severely active RA, also Crohn’s disease, active PA, activeAS |
|
|
golimumab: MOA, pharmacokinetics, principle uses |
Mechanism of action= Human monoclonal anti-TNF antibody witH high affinity for soluble and membrane-bound TNF-α --> down regulation of Mφ and T-cell function; Pharmacokinetics= Given subcutaneously every 4 weeks, Clearance is decreased when given with methotrexate, Formation of human anti-monoclonal antibody decreased with methotre; Principle uses= Adults with moderately to severely active RA, ankylosing spondylitis, psoriaticarthritis, moderate to severe ulcerative colitis |
|
|
belimumab: MOA, pharmacokinetics, principle use, adverse effects |
Mechanism of action= Humanized antibody that specifically inhibits B-lymphocyte stimulator (BLyS), BLyS is a naturally occuring protein required for survival and development of B cells into mature plasma cells that produce antibodies, Restores potential for autoantibody-producing B cells to undergo normal process of apoptosis; Pharmacokinetics= Administered IV: induction at weeks 0, 2, 4, and every 4 weeks thereafter, Terminal half-life of 19.4 days; Principle use= Approved only for the treatment of adult patients with active, seropositive SLE who are receiving standard treatment; Adverse effects= Nausea, diarrhea, and respiratory tract infection. |
|
|
intravenous immune globulin (IVIG): MOA, pharmacokinetics, uses, adverse effects |
Mechanism of action: a different approach to immunomodulation= Prepared from pools of 3000-10,000 of healthy donors, no single, specific antigen is the target, Expected to have a normalizing effect upon the patient’s immune networks (A reduction of T helper cells, increase of regulatory T cells, Decreased spontaneous immunoglobulin production, Fc receptor blockade, Increased antibody catabolism, Idiotypic-anti-idiotypic interactions with “pathologic antibodies”); Pharmacokinetics= Given in high doses 2g/kg, half-life 21 days; Uses= Kawasaki disease -reduces systemic inflammation, prevents coronary artery aneurysms, Systemic lupus erythematosus, dermatomyositis, scleroderma, other skin diseases, Refractory idiopathic thrombocytopenic purpura; Adverse effects= Infusion reactions – headache, flushing, chills, myalgia, wheezing, tachycardia, lower back pain, nausea, hypotension, Traces of IgA may cause severe anaphylactic reactions in IgA-deficient patients |
|
|
so treatment levels in rheumatoid arthritis |
initial therapy= 1. methotrexate 2. add leflunomide; moderate to high disease activity= 1. methotrexate plus hydroxychloroquine 2. methotrexate plus hydroxychloroquine salfasalazine; long duration disease= 1. anti-TNF drugs (etanercept, inflixumab) 2. with or without methotrexate 3. other drugs if failure or intolerance |
|
|
treatment levels in osteoarthritis |
nonphamacologic= a. lifestyle modification 2. weight loss 3. PE 4. assistive devices; pharmacologic= 1. acetaminophen (mild) 2. NSAIDs plus misoprotsol or PPI if high dose 3. intra articular glucocorticoids; surgery= 1. joint modification 2. joint replacement |
|
|
treatment levels in systemic lupus erythematosus |
if arthritis, myalgia = NSIADS, prednisone, methotrexate; if dermatitis, arthritis, serositis = hydroxychloroquine; if lupus nephritis = mycophenolate, mofetil, other immunsuppressives |
|
|
treatment levels in antiphospholipid syndrome |
with SLE= LMW heparin followed by warfarin, treat SLE as above; without SLE= LMW heparin followed by warfarin; high risk pregnancy= LMW heparin, warfarin post delivery |
|
|
treatment levels in mixed connective tissue disease |
SLE like features= NSAIDs, or hydroxychloroquine, or prednisone (arthritis), or methotrexate; raynaud syndrome= calcium channel blockers; GERD= proton pump inhibitors |
|
|
treatment levels in systemic sclerosis |
primary symptomatic= no therapy reverses source of disease; raynaud syndrome= calcium channel blocks; kidney disease= ACE inhibitors; GI tract= PPIs (omeprazole) |
|
|
treatment levels in inflammatory myopathies (dermatomyositis, poymyositis) |
muscle component= prednisone plus immunosuppressive agent (methotrexate, azathioprine, cyclophosphamide, mycophenolate mofetil, or leflunomide); akin disease= topical prednisone, hydroychlororquine, or methotrexate, or ycophenolate mofetil, or IVIG |
|
|
treatment levels in sjogren's syndrome |
dry tissues= lubricants (tears, saliva, vaginal); systemic symptoms= 1. acetaminophen, 2. NSAIDs, 3. prednisone; vascilitis= prednisone, IVIG |
|
|
A 48-year-old man presents with complaints of bilateral morning stiffness in his wrists and fingers and pain in these joints. The stiffness resolves with activity. On physical examination, the joints are slightly swollen. The rest of the examination is unremarkable. Laboratory tests were ordered and the patient was begun on symptomatic therapy immediately. What is the best treatmentfor a patient presenting with an undiagnosed arthritic condition?A.Acetaminophen B.Allopurinol C.Methotrexate D.NSAID E.Prednisone |
D. NSAID; A. Acetaminophen– osteoarthritis; B.Allopurinol– intercritical gout; C.Methotrexate– firstline drugof choice for RA; D.NSAID –inflammatory arthritis of unknown etiology; E.Prednisone– not at first for mild disease |
|
|
Hislaboratory findings are also negative except for slight anemia, elevatederythrocyte sedimentation rate, and positive rheumatoid factor. Whatis the best diagnosis for this patient?A.AnkylosingspondylitisB.OsteoarthritisC.ReactivearthritisD.RheumatoidarthritisE.Systemiclupus erythematosus |
D. rheumatoid arthritis; BILATERAL morning stiffness in his WRISTS AND KNEES and pain in these joints, the STIFFNESS RESOLVES WITH ACTIVITY |
|
|
with this diagnosis, and assessment of low disease activity, what therapy should be initiated? a. azathioprine b. infliximab c. leflunomide d. methotrexate e. sulfasalazine |
D. methotrexate; A. Azathioprine– not usually used for RA but for maintenance therapy in vasculitis; B. Infliximab– reserved until nonbiologicDMARDs are tried; C. Leflunomide –second line; D. Methotrexate- DOC; E. Sulfasalazine– second line |
|
|
what is the MOA of the drug of choice?A.Bindswith high affinity to soluble and possibly membrane-bound TNF-αB.Cross-linksDNAC.Inhibitsamino-imidazolecarboxamideribonucleotide (AICAR) transformylaseD.Inhibitsdihydroorotatedihydrogenase, arrestingstimulatedcells in G1 phaseE.Sulfapyridinemetabolite decreases IgAand IgM rheumatoid factor production |
C. inhibits AICAR; A. Bindswith high affinity to soluble and possibly membrane-bound TNF-α - infliximab; B. Cross-linksDNA – cyclosphosphamide; C. Inhibitsamino-imidazolecarboxamideribonucleotide (AICAR) transformylase – methotrexate at low doses for RA; D. Inhibitsdihydroorotate dihydrogenase, arrestingstimulated cells in G1 phase – leflunomide; E. Sulfapyridinemetabolite decreases IgA and IgM rheumatoid factor production – sulfasalizine |
|
|
Three months later, he returns with increased joint symptoms. His hands, wrists, elbows, feet, and knees are all now involved and appear swollen, warm, and tender. He now has moderate/high disease activity. What therapeutic option should be considered at this time? A.Add leflunomide B.Addsulfasalazine C.Addinfliximab D.Switch to abacept E.Any of these options would be acceptable |
E. any of these potions would be acceptable |
|
|
Thedecision is made to add infliximab to the methotrexate therapy he is currentlyreceiving. What major side effect could occur from the infliximab? A.CushingsyndromeB.DiarrheaC.Increasedriskof infectionsD.MucosalulcersE.Oculartoxicity |
C. increased risk of infections; A. Cushingsyndrome- glucocorticoids; B.Diarrhea- leflunomide; C.Increasedrisk ofinfections– all TNF-αinhibitors; D.Mucosalulcers- methotrexate; E.Oculartoxicity - hydroxychloroquine |
