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Pharm III Test III


What is a chronic inflammatory disease principally involving synovial membranes of joints but with extra-articular manifestations? Rheumatoid Arthritis
What does the unknown etiologic agent do in RA? initiate a nonspecific immune response
What is the earliest inflammatory changes in joints in RA? inflammation and occlusion of small subsynovial vessels suggesting agent carried in circulation
RA begins as a inflammatory lesion and progresses to a proliferative on and destroys what? adjacent cartilage and bone
What are the goals of therapy in RA? 1) relief of symptoms, 2) maintenance of joint function and ROM, and 3) prevention of deformity
What is the nonpharmacologic therapy for RA? education, psychosocial, systemic/articular rest, exercise, heat/cold, assistive devices, lifestyle/diet, and physical medicine
What is the Salicylate NSAID most patients are initially treated with? Aspirin
Why is Aspirin usually effective? due to anti-inflammatory action
What drugs are equivalent to ASA, and some respond to one better than others? Nonsalicylate NSAIDs (COX-2 specific inhibitors, Celebrex)
What is Glucocorticoids mechanism of action? Inhibit synthesis of chemical mediators; suppress infiltration of phagocytes averting damage from lysosomal enzymes; & suppress proliferation of lymphocytes reducing the immune component of inflammation
The anti-inflammatory effects of glucocorticoids are what in comparison to NSAIDs? greater
What treatment is glucocorticoids indicated for? adjunctive treatment of acute exacerbations of RA with generalized symptoms
When may Glycocorticoid injections be used? When one or two joints are effected
What type of use should oral administration of Glucocorticoids be restricted to? Short-term therapy whenever possible, most often given to provide relief until drugs with slower onset can provide control
Who should Long-term therapy of glucocorticoids be given to? limited to those who have failed to respond adequately to all other forms of treatment
What are the adverse effects of Glucocorticoids? adrenal insufficiency, osteoporosis, infection, glucose intolerance, myopathy, fluid and electrolyte disturbances, growth retardation, psychologic disturbances, cataracts, peptic ulcer disease, iatrogenic Cushing's Syndrome
who is Glucocorticoids contraindicated in? those with systemic fungal infections and those receiving live-virus vaccines
How is Glucocorticoids D/C? slowly; tappered off
What DMARD agent is considered first-line agent for most patients with RA? Methotrexate
How quick is Methotrexate's onset of action? Relatively rapid; therapeutic doses (6-8 weeks)
The majority of patient's continue to take Methotrexate for how many years and why? 5 years; and because of its efficacy and tolerability
What is Methotrexate effective in treating? reducing signs and symptoms of RA and slowing or halting radiographic damage, psoriatic arthritis and other spondyloarthopathies, and many other autoimmune diseases
What is Methotrexate's mechanism of action? Anti-inflammatory effects are related to interruption of adenosine and possible effects on TNF pathways. Immunosuppressive and toxic effects are due to inhibition of an enzyme involved in the metabolism of folic acid, dihydrofolate reductase
What is the dosage for Methotrexate? Starting at 10mg per week; increased to 20mg by week 8; Max dose is 25mg per week
How is Methotrexate administered? PO or SQ
What much you check prior starting a patient on Methotrexate? Renal insufficiency, acute or chronic liver disease, significant ETOH intake or abuse, leukopenia, thrombocytopenia, or untreated folate deficiency
What effect does Salicylates and other NSAIDs and Trimethoprim (Bactrim & Septra) have on Methotrexate? They block the renal excretion of Methotrexate
Can Methotrexate be administered with NSAIDs? Yes, as long as liver function tests are closely monitored
What are the usual time for Methotrexate to take effect? As early as 4-6 weeks
What trial is suggested in patients starting Methotrexate? a trial of 3-6 months at an increased dose (e.g. 20mg/wk)
What side effects are seen with Methotrexate? Hepatic cirrhosis, interstitial pneumonitis, severe myelosuppression, stomatitis, oral ulcers, mild alopecia and hair thinning, GI upset, HA, fatigue, feeling "wiped out" (Methotrexate fog)
What tests should be done prior to starting Methotrexate? CBC, liver chemistries, serum creatinine, hepatitis B and C serologies, and CXR
What routine tests should be done while taking Methotrexate? CBC, liver profile, serum albumin, and serum creatinine every 4-8 weeks
What should patients limit their ETOH intake to while taking Methotrexate? no more than 2 per week
What can be a risk while taking Methotrexate? increased risk of herpes zoster infection (shingles), cancer risk, lymphoma
Due to Methotrexate being tetrogenic, how does this effect contraception? Women should discontinue the drug one ovulatory cycle prior to attempting conception and males should wait 3 months.
What is antimalarial drug used to treat RA, that is relatively safe and well tolerated? Hydroxychloroquine (Plaquenil)
What patients should this Plaquenil be given to? limited to those with very mild and nonerosive disease; has a limited ability to prevent joint damage on its own
What other drugs can Plaquenil be combined with? Methotrexate and Sulfasalazine
What is Plaquenil's mechanism of action? unknown; thought to involve changes in antigen presentation or effects on the innate immune system
Why is Plaquenil not commonly used? greater toxicity on the eye
What is the dosage of Plaquenil? 400mg/day but sometimes 600mg/day; once per day or divided twice per day
When is Plaquenil's usual time to effect? 2-4 months; if no response after 5-6 months should be considered drug failure
What are the side effects of Plaquenil? toxicities on the eye, corneal deposits, extraocular muscular weakness, loss of accommodation and sensitivity to light, a retinopathy that may progress to irreversible vision loss
How often are ophthalmologic exams required while taking plaquenil? Baseline and then follow-up every 12 months
How effective is Sulfasalazine (Azulfidine) in comparison to Methotrexate? somewhat less effective
How does Sulfasalazine treat RA? reduce signs and symptoms and slows radiographic damage
What medications can Sulfasalizine be given with as part of a triple therapy to provide benefits to those who have had inadequate responses to methotrexate alone? Methotrexate and Hydoxychloroquine
What other disorders is Sulfasalazine used to treat? Inflammatory bowel disease and spondyloarthropathies
What may some of Sulfasalazine's effects be due to? folate depletion
What is the usual dosage for Sulfasalazine? 2-3 grams per day twice a day; may be starting at 1 gram per day and increased as tolerated
What is the usual time for effect for Sulfasalazine? 6 weeks to 3 months
What side effects may Sulfasalazine cause? hypersensitivity and allergic reaction to those allergic to sulfa, GI complaints, mild cytopenias
What lab tests may be needed prior to the start of Sulfasalazine? Screened for a deficiency of enzyme glucose-6-phosphate dehydrogenase (G6PD) which may predispose pt to RBC hemolysis and anemia, Liver function tests-drug my increase levels, blood monitoring every 1-3 months depending on dose
Which drug is similiar in efficacy to Methotrexate in terms of S/S, and is a viable alternative to patients who have failed or are intolerant to Methotrexate? Leflunomide (Arava)
Can Arava slow radiographic progression of RA? True
Which drug can Arava be combined with to treat patient's with NO preexisting liver disease, as long as the liver function tests are carefully monitored? Methotrexate
Which other disease has Arava been studied in, with some efficacy demonstrated? Psoriatic arthritis
What is Arava's mechanism of action? May be related to ability to inhibit de novo pyrimidine biosynthesis through the inhibition of the enzyme dihydroorotate dehydrogenase. Also has effects on stimulated T cells
Is the half-life of Arava long or short? Very long, extensively bound and undergo further metabolism before excretion
What is the dosage of Arava? 10-20 mg/day; may be reduced to 10 mg daily if not tolerated at 20 mg
What is the usual time for Arava to effect? Relatively rapid; 4-8 weeks
What are the side effects of Arava? mild diarrhea, GI upset, alopecia and hair thinning
What is the only contraindication for patients taking Arava? Arava has teratogenic effects, extreme care must be taken for treatment of women of child bearing potential; women should be warned about the possible risk to fetus and cautioned to use adequate birth control
What monitoring should be done for patients taking Arava? CBC, hepatic panel (at least every 2 months)
What is a pro-inflammatory cytokine, produce by macrophages and lymphocytes and is found in large quantities in the Rheumatoid joint and produced locally in the joint by synovial macrophages and lymphocytes infiltrating the joint synovium? Tumor necrosis factor alpha (TNF) inhibitors
What effect does TNF have on joint damage and destruction? it is one of the critical cytokines that MEDIATE joint damage and destruction due to its activities on many cells in the joint as well as effects on other organs and body systems
What effects do TNF inhibitors have on RA? decrease signs and symptoms, slowing or halting radiographic damage, and improving function and quality of life
What other disorders has TNF inhibitors been approved to treat? Psoriatic arthritis and Ankylosing spondylitis
What are the names of the three TNF inhibitors approved for treatment of RA? Etanercept (Enbrel), Infliximab (Remicade), Adalimumab (Humira)
Which drug is a fusion protein that combines two extracellular binding domains of the p75 form of the TNF receptor with the Fc portion of a human IgG1 antibody molecule? Etanercept (Enbrel)
When used as a monotherapy or in combination with Methotrexate, Enbrel has what effect on treating RA? reduces the signs and symptoms, and slows or halts the radiographic damage
What other disorders is Enbrel approved to treat? Psoriatic arthritis, Ankylosing spondylitis, and psoriasis
What is Enbrel's mechanism of action? it binds to TNF in the circulation and in the joint, preventing interaction with cell surface TNF receptors thereby reducing TNF activity
What is the dosage of Enbrel? 50 mg/week or 25 mg/ twice per week
How is Enbrel administered? SQ
What is the half-life of a 25 mg dose of Enbrel? 70 hours
What is Enbrel's usual time to effect? 1-4 weeks to 3-6 months
What are the side effects seen with Enbrel? increased risk of infection, upper respiratory symptoms, positive ANA, serious and opportunistic infections, lymphomas, non-Hodgkins lymphomas, transient neutropenia, other blood dyscrasias, injection site reactions
What screening is recommended prior to starting a patient on any TNF inhibitor? screening for latent TB
What patient's is TNF inhibitors not recommended in? demyelinating disease and congestive heart failure
What is a chimeric monoclonal antibody that binds TNF with high affinity and specificity? Infliximab (Remicade)
in combination with Methotrexate, what is Remicade used to treat? RA, psoriatic arthritis, ankylosing spondylitis, psoriasis, Crohn's disease
The antibody binding site for TNF of Remicade is where? of mouse origin. with the remaining 75% of the remicade antibody derived from a human IgG1 antibody sequence
Although Remicade is effective as a monotherapy in reducing S/S, what may develop and reduce the durability of the response? anti-infliximab antibodies
Co-treatment with what may reduce the frequency of anti-infliximab antibodies and is recommended with infliximab? Methotrexate
What is the combination of Methotrexate and Remicade effective in treating? reducing clinical manifestations and slowing or halting the radiographic progression of the disease
What is Remicade's mechanism of action? it binds TNF in the joint and circulation, preventing its interaction with TNF receptors on the surface of inflammatory cells, and eventually clearing TNF from the circulation. Monoclonal antibodies also bind to TNF. Remicade inhibits the activity of TNF
In what way is Remicade administered? IV and typically take 2-3 hours
What is the dosing of Remicade? Starting dose-3mg/kg; additional dosing at 2-6 weeks, then every 8 weeks after that; Maximum dose-10 mg/kg; frequency of infusion increased every 4-6 weeks
What is Remicade's usual time to effect? days to weeks
What are the side effects of Remicade? increased infections, sepsis, disseminated TB, opportunistic infections, fever, chills, body aches, HA, ANA, anti-double stranded DNA antibodies, SLE-like syndromes
The risk for Disseminated TB is what in Remicade in comparison to Etanercept? increased due to longer half-life
How may the infusion symptoms of Remicade be reduced? preadminister diphenhydramine (Benadryl), acetaminophen, and sometimes corticosteroids, or slowing the infusion
What drug is a fully human anti-TNF monoclonal antibody with high specificity for TNF? Adalimumab (Humira)
Like other TNF inhibitors, is effective as monotherapy or in combination with Methotrexate, how does Humira treat RA? reduces S/S, and slowing or halting the progression of the disease
How, and when is Humira administered? SQ injections, every two weeks, can be increased to weekly if needed.
What other disorders is Humira approved to treat? RA, Psoriatic arthritis, ankylosing spondylitis, and Crohn's disease
What is Humira's mechanism of action? binds specifically to TNF and blocks its interaction with the p55 and p75 cell surface TNF receptors, thereby interfering with endogenous TNF activity. Adalimumab binds to both soluble as well as cell bound TNF
What is the current dosage of Humira and how is it administered? 40 mg SQ every other week; may be increased to weekly if needed
What is the half-life of Humira? approximately 2 weeks (10-20 days) after 40 mg dose
How long is Humira's usual time to effect? 1-4 Weeks
What are the side effects of Humira? increased infections; upper respiratory tract infections; bronchitis; UTI; TB as reactivation of latent disease; positive ANA titers; lupus-like disease; lymphomas; injection site reactions
What drug is the first of a class of agents known as T-cell costimulatory blockers that interfere with the interactions between antigen-presenting cells and T lymphocytes and affect early stages in the pathogenic cascade of events in RA? Abatacept (Orencia)
If the T cells in Orencia recognize antigens as foreign and they receive a second stimulus, they will become active and what? proliferative, traffic to inflamed sites, and secrete proinflammatory cytokines including TNF.
With Orencia, one of the important second signals for T cells activation is mediated by what? molecules CD80 and CD86 found on antigen presenting cells and the CD28 molecule on the T cell surface
What is Orencia's mechanism of action? a fusion protein that combines the extracellular domain of the molecule CTLA4(CD154) with the Fc portion of a human immunoglobulin molecule. When binds to CD28 on Tcell surface, it prevents the second signal from being delivered, decreasing Tcell response
What are additional effects of Orencia's mechanism of action? decreasing the production of T cell derived cytokines including TNF
What is Orencia's dosing? How often? And how is it administered? IV; once per month; based on body weight; <60 kg receiving 500 mg, 60-100 kg receiving 750 mg, and >100 kg receiving 1000 mg
When does Orencia typically take effect? within 3 months; continue to show improvements through the first year
what are the adverse effects of Orencia? increased infections; respiratory infection; pneumonia; malignancies; opportunistic infections; mild infusion reactions
What are important inflammatory cells with multiple functions in the immune response, that serve as antigen presenting cells & can secrete cytokines, and differentiate into antibody-forming plasma cells? B cells
Why is B-Cell depletion (Rituximab [Rituxan]) effective in RA? reduces S/S and slows radiographic progression
Aside from RA, what other disorders has Rituxan been approved to treat? Non-Hodgkin's Lymphoma & malignant conditions of the lymphocytes and lymph nodes
What patient's are approved to take Rituxan? Those who have failed DMARD therapies and those who have failed TNF antagonists
What is Rituxan's mechanism of action? Chimeric monoclonal antibody that binds to the CD20 molecule on B cell surface that leads to B cell removal from circulation. Levels of autoantibody rheumatoid factor decrease but other antibodies levels remain in normal range
What is Rituxan's time of onset? up to 3 months; effects may last 6 months to 2 years following single infusion
What is the dosing of Rituxan and how is it administered? 1000 mg IV over 3-4 hours with two doses given 2 weeks apart. Give corticosteroids with each infusion and premedicate with Diphenhydramine and Acetaminophen
What are the adverse effects of Rituxan? Infusion reaction-hives, itching, swelling, difficulty breathing, fever, chills, changes in BP; Increased infections; reactivation of viral infections that were dormant (Hep B); progressive multifocal leukoencephalopathy; potentially fatal brain infection
What should patients prior to starting Rituxan and what should be avoided? Immunizations should be completed and live viruses should be avoided
What drug is a human recombinant IL-1 receptor antagonist and is approved for the treatment for RA? Anakinra (Kineret)
Anakinra can be used as a monotherapy or in combination with what drugs? DMARDS other than TNF blocking agents
Why is Anakinra not recommended for combination with TNF inhibitors? studies have shown infections without additive clinical benefit
What is Anakinra's mechanism of action? it blocks the biologic activity of IL-1 by binding to IL-1R type I with the same affinity as IL-1 beta
What is the typical dosage for Anakinra and how is it administered? 100 mg/day and SQ
How long is Anakinra's time to effect? 2-4 weeks
What are the side effects of Anakinra? injection site reactions-erythema, itching, discomfort; risk of serious infection; decreases in absolute neutrophil counts
What drug is effective in the treatment of RA when given IM and until the 1990s was the most often used DMARD agents but have been replaced by Methotrexate and other DMARDs as the preferred agents to treat RA? Gold
What are the 2 injectable gold compounds available? Myochrysine and Solganal
Why are gold compounds now rarely used? numerous side effects, monitoring requirments, limited efficacy, very slow onset of action
What oral gold compound is now available? Auranofin
What is the dosage of Gold 10 mg IM, 25 mg second week, 50 mg weekly until a response has occurred or until a total of 1 g has been given; If favorable response, therapy is tappered to 50 mg Q 2 weeks for 3 months, then Q 3 weeks for 3 months, then finally monthly maintenance dose
What is Gold's usual time to effect? 4-6 months or after administration of 1 g of gold
What are the side effects of Gold? rash*; severe exfoliative dermatitis; ulcerations and mucositis of mouth, tongue, and pharynx, mild proteinuria, glomerulonephropathy, isolated microscopic hematuria, immune thrombocytopenia, granulocytopenia, aplastic anemia, nitritoid reaction;blue skin
What tests should be done prior to starting Gold? CBC, urine test for protein
What drug is a purine analog that can cause bone marrow suppression and lowering of blood cell counts (WBC, WBC, and platelets) particularly in patients with renal insufficiency or when used concomitantly with allopurinol or ACE inhibitors Azathioprine (Imuran)
When may a patient see effects from Imuran? May take 8-12 weeks and has some activity in RA
What screening is recommended before initiating therapy with Azathiprine? screening for levels of the enzyme thiopurine methyltransferase (TPMT)
What blood tests are necessary for patients taking Azathioprine? blood counts and liver function tests
What are side effects of Azathioprine? nausea and alopecia
What drug is an immunosuppressive agent approved for use in preventing renal and liver transplant rejection and also has activity in psoriasis and other autoimmune diseases and has some activity as a disease modifying therapy in RA? Cyclosporine (Sandimmune, Neoral)
What other drug may Cyclosporine be combine with? Methotrexate
How does Cyclosporine inhibit T cell function? by inhibiting transcription of interleukin-2
What are the main toxicities of Cyclosporine? infection and renal insufficiency
What monitoring is needed while taking Cyclosporine? Renal function and blood pressure
What risks are increased while taking Cyclosporine? increased blood pressure; infection; malignancies including lymphoma
What rug is a potent immunosuppressive agent that is reserved for severe cases of refractory RA and those with manifestations such as Vasculitis? Cyclophosphamide (Cytoxan)
What other disorders has Cytoxan been approved to treat, aside from RA? Vasculitis and lupus
What must be carefully monitored due to the serious toxicities while taking Cytoxan? Blood counts
What are the serious toxicities of Cytoxan? bone marrow suppression, hemorrhagic cystitis, premature ovarian failure, infection and secondary malignancy particularly an increased risk of bladder cancer
Which drug is primarily prescribed for patients with persistently aggressive RA who have failed other available DMARDs? D-Penicillamine (Cuprimine, Depen)
What are the major side effects of Depen? severe rash, effects on renal function, lupus like illness
What must be carefully monitored while taking Depen? Kidney function
What allergy is contraindicated with Depen? Penicillin
What type of sedation induces an altered state of consciousness that minimizes pain and discomfort through the use of pain relievers and sedatives? Conscious sedation
What are patients under conscious sedation able to do? speak and respond to verbal cues throughout the procedure, communicating any discomfort they experience
What may occur do to conscious sedation? A brief period of amnesia that may erase any memory of the procedure
Where is conscious sedation administered? hospitals, outpatient facilities, ambulatory surgery, doctors offices, etc.
When is conscious sedation administered? biopsy, vasectomy, minor foot surgery, minor bone fracture repair, plastic/reconstructive surgery, endoscopy, diagnostic studies and tx of the stomach, colon, & bladder, radiation, bone marrow aspiration
What must be done prior to conscious sedation? assessment of medical conditions that interfere with sedation, risk factors, past medical history, severe heart/lung disease
Who can administer conscious sedation? certified registered nurse anesthetists, anesthesiologists, physicians, dentists, oral surgeons, specifically trained RNs
What must be monitored throughout and after the procedure do the risk of slipping into a deep sleep? HR, BP, breathing, oxygen, alertness, oxygen saturation & pulse oximeter is the most important
What is the most sensitive parameter affected during increased levels of conscious sedation? oxygen saturation
How often should vital signs be assessed before, during, and after conscious sedation? once before, a minimum of every 5 minutes during the procedure, and every 15 minutes for the first hour after the procedure, and then as needed
What equipment must be immediately available during conscious sedation? airway equipment, resuscitative medications, suction apparatus, supplemental oxygen delivery systems, medication reversal agents
What are the side effects of conscious sedation? amnesia, HA, hangover, nausea, vomiting, unpleasant memories of the surgical experience
What is the criteria to D/C conscious sedation? stable V/S and O2 sat, positive gag reflex, cough, and swallow, alert and appropriate to baseline, can sit unaided, walk with assist, minimal N/V, adequate hydration, dressing checked etc., physician order for discharge
What are the instructions after conscious sedation? Do not drive a vehicle or operate dangerous equipment or make any important decisions for at least 24 hours after conscious sedation
Created by: 100001274715924