Drugs for RA, Gout, Osteoporosis, Dementia, and Parkinson's PDF

1. Identify drugs for RA, gout, osteoporosis, dementia, parkinsons *RA: glucocorticoids (see #2), NSAIDs(1st gen: salicylates- aspirin, magnesium salicylates, salsalate. Nonsalicylates: diclofenac, ibuprofen, indomethacin, meclofnamate, naproxen, sulindac) (2nd gen [cox2 inhib]: celecoxib [cele...

1. Identify drugs for RA, gout, osteoporosis, dementia, parkinsons *RA: glucocorticoids (see #2), NSAIDs(1st gen: salicylates- aspirin, magnesium salicylates, salsalate. Nonsalicylates: diclofenac, ibuprofen, indomethacin, meclofnamate, naproxen, sulindac) (2nd gen [cox2 inhib]: celecoxib [celebrex]), disease-modifying antirheumatic (DMRDs)- conventional/traditional, biologics, targeted (methotrexate, sulfasalazine, leflunomide, hydroxychloroquine) (infrequently: penicillamine, gold salts, azathiooprine, cyclosporine, minocycline) *gout: acute gouty attacks-short term drugs- NSAIDs (1st line tx) or alternative glucocorticoids, colchincine reserved for pts unresponsive/intolderant to preferred agents. Lowering uric acid- long term drugs. Antigout drugs- anti-inflammatory agrents (NSAIDs, glucocorticoids), hyperuricemia drugs (allopurinol & febuxostat [inhibit uric acid formation], lesinurade & probenecid [accelerate uric acid excretion], pegloticase & rasburicase [convert uric acid to allantoin which can then be excreted in the kidney], lack anti-inflammatory & analgesic properties) *osteoporosis: calcium supplement, calcitonin, selective estrogen receptor modulators (agonist/antagonist), bisphosphate. Females- agets increasing bone resorption (estrogen, raloxifene, bisphosphonates [adendronate/fosamax]), risedronate [actonel, atelvia], ibandronate [boniva], zoledronic acid [reclast, zometa], calcitonin, denosumab [prolia] & agents promoting bone reformation [teriparatide/forteo]). Male- alendronate (fosamax), risedronate (actonel), zoledronic acid (reclast), teripaatide, denosumab *dementia: two AD drug classes: cholinesterase inhibitors (donepezil [aricept] [reverse inhibition], galantamine [razadyne] [reversible], rivastigmine [exelon] [irreversible]) & neural receptor N-methyl-D-aspartate (NMDA) blocker (memantine) *parkinsons: two drig classes- dopaminergic agents & anticholonergic agents, dopamine replacement (levodopa/carbidopa, levodopa/carbidopa/entacapone), dopamine agonists (directly activated DA receptors): Nonergot Derivatives- apomorphine, pramipexole, ropinirole, rotigotine. Ergot Derivates- bromocriptine, cabergoline. COMT inhibitors (inhibits levadopa breakdown by COMT)- entacapone, tolcapone. MAO-B inhibitors (inhibits DA breakdown by MAO-B)- rasagline, selegiline. Dopamine releaser (promotes release of DA from remaining DA neurons, may block DA reuptake)- amantadine 2. Glucocorticoids *penetrate cell membrane, then bind to cytplams (making it active) receptor-steroid complex migrates to cell nucleus (binds to chromatin in DNA) and alters target gene activity *relieves symptoms, slow disease progession, maintian joint function/ROM, minimize systemic involvement, also used in lupus, infalmmatory bowel disease, allegic condition, asthma, dermatologic disorders, preterm labor (neonate respiratory distress syndrome) *powerful anti-inflammatory/immunosuppressive effects for severe RA & may delay disease grogression generally used for acute exacerbations *note: routes- oral (rapid) for generalized symptoms, intraarticular (slower) for ONLY two or more joints affected, IM is also rapid w/ esters (sodium phosphate & sodium succinates) *short term therapy recommended only (long term therapy comploications can occur) *short acting systemic glucocorticoids: hydrocortisone & cortisone *intermediate acting systemic glucocorticoids: methylprednisolone, prednisolone, prednisone, triamcinolone *long acting systemic glucocorticoids: betamethasone & dexamethasone *produced in the adrenal gland *influence carbohydrate metabolism & other process (CV and hematologic integrity, CNS, stress response, F&E, neonatal respiratory system) *regulated by negative feedback loop through hypothalamus, anterior pituitary, & adrenal cortex *note: may decrease vaccine antibody response, live viruses risk for developing/spreading viral disease DO NOT GIVE *precautions in pediatrics, women who are pregnant/breastfeeding *abrupt termination of long term therapy may unmask adrebal insufficiency, gradual withdrawal is necessary, taper over 7 days *administer in AM to mimic natural physiological hormone response, administer w/ food/milk *increase r/f infection!, S/S fluid retention, assess vision (cataracts/glaucoma), GI bleeding, psychologic reactions 3. Methotrexate, sulfasalazine, hydroxychloroquine *Methotrexate: for rheumatoid arthritis, DMARDS, acts faster than other DMARS & first choice (80% improve). Can be used for severe psoriasis, acute lymphoblastic leukemia, polyarticular juvenile idiopathic arthritis *action: folate antagonist (folate is needed for DNA synthesis/cellular replication). Benefits from immunosuppression of B & T lymphocytes *contraindicated in pregnancy (congenital abnormalities, fetal death), alcoholism/hepatic impairment, immunosuppresion, decreased bone marrow reserve *adverse effects: hepatic fibrosis, bone marrow suppression, GI ulceration, pneumonitis, aplastic anemia, anemia, leukopenia, thrombocytopenia, n/v/d, anorexia, SJS, alopecia, nephrotoxicity, infections, secondary malignancy *BLACK BOX WARNING: fatal toxicities of the bone marrow, liver, lungs, kidneys, skin reactions, hemorrhagic enteritis, GI perforation  *MANY drug-drug interactions *routes: IM, PO, IV, Subcut. For RA- given 7.5 mg (PO, IM, SQ) weekly not to exceed 20mg/week, then titrate dose down *nursing considerations (mostly same for all DMARDS): HIGH ALERT MEDICATION!, injection solution- wear gloves, gown, makes while handling medication. Monitor for bone marrow suppression (bleeding gums, brusing, petechiae, guaiac stools, urine, emesis). Avoid injections, rectal temps w/ thrombocytopenia. Assess s/s infection & rash. Monitor renal system to include I/O, DWT, edema. Monitor for interstitial pneumonitis (early- dry non-productive cough). Monitor for gout & encourage 2 L fluid/day. Assess nutrition periodically. Labs: verify negative pregnancy (HcG), CBC, & diff, (leukopenia occur 7-14 days), renal/hepatic labs,uric acid, serum methotrexate levels DAILY during high dose therapy. Pt should avoid crowds! *Sulfasalazine: contraindicated in sulfa allergy *Hydroxychloroquine: therapeutic effects 3-6 months. Toxicity- retinopathy leading to blindness. Thorough eye exam prior and during treatment. Cardiomyopathy, BBB, prolonged QT interval 4. TNF inhibitors, B-lymphocyte depleting agent, & JAK inhibitor names, drug class adverse effects/overall nursing considerations *Tumor Necrosis Factor (TNF) inhibitors: 5 TNF inhibitors- adalimumab (SQ), certolizumab, pegol, etanercept (SQ), golimumab (SQ?IV), infliximab (IV) [all equally effective] *TNF is a cytokine (chemical messenger) produced by the WBC in response to an infection or antigen, too much TNF is found w/ autoimmune disease *prototype: etanercept (enbrel) *action: suppression inflammation by inhibiting TNF (two TNF receptors bind to IgG *adverse effects: injection site reactions, cough, abd pain, lymphoma/malignancies in children/adolescents, serious infections (especially w/ DM, HIV, use of immunosuppressant drugs), allergic reactions, HF, cancer, hematologic disorders, liver injury, CNS demyelinating disorders, may reactivate latent TB *nursing considerations: see methotrexate *B-Lymphocyte-Depleting Agents: reduce the number of B-lymphocytes cells that play an important role in the autoimmune attack on the joints, used in combination w/ methotrexate for moderate to severe RA who have not responded to TNF inhibitors *prototype: Rituximab (only one drug on this category) IV *action: monoclonal antibody against CD20 (found exclusively on the B-lymphocyte) causing B-lymphocyte lysis/death *adverse effects: flu like s/s, SEVERE infusion reactions. Post infusion renal failure/toxicity. Death occuring w/i 24 hrs (80% w/i first infusion), Hep B reactivation-hepatic failure, progressive multifocal leukoencephalopathy, transient neutropenia *considerations: see methotrexate *Jannus Kinase (JAK) inhibitors: newest RA drug where long-term safety had not been established (baricitinib) [Olumiant] & tofacitinib [Xeljanz, Xeljanz XR] *JAKs are intracellular enzymes that have a role in initiating cytokine signaling (part of the signal transduce & activation of transcription (STAT) pathway. STAT pathway is involved in inflammatory/immune responses. Inhibiting the DMARDs reduce immune & inflammatory responses from RA. *used in moderate to severe RA who cannot take methotrexate or have had adequate response *prototype: tofacitinib (oral) *action: prevents activation of the STAT pathway by preventing JAK enzyme signaling *adverse effects: approx 20% will develop infection. nasopharyngitis , herpes zoster, gastroenteritis, liver injury, malignancies, FATAL INFECTIONS (including TB), deceased lymphocytes, neutrophils, platelet count & erythrocytes *note: these are ALL biologic disease modifying antirheumatic drugs (DMARDS) 5. Gout- identify anti-inflammatory vs hyperuricemia drugs *anti-inflammatory: NSAIDs & glucocorticoids *hyperuricemia: allopurinol & febuxostat (inhibit uric acid formation), lesinurad & probenecid (accelerate uric acid excretion), pegloticase & rasburicase (convert uric acid to allantoin which can then be excreted in the kidney), lack anti-inflammatory & analgesic properties 6. Colchicine & allopurinol *COLCHICINE- reserved for pts unresponsive/intolderant to preferred agents, 2nd line for acute gouty attack *anti-inflammatory agent with effects specific for gout, can be used SHORT TERM for acute gouty attacks (high dose) or LONG TERM for maintenance/prevention (low dose) *does NOT decrease urate production or remove urate. May interfere w/ WBC function in initiating and perpetuating inflammatory response to monosodium urate crystals. *note: avoid during pregnancy if possible *adverse effects: narrow therapeutic index- toxic to any tissue that has a large # of proliferating cells. GI tract, bone marrow disruption causes much of the drug’s major toxicity. Myelosuppression (causing leukopenia, granulocytopenia, thrombocytopenia, pancytopenia). Myopathy (rhabdomyolysis [increases w/ renal/hepatic impairment, statin drugs]). Monitor for muscle pain, tenderness, weakness. *drug interactions: statins (rhabdo), drugs w/ P-glycoprotein (PGP) inhibitors (cyclosporine, ranolazine) and inhibitors of CYP3A4 (ketoconazole, clarithromycin, HIV protease inhibitors) can cause life threatening reactions by increasing colchicine levels. *adjust dosing levels for older adults w/ cardiac, renal, hepatic, GI disease *FUN FACT: colchicine may decrease MI risk and improve MI outcomes *ALLOPRINOL: xanthine oxidase inhibitors, drug of choice for chronic tophaceous gout, initial therapy can precipitate a gouty attack (colchicine or low dose NSAID decrease risk, maintenance dose *lowers uric acid levels, preventing new tophi formation and regression of current tophi, decreased risk for kidney urate crystal deposit *action: exhibits xanthine oxidase (XO) needed for uric acid formation *adverse effects: well tolerated. Mild GI (n/v/d, abd discomfort), neuro (drowsiness, HA, metallic taste). Prolonged use- cataract formation. Less common- bone marrow suppression, hepatoxicity, hypersensitivity. Most serious (rare) fatal hypersensitivity syndrome (fever, rash, eosinopgilia, liver/kidney dysfunction). Korean, chinese, thai ancestry should be tested for HLA-B*5801 as severe cutaneous adverse reactio (SCAR) syndrome can occur *note: hyperuricemia drug for gout 7. How to diagnosis osteoporosis and drug treatment needed *diagnosing: BMD screening tool= dual energy x-ray absortiometry (DEXA), osteropenia- 1SD below the mean (10% bone loss) (or T score -1), osteoporosis- 2.5 SD below the mean (20% bone loss) (or T score -2.5) *treatment: hip or vertebral fx, ospeoporosis (T score < -2.5 or less at the femoral eck or spine), low bone mass (T score between -1 and -2.5 at the femoral neck or spine PLUS 10 year probability fx risk based on FRAX score); GOAL: maintain or increase bone strength 8. Alendronate contraindications, adverse effects, nursing considerations *contraindications: esophageal abnormalities (delayed esophageal emptying [trictures, achalasia]), inability to stand/sit upright for 30 min, renal impairment (CCr