Presentation on theme: "Rheumatoid Arthritis/Osteoarthritis"— Presentation transcript:
1Rheumatoid Arthritis/Osteoarthritis Sarah DaoudFlorida A&M UniversityCollege of Pharmacy and Pharmaceutical Sciences10/02/13Seminar: Disease Presentation
2ObjectivesDiscuss the prevalence, epidemiology, risk factors, and pathophysiology of RA/OA.Discuss the signs and symptoms, diagnosis, and treatment of RA/OA.Assess treatment of disease states in special populations.Evaluate the role of the pharmacist in the overall approach of these conditions.Discuss key components of RA/OA which would serve as educational points for patients and healthcare practitioners.
3RHEUMATOID ARTHRITISThe normal joint structure appears on the left. On the right is the joint with rheumatoid arthritis. RA causes synovitis, pain and swelling of the synovium (the tissue that lines the joint). This can make cartilage (the tissue that cushions between joints) and bone erode, or wear away.-a chronic progressive disease causing inflammation in the joints and resulting in painful deformity and immobility, esp. in the fingers, wrists, feet, and ankles.
4PrevalenceRA is the most common form of autoimmune arthritis affecting more than 1.3 million Americans.Women encompass 75% of individuals diagnosed with this disease.1-3% of women may get RA in their lifetime.Usual occurrence is in individuals between years of age.
5EpidemiologyRA does not have any racial inclination and can occur at any age.Research has shown, this disease has a genetic predisposition and diagnosis may be necessitated by certain unknown environmental exposures.Major histocompatibility complex (MHC) molecules located on T-lymphocytes play a major role in patients with RA.Human lymphocyte antigen (HLA) typing can characterize these molecules and assess the risk of RA in those with presence of antigens on MHC molecules.-A majority of patients with RA have HLA-DR4, HLA-DR1, or both antigens found in the MHC region.-Patients with HLA-DR4 antigen are 3.5 times more likely to develop RA than those who have other HLA-DR antigens.-Although MHC region is important, it is not the sole determinant, because patients can have the disease without these HLA types.
6Risk Factors Sex (Female) Family history Older age Silicate exposure SmokingConsuming 3 or more cups of coffee/day (esp. decaffeinated coffee)
7PathophysiologyJoint damage in rheumatoid arthritis begins with the proliferation of synovial macrophages and fibroblasts after a triggering incident, possibly autoimmune or infectious. Lymphocytes infiltrate perivascular regions, and endothelial cells proliferate. Neovascularization then occurs. Blood vessels in the affected joint become occluded with small clots or inflammatory cells. Over time, inflamed synovial tissue begins to grow irregularly, forming invasive pannus tissue. Pannus invades and destroys cartilage and bone. Multiple cytokines, interleukins, proteinases, and growth factors are released, causing further joint destruction and the development of systemic complications (vasculitis, pulmonary fibrosis, inflammation of the sclera, pericarditis, Felty’s syndrome)
8Signs and SymptomsMorning stiffness lasting hours (sometimes whole day)FatigueWeaknessLow-grade feverLoss of appetiteJoint painFirm lumps***Joint involvement tends to be symmetrical-Joints affected most frequently by RA are the small joints of the hands, wrists, and feet. In addition, elbows, shoulders, hips, knees, and ankles may be involved.-Chronic inflammation with lack of an adequate exercise program results in loss of range of motion, atrophy of muscles, weakness, and deformity.
9DiagnosisAccording to the American College of Rheumatology Diagnostic Criteria
10-Chronic inflammation of the synovial tissue lining the joint capsule results in the proliferation of this tissue.-The inflamed, proliferating synovium characteristic of rheumatoid arthritis is called pannus.-Pannus invades the cartilage and eventually the bone surface, producing erosions of bone and cartilage and leading to destruction of the joint.-Factors that initiate the inflammatory process are unknown.
11Non-pharmacological Treatment RestOccupational therapyPhysical therapyUse of assistive devicesWeight reductionSurgery-rest alleviated pain and stress on the joints.-therapy provides pt with skills and exercises necessary to increase or maintain mobility.-wt reduction helps alleviate stress on the inflamed joints.-surgery options: tenosynovectomy, tendon repair, and joint replacement.
14Pharmacological Treatment Agents used for pain and inflammationDrugDosageAdverse EffectsWarnings/ContraindicationsNotesIbuprofen (Motrin, Advil)-> mg Q6-8H (mild to moderate pain)-> mg Q6-8H; max 3.2g/d (moderate pain or inflammation)-Dyspepsia-Heartburn-Increase BP-GI bleeding-NSAIDS have BBW of increased risk of adverse CV thrombotic events; contraindicated for CABG perioperative pain; increased GI adverse events (ulceration, bleeding, perforation)-Contraindicated in pregnancy 3rd trimester.-Avoid use in advanced renal disease.Celecoxib (Celebrex)-> mg BID-Diarrhea-Nausea-Warnings are the same as NSAIDS.-Contraindicated with sulfa allergy.-Lower risk of GI complications.-Max 400mgPrednisone (Rayos, Prednisone Intenson)->Initial 5-60mg daily indicated for acute inflammation->Can use twice daily dose every other day to decrease adrenal suppression.-Fluid retention-Stomach upset-Increase appetite.-Hyperglycemia-Osteoporosis-Muscle wasting-Contraindicated with live vaccines, systemic lung infections.-Must assess bone density if used long-term.-Must taper dose off.-Rapidly acting antiinflammatory medications, including nonsteroidal antiinflammatory drugs (NSAIDs) and systemic and intraarticular glucocorticoids
15Pharmacological Treatment Non-biologic Disease-modifying anti-rheumatic drugs (DMARDS)DrugDosageAdverse EffectsWarnings/ContraindicationsNotesMethotrexate (Rheumatrex, Trexall)-folate antimetaboline that inhibits DNA synthesis-> mg/week-N&V-Diarrhea-GI upset-Anorexia-Reddening of skin-BBW: fetal death or congenital abn.; hepatotoxicity; BMS; malignant lymphomas; acute renal failure.-Contraindications: pregnancy; alcoholism; chronic liver disease; blood dyscrasias-Never dose daily for RA (dose can be split into smaller doses taken over hours)-Pregnancy category XHydroxychloroquine (Plaquenil)->Initial: mg/day->Maintain: mg/day-Decreased visual acuity-Photophobia-Blurred vision-Corneal deposits-Can cause neuromyopathy with long-term use; SJS; alopecia; pigmentation of skin and hair (bleaching)-Used in mild RA-Take with food or milk-Mainly eliminated by the kidneySulfasalazine (Azulfidine, Sulfazine)-5-aminosalicyclic acid derivative->500-1,000mg BID; max 3g/day-Headache-Dyspepsia-Contraindications: pts with a sulfa or salicylate allergy, GI or GU obstruction-Can cause reversible oligospermia; folate deficiency d/t impaired folate absorption-Take with food and 8oz of water to prevent crytalluria-Can cause yellow-orange discoloration of skin/urine-May give 1mg/day folate supplement-Disease-modifying antirheumatic drugs (DMARDs), including nonbiologic (traditional small molecule or synthetic) and biologic DMARDs, and an orally-administered small molecule kinase inhibitor, which all have the potential to reduce or prevent joint damage and to preserve joint integrity and function
16Pharmacological Treatment Non-biologic DMARDS cont.DrugDosageAdverse EffectsWarnings/ContraindicationsNotesMinocycline (Dynacin, Minocin, Solodyn)->100mg BID-GI upset-N&V-May cause SJS and decreased LFTs-Used in mild RA-Pregnancy Cat. D-Do not use in children 8 yoa or younger.Leflunomide (Arava)-> 100mg x3days, then 20mg daily-Diarrhea-URTIs-Rash-Alopecia-BBW: women of childbearing potential should not use age until pregnancy is excluded; hepatotoxicity-Must have negative pregnancy test before starting and use 2 forms of birth control.-If pregnancy wanted, must wait 2 yrs after discontinuation or give cholestyramine.-Can use with or without methotrexate-Pregnancy Cat. X
17Pharmacological Treatment Biologic agents- TNFalpha inhibitorsBBW: serious infxs; lymphomas; malignancies; perform test for latent TB before initial therapy.Contraindication: sepsisCan cause worsening or new onset Heart Failure; hep. B reactivation; demyelinating disease.Do not give with other biologics or live vaccinesSE: infections and injection site reactionsAdministration: do not shake; require refrigeration; allow to reach room temp. before injectingThese agents are usually add-on therapy to methotrexateBiologics denature if hot.
18Pharmacological Treatment Biologic DMARD agents- TNFalpha inhibitorsDrugDosageNotesEtanercept (Enbrel)->50mg SC once/weekAdalimumab (Humira)->40mg SC every other week-If not taking MTX, can increase dose to 40mg SC weeklyInfliximab (Remicade)->3mg/kg IV at weeks 0,2,6 and then Q8W can increase to 10mg/kg-Higher dose=increase infx risk-Infusion reaction: hypotension, fever, chills, pruritis (benefit from APAP/ antihistamine/ steroids as pre-treatment)-Delayed hypersensitivity rxn 3-10d after admin (fever, rash, myalgia, HA, sore throat)Certolizumab pegol (Cimzia)->400mg SC at weeks 0,2,4 and then 400mg Q4W-Can maintain at 200mg every other weekGolimumab (Simponi)->50mg SC once/month-Give with MTXBiologics denature if hot.
19Pharmacological Treatment Biologic response modifiersDrugDosageAdverse EffectsWarnings/ContraindicationsNotesRituximab (Rituxan)-depletes CD20+ B cells->1g IV day 1 and 15 @50mg/hr (can increase to 400mg/hr if no rxn)-Fever-Chills-Angioedema-BMS-Abdominal pain-BBW: severe and fatal infusion related reactions; PML due to JC virus infection; tumor lysis syndrome leading to acute renal failure and dialysis; SJS, TEN can occur-Warnings: serious infxs-Pre-medicate with a steroid-Used with MTX-Do not give with live vaccines or other biologics-Screen for latent TB before initiatingAnakinra (Kineret)-IL-1 receptor antagonist->100mg SC daily-Headache-Infections-Injection site rxnAbatacept (Orencia)-Selective T cell costimulation blocker->500mg-1,000mg IV based on body wt; given over 30minPML- progressive multifocal leukoencephalopathyJohn cunningham virus
20Pharmacological Treatment Kinase InhibitorsDrugDosageAdverse EffectsWarnings/ ContraindicationsNotesTofacitinib (Xeljanz)-inhibitor of Janus kinase (JAKs)->5mg PO BID-URTIs-Diarrhea-Headache-BBW: can cause serious infections, lymphomas and other malignancies; screen for latent TB-Can cause GI perforation-Not recommended in severe hepatic impairment-Do not give with live vaccines-Do not use with potent 450 inducers; reduce dose to 5mg daily w/ potent 3A4 and 2C19 inhibitor.-Do not use with biological DMARDs or potent immunosuppressants-Monitor neutrophil count, hemoglobin, and lymphocyte count-Janus kinase inihibitors block cytokine signaling
24OSTEOARTHRITIS (AKA: Degenerative Joint Disease) -degeneration of joint cartilage and the underlying bone, most common from middle age onward. It causes pain and stiffness, esp. in the hip, knee, and thumb joints.
25Prevalence An estimated 15.8 million adults display symptoms of OA Prevalence increased with ageE.g. Those aged years, 85% have OA of the hands, whereas those 45 year and younger, only 1/5th have OA of the hands.Severity also increases with ageWomen are more affectedKnee OA twice as prevalent in black opposed to white women-Older women twice as likely as men to have OA of hands and knees
26Epidemiology Most prevalent of the rheumatic diseases Responsible for disability and loss of productivityOA at some skeletal sites occurs in nearly everyone 75 years and older½ million symptomatic cases of idiopathic OA occur yearly in the US white population
27Risk FactorsObesityRepetitive motion (constant stress on hand, knee, etc.)Joint injuryGeneticsType and intensity of physical activity-Obesity: increased body weight is strongly associated with hip, knee, and hand OA. The risk of developing OA increases by about 10% with each additional kilogram of weight, and in obese persons without OA, weight loss of even 5kg decreases the risk of future knee OA by ½.-Genetics: heberden’s nodes (hard or bony swellings that can develop in the distal interphalangeal joints (DIP))->higher risk if a woman’s mother had them [2fold increase]. Premature development of OA is associated with a defect in type 2 procollagen.
29PathophysiologyInitial thickening of articular cartilage as ECM is damaged and water content increases (from pressure on proteoglycan[component in cartilage matrix]).Decline in response of chondrocytes (only cells found in healthy cartilage) to stabilize or restore tissue, resulting in progressive cartilage loss.Increased turnover of adjacent subchondral bone (the layer of bone right below the cartilage), leading to release of vasoactive peptides and enzymes, causing cartilage degradation. Inc leakiness of adj cartilage.Loss of cartilage exposes the underlying subchondral bone and may lead to microfractures.Microfractures lead to callus and osteoid production. New bone formations at the joint margins distant from cartilage destruction are referred to as osteophytes (an attempt to stabilize the joint)Pain arises from the activation of nociceptive nerve endings within the joint by mechanical or chemical irritants. Osteophytes can have a significant clinical impact and can be a source of pain and loss of function. The latter mainly through nerve compression, limitation of joint mobility and obstruction of tissues and organs.
30Signs and Symptoms Pain with motion Joint stiffness lasting <30min (usually in the morning)Joint:TendernessCrepitusEnlargementCrepitus- a crackling or grating sound heard with joint movement (caused by irregularity of joint surfaces)
31Diagnosis 3 Goals: Differentiate between primary or secondary OA Clarify joints involvedAssess prior therapiesDiagnostic Parameters:OA of knee-Refer to signs and symptomsAge >50yoOA of hand-Heberden’s node (2 or more out of 10)OA of hip-Normal ESROsteophytes and joint space narrowing on on X-rayHeberden’s node- distal interphalangeal joints (osteocytes or bony enlargement)ESR-erythrocyte sedimentation rate
32Non-pharmacological Treatment Exercise programs (aquatic)Weight lossPatient education for self-managementWedged shoe insolesRestBraces (symptomatic relief)-The treatment of rheumatoid arthritis (RA) is directed toward the control of synovitis and the prevention of joint injury.
33Pharmacological Treatment Pain Relief (primary indication for pharmacological treatment)DrugDosageAdverse EffectsWarnings/ ContraindicationsNotesAcetaminophen (Tylenol)-> mg PO Q6H-Constipation-Headache-Vomiting-Contraindications; hepatic impairment-Alcoholism can increase hepatic injury-For mild to moderate pain-Max 4g/dayTramadol (Ultram)->initial: 25mg/day, increase by 25mg increments in separate doses every 3 days->maintain: mg PO Q4-6H-Flushing-Nausea-Xerostomia-Contraindications: hypercapnia, severe bronchial asthma, acute intoxication with alcohol, narcotics, etc.-For moderate to severe pain-Max 400mg/day-Adjust dose for renal impairment-Tx strategies include approaches directed at achieving remission or low disease activity by more rapid and sustained control of inflammation and by the institution of disease-modifying antirheumatic drug (DMARD) therapy early in the disease course.
34Pharmacological Treatment Opioid AnalgesicsDrugDosageAdverse EffectsWarnings/ ContraindicationsNotesCodeine sulfate->15-60mg PO Q4H-Somnolence-Dyspnea-Hypotension-Bowel obstruction-Pancreatitis-Contraindications: bronchial asthma, hypercarbia-Has potential for abuse-May cause diminished biliary and pancreatic secretions-May prolong GI obstruction-For mild to moderate pain-Max dose: 360mg/dayOxycodone hydrochloride->5-15mg PO Q4-6H-Constipation-Nausea-BBW: fatal respiratory depression-For moderate to severe pain
35Pharmacological Treatment NSAIDSDrugDosageAdverse EffectsWarnings/ ContraindicationsNotesAspirin->Up to 3g/day in divided doses-GI upset-Bleeding-GI ulcer-Caution with bleeding disorders, renal or hepatic disease-May take with food or milkIbuprofen(Advil)->1200 to 3200 mg/day PO in 3-4 divided doses-Dyspepsia-Heartburn-Increase BP-GI bleeding-NSAIDS have BBW of increased risk of adverse CV thrombotic events; contraindicated for CABG perioperative pain; increased GI adverse events (ulceration, bleeding, perforation)-Contraindicated in pregnancy 3rd trimester.-Avoid use in advanced renal diseaseNaproxen(Aleve)-> mg PO BID-Edema-Abdominal pain-Tinnitus-Dyspnea--NSAIDS have BBW of increased risk of adverse CV thrombotic events; contraindicated for CABG perioperative pain; increased GI adverse events (ulceration, bleeding, perforation)-Max 1500mg/day for up to 6 moCelecoxib (Celebrex)->100mg BID or 200mg daily-Diarrhea-Nausea-Warnings are the same as NSAIDS.-Contraindicated with sulfa allergy.-Max 200mg
36Pharmacological Treatment Topical NSAIDS (preferred over oral NSAIDs for pts >75 yoa) Topical AnalgesicsDrugDosageAdverse EffectsWarnings/ ContraindicationsNotesDiclofenac sodium 1% gel (Voltaren)->4g topically to lower extremities 4x/day->2g to upper extremities 4x/day-Application site rxn-Burning sens. in eye-Raised IOP-Same as NSAIDs BBWs-NSAID oral therapy not recommended concomitantly-Can cause anaphylaxis-Max 8g/day to any single joint of upper extremity; 16g/day for lower extremity; 32g/day total over all affected jointsTrolamine salicylate 10% cream (Arthricream)->Apply topically 3-4x/day-Erythema-Skin irritation-Contraindications: hypersensitivity to salicylates, severe renal insufficiency-May cause tinnitus-Beware of toxicity with over use-Do not cover area with occlusive materialDrugDosageAdverse EffectsWarnings/ ContraindicationsNotesCapsaisin 0.025% or 0.075%->Apply to affected joints 3-4x/day-Application site erythema-Pruritus-Nausea-Hypertension-May increase risk of cardiovascular adverse effects-Use nitrile gloves for handling
37Pharmacological Treatment Intra-acrticular Glucocorticoids (knee or hip)DrugDosageAdverse EffectsWarnings/ ContraindicationsNotesTriamcinolone acetonide (Kenalog, Aristocrat A, Nasacort)->initial mg as single injection->Additional doses can be adjusted to 20mg or more-Cushing’s syndrome-Headache-Pharyngitis-Flu-like symptoms-Contraindications: administration with live vaccines; idiopathic thrombocytopenic purpura-Increased risk of infections-Impaired skin healing-Weight gain-HyperglycemiaTriamcinolone hexacetonide (Aristospan)->up to 0.5mg/square inch of affected skin-Hypertension-Osteoporosis-Same as above-Total daily dose may vary from 2-48mg/dayUsed if condition has progressed to pure inflammation
38Pharmacist RoleBe aware of certain labs to order for particular agentsUnderstand patient populations, which certain medications should be avoided inCounsel patients on the disease state , SE, possible treatmentsAssess progression of disease and appropriate measures to takeMake recommendations to physicians regarding drug regimen*RA-We obtain a baseline complete blood count, serum creatinine, aminotransferases (AST/ALT), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) in all patients.-Serologic testing for hepatitis w/ MTX, biologic DMARDs, leflunomide-Opthalmology consult with hydroxychloroquine
39Clinical Pearls- Based on Guidelines RAEtanercept recommended for use in patients with hepatitis C.No biologics for hepatitis BRituxibam recommended for pts with malignancy <5yrs, treated skin melanoma, treated lymphoproliferative diseaseTNF inhibitor recommended for patients with CHFOAKneeAcetaminophenOral NSAIDsTopical NSAIDsTramadolIntraarticular corticosteroid injectionsHipSame as above without topical NSAIDsHandTopical capsaicin
40ReferenceAmerican College of Rheumatology 2012 Recommendations for the Use of Nonpharmacologic and Pharmacologic Therapies in Osteoarthritis of the Hand, Hip, and Knee. American College of Rheumatology. vol. 64, No. 4, April 2012, pp 465–4742012 Update of the 2008 American College of Rheumatology Recommendations for the Use of Disease-Modifying Antirheumatic Drugs and Biologic Agents in the Treatment of Rheumatoid ArthritisAmerican College of Rheumatology. vol. 64, No. 5, May 2012, pp 625–639Kenneth C Kalunian, MD. Patient information: Osteoarthritis symptoms and diagnosis (Beyond the Basics). UpToDate August 2013.Peter H. Schur, MD. General principles of management of rheumatoid arthritis in adults. UpToDate August 2013Micromedex