Term
| what is the most common joint disease that affects >21 million americans |
|
Definition
|
|
Term
| 3 characteristics of osteoarthritis |
|
Definition
1) articular cartilage loss
2) bone remodeling
3) bone hypertrophy |
|
|
Term
| 2 possible causes of osteoarthritis |
|
Definition
1) excessive load on joints
2) presence abnormal cartilage or bone
(any event that affects environment of chondrocyte) |
|
|
Term
| most common sites of osteoarthritis |
|
Definition
| weight bearing joints of hips, knees, lower back |
|
|
Term
| risk factors osteoarthritis |
|
Definition
| >50yo, acute joint injury, obesity, high bone density, long term immobilized joint, mechanical stress to joint, genetics |
|
|
Term
| 5 major Sx osteoarthritis |
|
Definition
1) joint soreness after overuse/inactivity
2) stiffness after rest - disappears w/ use
3) morning stiffness up to 30 min
4) redness, tenderness, swelling of joint
5) pain w/ movement |
|
|
Term
| 4 mech of pathophys of osteoarthritis |
|
Definition
1) loss cartilage elasticity: more easily damaged
2) wear & tear of cartilage: underlying bone changes: thickens, bone cysts/growths
3) bone/cart pieces float in joint space
4) inflammed synovium: inflamm mediator production: promotes cart breakdown, bone/joint damage |
|
|
Term
| 2 Tx goals for osteoarthritis |
|
Definition
1) control pain & Sx via meds
2) improve fcn and quality of life via wt loss, exercise, PT |
|
|
Term
| Rx mild/moderate pain osteoarthritis |
|
Definition
| analgesic (acetaminophen) |
|
|
Term
| MOA Capsaicin as topical analgesic |
|
Definition
|
|
Term
| what nt is present in painful joints and is involved in pain transmission to CNS? |
|
Definition
|
|
Term
| Rx - moderate/severe pain w/ inflamm in osteoarthritis |
|
Definition
|
|
Term
| limitations of NSAIDs in Tx osteoarthritis |
|
Definition
|
|
Term
| Rx - mild/moderate pain w/ inflammation in osteoarthritis that doesn't respond to acetaminophen or NSAIDs |
|
Definition
|
|
Term
| how often can you give cortisone injection for osteoarthritis? |
|
Definition
|
|
Term
| Rx - fast, targeted pain relief for osteoarthritis |
|
Definition
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|
Term
| Acetaminophen - does it inhibit COX-1 and COX-2 in periphery? |
|
Definition
|
|
Term
| what does acetaminophen selectively inhibit, and where is this expressed? |
|
Definition
| COX-3 (variant of COX-1), selectively expressed in CNS |
|
|
Term
| what therapeutic activity does acetaminophen have? |
|
Definition
| anti-pyretic, analgesic (equivalent to aspirin) |
|
|
Term
| What 2 therapeutic activities does acetaminophen lack and why? |
|
Definition
1) NO anti-inflamm (doesn't inhibit COX-2)
2) NO anti-plt/thrombotic (doesn't inhibit ply COX-1) |
|
|
Term
| pharmacokinetics: acetaminophen |
|
Definition
high oral absorption
metab in liver
peak serum levels in 30-60min
serum t1/2 = 2-3hrs |
|
|
Term
| Rx - mild/moderate pain NOT assoc w/ inflammation, and the dosage |
|
Definition
| Acetaminophen, 325-500mg 4x/day |
|
|
Term
|
Definition
1) pain assoc w/ headaches
2) pain assoc w/ muscle aches
3) mild forms arthritis |
|
|
Term
| is acetaminophen alone an effective therapy for arthritis and other inflamm conditions? |
|
Definition
| NO - use as adjunct w/ other NSAIDs |
|
|
Term
| Rx - analgesic for pts allergic to aspirin or pts that can't tolerate salicylates |
|
Definition
|
|
Term
| why is acetaminophen the preferred analgesic/anti-pyretic for children? |
|
Definition
|
|
Term
| Rx - pain relief/fever reduction in hemophiliacs or pts w/ ulcers |
|
Definition
acetaminophen
(doesn't affect bleeding time or GI bleeds) |
|
|
Term
| what should pts taking acetaminophen avoid and why? |
|
Definition
| alcohol - together they cause serious liver damage |
|
|
Term
| acetaminophen - does it affect uric acid levels? |
|
Definition
|
|
Term
|
Definition
| acetaminophen + Probenecid |
|
|
Term
| at what dose is acetaminophen essentially free of adverse SE? |
|
Definition
normal dose of 4g/day
(but can occassionally see mild inc liver enzymes) |
|
|
Term
| adverse SE - larger doses acetaminophen |
|
Definition
| dizziness, excitement, disorientation |
|
|
Term
| adverse SE of very large dose (>15g) acetaminophen and cause of this SE |
|
Definition
| Hepatotoxicity - due to N-acetyl benzoquinoneime buildup (toxic metabolite) |
|
|
Term
| why does N-acetyl benzoquinoneime build-up in very lg doses acetaminophen? |
|
Definition
| depletion of hepatic glutathione |
|
|
Term
| Tx hepatotoxicity from acetaminophen OD |
|
Definition
| N-Acetyl cysteine (replenishes glutathione) |
|
|
Term
| systemic autoimmune disease of unknown etiology |
|
Definition
|
|
Term
| characteristics: rheumatoid arthritis |
|
Definition
1) inflamm & pain in joints
2) progressive joint destruction
3) involvement skin, CV, lungs, muscle
4) significant disability and deformity |
|
|
Term
| pathophysiology: rheumatoid arthritis (4 mechanisms) |
|
Definition
1) chronic lymphocyte infiltration in synovium
2) swelling of synovium: pain, warmth, stiffness, redness in joint
3) rapid prolif. synovial fibroblasts & leukocytes: thickens synovium, which invades cartilage & bone
4) macrophages & lymphocytes secrete proteolytic enzymes (collagenases), inflamm mediators: more inflamm: bone & cartilage destruction |
|
|
Term
| 3 Tx goals for Rheumatoid Arthritis |
|
Definition
1) decrease pain
2) prevent/control joint damage
3) prevent loss of fcn, preserve quality of life |
|
|
Term
| 5 Meds for Rheumatoid Arthritis |
|
Definition
(BC DAN)
Biological Response Modifiers (BRM)
Corticosteroids
DMARDs
Analgesics (acetaminophen)
NSAIDs |
|
|
Term
| when do you start rheumatoid pts on NSAIDs? |
|
Definition
|
|
Term
| reason for using NSAIDS: rheumatoid |
|
Definition
| symptomatic relief only, do NOT affect disase course |
|
|
Term
| reason for using analgesics: rheumatoid |
|
Definition
|
|
Term
| Rx: prevent join damage and inflamm in rheumatoid arthritis |
|
Definition
| coticosteroids (Prednisone) |
|
|
Term
| frequently used DMARDs (Disease Modifying anti-Rheumatic Drugs) |
|
Definition
SHaLoM
Sulfasalzine (Azulifidine)
Hydroxychloroquine (Plaquenil)
Leflunomide (Arava)
Methotrexate (Rheumatrex) |
|
|
Term
| use of DMARDs in rheumatoid |
|
Definition
reduce/prevent joint damage
modifies disease course |
|
|
Term
| 3 BRMs (Biological Response Modifiers)that interfere w/ TNF-alpha |
|
Definition
Etanercept
Infliximab
Adalimumab |
|
|
Term
|
Definition
| interfere w/ pro-inflamm mediators (TNF-alpha, etc.), therefore inhibit immune responses |
|
|
Term
| why would you give an intra-articular corticosteroid (cortisone) injection for rheumatoid? |
|
Definition
| to relieve acute joint inflamm during a flare in disease Sx |
|
|
Term
| advatage and disadvantage: cortisone injection for rheumatoid |
|
Definition
adv: not assoc. w/ adverse SE of corticosteroids
disadv: local therapy for systemic disease |
|
|
Term
| maximum dose for low-dose oral corticosteroids (prednisone) in Tx rheumatoid |
|
Definition
|
|
Term
| 2 uses for low-dose oral corticosteroids (prednisone) in rheumatoid |
|
Definition
1) prevent new bone erosions
2) Tx extra-articular manifestations (Ex: pericarditis, vasculitis) |
|
|
Term
| Serious Adverse SE long term corticosteroid use |
|
Definition
| wt gain, fluid retention, hyperglycemia, HTN, infections |
|
|
Term
| what can happen if corticosteroid dose lowered or stopped? |
|
Definition
|
|
Term
| when should you prescribe DMARDs to rheumatoid pts? |
|
Definition
1) when NSAIDs haven't prevented ongoing joint pain & other Sx
2) do not delay use beyond 3 months |
|
|
Term
| 3 characteristics of DMARDs |
|
Definition
1) slow acting
2) take several weeks-months for efficacy
3) taken for extended time periods |
|
|
Term
| Less frequently used DMARDs |
|
Definition
(CC GAP)
Cyclosporin
Cyclophosphamide
Gold salts
Azathioprine
D-Penicillamine |
|
|
Term
| contraindication - DMARDs |
|
Definition
| Pregnancy - potentially teratogenic |
|
|
Term
| Drug of choice for rheumatoid pt w/ active disease |
|
Definition
|
|
Term
| 2 reasons to use low dose Methotrexate for rheumatoid |
|
Definition
1) decreases appearance of new bone erosions
2) improves long term clinical outcome |
|
|
Term
| how long does it take for effects of methotrexate to appear? |
|
Definition
|
|
Term
| do pts tolerate methotrexate? |
|
Definition
| well tolerated - most take for >3yrs |
|
|
Term
| current theory for low dose Methotrexate MOA |
|
Definition
| inhibits AICAR transformylase enzyme, which indirectly inc cellular conc ADENOSINE (immunosuppressive agent) |
|
|
Term
|
Definition
nausea, stomatitis, anorexia, mucosal ulcers, bone marrow suppression, dose-related hepatotoxicity
acute pneumonitis (1-2% pts) |
|
|
Term
| drug interactions: Methotrexate |
|
Definition
| NSAIDs - cause inc serum conc. Methotrexate by dec. renal excretion |
|
|
Term
| Contraindications: Methotrexate |
|
Definition
1) pre-existing liver disease
2) pregnancy
3) elderly |
|
|
Term
| anti-malarial drug that is moderately effective for mild rheumatoid arthritis |
|
Definition
|
|
Term
| how long does it take for effectiveness of Hydroxychloroquine? |
|
Definition
|
|
Term
| adverse SE: Hydroxychloroquine |
|
Definition
nausea, epigastric pain, rash, diarrhea
serious SE are RARE (e.g. retinal toxicity in elderly) |
|
|
Term
| compare Sulfasalazine to Hydroxychloroquine in Tx rheumatoid |
|
Definition
| effective, but greater toxicity |
|
|
Term
| makeup of sulfasalazine, and method of activation |
|
Definition
5-aminosalicylic acid covalently linked to sulfapyridine
5-asa cleaved off by colonic bacteria: sulfapyridine responsible for therapeutic effect |
|
|
Term
| how long does it take for effects of sulfasalazine? |
|
Definition
|
|
Term
| is sulfasalazine safe during pregnancy? |
|
Definition
|
|
Term
| is sulfasalazine tolerated by patients? |
|
Definition
| yes, generally well tolerated |
|
|
Term
|
Definition
| nausea, headache, anorexia, rash (30% pts) |
|
|
Term
| oral pyrimidine synthesis inhibitor used in Tx rheumatoid arthritis |
|
Definition
|
|
Term
|
Definition
| Pyrimidine synthesis inhibitor: blocks de novo synthesis Uridine: leads to arrest of cells in G1 phase: inhibits cell growth |
|
|
Term
| what cells does Leflunomide inhibit? |
|
Definition
T cell prolif
autoAb production by B cells |
|
|
Term
| compare Leflunomide to Sulfasalazine & Methotrexate in Tx rheumatoid |
|
Definition
| as effective in dec Sx of disease |
|
|
Term
|
Definition
| diarrhea (25% pts), alopecia, wt gain, rash, inc BP, inc liver enzymes |
|
|
Term
| serious adverse effect of taking both Leflunomide and Methotrexate |
|
Definition
|
|
Term
| contraindications: Leflunomide |
|
Definition
|
|
Term
| drug interactions: Leflunomide |
|
Definition
| Rifampin (anti-TB med): inc Leflunomide levels |
|
|
Term
|
Definition
D-penicillamine (more toxic than methotrexate or sulfasalazine)
Gold Salts (serious SE: dermatitis, proteinuria, thrombocytopenia, leukopenia, bone marrow supression) |
|
|
Term
| Rx: refractory Rheumatoid Arthritis |
|
Definition
|
|
Term
| orally active purine analog that is cytotoxic to inflamm cells, used to Tx rheumatoid |
|
Definition
|
|
Term
| limitations for cyclosporin A |
|
Definition
| toxicity, cost, need to accurately monitor drug levels |
|
|
Term
| rheumatoid drug that inhibits T cell activation pathways that lead towards production of cytokines and is also useful in pts w/ refractory arthritis |
|
Definition
|
|
Term
| rheumatoid drug that has a metabolite that promotes DNA crosslinks to inhibit DNA replication: inhibits T & B cell fcn |
|
Definition
Cyclophosphamide
(metabolite = phosphoramide mustard) |
|
|
Term
| adverse SE of long term cyclophosphamide use |
|
Definition
| leukopenia, cardiotoxicity, alopecia, inc risk of bladder cancer |
|
|
Term
| key cytokine in the pathogenesis of rheumatoid arthritis |
|
Definition
|
|
Term
| 3 cells that synthesize TNF-alpha |
|
Definition
1) macrophages
2) mast cells
3) activated Th1 CD4 cells |
|
|
Term
| 5 major fcns of TNF-alpha |
|
Definition
1) activates macrophages: inc phag, inc cytotoxic molecules
2) pyrogenic activity: causes fever
3) activates endothelium: promotes recruitment leukocytes to sites of inflamm
4) induces differentiation osteoclasts: inc bone resorption
5) induces prolif synoviocytes: inc production proteases & inflamm mediators |
|
|
Term
| 3 end results of inc TNF-alpha |
|
Definition
1) inc joint inflamm
2) cartilage breakdown
3) bone erosion |
|
|
Term
| what drugs act as anti-TNF-alpha and anti-IL-1 in Tx rheumatoid? |
|
Definition
| BRMs (Biological Response Modifiers) |
|
|
Term
| BRM that interferes w/ IL-1 in Tx rheumatoid |
|
Definition
|
|
Term
| BRM used as a monotherapy and in combination w/ methotrexate |
|
Definition
|
|
Term
|
Definition
reduces joint pain & swelling
dec formation new bone erosions |
|
|
Term
| contraindications: etanercept |
|
Definition
| pts w/ acute or chronic infections b/c opportunistic infections can occur |
|
|
Term
| what rheumatoid drug can cause the reactivation of latent TB |
|
Definition
|
|
Term
| MOA - BRMs specific for TNF-alpha |
|
Definition
| bind to soluble TNF-alpha and prevent it from binding to its receptor |
|
|
Term
what drug, given with low dose methotrexate, has been shown to significantly prevent rheumatoid progression
(vs. methotrexate alone) |
|
Definition
|
|
Term
| when should you discontinue Infliximab? |
|
Definition
| if serious infection or sepsis develops |
|
|
Term
| contraindications: Inflixamib |
|
Definition
| pts w/ acute or chronic infections |
|
|
Term
| why is it beneficial to take methotrexate w/ adalimumab for Tx rheumatoid? |
|
Definition
| methotrexate inhibits adalimumab clearance and formation of anti-adalimumbab Abs |
|
|
Term
| contraindications: adalimumbab |
|
Definition
| pts w/ acute or chronic infections |
|
|
Term
| Il-1 receptor antagonist used in Tx rheumatoid |
|
Definition
|
|
Term
|
Definition
| competitive inhibitor of pro-inflamm mediator IL-1 |
|
|
Term
| subcutaneous dose Anakinra causes |
|
Definition
1) modest pain & swelling reduction
2) significant reduction in new bone erosions |
|
|
Term
| when are the adverse SE of anakinra worse? |
|
Definition
| when given w/ anti-TNF-alpha drugs |
|
|
Term
| 4 step Tx strategy for Rheumatoid Arthritis |
|
Definition
1) Initial Sx Tx for pain/inflamm relief (NSAIDs, cortisone, prednisone)
2) DMARDs w/in 3 months diagnosis
3) BRMs or another DMARD if Methotrexate ineffective
4) combination therapy more effective |
|
|
Term
| DMARDs used for mild disease |
|
Definition
| Hydroxychloroquine and Sulfasalazine |
|
|
Term
| DMARD used for active moderate/severe rheumatoid |
|
Definition
|
|
Term
| what combo or Rheumatoid drugs has potential for serious hepatotoxicity |
|
Definition
| Methotrexate + Leflunomide |
|
|
Term
| extremely painful form of arthritis |
|
Definition
|
|
Term
| disease assoc w/ high serum levels uric acid |
|
Definition
|
|
Term
|
Definition
| deposition of insoluble monosodium urate crystals in joint and cartilage |
|
|
Term
|
Definition
| pain, swelling, redness, heat, stiffness in joints |
|
|
Term
|
Definition
intense periods painful swelling in single joints, usually in feet (esp BIG TOE)
resolve 3-10 days |
|
|
Term
| what population primarly Dx w/ gout? |
|
Definition
|
|
Term
| gout is commonly assoc with what conditions? |
|
Definition
| obesity, HTN, hyperlipidemia, diabetes 2, purine-rich diet, excessive alcohol consumption |
|
|
Term
| 6 step pathophysiological process of gout |
|
Definition
1) urate crystals deposited in joints
2) synoviocytes phag urate crystals
3) synoviocytes secrete PGs, IL-1, lysosomal enzymes
4) inflamm leukocytes recruited to joint
5) leukocytes phag urate crystals: release more PGs, IL-1, etc. to promote more inflamm
6) inflamm: pain, heat, swelling, joint damage |
|
|
Term
|
Definition
1) drugs that relieve acute Sx of gouty attack
2) drugs that lower plasma uric acid levels
3) drugs that decrease uric acid synthesis |
|
|
Term
| 2 drugs that relieve acute Sx gouty attack |
|
Definition
|
|
Term
|
Definition
|
|
Term
| MOA Colchicine in gout Tx |
|
Definition
blocks leukocyte migration and phag
anti-inflamm
NO analgesia |
|
|
Term
does colchicine have anti-inflamm activity?
analgesic activity? |
|
Definition
yes anti- inflamm
no analgesic |
|
|
Term
|
Definition
| burning throat, bloody diarrhea, renal failure, shock, fatal ascending CNS depression |
|
|
Term
| what 2 NSAIDs are particularly good replacements for Colchicine in Tx of gout? |
|
Definition
|
|
Term
| what 3 NSAIDs have not been shown to be successful in Tx of gout? |
|
Definition
Salicylates
Aspirin
Tolmetin |
|
|
Term
| Rx: symptomatic Tx gout in pt w/ Hx GI bleeds or onl blood thinners |
|
Definition
|
|
Term
Uricosuric Agents:
definition
specific drugs (2) |
|
Definition
Drugs that lower plasma uric acid levels
1) Probenacid
2) Sulfinprazone |
|
|
Term
| when do you use Uricosuric agents? |
|
Definition
1) several freq gouty attacks
2) when plasma levels uric acid so high that tissue damage inevitable |
|
|
Term
| MOA: probenacid and sulfinpyrazone |
|
Definition
weak organic acids: inhibit anion transporters in prox tubule of kidney: decrease reabsorption uric acid=======>
PROMOTES URIC ACID EXCRETION |
|
|
Term
| when do you start Tx w/ uricosuric agents for gout? |
|
Definition
| 2-3 weeks after initial attack |
|
|
Term
| adverse SE: uricosuric agents and method of preventing this SE |
|
Definition
inc risk of kidney stones (inc uric acid excretion)
prevent: keep urine vol high, keep urine pH>6 |
|
|
Term
| drug that dec uric acid synthesis in Tx gout |
|
Definition
|
|
Term
| MOA: allopurinol in Tx gout |
|
Definition
| structural analog of hypoxanthine: inhibits xanthine oxidase, which normally catalyzes final 2 steps purine degradation |
|
|
Term
| 4 types pts allopurinol is particularly useful for in Tx gout |
|
Definition
pts w/:
1) high endogenous uric acid synthesis
2) recurrent kidney stones
3) renal impairment
4) grossly elevated uric acid levels |
|
|
Term
| when shouldn't allopurinol be given and why? |
|
Definition
| during acute gouty attack b/c it can worsen Sx |
|
|
Term
| what is co-administered at onset of allopurinol Tx and why? |
|
Definition
| NSAIDs b/c they reduce chances of precipitating acute gouty attack |
|
|
