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70 Cards in this Set
- Front
- Back
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What are DMARDs used for? What is their onset of action? |
Disease-modifying anti-rheumatic drugs
Used in the treatment of RA to prevent irreversible damage to joints and minimize toxicities associated with NSAIDs and corticosteroids
Have no immediate analgesic effects but over time can control symptoms and have been shown to delay and possible stop progression of the disease
Slow onset of action |
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What is generally the first DMARD prescribed? |
Low dose Methotrexate
Can be used in mild, moderate, or severe RA |
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Methotrexate |
Nonbiologic DMARD
Antifolate that inhibits DHFR
Standard of care for RA
Decreases symptoms, limits joint damage, and improves long-term outcome
Also used in psoriasis and cancer treatments |
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Leflunomide |
Nonbiologic DMARD
Reversibly inhibits dihydroorotate dehydrogenase
Initial monotherapy instead of MTX, added in patients not responding to MTX alone, or replace MTX in patients who do not tolerate it
Reduces symptoms, limit damage to joints and improve function
Not for women of childbearing age |
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Salfasalizine |
Nonbiologic DMARD
Prevents joint erosion
Safe in pregnancy |
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Hydroxychloroquine |
Nonbiologic DMARD
Antimalarial
Moderately effective for mild RA
Well tolerated
Often used with MTX and sulfasalizine
Safe in pregnancy |
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Minocycline |
Nonbiologic DMARD
Antibiotic
Some benefit in the mildest cases of RA
Can cause drug-induced lupus
Contraindicated in young children and during pregnancy and nursing |
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What nonbiologic DMARDs are safe for pregnant women? |
Hydroxychloroquine
Sulfasalazine |
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How do biological DMARDs compare to nonbiological DMARDs? |
Relieve symptoms and may be more effective than MTX and other and other nonbiologic DMARDs in limiting joint destruction
TNF inhibitors also act more quickly than nonbiologic DMARDs, some patients report substantial improvement after the first dose
The use of TNF inhibitors in combination with MTX has synergistic beneficial effects |
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What is inhibited by glucocorticoids? What is stabilized by them? |
Inhibit phospholipase A2, cyclooxygenase COX-2, IL-2 synthesis
Stabilize membranes to reduce inflammatory mediator release |
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What are the three pathways by which glucocorticoids inhibit PG production? |
1) Genomic signaling: binding of the steroid to its receptor and translocation to a glucocorticoid responsive element (GRE) on DNA to increase anti-inflammatory proteins (annexin I and MAPK phosphatase 1)
2) Indirect, non-genomic effects: interaction with NF-kB to block its transcriptional activity required by cytokines (leads to decreased production of prostaglandins)
3) Direct repression of NF-kB and COX-2 |
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How do glucocorticoids interfere with prostaglandin production and the inflammatory cascade? |
Increased Annexin I inhibits phospholipase A2
Removing a phosphate from MAPK and interfering with Ca availability also helps inhibit PLA2
Glucocorticoids also directly interfere with COX2 |
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How does glucocorticoid therapy affect fluid and electrolytes? |
↓ K, ↑pH, edema, HTN, ↑Na |
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Aspirin |
Salicylate NSAID
Inhibits the constitutive COX-1 and the usually inducible isoform COX-2
Unique in that it covalently binds to a serine on the COX enzyme to irreversibly inhibit it for the life of the enzyme
Duration of COX inhibition in a given tissue is dependent upon the synthesis rate of new enzyme
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How does modifying the salicylate molecule to make diflurophenyl salicalyic acid (Diflunisal) affect its action? |
Makes it last longer, inhibit COX more, but not penetrate the CNS to reduce fevers
Can be used with warfarin (unlike other NSAIDs except celecoxib) |
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NSAID side effects |
Ratio of inhibition of COX-1 to COX-2 inhibition determines the severity and selectivity of some of the side effects
GI: pain, nausea, gastric erosion, ulcer or hemorrhage (COX-1 effect)
Renal: ↓ RBF, edema, ↓ diuretic effect, urate retention, hyperkalemia (from inhibition of PGI2), acid-base imbalance with ASA
CNS: headache, confusion, ↓ seizure threshold
Platelet: ↓ activation, bruising, hemorrhage |
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What are the signs of aspirin overdose? |
Tinnitus, hyperventilation, coma, vasomotor collapse
Initial response to overdose is respiratory alkalosis, then metabolic acidosis |
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What type of patient is more likely to be hypersensitive to aspirin? How is the hypersensitivity mediated? |
Patients with asthma or nasal polyps appear to have a higher propensity towards respiratory reactions and hypersensitivity
Most reactions are due to hypersensitivity towards inhibiting the COX-1 pathway so that leukotriene production is increased
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How does aspirin interact with NSAIDs? What if both drugs are needed? |
Even low anti-platelet doses of ASA can nullify the GI sparing effect of some of the other NSAIDs or COX-2 inhibitors
Conversely, NSAIDs can interfere with the binding of aspirin to the platelet
If both drugs are needed, administer aspirin 1-2 hours before the NSAID for an opportunity to irreversibly bind the platelet COX-1 first |
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Proprionic Acids |
Traditional NSAIDs
Ibuprofen, fenoprofen, naproxen, ketoprofen, flurbiprofen, oxaprozin
Useful group of drugs that tend to have less GI upset than aspirin |
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Sulindac |
Acetic acid, traditional NSAID
Longer lasting, less GI toxicity because it is a pro-drug |
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Ketorolac |
Acetic acid, traditional NSAID
The only oral and injectable NSAID
Used as a post surgical analgesic |
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Celecoxib |
Selective COX-2 inhibitor
Not more effective analgesic or anti-inflammatory drug than nonselective NSAIDs
Don't provide aspirin's CV protection
Beneficial for patients with GI intolerance to other drugs
Likely safe in patients hypersensitive to aspirin and COX-1 inhibitors |
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Acetaminophen |
Effective alternative to aspirin or NSAIDs as an antipyretic and analgesic drug but has only very weak anti-inflammatory effects |
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What is the major concern with acetaminophen overdose? |
Hepatotoxicity (potential hepatic necrosis may be fatal)
CYP mediated hydroxylation to a toxic metabolite but this is usually conjugated with glutathione and excreted without harm
Overdoses of acetaminophen deplete GSH so that the toxic metabolite (NAPQI) builds up and cells are also unprotected from oxidative stress |
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How can you treat an acetaminophen overdose? |
Activated charcoal
Substituting N-acetylcysteine (Mucomyst) from GSH
Plus aggressive support |
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Capsaicin |
Topical analgesic
Interacts with vanilloid receptors on sensory afferents and also depletes substance P
Local application of cream approved for shingles and diabetic neuropathy
Effect on joints is debatable and perhaps patient specific
Rule of 4's for treatment: minimum 4 weeks, 4x/day to figure out whether it will work for a patient or not |
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Anakinra |
Biologic DMARD
Genetically engineered IL-1 receptor antagonist
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Abatacept |
Biologic DMARD
Genetically engineered fusion protein blocks T-cell activation
Do not give with other biologics |
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Rituximab |
Biologic DMARD
Chimeric mab against CD20
A B cell specific surface antigen
Can use with MTX or other non-biologics, but not biologics
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Tociluzumab |
Biologic DMARD
Humanized mab that binds receptors for the pro-inflammatory cytokine IL-6 |
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Adalimumab |
Biologic DMARD
TNF inhibitor
As effective as entanercept or infliximab with MTX
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Certolizumab pegol |
Biologic DMARD
TNF inhibitor
Pegylated Fc-free anti-TNF monoclonal antibody |
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Entanercept |
Biologic DMARD
TNF inhibitor
Fusion protein used with MTX or alone |
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Golimumab |
Biologic DMARD
TNF inhibitor
New, higher affinity for TNF than the approved agents |
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Infliximab |
Biologic DMARD
TNF inhibitor
Chimeric human/mouse anti-TNF monoclonal antibody with MTX |
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Treatment for RA |
NSAIDs (for no longer than three months alone)
Gold standard: MTX
HCQ: benefits after 2-6 months
When patient does poorly on MTX → biological tx (usually a TNF antagonist)
Rituximab (directly targets B cells)
Tocaluzimab (binds to surface bound or soluble IL-6 receptors)
Tofacitinib (oral JAK3 kinase inhibitor)
DO NOT rely on analgesic/anti inflammatory rx alone
DO NOT wait for x ray erosion to begin DMARD therapy
Pre-op: discontinue all meds except HCQ and MTX |
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Treatment for OA |
Minimal response to steroids or antiinflammatory tx
Pt who modify both diet and exercise show statistically relevant improvement
Analgesics: acetaminophen (first line)
Duloxetine (blocks nociceptive pain)
IA steroids for acute exacerbations
DO NOT use hyaluronates
Joint replacement therapy for refractory pain associated with disability |
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Spondylarthritis treatment? |
NSAIDs (first line)
Anti TNF agents (if NSAIDs are contraindicated)
Secukinumab and ustekinumab (IL-17, IL23/17)
Apremilast (PDE4)
SpA controlling treatments don't affect uveitis |
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Axial SpA treatment? |
Good response to NSAIDs |
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Peripheral SpA treatment? |
Sulfasalazine
MTX |
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Ankylosing spondylitis treatment? |
NSAIDs
DMARDs - MTX, cyclosporine, corticosteroids
TNF alpha inhibitors (EXTREMELY EFFECTIVE in slowing down progression of disease) |
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IBD peripheral arthritis treatment |
NSAIDs/COX2 inhibitors (unless associated with IBD flares)
Sulfasalazine, MTX, Azathioprine/6-MP, anti-TNF |
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Lupus treatment |
NSAIDs
Steroids
Immunosuppressants
Hydroxychloroquine (good combo drug, promotes abilities of the other drugs) |
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Sjogrens treatment |
Hydration, flouride rinses/gels/toothpastes. eye drops, artificial tears, stimulate glandular secretion, chew xylitor gum, symptomatic tx and immunosuppressants (corticosteroids for serious organ involvement)
Avoid alkylating agents (re: lymphoma risk) |
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IgG4 related disease treatment |
Glucocorticoids |
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Polymyalgia rheumatica treatment |
Rapid response to low dose corticosteroids |
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Polymyositis/dermatomyositis treatment |
Corticosteroids, MTX, azathioprine
Graded exercise rehab program |
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Sporadic Inclusion Body Myositis treatment |
TRICK QUESTION: poor response to medical therapy common (resist the urge to treat)
PT program of graded strength training |
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What is the only treatment shown to decrease mortality in scleroderma? |
ACE-inhibitors |
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Eosinophilic fasciitis treatment |
Prednisone
Can also use: hydroxychloroquine, MTX |
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Linear scleroderma treatment in children |
MTX has been somewhat useful in reversing linear scleroderma in children |
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Giant Cell Arteritis treatment |
High dose prednisone (immediately) |
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Wegner's (Granulomatosis with polyangiitis) treatment |
Corticosteroids
Cyclophosphamide
Maintenance: MTX, azathioprine, PCP prophylaxis |
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Eosoniphilic granulomatosis with polyangiitis (Churg Strauss) treatment |
Steroids
Cytotoxic (i.e. cyclophosphamide) for severe disease (i.e. if heart, CNS, or renal involvement)
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Henoch Schonlein Purpura treatment |
Supportive - IV fluids, NSAIDs for joint pain
Glucocorticoids (may not affect renal involvement)
Surgical intervention |
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Kawasaki Disease treatment |
Important to treat within first 10 days
IVIg
Aspirin
Corticosteroids contraindicated --> danger of vessel rupture, only give if high fever persists after IVIg treatment
TNF receptor blocker
Plasmapheresis |
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Infantile Polyarteritis Nodosa (IPAN) treatment |
Steroids
CTX (cytotoxic treatment) |
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Hypersensitivity vasculitis/serum sickness treatment |
Remove precipitating agent
Usually self limiting (especially if only cutaneous)
NSAIDS, antihistamines
Steroids for severe cutaneous sx or systemic involvement |
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Behcet's disease treatment |
Systemic steroids
Systemic immunosuppressive agents (steroid sparing agents, i.e. azathioprine)
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Juvenile Ideopathic Arthritis first line treatment |
NSAIDs (ibuprofen, naproxen, indomethacin)
IA steroid injection |
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Calcium pyrophosphate dihydrate and pseudogout treatment |
Mostly just symptomatic treatment
NSAIDs
If they have underlying metabolic problems treat those |
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Acute gout treatment |
NSAIDs → short half life and at full dose
Colchicine → helps manage acute attack, inhibitis tyrosine phosphorylation in PMNs in response to crystals, makes joints less hospitable to attack |
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Chronic gout treatment |
Probenecid sulfipyrazone (aka uricosuric) → inhibit resorption of urate from kidney bu interfering with urate transporter URAT1 (for underexcretors)
Allopurinol → xanthine oxidase inhibition, don't use with azathioprine (broken down by xanthine oxidase) -concomitant prophylaxis against drug-induced flare (typically colchicine) -check uric acid levels 3-4 weeks after dose change, adjust for target level <6, maintain colchicine for 6 months past achieving target
Febuxostat → non-purine xanthine oxidase inhibitor
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Osteonecrosis treatment |
Decreased weight bearing
Bisphosphonates (to slow down osteoclastic activity → working faster and quicker than osteoblasts)
Operative prophylactic procedures to prevent collapse -drilling or decompression, bone grafting, osteotomy, electrical stimulation, arthroplasty |
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Paget's treatment |
Mainstay: second generation bisphosphonates (ability to inhibit osteoclast activity)
Calcitonin
Surgery |
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Osteosarcoma treatment |
Considered curable
MTX (requires leucovorin rescue), doxorubicin, high dose ifosfamide (requires mensa), high dose cisplatin |
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Ewing's sarcoma treatment |
Considered a curable cancer
Prolonged chemo with vincristine, adriamycin, and cytoxan with definitive surgery |
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Rhabdomyosarcoma treatment |
Curable in early stages, possibly in advanced stages
Curative regimen: combination chemo (vincristine, actinomycin D, cytoxin), surgery, and radiation |
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Soft tissue sarcoma treatment |
Doxorubicin
Complete resection of pulmonary or hepatic mets |
