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Pharmacology > Arthritis, Gout, Muscle Relaxants > Flashcards

Arthritis, Gout, Muscle Relaxants Flashcards

1
Q

OA affected joints

A

hips, DIP, PIP. can be asymmetrical. (No change in ESR)

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2
Q

RA pathophys

A

inflammatory ctyokines and chemokines (IL-1, IL-6, IL-10, TNF-a)

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3
Q

RA sx

A

fatigue, weight loss, loss of apetite, fever, joint pain. Increased ESR, + rheumatoid factor, +antinuclear antibodies, elevated CRP

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4
Q

RA criteria

A

5/7: morning stiffness at least 1 hr, arthritis of at least 3 joints: POP, MCP, wrist, elbow, knee, ankle, MTP; arthritis of at least one hand joint: wrist, MCP, PIP; symmetrical arthritis; rheumatoid nodules over bony prominences; positive serum rheumatoid factor; radiography with soft tissue swelling, bony decalcification or erosions. 1-4 must be present for at least 6 weeks.

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5
Q

Psoriatic Arthritis

A

often asymmetric (60%), axial involvement, has both components of enthesitis and synovitis. Sx: nail pitting, yellow nails, arthritis mutilans.

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6
Q

Ankylosing spondylitis

A

Begins age 20-40. Risk: family hx, males.

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7
Q

Acetaminophen

A 
OA ONLY!!
Regimen: up to 4g/day
effective for mild to moderate pain
NOT ANTI-INFLAMMATORY 
Dose: 160-650mg PO QID.
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8
Q

Acetaminophen OD antidote

A

N-acetylcysteine

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9
Q

NSAIDs and COX-2 Inhibitors

A

Moderate to severe pain
ADRs: GI, renal dysfunction, DIs
Use if no response to Tylenol

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10
Q

Cox 1

A

GI protection, platelet function, regulation of blood flow, kidney function

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11
Q

Cox 2

A

Inflammation, pain, feverq

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12
Q

Ibuprofen

A

200-800mg TID/QID

MDD: 3200 mg

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13
Q

Indomethacin

A

25-50mg TID

MDD: 200mg

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14
Q

Nabumetone

A

1-2gm q day

MDD: 2 g

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15
Q

Naproxen

A

250-500mg BID/TID

MDD: 1250mg

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16
Q

Cox 2 inhibitors

A

Celecoxib (Celebrex) 100-200mg PO q D to BID

Meloxicam (Mobic) 7.5-15mg daily

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17
Q

Nonacetylated salicylates

A

Salsalate 500-750mg PO BID
Choline magnesium trisalicylate 500-750mg PO TID
Advantages: moderate to severe pain, less risk for GI toxicity, does NOT affect platelet aggregation. Alt to NSAIDs d/t ADRs or DI w/ warfarin
Disadvantages: potential GI, renal dysfunction

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18
Q

Intraarticular glucocorticoids

A

Methylprednisolone 4-80mg based on joint size 1-5 wks
Advantages: effective for knee OA, not studied in hip, but common
Adjunct

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19
Q

Intraarticular hyaluronic acid

A

Hyalgan
Synvisc
Supartz
Moderate to severe pain for OA only, in knees
SEs: injection site, knee swelling, GI, HA
Advantages: relief may last up to 6 mo
Disadvantages: delayed onset of action, not approved for hip

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20
Q

DMARDs

A

Disease modifying anti-rheumatic Drugs
RA, PsA, psoriasis, ankylosing spondylitis. NOT OA!!
SE: myelosuppresion
FIRST LINE THERAPY for RA!! Only use NSAIDs/prednisone for breakthrough pain and inflammation or until DMARDs work!
Agents: methotrexate, hydroxychloroquine, leflunomide, azathioprine, sulfasalazine, cyclosporine, mycophenolate

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21
Q

Methotrexate

A

ROA: dihydrofolate reductase inhibitor – inhibits DNA syn thereby inhibiting immune function
Dose: low-dose pulse therapy. 7.5-20mg PO q wk or SC/IM q wk (NOT DAILY!!)
Onset: 1-2 MONTHS
First line for active RA!

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22
Q

Methotrexate side effects

A 
myelosuppresion
N/V/D
mucosal ulcers, stomatitis
hepatotoxivity w/ long term use
pulmonary toxicity
*monitor LFTs! CBC, SCr x 6mo, then 1-2 mo, liver bx after cumulative dose of 2.5-4g and after every 1.5g thereafter
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23
Q

Methotrexate DIs

Precautions

A

NSAIDs-decrease MTX tubular secretion
Theophylline–decrease theophylline clearance
Bactrim/Septra–increase risk of bone marrow suppression
Preg Cat X
Avoid in liver dz!
FOLIC ACID REPLACEMENT NEEDED

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24
Q

Leflunomide

A

MOA: pyrimidine synthesis inhibitor. Inhibits T-cell activity
Dose: 100mg PO qd x 3 d, then 10-20 mg PO qd
Onset: 1-3 MONTHS
SE: diarrhea, alopecia, rash, h/a, immunosuppresion, infection, hepatotox
Monitor LFTs, CBC, SCr
Overdose antidote: cholestyramine

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25
Q

Other DMARDs

A 
Hydroxychloroquine
Sulfasalazine
Penicillamine
Azathioprine
Cyclosporine
Cyclophosphamide
Gold sodium thiomalate
Mycophenolate Mofetil
Biologic DMARDs
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26
Q

Hydroxychloroquine

A

MOA: unknown
Dose: 200mg PO BID
Onset: 2-6 mo
First line for early or mild RA or add-on
SE: hemolysis in G6PD-deficient pts; retinal damage (baseline ophthalmic exam and every 6-12mo)

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27
Q

Sulfasalazine

A

MOA: possibly from prostaglandic inhibition
Dose: 1000 mg PO BID-TID
Onset: 1-3 mo
Place in therapy: First line for early or mild RA or add-on
SE: nausea, anorexia, rash, myelosuppresion, sulfa-cross reactivity
Monitor CBC q 2-4 wks x3 mo, then q 3 mo

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28
Q

Mycophenolate Mofetil

A

MOA: converted to acid form – cytosine monophosphate dehydrogenase and T-cell inhibition.
Dose: 2-3 gram per day

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29
Q

Azathioprine

A

MOA: inhibits T cells, anti inflammatory
Dose: 50-150mg/d
Onset: 2-3 mo
Rarely used, refractory RA
SE: myelosuppresion, hepatotox, lymphoproliferative disorders
Monitor: CBC q 1-2 wks, then q 1-3 mo

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30
Q

Cyclophosphamide

A

MOA: active metabolite phosphoramide mustard cross links DNA – prevents cell replication, T cell and B cell suppresion
Dose: Only active in RA when given orally (not IV) at 2mg/kg/d

31
Q

Cyclosporine

A

MOA: inhibits IL-2 and T lymphocytes via gene transcription
Dose: 2.5-4mg/kg/d
Onset: 2-4 mo
Limited use d/t toxicity, reserved for refractory RA
ADRs: renal insufficiency, anemia, htn
Monitor Scr and CBC, LFTs, and K+

32
Q

Penicillamine

A 
MOA: removes complement deposits in synovium
Dose: 250-750mg/d
Onset: 3-6mo
Use limited by toxicity
SEs: myelosuppresion, proteinuria
33
Q

Biologic DMARDs

A

Etanercept, Adalimumab, Golimumab, Certolizumab, Infliximab, Anakinra, Tocilizumab, Ustekinumab, Abatacept, Rituximab, Tofacitinib

34
Q

TNF Alpha Inhibitors Uses

A 
Malignancies
New onset psoriasis
invasive fungal infections
Sepsis and TB
RA, psoriasis, PsA, plaque psoriasis, ankylosing spondylitis, Crohn's, UC
35
Q

TNF Inhibitors

A 
Infliximab
Adalimumab
Entanercept
Certolizumab Pegol
Golimumab
36
Q

Infliximab (Remicade)

A

MOA: TNF Inhibitor
Dose: 3-10 mg/kg IV q 8 wks
Onset: 1 wk - 4 mo
Only recommended in combo with MTX
ADR: h/a, aseptic meningitis, infection (reactivation of TB and bacterial sepsis) infusion rxs, exacerbation of heart failure. lymphopma, liver tox.
Monitor: infection, TB skin test, chest x-ray, LFTs

37
Q

Adalimumab (Humira)

A 
TNF inhibitor
dose: 40mg sub q every other wk
Onset: 1 wk - 2mo
May be used as monotherapy or with MTX
ADRs: injection site, serious infections
Monitor. TB skin test.
38
Q

Etanercept (Enbrel)

A

MOA: TNF inhibitor. Recombinant fusion protein that binds TNF alpha
Dose: 25 mg 2x/wk or 50mg 1x/wk Sub Q
Onset: 1 week - 3 mo
Monotherpay or MTX
ADRs: Injection site, demylinating disorders, serious infections, lymphoma, CHF
Monitor. TB

39
Q

Certolizumab Pegol

A 
MOA: TNF inhibitor. Pegylated Fab fragment of TNF-alpha
Dose: every 2-4 wks
Onset: 2-7 days
Monotherapy or combo with MTX/DMARDs
ADRs: similar to others
Monitor-same, TB
40
Q

Golimumab

A 
MOA: TNF inhib, binds to human TNF alpha
Dose: 50mg subq every 30 days
Onset: 2-6d
Mono or combo w/ mtx/dmards
ADRs/Monitors: same
41
Q

Interleukin inhibitors

A

Anakinra
Tocilizumab
Ustekinumab

42
Q

Anakinra

A

Interleukin 1 receptor antagonist
Onset: 1-3 weeks
Place in therapy: TBD. Mono or combotx with MTX/DMARDs EXCEPT ANTI-TNF OR OTHER ANTI-IL AGENTS!!!!!
ADRs: Injection site rx. Neutropenia and severe infections (no TB)

43
Q

Tocilizumab

A

Antagonist of IL 6 at receptor site
Potential to cause fatal anaphylaxis!
IV
Dose adjustments: Liver enzyme abnormalities, low neutrophil counts, low platelets

44
Q

Ustekinumab

A

MOA: binds to and intergeres with IL-12 and IL-23.

Check PPD

45
Q

Other biologics

A

Abatacept
Alefacept
Rituximab
Tofacitinib

46
Q

Abatacept

A

Selective co-stimulation modulator
Recombinant fusion protein–prevents full T cell activation
ADRs: serious infection, H/A. screen for TB

47
Q

Alefacept

A

Moderate to severe chronic plaque psoriasis
Binds to lymphocyte receptor surface (CD2) inhibiting interaction with LFA-3
Check PPD

48
Q

Rituximab

A 
Chimeric monoclonal AB that targets CD20 B lymphocytes. 
RA refractory to anti-TNF agents
May be combined with MTX
IV infusion 
TB SCREEN NOT REQUIRED
49
Q

Tofacitinib

A

Janus Associated Kinase (JAK) inhibitor
Mod-severe monotx or combined with NONBIOLOGIC DMARD’s in pts who fail MTX
Dose: 5mg ORALLY BID. reduce with CYP3A4 inhibitors, renal dysfunction, hepatic impairment, lymphocytes <500, ANC decreased, Hgb decreased
DIs: avoid with azathiprine, tacrolimus, pimecrolimus, cyclosporine, and biologic DMARDs (increase immunosuppression risk)
ADRs: same as other biologic DMARDs, plus HTN, h/a

50
Q

Prednisoe

A

Prompt and dramatic affects
Capable of slowing the appearance of new bone erosions
Should not exceed 7.5mg daily if used long term for RA

51
Q

Fludrocortisone

A

Has high salt-retaining activity

52
Q

RA tx algorithm

A

RA dx
Document baseline dz activity (ACR assessment)
Tx goal: eliminate or control synovitis and or disease activity
Pt Ed, PT/OT
DMARD w/in 3 mo of dx (mild–hydroxychloroquine or sulfasalazine; moderate-severe–MTX or leflunomide (or both, monitor LFTs).
Consider addition of NSAID, local steroids or low dose systemic
If inadequate response (sx at 3mo): change or add DMARDs, MTX if not yet started
If continued inadequate response: consider surgery

53
Q

Gout pathophys

A

Hyperuricemia (uric acid >7mg/dL)
Overproduction of UA (dietary purines, conversion of tissue nucleric acid to purine nucleotides)
Underexcretion of UA (mostly renal, some GI)

54
Q

Gout risk factors

A

Thiazide diuretics, diuretics, alcohol, cyclosporine, ethambutol, pyrazinamide, aspirin, levodopa, niacin, cytotoxic drugs, B12, heredity, renal insuff, purine-rich foods, obesity

55
Q

Gout TX

A

NSAIDs: DOC–Indomethacin (large dose, then taper)
Colchicine
Corticosteroids: for resistant cases

56
Q

Colchicine

A

Alt to NSAIDs for gout
Anti-inflammatory properties, NO ANALGESIC EFFECTS
MOA: leukocyte migration inhibition (reducing inflammatory response)
Can be used continuously for prophylaxis or for attacks. DOES NOT AFFECT UA METABOLISM
ADRs: N/V/D, bone marrow depression
DIs: decreases cyanocobalamin absorption. ETOH–increase GI toxicity. Erythromycin–colchicine toxicity. Grapefruit juice.
Precautions: Renal/hepatic insuff, peptic ulcer sz, spastic colon

57
Q

Allopurinol

A

MOA: inhibits xanthine oxidase (enzyme responsible for conversion of hypoxanthine and xanthine to uric acid)
Most widely used drug to lower serum UA
Dose: 300mg PO daily, reduce for renal insuff
Can be used for gout attacks or as prophylaxis
ADRs: acute attack w/ initiaion of therapy, skin rash (D/C!), leukopenia, N/D, increased LFTs

58
Q

Allopurinol DIs and contraindications

A

DIs: uricosuric gents–may increase the excretion of oxypurinol; amoxi, ampi, AZATHIOPRINE (metabolized by XO!)–can cause increased levels of azathiprine, can go into bone marrow suppression and leukopenia; increased theophylline level; warfarin–increased INR
Precautions: occurence of hypersens rxs may be increased in pts with decreased renal fx, receiving thiazides and pcns concurrently.

59
Q

Probenecid

A

Prophylactic gout tx
MOA: uricosurics–increases UA excretion; inhibits renal tubular reabsorption of UA. Used for under-excretors of UA
Dose: 250mg PO bid x 1 wk, then 500mg PO BID. MDD 2g/d–take with food or antacids
SEs: GI, rash, kidney stone formation, precipitation of acute gouty arthritis
DIs: aspirin and diuretics decrease effectiveness
Precautions: impaired renal function (CrCl <50)

60
Q

Febuxostat

A

Prophylactic gout tx
Pts who fail allpurinol cal take this.
Take with colchicine or NSAID

61
Q

Pegloticase

A

Gout
Pegylated recombinant form or urate-oxidase enzyme (uricase. absent in humans, high in primates) converts uric acid to allantoin.
Used in very severe pts when crystals are not going away
Infusion, expensive
Use with NSAIDs or colchicine
ADRs: bruising, nausea, antibody formation
Contraindications: G6PD deficiency

62
Q

Treatment options for OA

A

Tylenol, NSAIDs, Cox2 inhibi, corticosteroid, opioids, synvisc

63
Q

Treatment options for RA

A

NSAIDs, Cox-2 inhibs, corticosteroid, DMARDs

64
Q

Treatment options for Gout

A

NSAIDs (indomethacin), corticosteroids, uricosurics, allopurinol/febuxostat, colchicine

65
Q

Skeletal muscle relaxants drug interations

A

CNS depressants

66
Q

Baclofen

A

Indications: spasticity secondary to MS
Oral or intrathecal
MOA: thought to inhibit both monosynaptic and polysynaptic reflexes as the spinal level via GABAb receptors
DIs: antidiabetic agents–increase blood glucose
Precautions: DM, elderly, h/o seizure
ADRs: drowsiness, seizures. withdraw SLOWLY

67
Q

Cyclobenzaprine

A

Relieves skeletal muscle spasm of local origin w/o interfering with muscle function. Acts primarily at brain stem level. Used in acute spasm in trauma/strains
MOA: similar in structure to TCA
DIs: MAOIs, anticholinergic agents
Precautions: CV, glaucoma, seizure dz, elderly
ADRs: sedation, confusion, hallucinations, anticholinergic

68
Q

Dantrolene

A

Indications: general muscle spasticity, malignant hyperthermia (b/c muscles are contracting so quickly)
MOA: produces relaxation by affecting contractile response of the skeletal muscle at the site beyond the myoneural junction and directly on the muscle itself.
DI: calcium channel blockers, estrogens
Precautions: cardiac dz, liver dz
ADRs: muscle weakness, sedation, hepatitis
Derived from phenytoin

69
Q

Tizanidine

A

Muscle relaxant
MOA: similar to clonidine; acts as alpha 2 receptor agonist
ADRs: hypotension, drowsiness, dry mouth

70
Q

Skeletal muscle relaxants ADRs

A 
Drowsiness-most common
HA, dizziness, blurred vision
N/V, anorexia
ANTICHOLINERGIC EFFECTS--cyclobenzaprine, orphenadrine
Potential for abuse with long-term use
71
Q

Drugs that decrease UA production

A

allopurinol and febuxostat

72
Q

Drugs that increase UA excretion

A

Probenecid and sulfinpyrazone

73
Q

Effects of Aspirin on UA

A

slows UA renal secretion and increases UA blood levels

Pharmacology (10 decks)

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