Bone/Joint Flashcards
1
Q
role of COX 1 and COX 2
A
COX 1- preserves GI mucosal integrity, platelet activity, maintain intragolmerular pressure (kidneys)
COX 2- pain & inflammation
2
Q
COX 2 selective NSAID exs
A
celecoxib & diclofenac
3
Q
first line tx OA
A
NSAIDs
4
Q
what NSAID strongly recommended for OA in knee
A
topical (& also maybe for hand)
5
Q
should OA in hip be tx with topical NSAID
A
NO bc won’t penetrate deep joint
6
Q
how long to trial NSAID agent for OA and why
A
2-3 weeks bc analgesia works within hours but anti-inflammatory takes 2-3 weeks
if insufficient response after this timeframe, consider another NSAID
7
Q
SE of all NSAIDs
A
GI, renal, hepatic, CV, CNS, HTN
8
Q
preferred OA agent if patient has high GI risk
A
COX 2 inhibitor
with PPI if severe risk, without for moderate risk OR non selective with PPI
9
Q
COX 2 inhibitors have great risk of what complication
A
MI
10
Q
common drug interactions with NSAIDs
A
aspirin, warfarin, oral hypoglycemics, antiHTN, lithium
11
Q
when is APAP used for OA
A
short-term, episodic use in those who can’t tolerate/contraindications to NSAIDs
12
Q
when to start duloxetine for OA
A
if suboptimal response to NSAIDs
use as adjunct
13
Q
what SNRI/SSRI/TCA etc should be used to tx OA?
A
ONLY duloxetine
14
Q
duloxetine SE
A
nausea, dry mouth, somnolence, constipation, decreased appetite, hyperhidrosis
15
Q
what opioid is recommended for OA and when
A
tramadol only when other tx has failed or if pt has contraindications
16
Q
adverse effects tramadol
A
dizziness, vertigo, n/v/c, lethargy
RARE seizures
serotonin syndrome if used w/ other serotenergic agents
17
Q
ex of when opioid other than tramadol to tx OA and why
A
severe pain where alternatives inadequate or contraindicated
Ex: renal fail, HF, anticoagulation
18
Q
special pt education for opioid combo
A
clear instructions to limit OTC APAP to avoid accidental OD
19
Q
intra-articular therapy
ex
when is it used
A
after failure of first-line oral/topical NSAIDs
glucocorticoids and hyaluronic acid for IA injection
(glucocorticoids strongly > hyaluronic acid)
20
Q
what glucocorticoids for OA
A
less solubility (& injection)
methylprednisolone & triamcinolone
21
Q
how long does IA (intra-articular therapy) last and how often dosing interval
A
lasts for 3 weeks but cannot be injected more than every 3 months d/t risk of joint damage
22
Q
concerns with IA
A
loss of hyaline cartilage and acceleration of OA progression
23
Q
postinjection flare after IA
A
mimics flare of arthritis
tx with cold compresses
24
Q
glucosamine and chondroitin for OA
A
not supported d/t inconsistent efficacy
if used should be adjuncts to evidence-based therapies and d/c after 3-6 mo if no benefit noted
25
SE glucosamine
shellfish allergy
high glucose
26
Capsaicin for OA
not effective for acute pain, takes 2 weeks of daily admin to relieve pain
superficial joints only
27
how long to try APAP for OA tx
4000mg daily in divided doses x4-6 weeks
28
risk factors for osteoporosis (OP)
menopause d/t loss of estrogen (esp if early < 45 y/o)
female
> 65
asian, white
hx fragility fx before age 50
osteoporatic fx first degree relative
low BMI
RA
glucocorticoid therapy
smoking
ETOH (> 3 drinks daily)
loss of height
secondary osteoporosis
29
secondary causes of OP
ETOH
CKD
COPD
cushings
DM
CF
ED
GI
vit D deficiency
anticoag
anticonvulsants
steroids
lithium
PPI
SGLT2i
Thiazolidinedoines
thyroid supps d/t overreplacement
TPN
30
recommended amount calcium men/women/ages
calcium
1000mg men age 51-70
1200mg women > 51 y/o and men > 71
31
osteopenia T score
-1.0 to -2.5
32
osteoporosis T score
less than -2.5
33
how much Ca intake from diet men/women > 50 typically get
600-700mg/day
34
when to start pharm. therapy for OP (3 situations)
1. h/o hip/vertebral fx
2. T score -2.5 or less femoral neck/spine
3. osteopenia and at least 3% 10 year probability of hip fx or 20% 10 year probability major osteoporosis fx
35
risk of too much Ca
> 1200 mg/day > kidney stones
> 2500 mg/day > hypercalciuria/hypercalcemia
increase CV event
36
supplement doses of Ca limit
500-600mg of elemental Ca per dose
37
Ca carb consideration
Take WITH food for absorption
38
Ca citrate consideration
better absorbed in pt on PPI/acid suppression bc acidic environment not needed for absorption
Take w/ or w/o food
39
adverse effects Ca supplement
constipation, bloating, cramps, flatulence esp. calcium carb
changing diff. salt form may help
40
Ca with other meds
Ca salt reduce absorption of iron, antibiotics like tetracycline and fluoroquinolones so take 2 hr prior to 6 hours after
41
vit D supplement dose
800-1000 IU daily all adults 50 and older
MAX 4000 IU daily
42
tx vit d deficienct
5000 IU of cholecalciferol (d3) daily x8-12 weeks
then decrease to 1500-2000 IU after labs rise above 30
43
biphosphonate names &
mech. of action
first line tx osteoporosis
alendronate, risedronate, zoledronic acid ..... ibandronate for postmenopausal osteoporosis only & is second line therapy
bind to bone matrix & inhibit osteoclast activity; tx osteopenia & osteoporosis mostly in hip & spine
44
what happens when biphosphonate d/c'd
sustained benefits in fracture risk reduction up to 5 years after
45
bisphosphonate adverse effects (acute)
bone/muscle/joint pain (resolves when med stopped)
upper GI (n/v/d, severe esophageal irritation)
once week admin of oral can decrease risk
IV zoledronic acid= acute phase rx (flu-like sx); prevent and tx with APAP
AKI if renal disease, dehydration, diuretics
46
adverse effects long term biphosphonate use
osteonecrosis of jaw (ONJ) & atypical femoral fractures (AFF)
47
what should pt do BEFORE starting biphosphonate
major dental work
48
how long should you be on biphosphates and what is recommended to min SE
10 years oral, 6 IV
drug holidays after 5 years oral, 3 years IV
49
admin considerations with biphosphates
after overnight fast, plain water, remain upright x30 min
dont take w/ other meds
50
contraindications biphosphates
hypersensitivity, hypercalcemia, pregnancy, renal impair (cr clear < 30-35), esophageal abnormalities, GI malabsorption, can't remind upright x30 min
51
denosumab
broad-spectrum twice yearly inj. human monoclonal antibody decreases osteoclasts to tx OP /reduce fx
first line for osteoporosis in many people and if can't tol biphosphates.
52
downfall of denosumab vs bisphos.
BMD decreases will be seen within months of discontinuation unlike with biphos.
53
denosumab SE
back pain, arthralgia, fatigue, HA, derm rx, diarrhea, nausea
SERIOUS
hypophosph./Ca, dyspnea, skin/other infections
**** hypocalcemia needs to be corrected before use
Drug holidays NOT recommended
54
what to do before denosumab therapy
correct hypocalcemia (risk higher in CKD but can still be used)
55
first line tx for OP in patients with prior fractures or those deemed very high risk
parathyroid hormone analogs (injections)
teriparatide & abaloparatide (postmenopausal only)
56
adverse effects parathyroid hormone analogs
nausea, HA, leg cramps, ortho hypotension, inject .iste, hypercalciruia, hypercalcemia
abaloparatide= palpitations
osteosarcoma observed in animals
57
contraindications parathyroid hormone analogs
preexisting hypercalcemia, hyperparathyroid, hx skeletal radiation
58
tx duration parathyroid hormone analogs
2 years
BMD declined once stopped but fx reduction x1-2 years
switch to biphos. or denosumab once tx maxed out to prevent BMD loss
59
antisclerostin antibody & when indicated
romosozumab 210mg 2 SQ injections once monthly
tx for OP; greater reduction in vertebral fx rate
indicated for postmenopausal women at high risk fx who failed/intolerant other tx
60
tx duration romosozumab
12 months
effect wanes after 1 year
start biphosph. or denosumab once stopped
61
romosozumab SE
inject. site, arthralgias, HA, skin-related hypersensitivity
SERIOUS
increased CV events > MI, stroke, CV death so contraindicated if MI or stroke within past year
62
estrogen agonists/antagonists for OP
raloxifene (and less common bazedoxifene)
estrogen like activity on bones > reduces bone resorption decrease bone turnover
decrease breast cancer risk
Only used in select women w/ high risk breast cancer and inability to take other agents
63
adverse effects raloxifene
hot flushes, leg cramps, increase risk venous thromboembolism
64
adverse effects raloxifene
hot flushes, leg cramps, increase risk venous thromboembolism
65
calcitonin
regulates Ca levels; inhibits bone resorption, reduces vertebral fx risk ONLY for OP (only nasal formulation shows benefit)
reserved for pt who can't tolerate other agents
short-term relief back pain
66
adverse effects calcitonin
(intranasal) rhinitis, dryness, irritation
67
hormone therapy for OP
estrogen alone or w/ /progestin (HRT) reduces vertebral & hip fx risk but risks limit use (breast cancer, clot)
considered in post-menopause with hysterectomy intol. of other therapies and has vasomotor sx
68
combination therapy recommendations for OP
not recommended d/t high cost and lack of long term safety
reasonable to add biphosph. or denosumab if pt using raloxifene to reduce breast cancer risk
69
what's recommended for mod-high risk of fx, 40 y/o and up, taking glucocorticoids for 3 months or longer
biphosphonate therapy
if younger than 40, DXA with z-score recommended and optimal Ca/vit D intake
**BMD testing every 1-3 years
70
if pt taking steroids who qualify for biphosph. therapy cannot take it, what do you do
IV bisphosh, then teriparatide, denosumab, raloxifene in that order
BMD testing every 1-3 years
71
contraindications to biphosphonates
inability to remain upright x30 min, renal insufficiency (CrCl < 30)
72
special factors to consider for indications of meds for OP
most tx regimens are only for post menopausal women or male osteoporosis
73
OP meds that are only for PM women
antisclerostin antibody (romosozumab)
estrogen agonists/antagonists aka SERMS (raloxifene & bazedoxifene/conjugated estrogens)
calcitonin
ibandronate (a biphosphonate)
abaloparatide (a parathyroid hormone analog)
74
first line tx for OP if prior fractures or very high risk
parathyroid hormone analogs: teriparatide (injection; men & women) & abaloparatide (PM women only)
75
what's recommended for postmenopausal women at high risk of fx (hx or mult risk factors) who FAILED/intolerant of other tx options
antisclerostin antibody (Romosozumab)
76
tx for select women with high risk breast cancer and inability to take other agents
SERMS (estrogen agonists/antagonists)
raloxifen & bazedoxifene
77
what role do glucocorticoids play in OP
increase bone resorption, inhibiting bone formation, and changing bone quality
Bone mass lost in initial 3-6 mo of therapy
higher incidence of vertebral fx
78
meds for preventing OP in pre menopausal women
alendronate (a biphosphonate)
zoledronic acid (a biphosphonate)
79
whats hyperuricemia
high serum uric acid > 6.8
not all people show sx
80
risk factors to gout
unhealthy diet (purines, fructose, alcohol), lack of exercise, obesity, male sex
trauma & surgery may trigger by increasing uric acid
certain meds
CKD
81
gout is an independent risk factor of....
coronary heart disease
82
should people with gout continue low dose aspirin for MI/stroke prevention
yes- benefits outweigh risks
83
long term consequences of gout and hyperuricemia
joint destruction, tophi, nephrolithiasis, nephropathy
84
signs of acute gout attack
elevated WBC, ESR, tenderness/swelling/loss of function to one joint
not all pt have hyperuricemia
85
opioids and gout
play NO role bc it's inflammatory
86
NSAIDs for gout
all similar efficacy, FDA approved:
naproxen
indomethacin (greater SE esp GI)
sulindac
dose at higher end of therapeutic range for shortest duration possible (until 24 h after sx resolve)
87
who should avoid NSAIDs for acute gout
risk of peptic ulcers, anticoagulants, renal insufficiency, uncontrolled HTN, HF
88
why is colchicine used less for gout
low therapeutic index and increased cost
89
when is colchicine indicated for gout
when given within 36 hours of attack; best within 24 hours
90
SE colchicine and what to do
GI (n/v/d & abdominal pain) which warrant LOWER DOSE because GI effects are forerunner of more serious systemic toxicity including myopathy and bone marrow suppression (neutropenia). Can occur w/o GI effects esp in renal impairment < 30
91
what meds require colchicine dose reduction when given concurrently
p-glycoprotein or strong CYP3A4 inhibitors (clarithromycin, verapamil, ritonavir, cyclosporine, ranolazine)
use with caution with statins and liver failure
92
tx of choice for acute gout attack
NSAIDs
then colchicine if have SE or failed NSAID therapy
93
colchicine doses
1.2mg (two 0.6mg tabs) at onset of acute flare f/b 0.6mg 1 hour later
OR
0.6mg TID on first day of attack
*dose adjustment for renal insufficiency
94
contraindications to colchicine
never used if currently taking for prophylaxis
was treated with med within past 14 days
cautions with liver disease
dose adjustment with renal insufficiency
95
glucocorticoids for gout
when NSAIDs or colchicine contraindicated or not tolerated (esp d/t renal impair) or for polyarticular attacks or in the elderly
equally effective as NSAIDs
if 1-2 joints then can get intra-articular injection
96
adverse effects & contraindications glucocorticoids
fluid retention, hyperglycemia, CNS stimulation, weight gain, GI upset, increased risk of infection
avoid in diabetes or monitor sugars closely
caution if h/o PUD
97
corticotropin/adrenocorticotropic hormone (ACTH) for gout
efficacy and when indicated
similar efficacy to other gout tx but expensive; not first-line
indicated in pt unable to take meds orally
98
interleukin-1 inhibitors for gout
canakinumab and anakinra
conditionally indicated if patients can't tolerate or have contraindications to other anti-inflammatories
injective side rxn
99
combo therapy for gout
severe polyarticular attacked esp in large joints
colchicine with NSAIDs or glucocorticoids
glucocorticoid injections can be used with any first line agents)
100
when is urate-lowering therapy for gout indicated/not indicated
NOT indicated:
first gout attack, asymptomatic hyperuricemia
conditionally recommended if more than one acute attack but less than two per year but ALSO have mod/severe CKD, SUA > 9, urolithiasis
INDICATED:
freq. gout flares 2+ per year, radiographic evidence of gout, or at least one SQ tophus
101
non pharm tx gout
exercise/weight loss
DASH diet , low/no alcohol, manage other comorbidities
low-nonfat dairy and veggies
cheery juice, flaxseed, celery root
d/c contributing meds if clinically appropriate (like hydrochlorothiazide)
102
prophylactic gout tx exs
allopurinol, febuxostat, probenecid, and/or pegloticase
103
can urate-lowering therapy be started during acute gout attack
yes IF anti-inflammatory tx was started and should be continued during acute attacks
104
prophylactic treatment reserved for refractory gout
Pegloticase (recombinant urate oxidase)
105
first line tx gout prophylaxis
allopurinol
affordability and efficacy NOT associated with renal decline in CKD
106
allopurinol
first line therapy most patients
XOI agent
half life 2-3 hours
recommended in mod-severe CKD
ONLY start if anti-inflammatory tx is also initiated
107
Why should allopurinol ONLY start if anti-inflammatory tx is also initiated
sudden shifts in SUA level from mobilization of tissue urate stores may precipitate or exacerbate gouty arthritis
108
if person being treated with colchicine for acute attack, when do you initiate prophylactic colchicine
12 hours after last tx dose
109
how long to continue prophylactic gout therapy
acute gout receive prophylaxis when ULT is started and continue 3-6 months after no clinical evidence of gout activity and SUA target reached
110
allopurinol start dose and titration in pt with and w/o renal insufficiency
100mg normal
50mg renal
*taper up Q2-5 weeks as tolerated to the SUA target even in pt with renal disease as long as monitored/educated
when not titrating, check SUA Q6 months
Treat for sx NOT to target SUA
111
allopurinol SE
nausea, diarrhea uncommonly
generalized maculopapular rash can progress to Stevens-Johnson syndrome within first few months of therapy
*allopurinol hypersensitivity syndrome (rare but high mortality); patients should be screened via HLA and other risk factors (thiazide use, renal impairment, African american)
112
allopurinol drug interactions
theophylline & warfarin effects increased
azathioprine & 6-mercaptopurine inhibited
increase risk skin rash if take with ampicillin
113
febuxostat
nonpurine XOI structurally diff than allopurinol
no dose adjustment for renal
114
what should be given with febuxostat and why?
when rx indicated?
low dose colchicine or NSAID for at least 6 months for anti-inflammatory prophylaxis d/t rapid reduction of SUA levels
rx febuxostat indicated if can't tolerate allopurinol or cannot achieve SUA < 6
115
adverse effects febuxostat, risk, and requirements during therapy
nausea, arthralgias, rash, transient elevation of hepatic transaminases, CV events
higher CV mortality
period LFT
116
probenecid mech of action, when indicated/not indicated/avoided
SE & pt education
uricosuric agent that bocks tubular reabsorption of uric acid & increases excretion
indicated= alternative first line if XOI therapy not tolerated/contraindicated ; can be added to XOI
contraindicated= urate overproducers, h/o urolithiasis or urate nephropathy. Avoided in CKD.
SE= GI (nausea), fever, rash, rarely hepatic toxicity
education= hydration and u/o to decrease stone formation. Some adovate alkalinizing urine
117
when to switch XOI agent (allopurinol, febuxostat) or add uricosuric agent (probenecid)
when SUA remains > 6, more than 2 gout flares annually, SQ tophi
118
agent w/ mild uricosuric effects for HTN and gout
losartan
can combine with XOI
119
agent w/ mild uricosuric effects for dylipidemia and gout
statins
can combine with XOI
fenofibrate not recommended bc of risks/SE
120
lesinurad/when indicated
urice acid transporter 1
increases renal excretion SUA
coadmin w/ XOI if fail to meet target on XOI alone
withdrawn from market r/t business reasons
121
Denosumab risk & how it's mitigated
Denosumab has a Risk Evaluation and Mitigation Strategy (REMS)
program, in which the FDA requires that patients be informed of the risks associated with
denosumab use. In clinical trials, patients treated with denosumab had a higher rate of
infection.
122
Raloxifene black boxed warning
Raloxifene carries a black boxed warning for increased risk of venous
thromboembolism and should be avoided in patients with a history of DVT.
123
Zoledronic acid contraindication
Zoledronic acid is contraindicated in patients with CrCl less than 35
mL/min (0.58 mL/s)
124
Romosozumab black boxed warning
Romosozumab carries a black boxed warning for increased risk of
myocardial infarction (MI), stroke, and cardiovascular death and should be avoided if stroke
or MI occurred within the past year.
125
antiresorptive agents for OP
Denosumab
Raloxifene
