Module 6: Bone & Joint Disorders Flashcards
1
Q
Osteoar_______:
- Characterized by slow onset, usually after the age of 50 and is associated with absent or minimal inflammation. Pain in the hips, knees and hands (symmetrical or asymmetric) +/- bony enlargements. A hall mark is morning stiffness lasting < 30 minutes.
A
Osteoarthritis
2
Q
Osteoa________:
Non-pharmacological approaches include Rest, Weight loss (if overweight), Exercise (low impact, aerobic, strength training), Heat / Ice, Occupational/physical therapy (OT/PT) and Surgery
A
Osteoarthritis
3
Q
A___:
First line therapy for mild to moderate osteoarthritis
(Recognized by American College of Rheumatology, European League Against Rheumatism, Academy of Orthopedic Surgeons)
A
APAP
4
Q
A___: First line therapy for mild to moderate osteoarthritis.
- 325 to 650 mg by mouth every 4 to 6 hours
- 4 g per day
- 2-3 g per day, if patient is >75 years (also recommended by some clinicians for the general population to reduce the risk of hepatic injury) (AGS 2009)
- 2 g per day, if heavy alcohol use, malnutrition, fasting, low body weight, advanced age, febrile illness, select liver disease, and use of drugs that interact with acetaminophen metabolism may increase risk of hepatotoxicity (Hamilton 2019b; Hayward 2016; Larson 2007).
A
APAP
5
Q
Regarding A___ and OA:
A common reason for inadequate response is failure to use sufficient dose for adequate duration (4-6 week). Some patients may require scheduled (ATC) dosing vs PRN dosing
A
APAP
6
Q
Regarding OA:
A___ should be tried initially at an adequate dose and duration before considering an NSAID.
A
APAP
7
Q
A___ is considered as effective as NSAID for mild-moderate OA pain
A
APAP
8
Q
Regarding A___ and OA:
Consider alternative pharmacologic therapy if inadequate response or in presence of severe pain and/or inflammation, based on relative efficacy and safety, as well as concomitant medications and comorbidities
A
APAP
9
Q
N_____ for OA:
a reasonable adjunct or alternative therapy when APAP fails to provide an acceptable analgesic response (despite adequate dose / duration / ATC dosing) or if there is an inflammatory component. ACR conditionally recommends use of oral N____s as an option for the initial management of moderate-severe OA.
A
NSAIDs
10
Q
All N_____ (regarding OA) are equally effective when used at comparable doses.
A
NSAIDs
11
Q
Regarding OA:
selection of a specific oral N____ should be based on patient preference, previous response, tolerability, side-effect profile, dosing frequency, cost, and underlying GI risk.
A
NSAID
12
Q
Regarding N____s and OA:
use lowest effective dose and avoid long-term use if possible
A
NSAID
13
Q
Regarding OA:
C__-2 i_________ are equally effective, but no more effective than non selective NSAIDs and should be reserved for those at high risk for GI events.
A
COX-2 inhibitors
14
Q
Regarding OA:
Gastroprotection or COX2:
- Cox2 inhibitors may be associated with increase CV risk
- Non-selective N____s such as diclofenac also have increased CV risk vs other non-selective N____s
A
NSAIDs
15
Q
Regarding OA and N_____:
Acetaminophen in combination with low-dose naproxen or ibuprofen could help to control pain and reduce GU risk.
A
NSAIDs
16
Q
Regarding OA:
- use N_____ (including nonselective and COX-2-selective agents) with caution if cardiovascular risk factors are present
A
NSAIDs
17
Q
Regarding OA:
Glu________ and chon_______:
In the landmark GAIT trial sponsored by NIH, the use of this was no more effective than placebo in decreasing pain. However, in the context of study limitations, there may be a modest reduction in pain and improved mobility in some patients. They may also slow disease progression, although the clinical impact is unclear at this time.
- Can be extrapolated to other remedies such as turmeric (curcumin), white willow bark, MSM, SAMe
- As over the counter supplements, it is important to note that they are not regulated by the FDA
A
Glucosamine and chondroitin
18
Q
Regarding Intraarticular Injections and O_:
- May be considered as an option in the initial management (ACR conditional recommendation), especially in patients with moderate-to-severe pain refractory to oral analgesic/anti-inflammatory agents
A
OA
19
Q
Regarding intraarticular injections and O_:
Corticosteroids:
Onset in days, but duration does not persist for beyond 4 weeks. Safe frequency of injection is not an absolute number but varies according to the risk to chondrocyte viability and cartilage depth inherent to each disease. Serial injections (every three months) are discouraged due to potential negative effects on the progression of cartilage damage in knee OA patients
- The use of systemic corticosteroids is discouraged in OA
A
OA
20
Q
Regarding intraarticular injections and O_:
Hyaluronic acid:
- Viscous substance believed to facilitate joint lubrication and shock absorption
- Effect persists for longer than the residence time in the synovium
- Greater pain relief than corticosteroids, but longer time to onset
A
OA
21
Q
Regarding O_:
Tramadol / Opioids - Reserved for moderate or severe pain which impairs function or quality of life, for which potential benefits outweigh risks, and for which no alternative has better risk/benefit profile, patients unresponsive to other therapies or when other therapies are contraindicated
A
OA
22
Q
Regarding Ost__a_______s and pain:
- Opioids (including tramadol) should be initiated with short-acting agents at low doses and titrated to the lowest effective dose
- Opioids (including tramadol) should be combined with acetaminophen or NSAIDs to reduce the opioid requirement
- Clinicians should establish realistic pain and function goals
- response to opioid therapy should be assessed within 1 to 4 weeks of initiation or dose increase and every 3 months thereafter
A
OA
23
Q
Tram____ (med, regarding OA):
weak μ receptor agonist, serotonin re-uptake inhibitor, nor-epinephrine re-uptake inhibitor
- Increase seizure risk
- Serotonin syndrome
- Adverse effects: similar to opioids
A
Tramadol
24
Q
S___ (duloxetine) - FDA approved for the management of chronic musculoskeletal pain, including OA
A
SNRI
25
Regarding dul_______ (SNRI) and OA pain:
May be of benefit in those with concomitant neuropathic pain
- use not recommended if hepatic insufficiency, excessive alcohol use, or severe renal impairment (creatine clearance < 30 mL/minute)
- geriatric patients may be at greater risk for clinically important hyponatremia
- urinary hesitation and urinary retention have been reported
- orthostatic hypotension reported, especially within first week of therapy
- Concomitant use with tramadol should be pursued cautiously owing to an increased risk of serotonin syndrome.
duloxetine
26
dulox_____ (SNRI) and OA:
Concomitant use with tramadol should be pursued cautiously owing to an increased risk of serotonin syndrome.
Duloxetine
27
Ost__p______ is a skeletal disease characterized by Low bone density, decreased bone strength and deterioration of bone micro-architecture
Osteoporosis
28
Regarding Osteop______:
The key players involve vitamin D, PTH, calcitonin, calcium and FGF23
Osteoporosis
29
Regarding Osteop______:
Involves men and women to different extent and with different underlying pathologies.
- ♀ Accelerated bone loss as a result of loss of estrogen
- ♂ Age or secondary cause (hypogonadism)is usually the most contributing factors to disease
Osteoporosis
30
Regarding O___________:
Bone healthy lifestyle including exercise, no smoking, limiting EToH (<3 drinks/d), limiting caffeine and fall prevention measures, calcium and vitamin D to SUPPLEMENT DIETARY SOURCES
Osteoporosis
31
Regarding Osteoporosis:
Calcium (not all salts provide the same amount of elemental calcium or have the same absorption profile). Remember: It's the elemental Ca that counts!
C______ c________
- 40% elemental calcium
- Available in tablet, chewable, and liquid formulations
- Dose: 500-600mg taken with food
- Acid dependent disintegration and dissolution
Calcium carbonate
32
Regarding Osteoporosis:
Calcium (not all salts provide the same amount of elemental calcium or have the same absorption profile). Remember: It's the elemental Ca that counts!
Cal____ ci____e
- 21% elemental calcium
- Available in tablet and chewable formulations
- Dose: 200-625mg with or without food
- Acid independent absorption
- Who would benefit from calcium citrate vs calcium carbonate?
- Recommendations of NOF, IOM, ACCE
Calcium citrate
33
Acid dependent disintegration and dissolution.
Citrate or Carbonate?
Calcium carbonate
34
Acid independent absorption.
Citrate or Carbonate?
Calcium citrate
35
Regarding v______ D and osteoporosis:
- OTC: Vit D3 (Cholecalciferol) dose 200-1000 IU daily
-- Available as individual supplement (200, 400, 1000, 2000, 5000 IU), in MVI or in combination with calcium supplements
- RX: Vit D2 (Ergocalciferol) 50,000 IU weekly or monthly based on 25(OH)D concentrations
-- Goal: serum 25-OH vit D > 30 ng/mL
Vitamin D
36
Pharmacological therapy regarding osteop______:
The NOF recommends that all men and women older than 50 years be considered for pharmacologic treatment if they meet any of the following criteria:
- (a) history of hip or vertebral fracture
- (b) T-score –2.5 or less at femoral neck or spine
- (c) osteopenia and at least a 3% 10-year probability of hip fracture or at least a 20% 10-year probability of major o___________-related fracture as determined by FRAX.
Osteoporosis
37
Calcium and Vitamin D supplement should be added to all drug therapy regimens for o___________ to increase bone density and decrease the risk of hip and vertebral fractures.
osteoporosis
38
Regarding osteoporosis:
Bisph_________s: Of the antiresorptive agents, these consistently provide greatest fracture risk reduction and BMD increases.
- ≈ ½ of absorbed drug accumulates in bone, Remainder of absorbed drug eliminated renally.
Bisphosphonates
39
Regarding osteoporosis and B______________:
Select CIs/ADRs:
- oral agents contraindicated in patients who cannot remain upright or who have esophageal abnormalities
- risk of osteonecrosis of the jaw
- Contraindicated in renal insufficiency or failure (CrCl < 30-35 ml/min)
- increased risk of Afib with zolendronic acid
Bisphosphonates
40
Regarding o___________:
Counseling for oral agents:
- Must be taken on an empty stomach, first thing in the morning, with 8 ounces of plain water (no other liquid).
- After taking this medication, patients must wait at least 60 minutes before eating, drinking or taking any other medication.
- Patients must remain upright for at least one hour after taking the medication
Osteoporosis
41
Regarding osteop______:
Patients should still be advised of the importance Ca and vitamin D and weight bearing exercise
Osteoporosis
42
Regarding osteoporosis:
Specific agents have varying indications.
For example: iband____te is indicated only in women for prevention and treatment of OP and has no indication in men or for GIOP (glucocorticoid-induced osteoporosis).
ibandronate
43
Regarding osteoporosis and b______________:
- Typical duration of treatment with bisphosphonate is 3-5 years
- Long-term efficacy of bisphosphonates are not known, but safety data exists for use >10 years
Bisphosphonates
44
Regarding o___________:
Estrogens/HRT:
Estrogen deficiency is associated with a gap between bone resorption and bone formation. While there are multiple possible mechanisms for this, estrogen effects on decreasing osteoblast apoptosis, oxidative stress, and osteoblastic NF-κB activity appear to be key mediators of the ability of estrogen to maintain bone formation.
osteoporosis
45
Regarding o____p______:
Estrogen/hormone therapy is approved by the FDA for the prevention of *this*, relief of vasomotor symptoms, and vulvovaginal atrophy associated with menopause.
Refer back to Men's/women's health. Estrogen must be used in combination with a progestin for women with an intact uterus
osteoporosis
46
When ET/HT use is considered solely for prevention of osteop______, the FDA recommends that approved non-estrogen treatments should first be carefully considered
osteoporosis
47
Regarding osteoporosis and the use of estr____ as treatment:
The study was halted early despite demonstrated reduction in fracture because it was also shown
- increase risk of heart disease
- increase risk of stroke
- increase risk of blood clots in lungs
- increase risk of breast cancer
- increased endometrial cancer
- increase in dementia
estrogen
48
Regarding osteoporosis:
Because of the risks, E_/H_ should be used in the lowest effective doses for the shortest duration to treat moderately severe menopausal symptoms and should be considered primarily for women within the first few years of menopause.
- lower doses of transdermal estrogen may be preferred route of administration in women who are older, or those with metabolic syndromes such as fatty liver or hypertriglyceridemia with risk of pancreatitis
- transdermal estrogen is preferred in smokers
ET/HT
49
Regarding o___ep______ and ET/HT:
Patients should still be advised of the importance Ca and vitamin D and weight bearing exercise
osteoporosis
50
SERMs (ralox_____):
FDA-approved for the prevention and treatment of osteoporosis in postmenopausal women
raloxifene
51
SERMs (ralo_____e):
Also indicated for the reduction of risk of invasive breast cancer in postmenopausal women with osteoporosis
raloxifene
52
SERMs (ralox_____):
Raloxifene appears to act as an estrogen agonist in bone. It decreases bone resorption and bone turnover, increases bone mineral density (BMD) and decreases fracture incidence
raloxifene
53
SERMs (ralox_____):
Preclinical data demonstrate that raloxifene is an estrogen antagonist in uterine and breast tissues.
raloxifene
54
SERMs (ralo_____e):
(+) risk of VTE or previous history of VTE is contraindication to therapy, Pregnancy Category X, Slight increase in TG and fatal stroke (black box warning)
This medication can treat and prevent osteoporosis in women who have gone through menopause
raloxifene
55
SERMs (ralox____e):
Patients should still be advised of the importance Ca and vitamin D and weight bearing exercise
raloxifene
56
Conj______ estr_____/Bazed____ene:
FDA approved for women who suffer from moderate-to-severe hot flashes (vasomotor symptoms) associated with menopause and to prevent osteoporosis after menopause
- B___________ component reduces the risk of endometrial hyperplasia that can occur with the estrogen. Therefore progestins do not need to be taken
- See estrogen precautions
- - Like other products containing estrogen, it should be used for the shortest duration consistent with treatment goals and risks for the individual woman.
- - When using this drug only for the prevention of osteoporosis, such use should be limited to women who are at significant risk of osteoporosis and only after carefully considering alternatives that do not contain estrogen.
Conjugated estrogens/Bazedoxifene:
57
Calc______:
FDA approved for the treatment of osteoporosis in women who are 5 years past menopause
- Less robust decrease in reduction of fracture (3rd line therapy)
- Due to the possible association between malignancy and c_________-salmon use, the need for continued therapy should be re-evaluated on a periodic basis.
Calcitonin
58
Advantages of Calc______ (Safety):
- No increased risk of breast and uterine cancer or VTE
- No renal restrictions
Calcitonin
59
Advantages of Calcit____ (Efficacy):
- Increased BMD
- Decrease in vertebral fractures
- analgesic effect on bone pain associated with acute fractures
Calcitonin
60
Disadvantages of Calc_____n (Efficacy):
- Less robust decrease in reduction of fracture (3rd line therapy)
- no decreased in nonvertebral or hip fracture
Calcitonin
61
Disadvantages of Calci_____ (Tolerability):
Nasal: rhinitis, mucosal ulceration (rare), backache, HA
SQ: nausea, local inflammatory response, flushing, backache, HA
Calcitonin
62
Disadvantages of Calc_____n (Simplicity):
- nasal spray once daily
- SQ injections every other day
Calcitonin
63
Disadvantages of Cal_______ (Safety):
- Allergenicity (derived from salmon)
Calcitonin
64
Denos____:
First line therapy and should be considered in those that cannot tolerate bisphosphonates
- Treatment of post-menopausal osteoporosis
- Treatment of osteoporosis in men at high risk of fracture, defined as history of osteoporotic fracture or multiple risk factors for fracture.
- Treatment in women with breast cancer on aromatase inhibitor therapies and in men receiving gonadotropin-reducing hormone treatment for prostate cancer
- Treatment of osteoporosis in postmenopausal women and men who have failed or are intolerant of other available osteoporosis therapies.
- Prevention of OP NOT an approved indication
Denosumab
65
Deno_____:
- Treatment of post-menopausal osteoporosis
Denosumab
66
Deno_____:
- Treatment of osteoporosis in men at high risk of fracture, defined as history of osteoporotic fracture or multiple risk factors for fracture.
Denosumab
67
Denos____:
- Treatment in women with breast cancer on aromatase inhibitor therapies and in men receiving gonadotropin-reducing hormone treatment for prostate cancer
Denosumab
68
Deno____b:
- Treatment of osteoporosis in postmenopausal women and men who have failed or are intolerant of other available osteoporosis therapies.
Denosumab
69
Deno_____:
- Prevention of OP NOT an approved indication
Denosumab
70
Denos___b may cause hypocalcemia. Hypocalcemia must be corrected before starting denosumab.
Denosumab
71
Denos____:
Administered by a health professional, 60 mg every 6 months as a subcutaneous injection.
- Dose adjustment not needed in renal patients
Denosumab
72
Denos___b:
increased the risk of serious skin infections (cellulitis) and skin rash.
Denosumab
73
Disadvantages of Deno_____ (Safety):
- Patients with CrCl <30: monitor for hypocalcemia
Denosumab
74
Disadvantages of Denos____ (Tolerability):
- Fatigue, HA, dermatitis, rash, eczema, cellulitis, myalgia, limb pain, peripheral edema, angina, hypocalcemia, hypercholesterolemia, ONJ
Denosumab
75
Disadvantages of Deno_____ (Price):
- very expensive
- $1,650 per year plus the cost associated with an office visit
Denosumab
76
Disadvantages of Denos____ (Simplicity):
- Patient must come to provider for injection
Denosumab
77
Advantages of Deno_____ (Simplicity):
- dosing every 6 months
Denosumab
78
Advantages of Deno_____ (Price):
- Can bill for administration fee at practice
Denosumab
79
Advantages of Denos___b (Efficacy):
- 68% RRR in vertebral fracture at 3 years
- 40% RRR in hip fracture at 3 years
- 20% RRR in non-vertebral fractures at 3 years
Denosumab
80
Advantages of Den___mab (Safety):
- Dose adjustment not needed in renal patients
Denosumab
81
Terip______e:
Stimulates osteoblast number and function, Increase GI Ca absorption, Increase renal tubular reabsorption of Ca
Indications:
- Postmenopausal women at high risk for fracture
- Men with primary or hypogonadal osteoporosis as high risk for fracture
- Men and women at high risk of fracture on sustained systemic glucocorticoid therapy
- Unresponsive or intolerant to other therapies
Teriparatide
82
The pharmacokinetics of single-dose terip______e were not significantly affected in adult patients with mild-to-moderate renal impairment, suggesting no need for dose adjustment
teriparatide
83
Contraindications of terip_______:
should not be prescribed for patients who are at increased baseline risk for osteosarcoma (including those with Paget’s disease of bone or unexplained elevations of alkaline phosphatase, open epiphyses, or prior external beam or implant radiation therapy involving the skeleton).
Teriparatide
84
Ter_________:
Treatment duration maximum of two years
Teriparatide
85
Advantages of Terip______e (Safety):
- No increased risk of breast cancer or uterine cancer or VTE
- Appears to be safe in moderate kidney impairment (40-49mL/min)
Teriparatide
86
Advantages of Terip_______ (Efficacy):
- Increases in BMD of spine (9%) and hip (3%)
- Decrease in vertebral (RR 65%) and non-vertebral (RR 35%) fractures
Teriparatide
87
Disadvantages of Terip______e (Safety):
- osteosarcoma has been observed in animal studies
- Contraindicated in patients with Paget's disease, open epiphyses, history of radiation involving skeleton, bone cancer or bone metastasis
- unexplained elevations in alkaline phosphatase
Teriparatide
88
Disadvantages of Teripa______ (Tolerability):
Nausea, HA, leg cramps, dizziness, injection site discomfort, hypercalcemia, hyperuricemia, orthostatic hypotension (1st few doses), muscle weakness, cramps
If bone pain, seek medical attention
Teriparatide
89
Disadvantages of Teripa_____e (Efficacy):
Treatment duration maximum of two years.
Teriparatide
90
Abalopa______ is a PTH analog which acts as an agonist at the PTH receptor. This results in activation of the cAMP signaling pathway in target cells. In rats and monkeys, this had an anabolic effect on bone, demonstrated by increases in BMD and bone mineral content (BMC) that correlated with increases in bone strength at vertebral and/or nonvertebral sites
- Indicated for the treatment of postmenopausal women with osteoporosis at high risk for fracture defined as a history of osteoporotic fracture, multiple risk factors for fracture, or patients who have failed or are intolerant to other available osteoporosis therapy
Similar effectiveness and adverse event profile to teriparatide .. possibly with a lowr risk of hypercalcemia
Abaloparatide
91
Abalopar____e is a PTH analog which acts as an agonist at the PTH receptor. This results in activation of the cAMP signaling pathway in target cells. In rats and monkeys, this had an anabolic effect on bone, demonstrated by increases in BMD and bone mineral content (BMC) that correlated with increases in bone strength at vertebral and/or nonvertebral sites
Abaloparatide
92
Abalopa_____e:
Indicated for the treatment of postmenopausal women with osteoporosis at high risk for fracture defined as a history of osteoporotic fracture, multiple risk factors for fracture, or patients who have failed or are intolerant to other available osteoporosis therapy
Similar effectiveness and adverse event profile to teriparatide .. possibly with a lowr risk of hypercalcemia
Abaloparatide
93
Romo______b is a humanized monoclonal antibody that inhibits the action of sclerostin, a regulatory factor in bone metabolism leading to increased bone formation and, to a lesser extent, decreased bone resorption
- - Not considered initial therapy.
Possible candidates include:
- Patients with multiple fragility fractures
- Those at high risk for fracture who cannot tolerate any other osteoporosis therapies
- Those who fail other osteoporosis therapies (fracture with loss of BMD in spite of compliance with therapy).
- In a randomized controlled trial in postmenopausal women, there was a higher rate of major adverse cardiac events (MACE). Therapy should not be initiated in patients who have had a myocardial infarction or stroke within the preceding year.
- The anabolic effect of R__________ wanes after 12 monthly doses of therapy. Therefore, the duration of use should be limited to 12 monthly doses
- Must be administered by healthcare professional
- Patients should be adequately supplemented with calcium and vitamin D during treatment
Romosozumab
94
Romos_____b:
Not considered initial therapy. Possible candidates include
- Patients at with multiple fragility fractures
- Those at high risk for fracture who cannot tolerate any other osteoporosis therapies
- Those who fail other osteoporosis therapies (fracture with loss of BMD in spite of compliance with therapy).
Romosozumab
95
- In a randomized controlled trial in postmenopausal women, there was a higher rate of major adverse cardiac events (MACE). Therapy should not be initiated in patients who have had a myocardial infarction or stroke within the preceding year.
- The anabolic effect of Romos___mab wanes after 12 monthly doses of therapy. Therefore, the duration of use should be limited to 12 monthly doses
- Must be administered by healthcare professional
- Patients should be adequately supplemented with calcium and vitamin D during treatment
Romosozumab
96
Calcitr___:
This synthetic vitamin D analogue, which promotes calcium absorption, has been approved by the FDA for managing hypocalcemia and metabolic bone disease in renal dialysis patients. It is also approved for use in hypoparathyroidism, both surgical and idiopathic, and pseudohypoparathyroidism. No reliable data demonstrate a reduction of risk for osteoporotic fracture.
Calcitriol
97
Other bisp__________s (etidronate, pamidronate, tiludronate). These medications vary chemically from alendronate, ibandronate, risedronate and zoledronic acid but are in the same drug class. At this time, none is approved for prevention or treatment of osteoporosis.
bisphosphonates
98
Sod___ fluo____:
Through a process that is still unclear, this stimulates the formation of new bone. The quality of bone mass thus developed is uncertain, and the evidence that it reduces fracture risk is conflicting and controversial.
Sodium fluoride
99
GIOP =
Glucocorticoid-induced osteoporosis
100
Glucocorticoid-induced osteoporosis =
GIOP
101
G__P:
Most common secondary cause of osteoporosis and 3rd most common cause overall
GIOP
102
Regarding G__P:
The American College of Rheumatology (ACR) recommends oral bisphosphonate therapy for all patients age 40 and over at moderate to high risk of fracture receiving glucocorticoids (prednisone 2.5 mg or more daily or equivalent) for 3 months or longer.
GIOP
103
Treatment for G__P regarding men and postmenopausal women:
- Bisphosphonates as first-line therapy. Alendronate or risedronate preferred because of clinical trial data demonstrating efficacy
- Zoledronic acid is an acceptable alternative for those intolerant of bisphosphonates or the dosing requirements
- Teriparatide is reserved for patients with severe osteoporosis (T-score of -3.5 or below even in the absence of fractures or a T-score of -2.5 or below plus a fragility fracture), those who are unable to tolerate any of the available bisphosphonates or who continue to fracture after one year of bisphosphonate therapy.
GIOP
104
Treatment for G___ regarding premenopausal women:
- Bisphosphonates as first-line therapy
- Teriparatide is an alternative as long as epiphyses are fully fused and potential short and long-term risks, as well as potential effects on the fetus are considered
- ¨Denosumab - Potential alternative in those with CI or intolerant to other therapies. NOT FDA approved
GIOP
105
For patients unable to take oral biphosphonates, alternative therapy in order are:
1) IV Biph___________
2) Terap_______
3) Denos____
4) Ralox_____
1) IV Bisphosphonates
2) Teriparatide
3) Denosumab
4) Raloxifene
106
G___ is defined as an arthritis associated with the presence of monosodium urate crystals (MSU) in synovial fluid or tissue leading to inflammatory reaction that causes intense pain, erythema and joint swelling
Gout
107
H____________ is defined as serum uric acid as >7.0 mg/dL in ♂ and >6.0 mg/dL in ♀
Hyperuricemia
108
Regarding hyp__u_______:
It is not recommended to treat an elevated serum uric acid concentration in an asymptomatic patient
Hyperuricemia
109
Many secondary causes of h____________ (which can lead to gout):
- Overproduction: purine rich diet, EToH, fructose, myeloproliferative disorders.
- Underexcretion: Ethanol, cyclosporine, thiazides, furosemide, ethambutol, pyrazinamide, levodopa, niacin, low dose ASA, CTX agents , CKD.
- Other risk factors include weight, gender, HTN and others.
Hyperuricemia
110
Non-pharm treatment of g___/hyperuricemia:
- Correction or modification of underlying factors - SEE secondary causes above
- Medications, weight loss
- Reduce dietary intake of purine-rich foods
- Increase fluid intake
- Decrease salt consumption
- Joint rest / immobilization for 1-2 days
- Application of ice to affected area
gout
111
For attacks of mild/moderate g___ severity (6 of 10 on a 0–10 pain VAS) particularly those involving 1 or a few small joints or 1 or 2 large joints, monotherapy is appropriate
gout
112
Regarding g___ treatment:
No specific preference was given to NSAIDs, colchicine or corticosteroids as initial management in the absence of comorbidities
- Current practice is often NSAIDs > colchicine > corticosteroids
- Must consider patient specific factors and comorbidities
gout
113
- Current practice is often NSAIDs > colchicine > corticosteroids
(regarding g___)
gout
114
Regarding g___:
NSAIDs: Most effective if started within 1st 24 hours of onset and continued for 24 hours after resolution
- All NSAIDs (except ASA and Tolmetin) are effective when given at full anti-inflammatory doses
- Avoid use in Active peptic ulcer disease, Uncompensated congestive heart failure, Uncontrolled hypertension, Severe renal impairment (<30-35ml/min)
gout
115
Regarding g___:
COXibs: The risk/benefit ratio is not yet clear for celecoxib in acute gout.
- Option in patients with gastrointestinal contraindications or intolerance to NSAIDs
gout
116
Regarding gout:
Colc______: Possesses no analgesic or uric acid lowering effects
Colchicine
117
Regarding gout and c_________:
1.2mg initially, then 0.6mg 1h later; total 1.8mg over 1 hour.
- This "acute dosing regimen" should be avoided in renal and hepatic dysfunction and in the elderly and frail.
- In patients with severe renal impairment (CrCl <30ml/min), this "acute dosing regimen" should not be repeated for 14 days.
- CrCl 30-80ml/min. no renal adjustment necessary.
Colchicine
118
Colc______ place in therapy for gout:
- NSAID intolerance - Patients at risk for NSAID induced gastropathy (active PUD)
- Moderate CKD (with proper dose modifications)
- Failed NSAID therapy
Colchicine
119
Regarding colc______ for gout:
Many ADRs (mostly GI) and CIs (Severe renal/hepatic impairment, etc)
- - Gastrointestinal (nausea, abdominal cramps, diarrhea)
- Alopecia
- Malabsorption of vitamin B12
- Myopathy
- Myelosuppression
- - CIs(Severe renal/hepatic impairment, etc)
- Neutropenia
- Severe renal/hepatic impairment
- Concomitant use of a P-glycoprotein (P-gp) or strong CYP3A4 inhibitor in presence of renal or hepatic impairment
- Severe cardiac / GI disease
Colchicine
120
Cor__________ds (regarding gout):
Indicated with NSAIDS or colchicine contraindication (eg renal impairment) or treatment failure.
Corticosteroids
121
Corticosteroids and NSAIDs have been shown equally effective in acute g___ treatment
gout
122
Cor___________s (regarding gout):
Used either systemically (PO/IV/IM) or by intraarticular injection.
Corticosteroids
123
Cort__________s (regarding gout):
Rebound attacks are relatively common once glucocorticoids are withdrawn, especially in patients who have previously suffered a number of prior attacks, whose intercritical periods have progressively shortened, and who are not receiving prophylactic therapy. For this reason, slower tapering of the glucocorticoid dose with extension of the course to 10 to 14 or even 21 days is advisable in such patients.
Corticosteroids
124
Corti_________s (regarding gout) ADRs:
Hyperglycemia, hypertension, headache, mood changes, fluid retention
Corticosteroids
125
Corti__________ (regarding gout) precautions:
- Diabetes
- Uncontrolled HTN
- Severe infections
- Active peptic ulcer disease
- Severe cardiovascular disease (HF)
Corticosteroids
126
Inter______-1 (IL-1) inhi______ potentially have a role as anti-inflammatory agents in refractory gout or for patients who are unable to tolerate conventional therapy, such as nonsteroidal anti-inflammatory drugs (NSAIDs), colchicine, or glucocorticoids, for acute attacks
- After NSAIDs, colchicine, and steroids, these are beneficial as fourth-line therapy for acute gout attacks due to their high cost and limited clinical experience
Interleukin-1 (IL-1) inhibitors
127
Regarding gout, Cort________n:
Exogenous administration of intramuscular adrenocorticotropic hormone (ACTH) stimulates production of cortisol and corticosterone by the adrenal cortex.
Corticotropin
128
Cortico_____n (regarding gout):
- May require several repeat injections and cannot be used in patients with recent prior use of systemic steroids, since the action of ACTH requires an unsuppressed adrenal axis
- A dose of 40 IU given intramuscularly and repeated every eight to 24 hours, as needed
- Issues: ACTH has not been shown to be any more effective than systemic corticosteroids and may require significantly more doses, even comparing IM to IM administration
Corticotropin
129
Regarding g___:
Combination therapy:
In severe polyarticular attacks, particularly attacks involving multiple large joints:
- colchicine may be used in combination with an NSAID or oral corticosteroid
- Intraarticular corticosteroid injections may be used in combination with any other first-line agent (NSAID, colchicine, oral corticosteroid)
gout
130
Non-pharm interventions for a____ g____ a________:
- lose weight if obese
- discontinue ETOH
- low-purine diet
- d/c contributing drugs if possible
- maintain adequate hydration
acute gouty arthritis
131
Regarding g___:
High purine foods:
- sweetbreads
- yeast (Baker's and Brewer's)
- sardines, mackerel, anchovies, herring
- organ meats, meat extracts, mincemeat
- gravies
- beer and alcoholic products
- dried beans
- mussels, scallops
gout
132
Regarding g___:
Moderate purine foods:
- wheat, wheat bran, oatmeal, bread
- wheat germ, brown rice, whole grains
- asparagus, cauliflower, spinach
- mushrooms
- green peas
- lean meat
- pultry without skin
- tofu
- fish, shellfish (shrimp, crab, oysters, clams)
- meat soups and broths
gout
133
Regarding g___:
Low purine diets are not well tolerated
gout
134
Regarding g___:
While the ACR guidelines encourage patients to consume low/non-fat dairy products and vegetables, they also cite a lack of specific evidence
gout
135
Regarding g___:
When to start a low purine diet:
- May be started during an acute gout attack only if anti-inflammatory treatment is also initiated, because sudden shifts in SUA levels from mobilization of tissue urate stores may precipitate or exacerbate gouty arthritis
OR
- After resolution (4-6 week) of acute attack.
Some clinicians may use colchicine or low dose NSAIDs prophylactically upon initiation until [serum UA] returns to normal or maximum of 3-6 months
gout
136
Xanthine oxidase inhibitors (e.g. allo_______) for gout:
Reduces the serum uric acid level while increasing the renal excretion of the more soluble oxypurine precursors
- Good for overproducers and underexcretors
- 1st line
allopurinol
137
Febux____t: Reserved for those hypersensitive, intolerant or had failure with allopurinol.
- Several clinically significant DIs
Febuxostat
138
Uricosurics (Probe_____):
Blocks (competes with) uric acid reabsorption at the proximal convoluted tubule increasing the rate of uric acid excretion.
- - Best efficacy with underexcretors
- - CIs
- Hypersensitivity reactions, renal dysfunction (Clcr <50m/min), history of kidney stones, acute attack, and overproducers of uric acid
- - May share allergenicity with other classes of sulfonamide drugs
Probenicid
139
Uric acid transporter 1 (URAT1) and organic anion transporter 4 (OAT4) inhibitor: Lesinurad
- American College of Rheumatology states that serum urate concentrations in gout patients should be reduced sufficiently to result in durable improvement in signs and symptoms of the disease and recommends a target serum urate concentration of <6 mg/dL (or <5 mg/dL if necessary to achieve such clinical improvements).
- Use in combination with xanthine oxidase inhibitor in patients who have not attained target serum uric acid concentrations
- Do not use as monotherapy.
- Ironwood discontinued U.S. commercialization of lesinurad (DUZALLO and ZURAMPIC), effective February 1, 2019
Lesinurad
140
Losar___
Increases uric acid secretion and urinary pH.
- Option for hypertensive patients with gout
Losartan
141
Fibr___s (for gout):
Increases uric acid secretion
- Option for select patients with hypertriglyceridemia
Fibrates
142
Colc______ (for gout):
Daily use (0.6-1.2mg/day) for prophylaxis.
- Renal dosage adjustments required with CrCl < 30ml/min
Colchicine
143
Herbal treatments for g___:
Anecdotal claims for many herbs but no acceptable clinical evidence of efficacy or safety
gout
144
Peglo_____e:
FDA approved for the treatment of refractory chronic gout.
Pegloticase
145
Romosozumab is a humanized monoclonal antibody that inhibits the action of sclerostin, a regulatory factor in bone metabolism leading to increased bone formation and, to a lesser extent, decreases bone resorption
-
146
Bisp__________s:
Any of a group of drugs used to limit the loss of bone density in conditions such as osteoporosis and bone cancer.
Bisphosphonates.
