Joint & Bone health Flashcards
What are the indications of the following medications?
- Xanthine oxidase inhibitors: allopurinol, febuxosta
- Colchicine
- Probenecid
- Prednisone
- Xanthine oxidase inhibitors: allopurinol, febuxosta: chronic gout
- Colchicine: acute gout
- Probenecid: chronic gout
- Prednisone: acute gout, RA
What are the indications of the following medications?
- Acetaminophen
- NSAIDs
- Tramadol
- Acetaminophen: mild to moderate OA
- NSAIDs: mild to moderate OA, RA
- Tramadol: consider when pain associated with OA progresses past responsivenes to APAP and NSAIDS
What are the indications of the following medications?
- Methotrexate
- TMF inhibitors (Rituximab, abatacept)
- Methotrexate: RA
- TMF inhibitors (Rituximab, abatacept): RA
Bisphosphonates
Indications
- osteoporosis
- high fracture risk (long-term glucocorticoid tx, high FRAX score)
- hypercalcemia
- metastatic bone disease
- paget disease
Bisphosphonates
Formulations & prescribing considerations
- Risedronate (Actonel) inhibits bone resorption without inhibiting bone formation - 35mg oral once weekly or 150mg oral once monthly
- Alendronate (Fosamax): highly selective inhibitor of bone resorption - 70mg oral once weekly
- Ibandronate (Boniva): lack of evidence for prevention of hip or non-vertebral fracture
- Zoledronic acid (Reclast): 5mg IV once yearly
- Higher risk of renal toxicity
- Check creatinine before each dose
- Push fluids before and after each dose
- Acetaminophen after infusion may reduce acute-phase reaction
Xanthine oxidase inhibitors
allopurinol, febuxostat
MOA
decreases uric acid levels by selectively inhibiting xanthine oxidase (enzyme responsible for conversion of hypoxanthine to uric acid), reducing the risk of crystallization and gout attack; allows for biosynthesis of vital purines
Xanthine oxidase inhibitors
allopurinol, febuxostat
Prescribing considerations
- Febuxostat may increase risk for cardiac related deaths - first line is allopurinol
- Administer with NSAID or colchine for up to 6 months to prevent gout flare
- Allopurinol: prescribe an alternative agent for Korean patients with stage 3 or worse CKD or Han Chinese and Thai patients should receive genetic testing for HLA-B 5801 allele - may cause severe cutaneous adverse reaction
Xanthine oxidase inhibitors
allopurinol, febuxostat
Avoid, caution, pregnancy, peds
- Avoid: severe hepatic dysfunction
- Caution: renal impairment - can be used
- Pregnancy: avoid; lactation: allopurinol with caution
- Peds: 6+ related to hyperuricemia from cancer therapy
Xanthine oxidase inhibitors
allopurinol, febuxostat
Drug interactions, what is the goal uric acid level while on this therapy?
- Interactions
- azathioprine, mercaptopurine, theophylline
- Thiazides - risk for toxicity in older adults
- Monitoring: Aim for serum uric acid level of less than 6 mg/dL
Xanthine oxidase inhibitors
allopurinol, febuxostat
Adverse fx (5, 2 rare)
- Maculopapular skin rash
- Arthralgias
- Nausea
- Diarrhea
- Elevated transaminases
- Rare: hypersensitivity, hepatotoxicity
Colchicine
MOA, how long before this medication takes effect?
- inhibits activation, degranulation and migration of neutrophils to the area of a gout attack, decreasing inflammation and pain associated with a gout attack; does not impact purine metabolism
- Takes 18-24 hours to take effect, full effects at 48 hours
Colchicine
Caution, pregnancy/lactation, peds
- Caution: renal and hepatic impairment, elderly
- Pregnancy/lactation: caution
- Peds: 16+
Colchicine
Interactions
- Thiazides - risk for toxicity in older adults
- P450 medications
- grapefruit juice
Colchicine
Adverse fx (7, 5 rare)
- GI: Nausea, GI disturbance, diarrhea, abd pain, malabsorption of B12
- Other: Neuropathy, weakness
- Rare: agranulocytosis, aplastic anemia, alopecia, hepatic dysfunction and hepatotoxicity
Probenecid
MOA
increases excretion of serum uric acid by competitively inhibiting reabsorption of uric acid at the proximal convoluted tubule
Probenecid
Which population is this the drug of choice for?
Avoid, drug interactions, pregnancy/lactation, peds
- Drug of choice for older adults
- Avoid: blood dyscrasias, CrCl less than 30, G6PD deficiency, sulfa allergy
- Interaction: aspirin
- Pregnancy/lactation: OK
- Peds: 2+
Probenecid
Adverse fx (11, 2 rare)
- CNS: headache, dizziness
- GI: anorexia, N/V, gingival soreness
- Skin/bones/joints: dermatitis, pruritis, flushing, gout exacerbation
- Other: Urinary frequency, fever
- Rare: anaphylaxis, blood dyscrasias
Acetaminophen
MOA, patient education/prescribing considerations
- MOA: decreased prostaglandin synthesis - analgesic and antipyretic not anti-inflammatory
- Does not affect COX, so does not affect platelet aggregation or cause GI irritation
- Takes 1 week for patients to see benefits, better to take routinely
Acetaminophen
Avoid, pregnancy/lactation, peds, when to d/c, what monitoring is needed with long term use?
- Avoid: severe hepatic impairment and severe active liver disease
- Pregnancy/lactation: OK
- Peds: OK
- D/c if skin reaction develops
- Liver function for high dose or long-term therapy
Acetaminophen
Adverse fx (3)
- Skin rash
- Dizziness
- Rare: hypersensitivity reactions
NSAIDs
Ibuprofen, naproxen, voltaren gel
MOA
exerts anti-inflammatory action by inhibiting conversion of arachidonic acid to prostaglandin, prostacyclin and thromboxanes (mediators of pain and inflammation)
NSAIDs
Ibuprofen, naproxen, voltaren gel
Avoid, caution, pregnancy/lactation, peds, which is preferred for the elderly and why?; black box warning
- Avoid: GFR less than 30
- Caution: cardiovascular disease, elderly patients, renal and hepatic impairment
- Pregnancy: avoid; lactation: compatible
- Peds: 6 months +; ASA not in children with viral infection d/t risk for Reye’s syndrome
- Voltaren gel is preferred in elderly due to decreased systemic fx
- BBW: increased risk for thrombotic events; serious GI bleeding, ulceration and perforations
NSAIDs
Ibuprofen, naproxen, voltaren gel
Adverse fx (9)
- GI: GI disturbances, dyspepsia
- Edema
- Dizziness
- Skin rash
- Elevated transaminases
- HTN
- Bleeding due to reversibly impacting platelet aggregation
- Indomethacin: may aggravate depression or other psychiatric disturbances
Bisphosphonates
Risedronate, alendronate, ibandronate, zoledronic acid
MOA
inhibit bone resorption by reducing osteoclast number and function
Bisphosphonates
Risendronate, alendronate, ibandronate, zoledronic acid
Prescribing considerations/patient education
- given on an empty stomach with eight ounces of water to enhance absorption and stay upright for at least 30 minutes (Boniva is 1 hour); ensure patient is also taking calcium and vitamin D
- First-line for postmenopausal women with osteoporosis
- First-line therapy for men older than 70 with osteoporosis
- Fracture risk high after 5 years - consider changing to alternative therapy or extending for up to 10 years
- Consider drug holiday after 5 years if bone mineral density is stable
- High risk patients: caucasian, asian, history of eating disorders, long term steroid or thyroid medications
- Correct preexisting Vit D deficiency or hypocalcemia before starting
- IV can be used for those with GI intolerance
Bisphosphonates
Risendronate, alendronate, ibandronate, zoledronic acid
caution, avoid, contraindication
- Caution: moderate to severe kidney disease, upper GI pathology, bariatric surgery
- Avoid: CrCl less than 35
- Contraindication: hypocalcemia, delayed esophageal emptying, inability to stand/sit upright for 30 minutes, increased risk of aspiration
Bisphosphonates
Risendronate, alendronate, ibandronate, zoledronic acid
What medication alters the bioavailability of alendronate?
Ranitidine doubles the bioavailability
Bisphosphonates
Risendronate, alendronate, ibandronate, zoledronic acid
Adverse fx (17)
- GI: upper GI mucosa irritation, diarrhea, constipation, flatulence, N/V; abd pain, dyspepsia
- Bones/Joints: Femur fractures (higher risk in therapy past 5 years), severe bone, joint, muscle pain; jaw osteonecrosis, arthralgia, myalgia
- Other: Hypocalcemia, hypophosphatemia, HA, rash, a.fib
Prednisone
MOA, avoid, caution, other considerations, pregnancy/lactation, peds
- MOA: decreases inflammation by suppression migration of polymorphonuclear leukocytes and reversing increased capillary permeability
- Avoid: uncontrolled active infections
- Caution: diabetic patients, active GI disease, renal and hepatic impairment
- Other considerations: prolonged use may lead to adrenal suppression and immunosuppression
- Pregnancy/lactation: caution
- Peds: OK
Prednisone
Adverse fx (6)
Adverse fx with chronic use (6)
- Hypertension
- Insomnia
- Mood changes
- Increased appetite
- Glucose intolerance
- Peptic ulcer
- Chronic use: cutaneous atrophy, cataracts, glaucoma, osteoporosis, growth suppression, Cushing’s syndrome; use calcium and vitamin D
Tramadol
MOA
Mu opioid receptor agonist that inhibits ascending pain pathways; inhibits reuptake of serotonin and norepinephrine
Tramadol
avoid, caution, peds, drug interactions
- Avoid: hx of seizures (lowers seizure threshold)
- Caution: substance abuse hx, renal and hepatic impairment, elderly
- Peds: caution
- Interactions: other CNS depressants, serotonergic agents (r/f serotonin syndrome)
Tramadol
Adverse fx (6)
- CNS fx: Dizziness, drowsiness, dependency, euphoria
- Sweating
- Constipation
Disease modifying antirheumatic drugs (DMARDs): methotrexate
MOA, prescribing considerations
- folic acid antagonist; thought to affect leukocyte suppression, decreasing inflammation that results from immunologic byproducts
- Considerations
- Need to give folic acid supplementation
- Time to response = 3-8 weeks - need to supplement with another treatment option until the medication can take effect
Disease modifying antirheumatic drugs (DMARDs): methotrexate
Avoid, caution, black box warning, pregnancy/lactation
- Avoid: blood dyscrasias
- Caution: renal and hepatic impairment
- BBW: risk of hepatotoxicity, renal impairment, pneumonitis, bone marrow suppression, GI toxicity, active stomatitis, dermatology reactions, opportunistic infections
- Pregnancy/lactation: avoid
Disease modifying antirheumatic drugs (DMARDs): methotrexate
Adverse fx (9)
- GI: Nausea, diarrhea, oral ulcers
- Skin/hair: photosensitivity, alopecia, skin rash
- Other: Arthralgias, dizziness, increased serum transaminases
Biologic DMARDS - TMF inhibitors: Rituximab (Rituxan), abatacept (Orencia)
MOA
inactivates circulating TNF-alpha, reducing the chemotactic fx of TNF-alpha by reducing IL-6 and CRP; results in reduced infiltration of inflammatory cells into the joint; cell lysis occurs
Biologic DMARDS - TMF inhibitors: Rituximab (Rituxan), abatacept (Orencia)
What needs to be updated before initiating therapy? Any other considerations?
update immunizations before initiating, any live immunizations should be given 3 months before initiating therapy
Biologic DMARDS - TMF inhibitors: Rituximab (Rituxan), abatacept (Orencia)
Caution, pregnancy/lactation, peds
- Caution: new/recurrent infections
- Pregnancy/lactation: limited data
- Peds: 2+
Biologic DMARDS - TMF inhibitors: Rituximab (Rituxan), abatacept (Orencia)
Adverse fx (6)
- Injection site reactions
- Infusion reaction
- Infections
- Dizziness
- Headaches
- nausea
