NSAIDs, Gout, and Osteoporosis Drugs Flashcards
What is the primary side effect of NSAIDs and why?
Gastrointestinal bleeding / peptic ulcers - Nonselective NSAIDs will block COX-1 activity and thus stop the production of prostaglandins which are needed to stimulate secretion of protective mucus and increased mucosal blood flow in the stomach.
What drug greatly increases your risk of NSAID induced ulcers? What drug can be given to prevent this complication?
Corticosteroids - block arachidonic acid metabolism entirely. Anticoagulants also increase bleeding risk.
Complications can be prevented by giving with proton pump inhibitors to prevent stomach acid from ripping thru the stomach.
Why are COX-2 inhibitors potentially preferred, and why are they not actually preferred?
Preferable because they do not block COX-1 and thus are less upsetting to the GI tract.
Not actually preferred because increased AA flux through the COX-1 pathway increases the synthesis of TXA2 which leads to increased cardiovascular risk (exactly what aspirin is trying to block)
In what demographic of patients does taking NSAIDs precipitate renal failure and why?
Prostaglandins are needed to maintain the patency of the afferent arteriole
Particularly important in patients with heart failure, cirrhosis, chronic kidney disease, and hypovolemia who have decreased renal perfusion.
NSAIDs can lead to edema / fluid retention (stop the effectiveness of diuretics by decreasing RBF)
What NSAIDs can be used in acute gout? Can aspirin be used?
Ibuprofen, naproxen should be used first line. Indomethacin is okay but is worse tolerated
Aspirin cannot be used because it needs too high of a dose for effective pain relief. It is only used low-dose as an anti-platelet agent.
What is colchicine’s mechanism of action? Does it affect serum uric acid levels? What is the dosing regimen in acute gout?
Decreases leukocyte motility and phagocytosis by binding microtubules.
Does not affect serum uric acid level
Give 2 doses at first sign of flair, and repeat in 1 hour. Best if done earlier.
What are the possible side effects of colchicine?
- Bone marrow suppression
- Neuropathy and myopathy
- Diarrhea - if taken repeatedly like old regimen
What are the dose adjustment considerations which should be made with colchicine?
Decrease dose in severe renal impairment, and don’t give with CYP3A4 inhibitors
-> metabolized by P-glycoprotein system of kidney and CYP3A4
What other drug can be used in acute gouty attack other than colchicine and NSAIDs?
Corticosteroids -> systemic or intra-articular
What patients require gouty prophylaxis? What is the goal uric acid level? Should you treat asymptomatic hyperuricemia?
Patients with >2 gouty attacks per year
Tophi or joint damage seen on radiography
Severe attacks or polyarticular attacks
Urate nephropathy / interstitial nephritis or nephrolithiasis
Goal is <6 mg/dL. Do not treat if asymptomatic
Give the three broad classes of drugs used in gout prophylaxis and an example of each.
- Xanthine oxidase inhibitors - allopurinol / febuxostat
- Uricosurics - i.e. probenecid
- Colchicine
What should be done when starting allopurinol? What are the possible side effects?
Do not start during acute attack, and give colchicine prophylaxis for the first 6-12 months.
Side effects include GI upset and rash. Start low to prevent rash which can become Allopurinol hypersensitivity syndrome (AHS): progression to SJS or DRESS syndrome.
What is one benefit febuxostat may have over allopurinol? Why is it not often used?
Febuxostat does not require dose adjustment for mild to moderate renal impairment (allopurinol does)
Not often used because it may be cardiotoxic and is also more expensive
How long is colchicine prophylaxis generally continued, and what is the drug interaction of worry?
Generally 6 months until urate level is dropped by a XO inhibitor, or until tophi disappear.
Interaction of worry: statins, especially in renal disease -> neuromyopathy is common
What is probenecid’s role in gout therapy? Where else is it used clinically?
Generally used second line as an adjunctive agent to xanthine oxidase inhibitors for patients who were unable to get uric acid levels <6 mg/dL.
Also used clinically to increase serum levels of penicillin and cidofovir by inhibiting their excretion
What are the contraindications to probenecid?
- Impaired renal function: CrCl<50 mL/min
- History of renal calculi or nephrolithiasis -> will increase uric acid excretion thru urine and precipitate stones
- Overproducers of uric acid causing gout -> stones are likely
Is pegloticase effective? Why is it not given first line?
Very effective -> reduction in uric acid of up to 90% of patients who have failed other treatment.
It is costly, may cause anaphylaxis and infusion related reactions, and its treatment duration is not well studied
What should be given before giving pegloticase, and what is the one definite contraindication?
Give corticosteroids and antihistamines to prevent infusion reaction
Contraindication: G6PD deficiency -> precipitates hemolytic anemia
What is the primary indication for rasburicase? Contraindication?
Hyperuricemia in tumor lysis syndrome
Contraindication: G6PD deficiency.
How should patients be getting their calcium everyday?
Give calcium as calcium carbonate, separate the doses by several hours to increase absorption. Older people need even extra calcium to prevent PTH release and bone mineral density loss.
Calcium from foods is technically safer but like we take what we can get.
What is the definition of vitamin D deficiency and when should it be given?
Vitamin 25-D3 deficiency at <20 ng/day. Need to give IV vitamin D if less than this. Treat with daily vitamin D3 until at 30 ng/day
What is the mechanism of action of bisphosphonates? How should they be taken?
Reduce osteoclast activity by mimicking pyrophosphate and interfering with farnesyl pyrophosphate synthase.
They should be taken without food and with 8 oz of plain water only. Do not ingest other foods for at least 60 minutes (poorly absorbed) and must sit upright after taking (otherwise GI damage may occur).
What are the side effects of bisphosphonates?
Dyspepsia, acid reflux, esophagitis
Can cause bone pain atypical fractures such as fractures of the femur
What is the contraindication of bisphosphonates and what could be used instead in this case?
Contraindicated in renal insufficiency (<35 ml/min)
Can use denosumab instead
What are the risk factors for osteonecrosis of the jaw due to bisphosphonates and how can it be prevented?
Chemotherapy, corticosteroid use, and poor oral hygiene
Preventative dentistry and dental work should be done prior to starting the medication -> that way you don’t have the issue of needing proper bone turnover when using a bisphosphonate
How long do bisphosphonates continue working after you stop using them? How long should you continue taking them?
Several years -> they have high affinity for bone tissue
Studies have shown no increased risk for nonvertebral fractures several years after stopping.
Generally: stop taking after 5 years unless a high risk patient (i.e. past vertebral fractures)
What is the use for calcitonin and what are its side effects?
Side effects: rhinitis, epistaxis, and flu-like symptoms since given as a nasal spray
There is no use for calcitonin now because it increases risk of malignancy
How is teriparatide given and who is it used in?
Given as a once daily subQ injection
used in those with h/o fracture, high risk of fracture, or failed previous osteoporosis therapy
Stimulates osteoblasts if you give PTH in bursts.
Who should teriparatide be avoided in and how long can it be used?
Avoid in patients with Paget disease
Increased risk of osteosarcoma due to increased osteoblast activity -> limit therapy to 2 years
What is raloxifene’s mechanism of action? Why other side benefit does this make?
SERM which is an estrogen agonist in bone but antagonist in breast and uterus
This also makes it pretty good at preventing breast cancer
What is the primary indication for raloxifene? What are the side effects?
Best in those who are intolerant to bisphosphonate
Side effects include hot flashes (vasomotor symptoms), and increased risk of thromboembolic disease (since an estrogen agonist)
What are the contraindications for raloxifene?
- Acute or previous thromboembolism
2. Prolonged immobilization (bed rest increases risk of thrombosis, and therapy should be stopped).
What is the mechanism and therapeutic role of denosumab? What patients should it be used with caution in?
Useful for those with renal impairment who cannot take bisphosphonates. Inhibits osteoclast formation by binding RANKL on osteoblasts.
Should be used with caution in patients with hypocalcemia -> osteoclasts will be suppressed, can’t raise Ca+2 levels
What are the side effects of denosumab?
Same as bisphosphonates. Suppression of bone turnover predisposes to osteonecrosis of the jaw. Also some dermatologic reactions
