NSAIDS, RA and OA Flashcards
4 Goals of NSAIDS
- decrease inflammation
- reduce fever
- relieve mild-moderate pain
- inhibit platelet aggregation (anticoagulation)
What is the original NSAID?
Aspirin
Is Acetaminophen an NSAID?
No, Tylenol does not decrease inflammation or have anticoagulation properties
What are Prostaglandins?
A hormone that helps to regulate cell function under normal conditions and pathological conditions- all cells expect RBCs can produce them
How do NSAIDs work?
During an injury there is an increase in prostaglandin production. NSAIDs Interfere with the synthesis of prostaglandins by inhibiting the COX enzyme (this enzyme is the first step in the synthesis of prostaglandin)
Which COX enzyme is considered more harmful?
COX-2. It produces prostaglandins that mediate pain and other aspects of the inflammatory response primarily in injured cells. However, NSAIDS are non-selective and thus block COX-1 and COX-2.
Why is it beneficial to take a regular aspirin?
-decreases chances of colorectal cancer
-prevent GI cancers and non-GI cancers
-prevents tumor growth by inhibiting COX-2 enzyme which could cause abnormal cell division in these tissues
Side effects of NSAIDS
-GI damage (most common)
-cardiovascular issues
-liver problems
-kidney problems
-associated with Reye Syndrome
-inhibits bone healing
What is Aspirin Intoxication or Positioning? What are the Symptoms?
Aspirin overdose
-HA
-tinnitus
-difficulty hearing
-confusion
-GI distress
-metabolic acidosis
Is Aspirin beneficial for those with a fracture or s/p spinal fusion?
No! Aspirin inhibits bone healing
Aspirin Vs. other NSAIDs
Aspirin:
-10-20x cheaper than prescription NSAIDs
-5x cheaper than nonprescription NSAIDs
Others:
-less GI discomfort, but has some stomach irritation
-some are less toxic to liver and kidneys
What is the only COX-2 selective drug still on the market?
Celebrex- most NSAIDs are nonselective, meaning they inhibit both COX-1 and COX-2 enzymes
Why have most of the COX-2 selective drugs been taken off the market?
The cause an increase in upper respiratory infections, along with an increased risk of heart attack and stroke in those with cardiac risk factors
What is Acetaminophen used for mostly?
Used to treat non-inflammatory conditions and used in early stages of OA or other non-inflammatory MSK conditions. Also used for fevers in children and teens
-especially used when the patient has a history of gastric damage =
How does Acetaminophen work?
inhibits the COX enzyme- it is unknown why it doesn’t have anti-inflammatory or anti-coagulant effects like NSAIDS
What is RA?
A chronic systemic disorder that causes destruction of the articular cartilage within joints- results in pain, stiffness, and inflammation of joints of the hands, feet, and knees
What are the two goals of RA treatment?
- Decrease joint inflammation
- Decrease or stop the progression of the disease
What are the three categories of drugs used for RA?
- NSAIDs
- Glucocorticoids
- Disease-modifying antirheumatic drugs (DMARDs)
Which drugs are used first to treat RA?
DMARDs are used first because they slow the progression of RA- NSAIDs are used for reducing inflammation and pain
Why are NSAIDs typically used over Glucocorticoids?
Glucocorticoids reduce inflammation to a great extent, however large doses are required to have an effect which can result in serious side effects
Why is Acetaminophen not recommended for treating RA?
It has no anti-inflammatory properties
Should DMARDs and Glucocorticoids be taken together?
Yes. Since DMARDs take several weeks to become effective, using small doses of glucocorticoids in combination with DMARDs can help control pain and inflammation until DMARDs take effect
When can glucocorticoids be used?
Can be used during acute-flare ups or exacerbations of RA- can be injected directly into the joint but only 2-3 injections per joint per year are allowed
What is the Mechanism of Action of Glucocorticoids?
Binds to a receptor to form a glucocorticoid-receptor complex, this complex binds to genes that regulate the inflammatory process which inhibits the production of inflammatory substances and then the production of anti-inflammatory proteins occurs
Side effects of Glucocorticoids
-osteoporosis
-muscle wasting/weakness
-HTN
-aggravation of MD
-glaucoma
-cataracts
-increased risk of infection
Why are DMARDs so beneficial?
These can slow the disease progression of RA and promote remission before the joints become too damaged- they inhibit certain aspects of the immune response that is the cause of RA
What are the the different DMARDs drugs?
-Antimalarials
-Gold Compounds
-Nonbiological DMARDs
-Biological DMARDs (Tumor Necrosis Factor Inhibitors)
-Other
When are Antimalarials used?
They are not the first choice of DMARD of choice and are only used for those who cannot tolerate other DMARDs
Why has the use of Gold Compounds decreases significantly?
There is a concern that gold therapy suppresses the immune system long term- only used for patients who don’t respond to other DMARDs
Which drug is a cancer treatment but also used to treat RA in children and adults?
Methotrexate- decreases synovitis, decreases bone erosion, and decreases the narrowing of the joint space
Side effects of Methotrexate
-very toxic drug (low TI)
-GI problems
-pulmonary problems
-hematological disorders
-liver dysfunction
-hair loss
**primarily with long term use
What is TNF-alpha?
A protein that is released from cells involved in inflammatory responses. This protein promotes joint erosion and inflammation in those with RA
How do Tumor Necrosis Factor Inhibitors work?
Inhibits TNF-alpha which slows the progression of the destructive effects of RA- must be given as subcutaneous injection or by slow IV fusion
When will physicians choose to prescribe other immunosuppressants for RA management?
When patients haven’t responded to traditional DMARDs because these other drugs are more toxic
What is considered the cornerstone drug for RA and what is it often combined with?
Methotrexate is the cornerstone and Tumor Necrosis Factor Inhibitors are usually combined with it- combining DMARDs may provide the best success for RA remission
Beneficial Foods for RA Treatment
-food high in fish oil and omega-3 fatty acids: helpful in controlling inflammation
-fruits and veggies: high in antioxidant properties
-low meat and proteins: these foods can exacerbate symptoms
-no smoking
What causes OA?
An intrinsic defect in the remodeling of joint cartilage and underlying subchondral bone which causes progressive deterioration of articular cartilage- NOT an immune system response
Treatment Goals for OA
-PT
-weight loss
-joint replacements in advanced stages
**non-pharmacological interventions- joint inflammation is NOT a major focus
What is the goal of drug therapy for OA?
Used to manage pain and maintain active lifestyle- focuses on acetaminophen and NSAIDS
What is the first drug used for OA?
Acetaminophen
Why are NSAIDs used for OA?
They are used to treat pain. Their anti-inflammatory properties can also help with mild synovitis that occurs with the joint destruction
Which drugs have started to emerge that slow or reverse the pathological changes of OA?
DMOADs
Which type of DMOAD uses hyaluronic acid to restore the lubricating properties of synovial fluid in arthritic joints?
Viscosupplementation- it is injected into the joint to restore viscosity which helps limit joint destruction progression in OA patients
Viscosupplementation Timeline
-3-5 weekly injections can be given
-there will be a decrease in pain within days
-is beneficial for 6 months-1 year after a series of injections
-delays the need for more aggressive treatment: joint replacement
What are two key ingredients in dietary supplements are needed to produce synovial fluid and articular cartilage?
Glucosamine and Chondroitin Sulfate- may help to protect cartilage or reverse the joint deterioration in OA- types of DMOADs
