Drugs for Arthritis Disorders & Osteoporosis Flashcards
What is arthritis?
-A general term that refers to a group of more than 100 disorders affecting the joints
-Inflammation, pain, and stiffness in the joint
What are different types of arthritis?
-Osteoarthritis
-Rheumatoid arthritis
-Psoriatic arthritis
-Gout
-Ankylosing spondylitis
What is rheumatoid arthritis?
-Autoimmune disorder
-The body’s immune system attacks the joints
What are signs and symptoms of rheumatoid arthritis?
-Often affects joints symmetrically
-Commonly affects wrists, fingers, knees, feet, and ankles
-Usually starts at middle age
-Joints may be swollen, warm, and puffy
-Morning stiffness > 30 minutes
-Systemic inflammation
-Pain worse after periods of inactivity
-May be accompanied by fever, fatigue, and weight loss
What drugs can be used to treat RA?
-Disease modifying antirheumatic drugs (DMARDS)
-NSAIDs
-Corticosteroids
-Biologic agents
What is osteoarthritis?
-Degenerative disorder
-Wear and tear of the joint cartilage
What are the signs and symptoms of osteoarthritis?
-Usually affects weight bearing joints (hips, knees, spine)
-Usually starts at middle age or older adults
-Morning stiffness < 30 minutes
-Reduced ROM
-Inflammation localized to affected joint
-No systemic symptoms
What drugs can be used to treat osteoarthritis?
-Acetaminophen
-NSAIDs
-PT
-Weight management
-Joint injections
-Surgery
What is typically the first-line treatment for pain relief in osteoarthritis?
Acetaminophen
What is the most significant concern with high doses of acetaminophen?
Liver toxicity
What are common side effects from acetaminophen?
-Nausea or vomiting
-Loss of appetite
-Allergic reactions like skin rash, itching, or hives
What is the maximum recommended daily dose of acetaminophen?
4,000mg for adults but lower limits are often recommended
What are the most common NSAIDs used for osteoarthritis?
-Ibuprofen
-Naproxen sodium
-Celecoxib
-Diclofenac
-Meloxicam
What is the mechanism of action of hyaluronic acid injections for osteoarthritis?
-Hyaluronic acid is a polysaccharide similar to the natural joint fluid that lubricates the joint
-When injected into the joint, it acts as a lubricant and shock absorber
-Helps to reduce pain and friction in the joint
What are the side effects of hyaluronic acid injections?
-Pain at the injection site
-Joint stiffness
-Headache
What is the mechanism of action of chondroitin sulfate for osteoarthritis?
-Chondroitin sulfate is one of the building blocks of cartilage
-It is believed to help prevent the breakdown of cartilage and stimulate its repair mechanism
-Also thought to have anti-inflammatory properties and improve the consistency of synovial fluid
What are side effects of chondroitin sulfate?
-Stomach pain
-Nausea
-Diarrhea
-Constipation
-Headache
-Swelling of the eyelids or legs
What are physical therapy considerations when working with patients with osteoarthritis that are taking medication?
-Medication schedule
-Monitor for overuse
-Educate on medication limits
-Check for side effects
-Patient feedback
What is the prevalence of rheumatoid arthritis?
1% of the population and is more common in women
What is the pathogenesis of RA?
-Antigen presenting cells process and present antigens to T cells, which may stimulate B cells to produce antibodies and osteoclasts to destroy and remove bone
-Macrophages stimulated by immune response can stimulate T cells and osteoclasts to promote inflammation
-Activated T cells and macrophages release factors that promote tissue destruction, increase blood flow, and result in cellular invasion of synovial tissue and fluid
What are the main pro-inflammatory cytokines that are involved in the pathogenesis of RA?
-Interleukin-1 (IL-1)
-Tumor necrosis factor-⍺ (TNF-⍺)
What is the difference between traditional Disease Modifying Anti-Rheumatic Drugs (DMARDs) and targeted DMARDs?
-Traditional DMARDs restrict your immune system broadly
-Targeted DMARDs block precise pathways inside immune cells
How are biologic drugs produced? How do they work?
-Produced by living cells
-Work on individual immune proteins called cytokines
What is the general strategy of biologic drugs for RA?
-Inhibit autoimmune response underlying RA
-Inhibition of cytokines
-Inhibit cellular activation
What is the mechanism of action of Methotrexate for RA?
Inhibits dihydrofolate reductase enzyme, which reduces nucleotide synthesis
What are the adverse effects of Methotrexate?
-Hepatic fibrosis
-Rash
-Thrombocytopenia
-Leukopenia
What is the mechanism of action of hydroxychloroquine for RA? What are the adverse effects?
-Not well understood
-Thought to be an immunomodulator
-Retinal damage
-Rash
What is the mechanism of action of Leflunomide for RA? What are the adverse effects?
-Inhibits pyrimidine synthesis
-Hepatitis
What is the mechanism of action of Sulfasalazine for RA? What are the adverse effects?
-Not well understood
-Rash
-Photosensitivity
What are common TNF-⍺ blockers used for RA?
-Etanercept
-Infliximab
-Adalimumab
-Certolizumab
-Golimumab
What are adverse effects of TNF-⍺ blockers?
-Local injection site reactions
-Infection
-Immune reactions
-Malignancy
What are common non-TNF-⍺ biologics that are used to treat RA?
-Rituximab
-Abatacept
-Tocilizumab
-Baricitinib
-Anakinra
What are physical therapy considerations for patients on medications for RA?
-DMARDs can cause fatigue or reduced tolerance to exercise
-Injection site
-Steroids can increase risk of fx
-Pain masking: monitor for signs of overuse
-Understanding interactions of medications and PT
What is osteoporosis?
A bone disease characterized by a decrease in bone density and an increases risk of fractures
What is the prevalence of osteoporosis?
-10 million diagnosed with osteoporosis
-34 million with low bone density
-1.5 million fractures annually
What are risk factors for osteoporosis?
-Postmenopausal women
-Old age
-Medications
-Endocrine disorders
-Inflammatory arthropathy
-Hematopoietic disorders
-Nutrition disorders
What is used to diagnose osteoporosis and measure bone density?
Dual X-ray absorptiometry (DEXA)
What are the different bone cell types?
-Osteogenic cell: bone stem cell
-Osteoblast: bone forming cell
-Osteoclast: bone resorption
-Osteocyte: maintains bone tissue
How does parathyroid hormone effect bone density?
-In low and intermittent doses, it increases bone formation
-In excess doses, it increases bone resorption
What stimulates the release of parathyroid hormone? What does this cause?
-Low Ca2+ levels in the blood trigger the release of PTH which increases bone resorption to release calcium from bone tissue
-PTH release increases renal reabsorption of Ca2+
How does vitamin D effect bone formation?
It stimulates intestinal absorption of Ca2+ and phosphate
How does calcitonin effect bone tissue?
Lowers blood levels of Ca2+ and phosphate by inhibiting osteoclast activity
What is involved in normal bone homeostatis?
-PTH binds to receptors on osteoblasts
-Osteoblasts secrete RANKL and OPG (decoy receptor for RANKL)
-Osteoclasts are activated by RANKL
-There is a balance between osteoblast activity and osteoclast activity
What is involved in osteoporsis bone formation and resorption physiology?
-Osteocytes upregulates RANKL and down regulates OPG synthesis
-RANKL binds to osteoclasts and increases osteoclast proliferation
-Activated osteoclasts cause significant resorption
What are some common drugs that are used to treat osteoporosis?
-Bisphosphonates
-Selective estrogen receptor modulators (SERMs)
-Calcitonin
-RANKL inhibitors
-Parathyroid hormone (low doses)
-Calcium and vitamin D supplements
What is the mechanism of action of bisphosphonates?
-Binds to osteoclasts and promotes apoptosis
-Binds to hydroxyapatite and prevents osteoclast activity
What are common bisphosphonates used to treat osteoporosis?
-Alendronate
-Risedronate
-Ibandronate
-Zoledronic acid
What are side effects of bisphosphonates?
-GI disturbances: acid reflux
-Osteonecrosis of the jaw
-Atypical femur fractures
What are special instructions for patients taking bisphosphonates? Why?
-Swallow whole with water 30 minutes before breakfast
-Sit or stand upright for 30 minutes after taking the tablet
-To avoid gastric reflux
What is the mechanism of action of selective estrogen receptor modulators (SERMs)?
Mimic estrogen in bone, reducing bone resorption without stimulating breast or uterine tissue
What are common side effects of SERMs?
-Hot flashes
-Leg cramps
-Increased risk of venous thromboembolism
What is a common SERM used to treat osteoporosis?
Raloxifene
What is the mechanism of action of calcitonin?
Inhibits osteoclast activity
What are common side effects of calcitonin?
-Nasal irritation (with nasal spray)
-Hot flashes
What is a common calcitonin used to treat osteoporosis?
-Miacalcin
-Salmon calcitonin
What is the mechanism of action of parathyroid hormone analogs?
Stimulates osteoblast activity
What are common side effects of parathyroid hormone analogs?
-Leg cramps
-Dizziness
-Nausea
What are common parathyroid hormone analogs used to treat osteoporosis?
-Teriparatide
-Abaloparatide
What is the mechanism of action of monoclonal antibodies for osteoporosis?
Binds and inhibits RANKL, reducing osteoclast activity
What are some common side effects of monoclonal antibodies used to treat osteoporosis?
-Skin reaction at the injection site
-Osteonecrosis of the jaw
-Hypocalcemia
What is a common monoclonal antibody that is used to treat osteoporosis?
Denosumab (Prolia, Xgeva)
How does low levels of vitamin D effect PTH?
Low levels of vitamin D can stimulate the parathyroid gland to produce more PTH (secondary hyperparathyroidism)
What is the role of calcium in bone?
It forms hydroxyapatite crystals, which gives bone its hardness
What are PT considerations for patients taking bisphosphonates?
-Be aware of GI issues
-Have pt take medication at least 1 hour prior to session
-Rare risk of atypical femur fracture or osteonecrosis of the jaw
What are PT considerations for patients taking SERMs?
-Hot flashes or leg cramps
-Watch for signs of venous thromboembolism
What are PT considerations for patients taking calcitonin?
Monitor for nasal irritation side effects
What are PT considerations for patients taking parathyroid hormone analogs?
Monitor for leg cramps and dizziness
What are PT considerations for patients taking monoclonal antibodies?
-Monitor for joint pain: back and/or arm or leg pain
-Pts may have low calcium levels