NUR 221 - Musculoskeletal disorders: pathophysiology and medical management

Osteoarthritis

• Degenerative - wear and tear joint disease

• May be the result of increased weight-bearing or lifting

  • Obesity?

• Incidence increasing

• Genetic component identified in research with mice

Osteoarthritis etiolgy

• Causes

• Primary form

  • Weight-bearing, obesity, aging

• Secondary form

  • Follows trauma or repetitive use

• Genetic factors thought to play a role

• Weight-bearing joints most frequently affected but finger joints also involved

Osteoarthritis pathophysiology

• Articular cartilage is damaged

• Surface of cartilage becomes rough and worn

• Tissue damage causes release of enzymes, accelerating disintegration of cartilage

• Subchondral bone may be exposed

• Cysts, osteophytes, or new bone spurs develop

• Osteophytes and cartilage break off

• Joint space becomes narrower.

• Secondary inflammation of surrounding tissue

• Loss of normal range of joint motion

• Pain with weight-bearing and use

Osteoarthritis signs and symptoms

• Aching pain with weight-bearing and movement

• Joint movement is limited

• Recreational and social activities become limited because of pain

• Walking is difficult

• Predisposition to falls

• In temporomandibular joint (TMJ) syndrome, mastication and speaking are difficult

• Bony enlargement of distal interphalangeal joints

Osteoarthritis treatment

• Stress on joint minimized by use of adaptive devices such as a cane

• Mild exercise program to maintain fitness and joint function

• Supports such as hand brace to facilitate movement

• Massage therapy

• Physiotherapy

• Acupuncture

• Occupational therapy

• Glucosamine chondroitin supplements

• Injection of synthetic synovial fluid (hyaluronic acid)

• NSAIDs

• Analgesics

• Arthrotomy to stabilize joint

• Surgical joint replacement

Glucosamine/Chondroitin

• Naturally occuring

• Not approved by the FDA for any medical use

• May interact with warfarin to increase bleeding

Glucosamine

Sugar protein that helps the body build cartilage

Chondroitin

Believed to help the body maintain fluid and flexibility in the joints

Rheumatoid arthritis

• Considered an autoimmune disorder

• Causes chronic systemic inflammatory disease

• Higher incidence in women than in men

• Affects all age groups

Rheumatoid arthritis pathophysiology

• Synovitis

  • Marked inflammation, cell proliferation

• Pannus formation

  • Abnormal tissue forms within the joint

  • Granulation tissue spreads

• Cartilage erosion

  • Creates unstable joint

• Fibrosis

  • Calcifies and obliterates joint space

• Ankylosis

  • Joint fixation and deformity develop if untreated

Rheumatoid arthritis other changes

• Frequently occur around the joints

• Atrophy of muscles

• Bone alignment shifts

• Muscle spasms caused by inflammation and pain

• Contractures and deformity develop

Rheumatoid arthritis etiology

• Exact cause not known

• Suspected autoimmune problem

• Genetic factor is present

• Familial predisposition

• Some links to viral infections

Rheumatoid arthritis signs and symptoms

• Inflammation, first in the fingers or wrists

• Joints red and swollen

• Sensitive to touch as well as painful

• Joint stiffness

• Joint movement impaired

• Malocclusion of the teeth may develop from TMJ involvement asvthe condyle is damaged

Rheumatoid arthritis systemic effects

• Marked fatigue

• Depression

• Malaise

• Anorexia

• Low-grade fever

• Iron deficiency anemia that is resistant to iron therapy

Rheumatoid arthritis treatment

• Relieve symptoms

• Maintain joint function

• Minimize systemic involvement

• Delay progression of disease

• Nondrug measures

• Balance between rest and moderate activity

• Heat and cold applications

  • Heat can improve circulation and reduce stiffness, while cold can decrease inflammation and swelling

• Physical and occupational therapy

• NSAIDs

• Glucocorticoids for severe inflammation

• Analgesia for pain

• Disease-modifying antirheumatic drugs, such as gold salts, methotrexate, hydroxychloroquine

• Biologic response–modifying agents, such as infliximab, rituximab, anakinra

Drug selection for rheumatoid arthritis

• NSAIDs

  • Aspirin

  • Celecoxib

  • Naproxen

  • Ibuprofen

  • Meloxicam

  • Diclofenac sodium

  • Katorolac

  • Etodolac

Aspirin

• First NSAID

• Mild to moderate pain and inflammation

• Decreases platelet aggregation

  • Bleeding risk

• Gastric irritation

  • Risk for ulcer formation

• Tinitis, Headache

  • Salacylate levels

Celecoxib

• NSAID – Cox-2 inhibitor

• Used to treat pain and inflammation related to

  • Arthritis

  • Ankylosing spondylitis

• Increased risk for MI or Stroke (with or without risk factors)

• Stomach or intestinal bleeding

Ibuprofen

• NSAID

• Inhibits cyclooxygenase

• Antinflammatory, analgesic, and antipyretic

• Uses

  • Mild fever

  • Mild to moderate pain

  • Arthritis

• Well tolerated

• Less gastric bleeding than aspirin (less platelet aggregation)

• Increased risk of MI or stroke

Diclofenac sodium

• NSAID

• High first-pass effect

• Highly protein bound

• Topical use is most common (now OTC)

• Uses: Anti-inflammatory, analgesic, antipyretic

  • Osteoarthritis

  • Rheumatoid Arthritis

  • Ankylosing spondylitis

• Risk for liver injury

• Risk for renal impairment

Ketorolac

• NSAID

• Powerful analgesic – equivalent to opioids

• Mild anti-inflammatory effects

• Oral or parenteral

• Acute pain – moderate to severe

• Short term use only – 5 days

  • Increased risk of thrombotic events, renal failure, bleeding, peptic ulcers

• NSAID adverse effects

  • Peptic ulcer

  • GI bleeding renal impairment

Glucocorticoids

• Treatment of rheumatoid arthritis

• Generalized symptoms: oral glucocorticoids

• One or two joints are affected: intra-articular injections

• Adverse effects

  • Hyperglycemia/weight gain

  • Adrenal insufficiency

  • Water retention/edema

  • Weakness

  • Nervousness/restlessness

  • Increased risk for infection

• Prednisone and prednisolone

DMARDs (disease-modifying antirheumatic drugs) I: major nonbiologic DMARDs

• Methotrexate

• Etanercept

• Infliximab

• Adalimumab

Methotrexate

• First line treatment

• Most rapid-acting DMARD

• Therapeutic effect: 3 to 6 weeks

• Evaluate hepatic and renal function

• Adverse effects

  • Hepatic fibrosis

  • Bone marrow suppression

    • Risk for infection

  • GI ulceration

  • Pneumonitis

Etanercept

• Action

  • Inactivates TNF

• Tumor necrosis factor (TNF) inhibitors

  • Suppress immune function

  • Pose risk of serious infection

• Use

  • Moderate to severe rheumatoid arthiritis

Etanercept adverse effects

• Serious infections

• Severe allergic reactions

• Heart failure

• Hematologic disorders

• Liver injury

• Central nervous system (CNS) demyelinating disorders

Infliximab

• Immunomodulator

• Uses

  • Rheumatoid arthritis

  • Crohn’s disease

• Caution in hepatic dysfunction, active infection

Infliximab adverse effects

• Severe infections - neutropenia

• Dyspnea

• Seizures

• Thrombocytopenia

• Bone fractures

Adalimumab

• Immunomodulator

• Uses

  • Rheumatoid arthritis

  • Psoriatic arthritis

  • Crohn’s disease

  • Ulcerative colitis

• Caution in active infection

Adalimumab adverse effects

• Severe infection

• Abdominal Pain

• Headache

• Nausea

• Rash

Juvenile rheumatoid arthritis (JRA)

• Several different types

• Onset more acute than adult form

• Large joints frequently affected

Juvenile rheumatoid arthritis (JRA) forms

• Still disease (systemic form) - fever, rash, lymphadenopathy, hepatomegaly, joint involvement

• Second form of JRA causes polyarticular inflammation

• Third form of JRA involves four or fewer joints but causes uveitis (inflammation of iris, ciliary body, and choroid of eye)

Gout

• Also known as gouty arthritis

• Results from deposits of uric acid and crystals in the joint, causing inflammation

• Formation of tophus - large hard nodule of urate crystals

• Tophi cause local inflammation and occur after the first attack of gout

Gout pathophysiology

• Uric acid and crystals form because of inadequate renal excretion, chemotherapy, metabolic abnormality, and/or genetic factors

• Inflammation causes redness, swelling, and pain

Gout treatment and diagnosis

• Treated by reducing uric acid levels with drugs and dietary changes

  • Decrease “Purine” rich foods (spinach, shellfish, mushrooms, ALCOHOL)

• Diagnosed by examination of synovial fluid and blood tests

  • Note: use of NSAIDs prior to blood tests will cause a false-negative result

Short-term drug therapy for gout

• Short term to relieve symptoms of attack

  • Infrequent flare-ups (fewer than 3 times/year)

  • NSAIDs: first-line agents

  • Glucocorticoids also used

  • Indomethacin

  • Colchicine

Long-term drug therapy for gout

• Long term to lower blood levels of uric acid

  • Three or more times per year

  • Allopurinol

  • Febuxostat

  • Probenecid

Agents of first choice for acute gouty arthritis

• NSAIDs

  • Better tolerated and more predictable than colchicine

  • Relief should be occur within 24 hours; swelling subsides over the next few days

• Indomethacin [Indocin]

• Naproxen [Naprosyn]

• Diclofenac [Voltaren]

• Adverse effects

  • Gastrointestinal (GI) ulceration, decreased renal function, fluid retention, increased risk of cardiovascular events

Indomethacin

• NSAID

• Moderate to Severe gout

• Increases risk of MI or stroke even without risk factors

• GI irritation and bleeding risk

Colchicine

• Anti-inflammatory agent

  • No longer the first-line drug

  • Now reserved for patients who are unresponsive to or intolerant of safer agents

• Uses

  • Treats acute gouty attack

  • Reduces incidences of attack

  • Aborts an impending attack

  • NOT for long-term maintenance

Allopurinol

• Drug therapy for hyperuricemia

• Inhibits uric acid formation

• Febuxostat

Probenecid

• Drug therapy for hyperuricemia

• Increases uric acid excretion

Pegloticase

• Drug therapy for hyperuricemia

• Converts uric acid to allantoin, a compound readily excreted by the kidney

Xanthine oxidase inhibitors

• Allopurinol

• Febuxostat

Allopurinol

• Xanthine oxidase inhibitor

• Current drug of choice for chronic tophaceous gout

• Reduces blood uric acid levels

• Prevents new tophus formation and causes regression of tophi that have already formed

• Allows joint function to improve

• Reversal of hyperuricemia also decreases the risk of nephropathy from deposition of urate crystals in the kidney

Allopurinol mechanism of action

Inhibits xanthine oxidase (XO), an enzyme required for uric acid formation

Allopurinol adverse and side effects

• Adverse effects

  • Generally well tolerated

  • Rare but potentially fatal hypersensitivity syndrome

  • Initial therapy may elicit an acute gouty attack

• Mild side effects

  • GI reactions

  • Neurologic effects

  • Cataracts if used longer than 3 years

Febuxostat

• Xanthine oxidase inhibitor

• Uses

  • Gout/hyperuricemia

Febuxostat cautions, contraindications, and adverse effects

• Cautions/contraindications

  • Hepatic/renal dysfunction

  • Cardiac disease

  • Stroke

  • Chemotherapy

• Adverse effects

  • Bradycardia

  • Thrombocytopenia

  • Leukopenia

  • Neutropenia

  • Hepatic/renal impairment

  • Dysrhythmias

Uricosurics

• Probenecid

  • Increases rate of uric acid excretion

  • Inhibits uric acid reabsorption

• Treatment for chronic gout

  • Not for acute attacks

• Take with meals if GI upset occurs

Probenecid (generic only)

• Acts on renal tubules to inhibit reabsorption of uric acid

  • Prevents formation of new tophi and helps diminish existing tophi

  • May exacerbate acute episodes of gout

  • Add indomethacin for relief

Probenecid adverse effects and drug interactions

• Adverse effects

  • Usually well tolerated, but mild GI effects occasionally occur; take with food

  • Risk of kidney damage can be minimized by alkalinizing urine and drinking 2.5 to 3 L of fluid daily during the first few days of treatment

• Drug interactions

  • Aspirin

  • Other salicylates

Prednisone

• Glucocorticoid

• Anti-inflammatory

• Highly effective in relieving pain due to inflammation

• Useful for patients who are hypersensitive to, are unresponsive to, or have medical conditions that contraindicate the use of NSAIDs

• Avoid in patients prone to hyperglycemia

Ankylosing spondylitis

• Chronic, progressive, inflammatory condition

• Affects sacroiliac joints, intervertebral spaces, costovertebral joints

• More common in men age 20 to 40 years

• Cause has not yet been determined - thought to be an autoimmune disorder with a genetic basis

Ankylosing spondylitis pathophysiology

• The vertebral joints first become inflamed

• Fibrosis and calcification or fusion of the joints

• Inflammation begins in the lower back

• Kyphosis develops

  • Hunched back

• Osteoporosis is common

• Lung expansion may be limited at late stage, as calcification of the costovertebral joints reduces rib movement

Ankylosing spondylitis signs and symptoms

• Low back pain

• Morning stiffness

• As calcification develops, the spine becomes more rigid, and flexion, extension, and rotation of the spine are impaired.

• Some individuals (about one third of patients) develop systemic signs such as fatigue, fever, and weight loss.

• Uveitis, particularly iritis (inflammation in the eye), is a common additional problem

Bursitis

• Inflammation of the bursae associated with bones, muscles, tendons, and ligaments of various joints

• Most common cause

  • Repetitive motion on a particular joint

• Diagnosis

  • Physical examination

  • Ultrasound and/or MRI

• Treatment options

  • Rest

  • Antiinflammatory drugs

Synovitis

• Inflammation of the synovial membrane

• Movement of joint is restricted and painful

• Diagnosis

  • Swollen, red, and warm joint

  • Analyzing synovial fluid (for signs of infections)

• Treatment

  • Antiinflammatory drugs

  • Identification and treatment of underlying cause

Tendinitis

• Irritation or inflammation of the tendon

• Manifestation

  • Dull ache and mild swelling

• Cause

  • Single trauma or repetitive motion

• Diagnosis

  • Made by physical examination

• Treatment

  • Rest, application of ice

  • Pain relievers - maybe antiinflammatory drugs

  • Physical therapy