Drugs Used in the Treatment of Pain and Affecting the Musculoskeletal System: Part 2

Nonsteroidal Antiinflammatory Drugs (NSAIDs)

◦Large and chemically diverse group of drugs with the following properties:

◦Analgesic

◦Antiinflammatory

◦Antipyretic

◦Aspirin-platelet inhibition

Properties all NSAIDs share:

◦Antipyretic

◦Analgesic

◦Antiinflammatory

◦NSAIDs are also used for the relief of:

◦Mild to moderate headaches

◦Myalgia

◦Neuralgia

◦Arthralgia

◦Alleviation of postoperative pain

◦Relief of the pain in arthritic disorders

◦Rheumatoid arthritis (RA), juvenile arthritis, ankylosing spondylitis, and osteoarthritis (OA)

◦Treatment of gout and hyperuricemia

ANYTHING CAUSING PAIN AND INFLAMMATION

◦Acetic Acid Derivatives

◦indomethacin (Indocin)

◦ketorolac (Toradol)

◦diclofenac sodium (Voltaren)

◦Cyclooxgenase-2 Inhibitors

◦celecoxib (Celebrex)

◦Enolic Acid Derivatives

◦meloxicam (Mobic)

◦Propionic Acid Derivatives

◦naproxen (Naprosyn, Aleve)

◦ibuprofen (Motrin, Advil, others)

◦Salicylates

◦aspirin

◦diflunisal (Dolobid)

NSAIDs: Mechanism of Action

◦Inhibition of the leukotriene pathway, the prostaglandin pathway, or both à blocking the chemical activity of cyclooxygenase (COX)

COX1/COX2 whats the difference

◦Cyclooxygenase-1 (COX-1)

◦Maintains normal lining of the stomach (gastrointestinal mucosa)

◦Involved in kidney and platelet function

◦Cyclooxygenase-2 (COX-2)

◦Present primarily at sites of inflammation

aspirin effects

◦Irreversible inhibitor of COX-1 receptors within the platelets à reduces formation of thromboxane A2 (substance that promotes platelet aggregation)

◦Other NSAIDs lack these antiplatelet effects

-why it causes stomach pain

-aspirin especially causes tinnitus

NSAID Contraindications

◦Known drug allergy

◦Clients with documented aspirin allergy must not receive NSAIDs

◦Conditions that place the client at risk for bleeding:

◦Vitamin K deficiency

◦Peptic ulcer disease (PUD)

NSAID INTERACTIONS

◦Serious interactions can occur when given with:

◦Anticoagulants and aspirin: increased risk of bleeding

◦Corticosteroids and other ulcerogenic drugs: increased risk of GI ulceration

◦Protein bound drugs such as warfarin, sulfonylureas, methotrexate

◦Diuretics

◦Angiotensin-converting enzyme (ACE) inhibitors: NSAIDs block production of vasodilator/natriuretic prostaglandins; hyperkalemia, bradycardia à syncope

NSAIDs: FDA-Required Warnings (Black Box Warnings)

-cv risk

◦Increase risk for serious CV thrombotic events, myocardial infarction (MI), and stroke

◦Contraindicated in treatment of perioperative pain in the setting of coronary artery bypass graft (CABG) surgery

-GI risk

◦Increased risk for serious GI adverse events including bleeding, ulceration, and perforation of the stomach or intestines

◦Older adults are at greatest risk of serious GI events

NSAID ae

NSAIDs and Renal Function

◦Renal function depends partly on prostaglandins

◦Disruption of prostaglandin function by NSAIDs is sometimes strong enough to precipitate acute or chronic renal failure

◦Use of NSAIDs can compromise existing renal function

◦Renal toxicity can occur in clients with dehydration, heart failure, liver dysfunction, or use of diuretics or ACE inhibitors

Acetic Acid Derivatives: indomethacin (Indocin

◦Uses: RA, OA, acute bursitis or tendonitis, ankylosing spondylitis, acute gouty arthritis, and treatment of preterm labor

◦Promote closure of patent ductus arteriosus (PDA), a heart defect that sometimes occurs in premature infants

◦Oral, rectal, intravenous (IV) use

Acetic Acid Derivatives: ketorolac (Toradol)

◦Some antiinflammatory activity

◦Used primarily for its powerful analgesic effects (comparable to narcotic drugs)

◦Indication: Short-term use (up to 5 days) to manage moderate to severe acute pain

◦Adverse effects: Renal impairment, edema, GI pain, dyspepsia, and nausea

COX-2 Inhibitors: celecoxib (Celebrex)

◦First and only remaining COX-2 inhibitor

◦Indicated: OA, RA, acute pain symptoms, ankylosing spondylitis, and primary dysmenorrhea

◦Adverse effects: Headache (HA), sinus irritation, diarrhea, fatigue, dizziness, lower extremity edema, and hypertension (HTN)

◦Little effect on platelet function

◦NOT to be used in clients with known sulfa allergy

◦nabumetone (Relafen)

•Better tolerated by GI system than other NSAIDs

•Used for OA and RA

◦meloxicam (Mobic)

◦piroxicam (Feldene)

•Used to treat OA, RA, and gouty arthritis

Propionic Acid Derivatives

◦ibuprofen (Motrin, Advil, others) more short term, every 2-4 hrs

◦naproxen (Naprosyn, Aleve): extended release q12 hrs or daily

◦Uses: Analgesic effects in the management of RA, OA, primary dysmenorrhea, gout, dental pain, musculoskeletal disorders, antipyretic actions(used in patients who catch fever with tylenol)

Salicylates

◦Inhibits platelet aggregation

◦Antithrombotic effect: Used in the treatment of MI and other thromboembolic disorders

-aspirin only given if you have an actual issue, NOT given if you are at RISK

salicylates indications

◦HA, neuralgia, myalgia, arthralgia

◦Pain syndromes as a result of inflammation: Arthritis, pleurisy, pericarditis

◦Systemic lupus erythematosus (SLE)

◦Antipyretic action

Salicylate Toxicity

◦CV: Increased heart rate (HR)

◦Central nervous system (CNS): tinnitus, hearing loss, dimness of vision, HA, dizziness, mental confusion, lassitude, drowsiness

◦GI: N/V, diarrhea

◦Metabolic: sweating, thirst, hyperventilation, hypo- or hyperglycemia

-get blood level

Aspirin: Reye's Syndrome

◦Acute and potentially life-threatening condition involving progressive neurologic deficits that can lead to coma and may also involve liver damage

◦Triggered by viral illnesses such as influenza as well as by salicylate therapy itself in the presence of a viral illness

◦Survivors of this condition may or may not have permanent neurologic damage

◦Do not give to children and teenagers

aspirin allergy

-GI bleed but can give only if having an MI bc risk is outweighed by benefit

◦Do not give to children and teenagers

aspirin

GOUT

◦Gout: condition that results from inappropriate uric acid metabolism

◦Underexcretion of uric acid

◦Overproduction of uric acid

◦Uric acid crystals are deposited in tissues and joints, resulting in pain

◦Hyperuricemia

Antigout Agents: Indications

-ALLOPURINOL

-POBENACID

◦allopurinol (Zyloprim)

◦Prevents uric acid production

◦Prevents acute tumor lysis syndrome

◦probenecid

◦Inhibits the reabsorption of uric acid in the kidneys à increases the excretion of uric acid

◦Must have good renal function

◦colchicine

◦Reduces inflammatory response to the deposits of urate crystals in joint tissue

◦Used for short-term management or prevention of gout

◦For acute gout:

◦Initial dose of 0.6-1.2 mg, followed by 0.6 mg/hr until:

◦Pain is relieved

◦Severe nausea and diarrhea occur

◦Total of 6 mg has been administered

◦May cause short-term leukopenia and bleeding into the GI or urinary tracts

◦lesinurad (Zurampic)

◦Uric acid transporter inhibitors

◦Inhibits the transporter proteins involved in renal uric acid reabsorption resulting in lower serum uric acid levels and increase renal clearance of uric acid

◦Given in combination with xanthine oxidase inhibitor (allopurinol)

◦Teaching: Intake of at least 2 liters of fluid a day

Herbal Products: Glucosamine and Chondroitin

◦Used to treat the pain of OA

◦Adverse Effects

◦GI discomfort

◦Drowsiness, headache, skin reactions (glucosamine)

◦Drug Interactions

◦Enhances effects of warfarin (Coumadin)

◦May increase insulin resistance (glucosamine)

Nursing Considerations

◦Before beginning therapy, assess for conditions that may be contraindications to therapy, especially:

◦GI lesions or peptic ulcer disease (PUD)

◦Bleeding disorders

◦Assess for conditions that require cautious use

◦Perform laboratory studies as indicate:

◦Cardiac, renal, and liver function studies

◦Complete blood count (CBC)

◦Platelet count

Nursing Considerations (cont'd)

◦Perform a medication history to assess for potential drug interactions

◦Several serious drug interactions exist

◦Because these drugs generally cause GI distress, they are often better tolerated if taken with food, milk, or an antacid to avoid irritation

◦Explain to clients that therapeutic effects may not be seen for 3 to 4 weeks

◦Educate clients about the various adverse effects of NSAIDs, and inform them to notify their prescriber if these effects become severe or if bleeding or GI pain occurs

◦Inform clients to watch closely for the occurrence of any unusual bleeding

◦Advise clients that enteric-coated tablets should not be crushed or chewed

◦Monitor for therapeutic effects, which vary according to the condition being treated

◦Decrease in swelling, pain, stiffness, and tenderness of a joint or muscle area

◦Categories: for osteoporosis

◦Bisphosphonates

◦Selective estrogen receptor modifiers (SERMs)

◦Hormone Replacement

-must have caLCIUM AND VIT D

Bisphosphonates MOA and examples

alendronate

◦risedronate (Actonel)

◦zoledronic acid (Zometa, Reclast)

◦Work by inhibiting osteoclast-mediated bone resorption = indirectly enhances bone mineral density = preventing bone loss

◦Can reverse lost bone mass and reduce fracture risk

Bisphosphonates: Contraindications & Cautions

-hypocalcemia

-Inability to sit or stand upright for at least 30 minutes after taking the medication

-older adults at risk for femoral fractures, can happen without trauma and happen even during medication regime

-use with cautions in breast feeding

Bisphosphonates: Adverse Effects

-GI irritation (drink full glass of water)

-blurred vision

-eye pain

-occular inflammation

-osteonecrosis of the jaw (see dentist prior to taking)

-bone pain/joint pain (take analgesic)

Bisphosphonates can be given IV

monitor pt especially if they have kidney issues have high risk for toxicity

-check phosphorus levels (will be low due to decreased bone resorption ocurring none being released during bone resorption)

Bisphosphonates: Nursing Considerations

◦Ensure that clients have no esophageal abnormalities and can remain upright or in a sitting position for 30 minutes after the dose

◦Instruct clients to take medication upon rising in the morning, with a full glass of water, and 30 minutes before eating.

◦Emphasize that clients must sit upright for at least 30 minutes after taking the medication

-long half life: if the patient misses a dose it will not affect them badly

-taken daily or once a week

-monitor bone density every 8-12 months

-check calcium in blood(9-10.5)

alendronates decreased resorption with

-iron

-mag

-antacids

-orange juice

-caffeine

-wait two hours after given to have any of these

expected effects

=increased bone density

-no fractures

-increased calcium

Selective Estrogen Receptor Modifiers (SERMs) MOA and ex

◦Stimulate estrogen receptors on bone and increase bone density

◦Examples

◦raloxifene (Evista)

◦tamoxifen (Nolvadex)

◦Indications

◦Prevention of postmenopausal osteoporosis

◦Stimulate estrogen receptors on bone and increase bone density

serm contraindications

◦Venous thromboembolic disorder or history

◦Deep vein thrombosis (DVT)

◦Pulmonary embolus (PE)

◦Retinal vein thrombosis

nursing consideration SERM

Nursing Considerations: Instruct clients that the medication will need to be discontinued 72 hours before and during any prolonged immobility (such as surgery or a long trip)

-STOP 10 mins every hour to prevent DVT

-if gonna have surgery as well

SERM AE

◦Hot flashes

◦Leg cramps

◦Increase risk of venous thromboembolism

Hormone Replacement: Calcitonin. moa AND indications

◦Indications: Treatment of osteoporosis

◦Mechanism of Action: Directly inhibits osteoclastic bone resorption

-give additional

-given IM, SC, iontranasal

calcitonin contraindication

-allergic to fish protein and salmon

nasal prep used for

patients with postmenopausal osteoporosis

-inspect nares for ulceration bc can cause nasal drynness

AE

hypocalcemia

dry nose

-decreased lithium levels

flushing

N/D

Hormone Replacement: Teriparatide (Forteo)

◦Mechanism of action: Stimulates bone formation

◦Contraindications: Known drug allergy

AE

◦Chest pain

◦Dizziness

◦Hypercalcemia

◦Nausea

◦Arthralgia