Musculoskeletal Pharmacology

Cyclobenzaprine (Amrix, Fexmid, Flexeril)

• Classification: Skeletal muscle relaxant (centrally acting)
• Indications: Acute musculoskeletal pain with muscle spasm; unlabeled use for fibromyalgia
• Mechanism: Reduces tonic somatic muscle activity in the brain stem; structurally similar to tricyclic antidepressants
• Pharmacokinetics:
  • Absorption: Well absorbed from the GI tract
  • Distribution: Unknown
  • Protein Binding: 93%
  • Metabolism: Primarily by the liver
  • Half-life: 1-3 days
• Time/Action Profile (Skeletal Muscle Relaxation):
  • Oral: Onset within 1 hour; Peak 3-8 hours; Duration 12-24 hours
  • Extended-release: Onset and peak unknown; Duration 24 hours
• Contraindications/Precautions/Use Cautiously in: Hypersensitivity; MAO inhibitor use within 14 days; recent MI; severe/symptomatic cardiovascular disease; cardiac conduction disturbances; hyperthyroidism; cardiovascular disease; pregnancy (potential maternal/fetal risk); breastfeeding (potential maternal/infant risk); children under 35 years (increased risk of hepatotoxicity); older adults (lower dose needed due to increased risk of hepatotoxicity)
• Adverse Reactions/Side Effects: Many, including cardiovascular (BP changes, heart failure, tachycardia), dermatological (flushing, itching, sweating, hives), eyes/ears/nose/throat (increased tearing, vision changes), gastrointestinal (diarrhea, loss of appetite, cramps, difficulty swallowing, GI bleeding, hepatotoxicity, nausea, vomiting), genitourinary (crystalluria, painful urination, erectile dysfunction, increased urination, incontinence, nighttime urination), hematological (anemia, aplastic anemia, elevated white blood cell count, low white blood cell count, low platelet count), musculoskeletal (muscle pain), neurological (drowsiness, muscle weakness, confusion, dizziness, headache, insomnia, malaise, nervousness), respiratory (shortness of breath, fluid around the lungs, respiratory slowing), and miscellaneous (anaphylaxis, chills, drooling, fever)
• Interactions:
  • Drug-Drug: Calcium channel blockers may increase risk of cardiovascular collapse; avoid concomitant use with CNS depressants (alcohol, antihistamines, opioids, sedatives/hypnotics, parenteral magnesium sulfate); increased risk of hepatotoxicity with other hepatotoxic agents or estrogens; increased arrhythmia risk with verapamil; increased neuromuscular blocking effects with vecuronium
  • Drug-Natural Products: Increased CNS depression with kava-kava, valerian, chamomile, or hops
• Dosage: Varies by indication and age
• Nursing Implications/Lab Test Considerations:
  • Assess bowel function (diarrhea noted = possible discontinuation)
  • Assess muscle spasticity periodically
  • Assess anesthesia history & family history of malignant hyperthermia in surgical patients
  • IV administration: Monitor ECG, vital signs, electrolytes, and urine output continuously for malignant hyperthermia
  • Monitor for difficulty swallowing (oral)
  • Monitor liver function (AST, ALT, alkaline phosphatase, bilirubin, GGT) frequently
  • Monitor renal function and CBC (complete blood count) before and during prolonged therapy.
• Patient/Family Teaching:
  • Do not exceed prescribed dose
  • Avoid driving/hazardous activities due to potential side effects
  • Use caution when walking stairs & eating post IV dose (surgical)
  • Avoid alcohol and other CNS depressants
  • Report any rash, excessive itching, yellowing of eyes or skin, dark urine, or unusual stools -Wear sunscreen and protective clothing -Notify health care providers if required (Rep, OB)
  • Follow-up exams and blood tests are essential -Malignant hyperthermia patients should carry identification.

Alendronate (Binosto, Fosamax)

• Classification: Bone resorption inhibitor (bisphosphonate)
• Indications: Postmenopausal osteoporosis, osteoporosis in men, Paget's disease, corticosteroid-induced osteoporosis (≥ 7.5 mg prednisone/day)
• Mechanism: Inhibits osteoclast activity, reversing osteoporosis & slowing Paget's progression.
• Pharmacokinetics:
  • Absorption: Poor, ~0.6-0.8% orally
  • Distribution: To soft tissues, then bone
  • Metabolism & Excretion: Excreted in urine
  • Half-life: 10 years (reflects skeletal release)
• Time/Action Profile (Bone Resorption Inhibition):
  • Oral: Onset 1 month; Peak 3-6 months; Duration 3 wk - 7 months post-discontinuation
• Contraindications/Precautions: Esophageal abnormalities; Inability to remain upright for 30 minutes; Renal impairment
• Interactions/Use cautiously: -Drug-Food: Food significantly decreases absorption; Caffeine, mineral water, & orange juice also decrease absorption. -NSAIDs (nonsteroidal anti-inflammatory drugs) increase risk of GI adverse effects.
• Dosage: Varies by indication (osteoporosis, prevention, Paget's, corticosteroid-related)
• Nursing Implications/Lab Test Considerations:
  • Assess bone mass before and after therapy (osteoporosis)
  • Assess symptoms of Paget's disease
  • Monitor serum calcium before & during therapy (correct hypocalcemia/vitamin D deficiency before starting)
  • Monitor alkaline phosphatase before and periodically (for Paget's disease)
• Implementation:
  • Oral: First thing in the morning, with 6-8 oz plain water, 30 minutes before other medications/beverages/food. Swallow whole.
• Effervescent tablets: Dissolve in water at room temperature (not mineral or flavored).
• Patient/Family Teaching:
  • Take exactly as directed, by mouth, first thing in the morning with plain water
  • Remain upright for 30 minutes after taking
  • Report esophageal pain or difficulty swallowing promptly
  • Avoid crushing, chewing, or dissolving effervescent tablets in the mouth
  • balanced diet including supplemental calcium and vitamin D may be necessary. -Exercise and lifestyle modifications to reduce osteoporosis risk -Important to consult health care professional before starting, stopping, or changing dosage. -Inform health care professional about all other Rx/OTC meds, vitamins, or herbals. -Inform health care professional of alendronate therapy before dental procedures
• Evaluation/Desired outcomes: -Prevention/reduction of osteoporosis progression -Treatment of osteoporosis in men -Decreased Paget's disease progression -Treatment of corticosteroid-induced osteoporosis

Tamoxifen (Soltamox)

• Classification: Antineoplastic (antiestrogen)
• Indications: Estrogen receptor-positive metastatic breast cancer; adjuvant treatment of early-stage estrogen receptor-positive breast cancer; reducing contralateral breast cancer risk; preventing breast cancer in high-risk individuals; reducing invasive breast cancer risk after ductal carcinoma in situ.
• Mechanism: Competes with estrogen for binding sites; reduces DNA synthesis.
• Pharmacokinetics:
  • Absorption: Well absorbed
  • Metabolism: Primarily metabolized by liver enzymes (CYP3A and CYP2D6) into various active metabolites (endoxifen, 4-hydroxytamoxifen) with greater potency than tamoxifen. Genetic polymorphisms in CYP2D6 can affect effectiveness.
  • Excretion: Primarily feces.
  • Half-life: 7 days.
• Time/Action Profile (Tumor Response):
  • Oral: Onset 4-10 weeks; Peak effect several months; Duration varies
• Contraindications/Precautions/Use Cautiously in: Hypersensitivity; Concurrent warfarin therapy (in specific breast cancer cases); Pregnancy & breastfeeding; decreased bone marrow reserve; history of thromboembolic events; women of reproductive potential.
• Adverse Reactions/Side Effects: Many, including cardiovascular (DVT, swelling), dermatological (hot flashes), eyes/ears/nose/throat (blurred vision), fluid and electrolyte (high calcium), gastrointestinal (nausea, vomiting), genitourinary (uterine malignancies, vaginal bleeding), hematological (low white blood cell count, low platelet), musculoskeletal (bone pain), neurological (confusion, depression, headache, stroke, weakness), respiratory (pulmonary embolism), and miscellaneous (tumor flare)
• Interactions: -Drug-Drug: Estrogens may decrease tamoxifen effectiveness; bromocriptine may increase levels and risks; tamoxifen may increase warfarin's anticoagulant effects. Increased risk of thromboembolic events with other antineoplastics.
• Dosage: Varies by indication
• Nursing Implications/Lab Test Considerations:
  • Monitor for increased bone/tumor pain (analgesics may be necessary) -Verify negative pregnancy test before starting -Monitor CBC, platelets and calcium levels -Assess estrogen receptor status before starting -Monitor serum cholesterol and triglycerides (may be elevated) -Monitor liver function tests and thyroxine (T4) -Regular gynecologic exams
• Patient/Family Teaching:
  • Take as directed; skip missed doses; read Medication Guide
  • Inform health care professional of skin changes -Report bone pain promptly; analgesics may be prescribed -Monitor weight & report concerning changes. -Report hot flashes -Report any pain, swelling, breathing difficulty, weakness, sleepiness, confusion, severe nausea, vomiting, weight changes, dizziness, headaches, vision loss. -Report menstrual changes, vaginal bleeding or pelvic pain. -Reproductive potential: contraception and breastfeeding considerations,
• Evaluation/Desired Outcomes: Decrease in breast tumor size/spread; effects may be delayed. Reduced breast cancer incidence in high-risk patients

Celecoxib (CeleBREX, Elyxyb)

• Classification: Anti-rheumatic (COX-2 inhibitor)
• Indications: Osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, juvenile rheumatoid arthritis, acute pain, primary dysmenorrhea, acute migraine (oral solution only)
• Mechanism: Inhibits COX-2 enzyme, decreasing prostaglandin synthesis; analgesic, anti-inflammatory, and antipyretic
• Pharmacokinetics:
  • Absorption: Bioavailability is unknown
  • Distribution: Widely distributed
  • Protein Binding: 97%
  • Metabolism: Primarily by the liver via CYP2C9 isoenzyme (polymorphic). Poor metabolizers may have increased drug levels and risks.
• Dosage: Varies by indication/condition.