Pharmacology & Anesthesia: Nonnarcotic Analgesia

Acetaminophen (Tylenol/Paracetamol)

Basics

  • Mechanism: Not Completely Understood
  • Indications: Pain or Fever

Timing

  • Onset:
    • PO: 30-60 Minutes
    • IV: 5-10 Minutes
  • Duration: 4-6 Hours
    • Antipyretic Effect Lasts ≥ 6 Hours

Dosing

  • General Dosing: 325-650 mg Every 4-6 Hours as Needed or 1 g Every 6-8 Hours
  • Can Be Given PO, IV (Ofirmev) or Rectal
  • Rectal Absorption is Irregular (10-20% Reduced Bioavailability)
  • Max Dose: 4 g/Day
    • Limit to ≤ 2 g/Day in Liver Cirrhosis

Contraindications

  • Hypersensitivity
  • Liver Failure

Side Effects

  • Side Effects: Hepatotoxic
  • Overdose Treatment: N-Acetylcysteine

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)

Mechanism

  • Cyclooxygenase (COX) Inhibition
    • Inhibits Conversion of Arachidonic Acid to Prostaglandin, Prostacyclin & Thromboxane
  • COX-1: Regulate Some Normal Cellular Processes in Most Tissues in the Body
    • Inhibition Impacts the Stomach Lining (Mucous & Bicarb Secretion)
    • Inhibition Causes Constriction of the Renal Afferent Arterioles
    • Inhibition Causes Platelet Inhibition
      • Aspirin Inhibition is Irreversible, Others are Reversible
  • COX-2: Primarily Found at Sites of Inflammation

Agents

  • Nonselective NASIDs – Inhibit Both COX-1 & COX-2
    • Aspirin (ASA)
      • Dose: 325-650 mg Every 4-6 Hours
      • Onset: 30-60 Minutes
      • Duration: 4-6 Hours
        • Irreversibly Inhibits Platelet Function
    • Ibuprofen (Motrin/Advil)
      • Dose: 200-800 mg Every 6-8 Hours as Needed
      • Onset: 30-60 Minutes
      • Duration: 6-8 Hours
    • Naproxen (Aleve)
      • Dose: 250-500 mg Every 12 Hours as Needed
        • Extended Release: 750-1,000 mg Once Daily
      • Onset: 30-60 Minutes
      • Duration: 8-12 Hours
        • Up to 24 Hours with Extended Release
    • Diclofenac
      • Dose: 100-150 mg/Day
      • Highest Risk of Cardiovascular Events
    • Indomethacin (Indocin)
      • Dose: 20-40 mg Every 8-12 Hours
      • Onset: 30-60 Minutes
      • Duration: 4-6 Hours
    • Meloxicam (Mobic)
      • Dose: 5-15 mg/Day
      • Slow Onset but Long Duration of Action (15-22 Hour Half-Life), Generally Not Used for Acute Pain Relief
    • Ketorolac (Toradol)
      • IV Dose: 15-30 mg Every 6 Hours as Needed
      • Limit to 15 mg Doses if < 50 kg or ≥ 65 Years Old
      • Onset: 30 Minutes
      • Duration: 4-6 Hours
  • COX-2 Selective NSAIDs
    • Celecoxib (Celebrex)
      • Dose: 100-200 mg 1-2 Times Daily
      • Half-Life: 11 Hours

Complications

  • Gastritis, Peptic Ulcers & GI Bleed
    • Avoided in Selective COX-2 Inhibitors
    • May Be Prevented by Misoprostol
  • Renal Insufficiency
  • Increased Risk of Cardiovascular Events (Myocardial Infarction & Stroke)
    • Highest Risk with Diclofenac
  • Platelet Inhibition

Contraindications

  • Hypersensitivity
  • Renal Insufficiency
  • Recent Coronary Artery Bypass Graft (CABG)
    • Ketorolac – Inhibits Platelet Function (Contraindicated in ICH & High Bleeding Risk)
  • Pregnancy – Third-Trimester

Other Nonnarcotic Pain Medication

Muscle Relaxant

  • Used to Treat Muscle Spasm
  • Agents:
    • Cyclobenzaprine (Flexeril/Amirex)
      • Dose: 5-10 mg 3 Times Daily as Needed
    • Methocarbamol (Robaxin)
      • Dose: 1.5 g 3-4 Times Daily as Needed
    • Tizanidine (Zanaflex)
      • Dose: 2-4 mg Every 6-12 Hours as Needed
  • Side Effects:
    • Dizziness
    • Sedation & Delirium – Generally Avoided if ≥ 65 Years Old

Gabapentinoids

  • Used to Treat Neuropathic Pain
  • Mechanism: GABA Analog
  • Agents:
    • Gabapentin (Neurontin)
      • Dose: 100-300 mg 1-3 Times Daily
      • Can Increase to 1,200 mg TID
    • Pregabalin (Lyrica)
      • Dose: 25-300 mg BID
  • Side Effects:
    • Dizziness
    • Sedation & Delirium
    • Ataxia

Clonidine (Catapres)

  • Mechanism: Alpha-2 Agonist; Not Completely Understood
  • May Decrease Opioid Use – Benefit is Debated

Lidocaine Patch

  • Use: 5% Patch Applied to the Area of Maximal Pain
    • Should Be Changed Every 1-3 Days
  • May Decrease Opioid Use
  • Often Described in Rib Fracture Management