Dental Pharmacology: Analgesics and Pain Management

Pain Management in Dentistry

• Definition of pain: unpleasant sensory experience associated with actual or potential tissue damage (IASP)
• Impact of pain on quality of life: affects physical and emotional well-being
• Types of pain:
  • Acute pain: results from specific injury or disease, sudden onset, relieved when cause is treated
  • Chronic pain: persistent over long period, unknown cause, associated with long-term illness

Classification of Pain

• Nociceptive pain: initiated by stimulus outside the nervous system, localized to area of dysfunction
• Neuropathic pain: primarily caused by dysfunction in the nervous system
  • Can be further divided into central and peripheral neuropathic pain

Analgesics

• Definition: drugs that relieve pain without significantly altering consciousness
• Classification:
  • Opioids (narcotics)
  • Non-opioids (anti-inflammatory drugs)

Non-Opioid Analgesics (NSAIDs)

• Mechanism of action: inhibit synthesis of prostaglandins
• Types of NSAIDs:
  • Non-selective COX inhibitors
    • Salicylates (aspirin)
    • Propionic acid derivatives (ibuprofen, ketoprofen, naproxen)
    • Fenamic acid derivatives (mefenamic acid)
  • Preferential COX-2 inhibitors (nimesulide, meloxicam, nabumetone)
  • Highly selective COX-2 inhibitors (etoricoxib, parecoxib, lumiracoxib)
  • Analgesic-antipyretics with poor anti-inflammatory effect (paracetamol, nefopam)

Aspirin

• Mechanism of action: inhibits COX-1 and COX-2 enzymes
• Effects:
  • Analgesic effects
  • Anti-inflammatory effect
  • Antipyretic effect
  • Antiplatelet (antithrombotic) effect
  • Gastrointestinal tract (GIT) effects
  • Respiratory effects
  • Effects on kidneys
  • Cardiovascular effects

Other NSAIDs

• Ibuprofen:
  • Propionic acid derivative
  • Anti-inflammatory, antipyretic, and analgesic effects
  • Reversible inhibitor of COX
  • Used to relieve pain and inflammation in dentistry
• Naproxen:
  • More irritating to the GIT than ibuprofen
  • OTC maximum recommended daily dose is 660 mg
• Ketoprofen:
  • More potent than ibuprofen
  • OTC use of ketoprofen is 12.5 mg/8 hours
• Oxaprozin:
  • Long half-life (50 hours)
  • Administered once daily
  • Produces a significant incidence of photosensitivity
• Diclofenac:
  • Phenylacetic acid derivative
  • Potent anti-inflammatory effect
  • Concentrated in synovial fluid
  • Approved for long-term treatment of rheumatoid arthritis, osteoarthritis, ankylosing spondylitis
  • Available in topical gel and patch formulations, and as eye drops### NSAIDs (Non-Steroidal Anti-Inflammatory Drugs)
• Effective in relieving pain after third molar extraction at 50-100 mg doses
• Regular dental pain relief: 50 mg tab every 8 hours or 75 mg tab every 12 hours
• Types of NSAIDs:
  • Fenamic acid derivatives (e.g., mefenamic acid): no advantages over other NSAIDs, may cause severe diarrhea and hemolytic anemia
  • Indole derivatives (e.g., indomethacin): nonselective COX inhibitor, potent anti-inflammatory effect, but limited use due to severe GI side effects and contraindications
  • COX-2 selective NSAIDs (e.g., etoricoxib, celecoxib): lower risk of GI irritation and bleeding, but may cause diarrhea, abdominal pain, and dyspepsia

COX-2 Selective NSAIDs

• Advantages:
  • Lower risk of GI irritation and bleeding
  • Insignificant effects on platelet aggregation and no effect on TXA2
• Disadvantages:
  • May cause diarrhea, abdominal pain, and dyspepsia
  • Should be avoided in chronic renal disease and severe cardiovascular diseases
  • Celecoxib inhibits CYP2D6 and causes beta-blockers and antidepressants accumulation
• Important note: COX-selectivity is relative, not absolute

Acetaminophen (Paracetamol)

• Inhibits prostaglandin synthesis at the CNS, explaining its antipyretic and analgesic effects
• Has low effect at COX at periphery, explaining its poor anti-inflammatory effects
• No effect on platelet function or increase in blood clotting time
• Side effects: similar to those of aspirin, with advantages over narcotic analgesics (no dependency)
• Pharmacokinetics:
  • Rapidly absorbed from GI tract
  • Significant first-pass metabolism occurs in intestines and liver
  • Effective via oral and parenteral routes
  • Metabolized by glucuronidation in liver and excreted in urine
• Adverse effects:
  • At therapeutic doses: minor allergic reactions, minor transient alteration of leukocytes count
  • At toxic doses: nausea, vomiting, diarrhea, abdominal pain, hypoglycemia, hypotension, and hepatic necrosis (life-threatening situation)
  • Administration of N-acetylcysteine (antidote) can be lifesaving if administered within 10 hours of overdose

Opioid Analgesics (Narcotics)

• Classification:
  • Opioid agonists (e.g., morphine, codeine)
  • Opioid agonist-antagonists (e.g., pentazocine, butorphanol)
  • Partial μ-receptor agonist (e.g., buprenorphine)
• Mechanism of action: acts on opioid receptors (μ, k, and δ)
• Pharmacological actions:
  • Analgesia: potent analgesic effect without affecting other sensations
  • Euphoria: feeling of well-being, sedation, and drowsiness
  • Respiratory depression: affects respiratory center in medulla
  • Cough suppression: affects cough center in medulla
  • Hypothermia: depresses thermoregulating center
• Stimulating effects:
  • Miosis: pinpoint pupils
  • Nausea and vomiting: acts on chemoreceptor trigger zone (CTZ) in medulla
• Other effects:
  • Histamine release, causing skin rash and itching
  • Dependency: physical and psychological
  • Specific antidote: naloxone (opioid antagonist)
• Contraindications:
  • Severe head injury or increased intracranial pressure
  • History of addiction
  • Bronchial asthma or COPD
  • Very young and very old
• Therapeutic indications:
  • Relieve severe pain in terminal cancer stages, as palliative treatment
  • Post-surgery (except cholecystectomy)
  • Relieve pain of MI, fracture of mandible and long bones, and severe pulmonary edema