Dental Pharmacology: Analgesics and Pain Management

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

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

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

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

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

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

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