Analgesia

Objectives

1. Definition of analgesia
   
   

2. Physiology of pain
   
   

3. Classification of analgesia
   
   

Analgesia

• Etymology: Derived from Greek — "an-" (without) + "algesia" (pain) → "painlessness"
  
  

• Definition: Selective relief of pain without significant alteration of consciousness, differentiating it from general anesthesia.
  
  

• Mechanism of Action: Acts centrally, peripherally, or both; targets CNS to modulate or interrupt pain pathways.
  
  

Pain

• Unpleasant sensory/emotional experience due to actual or potential tissue damage.
  
  

• Importance of Pain Management:
  
  

  • Prevents perioperative stress (e.g., tachycardia, hypertension)
    
    

  • Reduces chronic post-surgical pain risk
    
    

  • Enhances patient comfort, recovery, satisfaction
    
    

Physiology of Pain

STEP 1: TRANSDUCTION

• Injury causes chemical release (bradykinin, prostaglandins, H⁺, K⁺) → activates nociceptors (pain receptors)
  
  

• Nerve fibers:
  
  

  • Aδ fibers: Sharp, fast pain
    
    

  • C fibers: Dull, slow pain
    
    

• Prostaglandins & Substance P lower nociceptor threshold (sensitization)
  
  

STEP 2: TRANSMISSION

• Signal travels from periphery → dorsal horn (spinal cord) → thalamus
  
  

• Neurotransmitters: Glutamate (AMPA & NMDA receptors), Substance P
  
  

STEP 3: MODULATION

• Brainstem sends inhibitory signals (serotonin, norepinephrine, endogenous opioids)
  
  

• Can suppress or enhance pain
  
  

STEP 4: PERCEPTION

• Thalamus → Somatosensory cortex (pain location)
  
  

• Limbic system (emotional aspect)
  
  

• Prefrontal cortex (awareness)
  
  

Physiologic Responses to Pain

Cardiovascular System (CVS):

• Tachycardia, increased BP, increased SVR and coronary resistance
  
  

Respiratory System (RS):

• Reduced tidal volume, FRC → hypoxemia, hypercapnia
  
  

• Poor cough, secretion retention
  
  

Gastrointestinal Tract (GIT):

• Decreased motility, gastric stasis, paralytic ileus
  
  

• Increased sphincter tone and secretions
  
  

Genitourinary Tract (GUT):

• Difficulty in micturition
  
  

• Catabolic metabolism → weight loss, negative nitrogen balance
  
  

Psychological Responses to Pain

• Fear, anxiety, anger, resentment
  
  

• Sleep deprivation
  
  

• Depression, helplessness
  
  

Classification of Analgesia

1. By Drug Type:
   
   

   • Opioid (e.g., morphine)
     
     

   • Non-opioid (e.g., NSAIDs)
     
     

2. By Site of Action:
   
   

   • Peripheral Nerve: NSAIDs, paracetamol, local anesthetics
     
     

   • Dorsal Horn: Opiates, ketamine
     
     

   • Descending Inhibitory Tracts: Paracetamol, tramadol, clonidine
     
     

   • Brain: Opiates, TCA, clonidine
     
     

Opioids

• MOA: Opioid receptor agonists; activate descending inhibitory pathways and reduce peripheral nociception
  
  

• Receptor Types and Effects:
  
  

  • μ (Mu): Analgesia, euphoria, respiratory depression, constipation
    
    

  • κ (Kappa): Analgesia, dysphoria, sedation
    
    

  • δ (Delta): Peripheral analgesia, GI effects
    
    

• Endogenous Opioids: β-endorphins, enkephalins, dynorphins (called opiopeptins)
  
  

• Receptor Locations and Effects:
  
  

  • Brainstem: Resp. depression, nausea, pupil constriction
    
    

  • Thalamus: Emotional pain suppression
    
    

  • Spinal cord: Pain signal attenuation
    
    

  • Hypothalamus: Neuroendocrine effects
    
    

  • Limbic system: Emotional behavior
    
    

  • Periphery: Substance P inhibition
    
    

Classification of Opioids

• By Origin:
  
  

  • Natural: Morphine, codeine
    
    

  • Semisynthetic: Heroin, buprenorphine
    
    

  • Synthetic: Fentanyl, pethidine
    
    

• By Efficacy:
  
  

  • High: Morphine, fentanyl, methadone
    
    

  • Moderate: Codeine, oxycodone, pentazocine
    
    

Pharmacologic Actions of Opioids

• CNS: Analgesia, sedation, respiratory depression, miosis
  
  

• GIT: Constipation, biliary spasm
  
  

• CVS: Vasodilation, bradycardia
  
  

• Immune: Suppression with long use
  
  

• Other: Piloerection, sweating
  
  

Morphine

• Dose:
  
  

  • Pre-med: 0.05–0.1 mg/kg
    
    

  • Anaesthesia: IV 0.05–0.2 mg/kg
    
    

  • Max daily: 1.5 mg/kg
    
    

• Pediatric Dose: 0.2 mg/kg
  
  

• Side Effects: Histamine release (hypotension), apnea, bradycardia, constipation, delayed gastric emptying
  
  

Pethidine

• Synthetic opioid (phenylpiperidine class)
  
  

• Dose: 0.5–2 mg/kg IV/IM QID
  
  

• Caution: Produces norpethidine (toxic metabolite)
  
  

• Contraindications: Renal failure, hypovolemia, MAOI use
  
  

Fentanyl

• Potent synthetic opioid (100x morphine)
  
  

• Dose: 0.5–100 mcg/kg
  
  

• Routes: IV, transdermal, epidural, spinal
  
  

• Duration: 30–45 min
  
  

• Use: Acute pain, short procedures
  
  

Tramadol

• Dual action: μ-receptor agonist + inhibits serotonin/norepinephrine reuptake
  
  

• Dose:
  
  

  • Oral: 50–100 mg q4–6h (max 400 mg/day)
    
    

  • IV/IM: Bolus 100 mg, max 600 mg/day
    
    

• Not for: <12 yrs, MAOI use, pregnancy/lactation
  
  

• Advantage: Minimal respiratory depression
  
  

Non-Opioid Analgesia

• NSAIDs:
  
  

  • MOA: Inhibit COX-1 and COX-2
    
    

  • Side Effects: GI bleeding, AKI
    
    

  • Types:
    
    

    • Non-selective: Aspirin, ibuprofen, diclofenac
      
      

    • COX-2 selective: Celecoxib, parecoxib
      
      

• Paracetamol:
  
  

  • MOA: Possibly inhibits COX-3
    
    

  • Use: Analgesic, antipyretic
    
    

  • Caution: Hepatotoxic in overdose
    
    

Ketamine

• Class: NMDA antagonist, dissociative anesthetic
  
  

• Analgesic Use:
  
  

  • Effective in opioid-resistant pain
    
    

  • Opioid-sparing
    
    

  • Maintains respiration, BP
    
    

• Contraindications: Renal failure, psychosis, raised ICP
  
  

• Side Effects: Emergence reactions (can be reduced with midazolam)
  
  

WHO Analgesic Ladder

(Cancer Pain but also applicable to acute pain)

1. Step 1: Non-opioids ± non-drug methods
   
   

2. Step 2: Mild opioids (e.g., codeine)
   
   

3. Step 3: Strong opioids (e.g., morphine)
   
   

• Principle: Give by the clock (scheduled), not on demand
  
  

Typical Analgesic Dose Regimens

• Simple Pain:
  
  

  • Paracetamol 1g QDS (IV/PO/PR)
    
    

  • NSAIDs: Diclofenac 50mg TDS, Ibuprofen 400mg TDS
    
    

• Moderate Pain:
  
  

  • Codeine 30–60mg QDS PRN
    
    

  • Tramadol 50–100mg QDS
    
    

• Severe Pain:
  
  

  • Morphine: PO 10mg q4h, IV 5–10mg q4h
    
    

  • Pethidine: IM/SC 25–100mg q3h; IV 25–50mg
    
    

More in the document above.

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