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Analgesics (Opioid analgesics (Tolerance (Different physiological response…

- - - - Promote opening of K channel
        
        Decrease excitability of neurons
      - Inhibit N-type Ca channel opening
        
        Prevent neurotransmitter release
      - Inhibit adenylate cyclase
        
        Activate MAP/ERK pathway
  - - - Sedation
      - Analgesia
      - Cough suppression
      - Temperature
    - - Euphoria
      - NV
      - Miosis
  - - - Disappear after discontinuation for several weeks
    - - Fast tolerance
        
        Sedation
        
        Analgesia
        
        Nausea and Vomitting
        
        Cough suppression
      - Little tolerance
        
        Convulsion
        
        Miosis
  - - - Characteristic withdrawal/abstinence syndrome when drug is discontinued or antagonist administered
      - Invariable tolerance associated with mu receptor agonists
      - Associated with withdrawal syndrome
    - - Reinforced by physical dependence
      - Craving for drug (addiction)
      - Link to dysregulation of reward and stress pathway
      - Rare at analgesic doses
- - - - Decrease release of substance P
    - - Severe respiratory depression
      - Vomitting
      - dysphoria
      - Histamine-induced hypotension
    - - Enhanced with benzodiazepines, MAOi and TCA
  - - - Large, continuous doses
        
        Tremors, anxiety, muscle tremors
        
        Miosis and hyperactivity
      - Hypotension
      - Dry mouth, blurred vision (antimuscarinic effect)
      - NOT REVERSIBLE by naloxone
  - - - ADR: Pupillary constriction
  - - - Physical dependence like morphine, but less neurotoxic
      - Torsades de pointes
    - - CYP450 inducers accelerate metabolism
        
        Precipitate withdrawal symptoms
- - - - Displaces most bound opioids on receptors
    - - Due to unmasking of physical dependence
  - - - Rapid opioid detoxification
- - - - Used for moderate-severe pain, post-op pain
      - Weak agonist for mu receptors
      - Enhance amine transmission by blocking reuptake mechanism
    - - Seizure
      - nausea
      - Dizziness