PCOL (OPIOID ANALGESICS)

• A drug extracted from the exudate of the poppy

  Opiate
• A natural or synthetic drug that binds to opioid receptors producing agonist effects


  Opioid
• Are agents that relieve pain by elevating pain threshold w/o disturbing consciousness or altering sensory modalities 


  Analgesics
• Pain threshold


  the point at which sensory stimuli are perceived as being noxious and unpleasant
• Narcotics

  • drugs which possess both analgesic and sedative properties
  • refer to a variety of substances with abuse or addictive potential
• Opium is extracted from poppy seeds
• Used for thousands of years to produce:

  • euphoria
  • analgesia
  • sedation
  • relief from diarrhea
  • cough suppression
• Opioids are used medicinally and recreationally
• Hippocrates & Galen employed opium to battle headaches, coughing, asthma and melancholy
• Friedrich Serturner isolated morphine in 1804
• µ (mu)

  • Functions: supraspinal & spinal analgesia; sedation; inhibition of respiration; slowed gastrointestinal transit; modulation of hormone and neurotransmitter release
  • Endogenous Opioid Peptide Affinity: Endorphins > enkephalins > dynorphines
• δ (delta)

  • Functions: supraspinal & spinal analgesia; modulation of hormone and neurotransmitter release
  • Endogenous Opioid Peptide Affinity: Enkephalins > endorphins > dynorphines
• κ (kappa)

  • Functions: supraspinal & spinal analgesia; psychomimetic effects; slowed gastrointestinal transit
  • Endogenous Opioid Peptide Affinity: Dynorphines > endorphins > enkephalins
• 3 Endogenous Opioids

  • Endorphins
  • Enkephalins
  • Dynorphins
• Mu opioid agonists

  A) Endogenous peptide

  B) Endorphins

  C) Morphine

  D) Exogenous drug

  
• Effects upon activation (mu):

  • Supraspinal analgesia
  • Respiratory depression
  • Euphoria
  • Sedation
  • Decreased GI motility
  • Miosis
  • Physical dependence
• Properties of Mu receptors;

  • Mu 1: analgesia, bradycardia, and sedation
  • Mu 2: respiratory depression, euphoria, and physical dependence
• Delta receptors:

  A) Endogenous peptide

  B) Exogenous drug

  C) Enkephalins

  D) DPDE

  
• Effects upon activation (delta):

  • spinal (mainly) and supraspinal analgesia
  • inhibition of gatrointestinal motility
  • respiratory depression (controversial)
• Kappa receptor agonits:

  A) Endogenous peptide

  B) Exogenous drug

  C) Dynorphin

  D) Ketazocine

  
• Effects upon activation (kappa):

  • Spinal analgesia
  • Sedation
  • Dyspnea
  • Dysphoria
  • Inhibition of ADH release
• Sigma receptors:

  • Dysphoria
  • Delirium
  • Hallucination
  • Tachycardia
  • Hypertension
• ORL1 receptor:

  • Opioid-like-subtype-1 receptor
  • AKA: nociceptin receptor (NOP)
• Effects upon activation (ORL1):

  • central modulation of pain
  • effects on locomotion, stress, anxiety, feeding, learning and memory, reward/addiction and urogenital activity
• MOA:

  • Before opioid receptor activation

  A) open

  B) closed

  
• MOA:

  • After opioid receptor activation

  A) closed

  B) open

  
• MOA:

  A) closed

  B) Ca2+

  C) K+

  D) open

  E) Presynaptic inhibition

  F) Glutamate, Ach, NE, 5-HT, substance P

  
• Distribution of Receptors (5 General Areas of the Brain):

  • Brainstem - respiration, cough, N/V, BP maintenance, pupillary diameter, control of stomach secretions
  • Medial thalamus - deep pain
  • Spinal cord - Attenuation of painful stimuli (substantia gelatinosa)
  • Hypothalamus - affect neuroendocrine secretion
  • Temporal lobe - amygdala (influence emotional behavior)
• Endogenous Opioid Peptides

  A) Endorphins

  B) endogenous

  C) morphine

  D) Met-Enkephalin

  E) Leu-Enkephalin

  
• CNS Effects of Morphine:

  • Analgesia
  • Euphoria
  • Sedation
  • Respiratory depression
  • Cough suppression
  • Truncal rigidity
  • Nausea & Vomiting
• Peripheral Effects of Morphine:

  • Cardiovascular system - bradycardia
  • Gastrointestinal tract - constipation
  • Biliary tract - biliary colic
  • Renal - decreased renal plasma flow
  • Uterus - prolong labor induction
  • Neuroendocrine - stimulates the release of ADH, prolactin, and somatotropin but inhibits the release of luteinizing hormones
  • Pruritis (flushing & warming of the skin)
• Clinical Uses of Opiod:

  • Analgesia
  • Acute pulmonary edema
  • Cough
  • Diarrhea
  • Shivering
  • Applications in anesthesia
• Classification of Opioid Analgesics:

  1. Strong Agonist
  2. Mild to Moderate Agonist
  3. Mixed Agonist-Antagonist
  4. Opioid Antagonist
• What are the strong opioid agonists or full agonist?

  • Morphine
  • Hydromorphone
  • Oxymorphone
  • Heroin
  • Fentanyl
  • Meperidine (Demerol)
  • Methadone (Dolophine)
  • Levorphanol
• The prototype of opioid analgesic

  Morphine
• What is the golden standard among opioid analgesics, to which the structure and strengths of all other drugs are compare?


  Morphine
• has poor bioavailability

  Morphine
• Used for severe pain

  Morphine
• Used in management of acute pulmonary edema

  Morphine
• Brand name of Hydromorphone

  Dilaudid