D.3 Opiates

Opium and opiates

  • Opium and its derivative have been used as painkillers for thousands of years
  • The primary ingredient of opium, morphine, is a natural analgesic which belongs to the group of alkaloids
  • Alkaloids: naturally occurring chemical compounds containing nitrogen atoms
  • Although morphine can be synthesized in the laboratory, its usually extracted from the opium poppy
  • Morphine and its derivatives (classified as opiates) are strong analgesics, which temporarily bind to opioid receptor sites in the brain, preventing the transmission of pain impulses without depressing the central nervous system (in contrast to mild analgesics which block transmission at site of pain)
  • Opiates are also known as narcotic analgesics because in addition to painkilling, they also cause a strong feeling of euphoria and provide relief from all forms of distress
  • As a result, these drugs lead to drug addiction and dependence

Crossing the blood-brain barrier

  • The physiological effects of opiates depend on their ability to cross the blood-brain barrier
  • Blood-brain barrier: a series of lipophilic cell membranes that coat the blood vessels in the brain and prevent polar molecules from entering the central nervous system (CNS)
  • The presence of hydroxyl and amino groups in morphine make it polar and soluble in water but reduces solubility in lipids. This limits the ability to reach opioid receptors in brain
  • The polarity of morphine can be reduced by chemical modification of one the hydroxyl groups creating codeine
  • Codeine passes the blood-brain barrier then slowly metabolizes into morphine and binds to opioid receptors
  • As a result, codeine is a 10x less potent analgesic than morphine and is thus used widely across the world. It has a wide therapeutic window as well.

Diamorphine (Heroin)

  • When both of the hydroxyl groups are substituted with ester groups, it reduces the polarity of the molecule producing diamorphine
  • Diamorphine can be prepared from morphine the same way as aspirin is prepared from salicylic acid and ethanoic anhydride
  • Diamorphine passes the blood brain barrier easily and quickly metabolizes into morphine
  • Diamorphine is a 5x more potent analgesic than morphine and has more severe side effects
  • Is responsible for 50% of all drug related deaths around the globe. This drug is banned in most countries around world

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