Opiates/Strong Analgesics, Codeine/Morphine/Diamorphine (Heroin)

Question 1

What are opiates?

What are they derived from?

Answer 1

Strong analgesics, kill pain by preventing the transmission of pain impulses IN THE BRAIN rather than at the source

derived from opium, found in unripe poppy seeds, contains a mixture of different nitrogen-containing compounds (alkaloids, most important of which is morphine and codeine (more mild analgesic)

Question 2

How do opiates work?

Answer 2

there are opioid receptors in the brain, to which they bind temporarily; binding blocks the transmission of impulses between brain cells that would signal pain

strong analgesics interfere with the perception of pain in the brain (act in brain, may cause possible changes in mood ad behaviour, narcotic)

Question 3

How do opiates cross the blood-brain barrier?

Answer 3

Structure is made largely of lipids which are non-polar molecules (for drugs that need to work on the CNS, most effective when it is non-polar and lipid-soluble, as well as its ability to move in the blood (aqueous solubility is important)

Question 4

How is codeine prepared from morphine?

Answer 4

prepared from morphine (semi-synthetic drug)

need to convert the OH groups into methyl ether (methylation); codeine can cross the blood brain barrier more easily, but it decreases the binding to opioid receptors, weaker analgesic)

Question 5

How is diamorphine (heroin) prepared from morphine?

What are the metabolic changes that it undergoes before it acts at the opioid receptors?

Answer 5

both OH groups converted into ethanoate (ester) groups by reaction with ethanoic acid or ethanoic anhydride (esterification process)

significantly reduces polarity, much more lipid soluble, able to cross blood-brain barrier

these ester links are broken by esterase enzymes (pro-drug, its metabolic products (mostly morphine) bring about its effects); molecular structure of diamorphine can be thought of packing the morphine so it reaches the target more efficiently