Download D,3 Opiates

Opiates
Opioids
 Opiates (opioids) are strong analgesics.
 Opiates bind to receptors in the brain, which means that they kill pain
by preventing the transmission of pain impulses in the brain, rather
than at the source.
 Opiates are derived from opium, which is found in poppy seeds.
Opioids
 Opiates bind temporarily to opioid receptors in the brain, which block the
transmission of impulses between brain cells that would signal pain.
 Because these analgesics act on the brain, they may cause possible changes in
behavior and mood, so they are known as narcotics.
 Opioids are very effective painkillers for severe pain, but have side effects and
potential problems of dependence, so their usage has to be monitored.
Opioids
 In order to enter the brain, opiates must pass through the blood-brain
barrier, which is a membrane that surrounds the brain and protects it by
restricting the chemicals that can enter from the blood.
 The blood-brain barrier is made largely of lipids, which are non-polar
molecules. So, polar molecules do not enter the brain.
 For the drug to penetrate the barrier and enter the brain, it will be more
effective if it is a non-polar and lipid soluble drug.
Opioids
 The narcotic drugs derived from opium are primarily morphine and its
derivatives.
 We will consider three of these: codeine, morphine, and diamorphine
(known as heroin).
Opioids
 Notice that the three drugs have a common basic structure that accounts
for their similar properties, as well as some different functional groups.
 Morphine is the main drug derived from opium. When administered
through intravenous injection, it has about six times the bioavailability as
when taken orally. The two –OH groups in morphine give it some polarity
which limits its ability to cross the blood-brain barrier.
Opioids
 Codeine is found in low levels in opium, but is more commonly prepared
from morphine. It is known as a semi-synthetic drug because it is produced
from a compound isolated from a natural source.
 Morphine is converted into codeine by methylation, a process in which a
methyl group replaces a hydrogen atom. This causes the –OH group to be
converted into the methyl ether.
methylation
Opioids
 The process of methylation makes codeine a less polar molecule than
morphine, which allows to cross the blood-brain barrier more easily.
 However the conversion also causes a significant drop in the binding at the
opioid receptors, which makes codeine a weaker analgesic than
morphine.
Opioids
 Diamorphine (heroin) is produced by an esterification reaction in which both
–OH groups are converted into esters groups by a reaction with ethanoic
acid or ethanoic anhydride.
 This reduces the polarity significantly, making diamorphine much more lipid
soluble than morphine, and more able to cross the blood-brain barrier.
 Diamorphine is faster acting than the other opioid drugs.
esterification
Opioids
Opioids
 Diamorphine has a much greater potency than morphine, reaching the
brain cells faster and in higher concentration. It is more active by a factor of
two.
 It also has greater side-effects as well as a greater potential for tolerance
and dependence.
 Inside the brain, diamorphine must undergo metabolic change before it can
act at the opioid receptors. The ester links are broken by enzymes called
esterase. For this reason diamorphine is described as a pro-drug, meaning
that its metabolic products, mostly morphine, actually bring about its effects.
 The molecular structure of diamorphine can be thought as a way of
“packaging” the morphine so that it can reach its target more efficiently.
Opioids
Opioids
 Pain management- the World Health Organization has developed a threestep “analgesic ladder” for pain management.
 1. Use mild analgesics
 2. Add a weak opioid such as codeine or tramadol
 3. In severe intractable pain, use strong opioids such as morphine,
methadone, or possibly diamorphine.
Opioids
 Side Effects- Strong analgesics have several other effects that can sometimes
be used for therapeutic purposes, but sometimes are considered adverse
side-effects. They include:
 The constipating effects of mild opioids are sometimes used in medication.
For example, a mixture of kaolin and morphine is used to treat cases of
diarrhea because the morphine reduces the muscle contractions in the lower
gut and slows down the passage of fecal matter.
Opioids
 Narcotic effects and addiction – Narcotics depress brain function, induce
sleep, and are potentially addictive.
 Diamorphine is the most potent narcotic, causing the problem of heroin
addiction.
 In the short-term, heroin induces a feeling of well-being and contentment,
as it causes a dulling of pain and a lessening of fear and tension. There is
often a feeling of euphoria in the initial stages after intake.
 Relatively quickly, heroin users start to show dependence, so they cannot
function properly without the drug and suffer from withdrawal symptoms
such as cold sweats and anxiety if not taken.
 This is compounded by an increasing tolerance to the drug, so higher doses
are needed to bring about relief.
Opioids
 Since the drug is taken by injection, the user commonly picks up infections
such as HIV and hepatitis from unclean needles.
Opioids
 Helping heroin addicts to break their dependence is a slow and difficult
process.
 Addiction Treatment – methadone is used as an alternative analgesic. It is
taken orally and has a longer duration of action.
 This can reduce drug craving and prevent withdrawal symptoms.