Opioids Flashcards
What are the 3 opiates?
Codeine, morphine and thebaine.
What is an opioid?
A natural or synthetic exogenous drug that mimics morphine.
What is the only semi-synthetic exogenous opioid?
Heroin.
What are the synthetic exogenous opioids?
Methadone and fentonyl.
What are the endogenous opioids?
Enkephalins and endorphins.
What are the semisynthetic narcotics that contain morphine?
Heroin and hydromorphone.
What are the semisynthetic narcotics that contain thebaine?
Oxycodone and etorphine.
What are some totally synthetic narcotics?
Pentazocine, meperidine, fentanyl, methadone, LAAM and propoxyphene.
What is the difference between an opioid and an opiate?
Opioids are any drug that mimics morphine, opiates are non-synthetic opioids.
How do you make heroin?
- Grow a papaver somniferum (sleep-inducing poppy)
- Wait until the flowers’ petals fall
- Slit the egg-shaped seed pod
- Collect the milky sap - crude opium!
- It thickens and darkens
- Boil it in lime, organic detritus sinks
- This leaves a white top layer of morphine, which can be modified to create heroin.
Approximately what percentage (by weight) of opium is morphine (McKim, 2003)?
10%
Approximately what percentage (by weight) of opium is codeine (McKim, 2003)?
0.5%
The pharmacological effects of morphine and heroin are essentially identical because…
Heroin is converted into morphine in the brain.
When is heroin more potent than morphine?
When injected - the acetyl groups in the molecule make it more lipid soluble and it gets to the brain faster.
Water molecule charge movement causes HOH to ionize, becoming…
H+ OH-
Where morphine has an two OHs (hydroxyls), heroin has…
CH3COO - acetyl/ethyls
Why does fat solubility increase heroin’s potency?
Because blood-brain barrier has a bilayered phospholipid membrane which is impenetrable to ionised molecules (morphine), but not for non-ionised molecules (heroin).
What do exogenous opioids do in the CNS?
They hijack the endogenous system (for endorphins etc.), affecting mu, kappa and delta receptors.
What is nociception?
Pain perception.
What is the pre-thalamic destination of nociception?
The dorsal horn of the spine. Then goes to the thalamus.
What is the cortical destination of nociception?
The somatosensory cortex.
What is the path for peripheral to central sensation for vision?
Optic chiasm, LGN (thalamus), visual cortex.
What is the path for peripheral to central sensation for audition?
Cochlear nucleus and inferior colliculus, medial geniculate nucleus (thalamus), auditory cortex.
How do opioids affect the nociception pathway?
Fibres from the periaqueductal grey (midbrain) descend onto the dorsal horn and turn down nociception sensitivity.
Where has evidence of opium use been found?
- Ceramic bowls in Brittany
- Paleobotanical evidence from Neolithic sites in Southern Spain (4200 BC)
- The Odyssey - mixed with wine by Helen to cheer up Telemachus.
- Galen prescribed it
- Paracelsus referred to it in 1520.
Who popularised Laudanum use in Britain?
Thomas Sydenham (1924-1689), mixed with wine.
Who isolated morphine, and when?
German pharmacist Friedrich Sertuerner in 1803. Named it after morpheus, Greek god of dreams.
Who isolated codeine?
French chemist Pierre Robiquet in 1821.
What is codeine also known as?
Methoxymorphine.
Why are over the counter pain drugs containing morphine illegal in some countries, such as Greece?
Because of how addictive they are.
Who produced diacetylmorphine?
English chemist C R Alder Wright in 1874. Cooked with acetic acid.
Also discovered by Hoffman and Dresser in 1898.
What is diacetylmorphine?
Heroin.
What company produced heroin, and when and why did they stop?
Bayer. In 1913 when it became apparent that it was in fact addictive.
What did Siegel et al (1982) do?
Divided rats into 3 groups - similarly tested, differently tested and control only - and gave them injections of heroin (dextrose for control only) in either the same or a different room to the test injection.
What did Siegel et al (1982) find?
Mortality rates were 32%, 64% and 96% respectively.
Therefore: slow does increase before test improves prospects, showing that some tolerance/adaptation occurs. Also, some of these are psychological - the environment is the CS which signals heroin.
What did Siegel (1978) do?
3 groups of rats again, two boxes, morphine and saline. Temperature first increased in response to morphine then developed tolerance. When sal-room condition given morphine in the room they usually had saline, they became hyperthermic - environment.
What bodily systems do opiates primarily affect?
The intestines and the CNS.
What follows an acute effect?
An opposing effect.
The initial effect of analgesia is followed by…
Pain
The subsequent effect of yawning is preceded by…
Respiratory depression
Opiate-induced euphoria is followed by…
Dysphoria
The acute effects of opiates include lowered BP and pupil constriction, which is later followed by…
Increased BP and pupil dilation
Flushed, warm skin immediately after taking opioids is followed by…
Goosebumps.
What is the term for pupil constriction?
Miosis
What is the term for pupil dilation?
Mydriasis
What changes in terms of the net effect of morphine after many injections?
The initial effect remains the same, but the opponent effect starts sooner and counteracts it, meaning that the net effect is a lower initial spike.
What happens to the effect graph of taking a larger dose of morphine having developed tolerance to a lower dose?
Although the opponent effect starts earlier, the net effect spike is as high as a normal dose without tolerance.
What hedonic assumption do theories of action-outcome learning (Thorndike, 1911) make?
Actions that obtain favourable outcomes are more likely to be repeated.
According to action-outcome learning, when might drug-related actions become more likely to re-occur?
When taken during opposing effect - e.g. dysphoria is -100, drug increases to +100 is a very large hedonic change.
What type of receptors does methodone affect?
It’s a mu-receptor agonist.
How is methodone usually taken?
Orally
How does methodone work in relieving heroin addiction?
It reduces craving, and thus relapse, whilst not giving extreme effects.
What are the long-term effects of methodone?
No organ damage, patient capable of working, but does produce problems with libido and excessive sweating.
