Flashcards in The Medicinal Chemistry of Opioid Analgesics 1 Deck (37)
What are opioid alkaloids?
Centrally acting analgesics
Possess strong narcotic effect in terms of side effects
What kind of narcotic side effects can come from opioid use?
Sedation and even loss of consiousness
What are the indications of opioids?
Moderate to severe pain analgesia
Cough e.g. codeine, dihydrocodeine, ethylmorphine
Diarrhoea e.g. loperamide
Opioid dependence e.g. methadone and buprenorphine
Common adverse reactions to opioids?
Nausea and vomiting
Problems associated with opioids?
Where do delta (δ) opioid receptors exist and what is the agonist function?
CNS (brain) and ENS
Analgesia, antidepressant and physical dependence
Where do kappa (k) opioid receptors exist and what is the agonist function?
CNS (brain, spinal cord) and ENS
Spinal analgesia, sedation, miosis, inhibition of ADH release (anti-diuretic hormone)
Where do mu (μ) opioid receptors exist and what is the agonist function?
CNS (brain, spinal cord,) and ENS and GI
μ1 Supraspinal (above spine) analgesia
μ2 Respiratory depression
Miosis and reduced GI motility
Agonist action at which opioid receptor causes respiratory depression and constipation?
μ2 opioid receptor
Agonist action at which opioid receptor causes anti depressant effects?
δ opioid receptor
Where are endorphins isolated from?
What are the two most important enkephalins?
Which amino acid is found at the terminal of leu and met enkephalin?
What is the difference between phenol and alcohol group?
Phenol is more acidic, can ionise more readily and is more polarised, making it a better H bond donor
What benefit do the rings in the morphine structure hold?
Rigidity which is good for receptor binding
What happens if you change the phenol group on morphine structure 3rd carbon?
All modifications lead to reduced analgesic activity
What is produced if you change the -OH phenol group on carbon 3 of morphine to an ether with a CH3 as the functional group?
What is produced if you change the -OH phenol group on carbon 3 of morphine to an ether with a Et (ethyl) as the functional group?
What is produced if you change the -OH phenol group on carbon 3 of morphine to an ether with an Acetyl as the functional group?
How does codeine act as a prodrug?
Codeine is metabolised in the liver into morphine which then has the analgesic effect
What happens in liver metabolism of codeine to produce morphine?
Methyl group is cleaved
What is produced if you change the -OH alcohol group on carbon 6 of morphine to a CH3 as the functional group?
What is produced if you change the -OH alcohol group on carbon 6 of morphine to an Et (ethyl) as the functional group?
What is produced if you change the -OH alcohol group on carbon 6 of morphine to a Acetyl as the functional group?
What happens to the analgesic activity of moprhine when the phenol at carbon 3 is modified?
Reduced analgesic activity
What happens to the analgesic activity of morphine when the -OH alcohol group at carbon 6 is modified?
4-5 fold increase in activity
What is the nomenclature of diamorphine / heroin?
3,6 - diacetylmorphine
The phenol group and -OH group at carbon 3 and 6 are replaced by acetyl groups
What is the ultimate resistance to CNS receptor access?
Blood Brain Barrier
What kind of molecules enter the CNS across the BBB easily?