L8: Medicinal chemistry Flashcards
What is pain management (WHO ladder)?
Based on pain intensity, more so for chronic, cancer pain
If acute pain, the ladder is is generally used in reverse
What are the stages of the WHO ladder?
- Paracetamol, NSAIDs
- Weak opioid eg. codeine, dihydrocodeine, tramadol
- Change to strong opioid eg. morphine, fentanyl, methadone, pethidine, oxycodone
Adjuvant treatments throughout
What types of opioid receptors are there & what is their distribution?
µ, δ, κ receptors
Found in brain, spinal cord, peripheral tissues
What happens when opioids bind to µ-opioid receptors?
Produces analgesic effects
Adverse effects
- Respiratory depression
- Decreased GI mobility (constipation)
- Euphoria
- Release of hormones
Morphine characteristics
µ opioid receptor agonist
- Poorly soluble in water
- Heroin more potent, designed to remove unwanted addiction BUT more lipophilic & experience high quicker
Codeine characteristics
µ opioid receptor agonist
- Prodrug of morphine –> genetic polymorphism: poor CYP2D6 metabolisers do not get much effect from codeine
- Methylated –> increased ability to cross BBB
- Lower analgesic property compared to morphine
- Lower addiction potential
Oxycodone characteristics
µ opioid receptor agonist
- Methylated –> increased ability to cross BBB
- More potent than morphine –> more selectivity for receptor
Tramadol characteristics
µ opioid receptor agonist
- If allergic to codeine or have epilepsy, do not give tramadol
- R enantiomer more potent than S, but racemic mixture better tolerated
- R enantiomer also inhibits serotonin reuptake at synaptic cleft (like SSRI) –> two modes of action
- S enantiomer also inhibits noradrenaline uptake
Fentanyl characteristics
µ opioid receptor agonist
Lipophilic, flexible long C-H chains
- Increased potency, quick onset & metabolism
Methadone characteristics
µ opioid receptor agonist
Long-acting –> used for rehabilitation for addicts
– Due to buildup of metabolites
Naloxone characteristics
Antagonist at all µ, δ, κ receptors –> used to treat OPIOID OVERDOSE
Competes for receptors with other opioid agonists
NSAIDs
COX inhibitors
Normal pathway
- Phospholipids converted to arachidonic acid by phospholipase A2
- Arachidonic acid converted into prostaglandins by COX
- Prostaglandins induce pain, inflammation, fever
Types of COX inhibitors
COX1 - “good”
- Normal function in GI tract, kidneys
COX2
- Induced upon injury, inflammation, infection
- Selective NSAIDs do not cause GI upset since COX1 not inhibited
- BUT more selective for COX2 = more CV effects –> only celecoxib is safest
