Overview of analgesic drugs and their mechanisms of action Flashcards
What is the difference between an opiate and opioid?
Opiates are natural, and drugs with a morphine like structure
Opioids are drugs with a morphine like action (but may have a significantly different structure)
Give examples of the morphine analogues
Morphine, codeine, diamorphine (heroin), naxolone (antagonist)
Give examples of synthetic opioids; not derived from morphine structure
Pethidine, fentanyl, methadone, pentazocine
What are the three types of opioid receptor and what class of receptor do they belong to?
G-protein coupled receptor
- μ (mu, MOP)
- k (kappa, KOP)
- δ (delta, DOP)
Where do each opioid receptor have analgesic effect?
μ receptors in periphery, spinal cord and brain
δ mainly peripheral (increased expression in inflammation)
k mainly spinal
What happens when an opioid drug stimulates a receptor ?
All primarily coupled to Gi proteins
- inhibit adenylyl cyclase / reduce cAMP levels
- open K+ channels
- close Ca2+ channels (less glutamate release)
- cause hyperpolarisation of neurons and reduce transmitter release
Where are opioid receptors expressed?
Mostly on neurons
How are opioids effective analgesics?
Effective in acute and chronic pain
Anti-nociceptive and reduce the affective component of pain (physcologial awareness)
How do opioids cause euphoria? Does anything counteract this?
Feelings of well being and reduced anxiety mainly μ mediated (possible off set by k mediated dysphoria)
How to opioids cause respiratory depression?
Decreased sensitivity of respiratory centre (medulla) to pCO2
What opioids are used as anti-tussives and when?
Codeine can be used at sub-analgesic doses as a cough supressant in treatment for terminally ill patients
What can happen to the pupils of patients taking opioids?
Pupillary constriction that is centrally mediated
What is one of the most common opioid side effect and where is the action of this?
Nausea and vomitting in 40% of patients
Action in area postrema (brain)
Often transient
How is constipation caused by opioids and how can this affect the ADME of the drug?
Inhibition of GI tone and motility
This slows drug absorption (caution if taking other drugs)
What causes urticaria / itch, possibly bronchoconstrction and hypotension in opioid use?
Opioid receptor dependent
Causes release of histamine from mast cells
What are endorphins, where are they distributed and how do they work?
Endogenous opioid peptides distributed in the brain that work on μ receptors as agonists
What are enkephalins, where are they distributed and how do they work?
Endogenous opioid peptides distributed in the CNS and in immune cells
μ and δ receptor agonists
What are dynorphins, where are they distributed and how do they work?
Endogenous opioid peptides distributed in the CNS and act through K receptors
What are endomorphins, where are they distributed, where do they work and what makes them different to other endogenous peptides?
μ receptor agonist, more potent than other endogenous opioids
What are the three roles of NSAIDs?
Anti-inflammatory
Analgesic
Antipyretic
What is the molecular mechanism of NSAIDs?
Inhibiting cycloxygenases thereby preventing prostaglandin and thromboxane formation from arachidonic acid
What is COX-1 responsible for?
Housekeeping, products involved in homeostasis and signalling
What is COX-2 responsible for?
Induced as part of the inflammatory response
What pathway leads to prostaglandin release?
Arachidonic acid transformed to PGH2 by COX enzymes
PG synthases then transform into 5 primary prostaglandins (including TxA2 thromboxane)
