Opioids Flashcards
What is the difference between opioids and opiates?
Opioids have a morphine-like effect
Opiates have a morphine-like structure
What are the three types of endogenous opioid peptides?
Enkephalins
Endorphins
Dynorphins
Describe the synthetic pathway for enkephalins
Preproenkephalin
Proenkephalin
Met-enkephalin or Leu-enkephalin
Describe the synthetic pathway for endorphins
Preproopiomelanocortin
Proopiomelanocortin
Beta-endorphin
Describe the synthetic pathway for dynoprhins
Preprodynorphin
Prodynorphin
Dynorphin
What are the four opioid receptors?
Mu
Delta
Kappa
Opioid like receptor
Which systems do opioids act on?
Central nervous system
Respiratory system
Gastrointestinal system
What is the action of opioids on the central nervous system?
Reduces pain and distress
Induces euphoria
What occurs when opioid receptors are activated?
Activation of potassium channels causing hyperpolarisation on the postsynaptic knob
Inhibition of voltage gated calcium channels inhibiting synaptic transmission.
Which nerves do opioids affect?
Descending pain pathway
Peripheral nerves
Which regions do opioids have a stimulatory effect on?
Nucleus reticularis paragigantocellularis
Periaquaductal grey matter
Which regions do opioids have an inhibitory effect on?
Dorsal horn and nociceptive afferents
How do opioids stimulate action in the descending pathway?
Inhibition of inhibitory interneurones halting nociceptive transmission
How do opioids reduce the affective component of pain?
Action in the limbic system
What are the adverse effects of opioids?
Euphoria Respiratory depression Cough reflex inhibition Nausea and vomiting Pupil constriction Decreased gut motility
Which receptors induce euphoria? How can this be counteracted?
Mu receptors
Can be counteracted by kappa receptor activation
What causes opioid induced- respiratory depression?
Mu receptors decreasing sensitivity of respiratory centres on carbon dioxide
What effects of opioids are subject to tolerance?
Analgesia
Euphoria
Respiratory depression
What may cause tolerance?
Downregulation of opioid receptors
Uncoupling of receptor from effector proteins
Changes to the effector proteins
What causes withdrawal?
The opioid causes decrease in cAMP, so adenylate cyclase concentration increases to compensate
When the opioid is withdrawn, the cAMP levels spike so cellular signalling goes into overload
Describe the beta arrestin pathway
The GPCR is phosphorylated
Beta arrestin binds to GPCR
GPCR is blocked from further signalling
Causes more opioid required for an effect due to less available GPCRs
What may influence dependence on opioids?
Desire for the drug
Unwillingness to go through withdrawal
Craving euphoria
Describe the properties of codeine
Much less potent than morphine
Antitussive in subanalgesic dose
Often given in combination with NSAIDs
Describe the properties of diamorphine
More potent than morphine
More permeable to the blood brain barrier
Much shorter duration of action
Describe the properties of pethidine
Similar properties to morphine
Causes restlessness
Antimuscarinic
Short duration of action
Describe the properties of fentanyl
100x more potent than morphine
Fast pharmacokinetics
Describe the properties of benzomorphanes
Kappa agonist, mu and delta antagonists
Similar to morphine at low doses
Causes hypertension, dysphoria, nightmares and hallucinations at high doses
Give an example of a benzomorphane
Pentazocine
Cyclazocine
Describe the properties of tramadol
Weak agonist of mu receptors
Also SNRI properties
Non-addictive
Describe the properties of methadone
Slow pharmacokinetics
Oral administration rather than IV
Why is methadone used to treat addiction
It doesn’t result in a drug high but also doesn’t allow for withdrawal due to the slow pharmacokinetics
Describe the properties of loperamide and what it treats
Poor blood brain barrier permeability
Acts on enteric nervous system
Treats diarrhoea
Describe the mechanism of nalaxone and what it treats
Competitive antagonist for opioid receptors
Reverses coma and respiratory depression
