L06 Opioid Analgesics Flashcards
What does “somniferum” means in Latin?
Somnus: sleep
Ferre: bring
Which opiate was the first to be isolated?
Morphine
Which chemical class of opiates do morphine & codeine originated from?
Phenanthrenes
Which phenanthrene is a stronger opioid agonist?
Morphine
What were opioid peptides formerly known as?
Endorphins
What are the three major families derived from precursors of opioid peptides?
1) Beta-endorphin (30 aa) from preproopiomelanocortin
2) Enkephalines (pentapeptides) from preproenkaphaline
3) Dynorphins (~18-20 aa) from preprodynorphins
Briefly describe the pathophysiology of pain.
The brain has modulatory circuits to regulate pain perception.
- Attitude, mood & physical exercise can influence the perception of pain (subjective).
- Better to control pain before it becomes severe
- Primary efferent neuron helps to modulate pain perception received from primary afferent A-delta-/C-fibre via depolarisation of afferent spinothalamic tract pathway
How does opioid analgesics modulate the perception of pain?
Opioid analgesics play on endogenous mechanisms to:
- Inhibit the propagation of pain signals
- Alter the emotional perception of pain
- Potentially elevate the pain threshold (i.e. level of noxious stimuli required to illicit pain is increased)
Via binding to respective major opioid receptor types (i.e. mu, delta or kappa G-protein coupled receptors) for corresponding therapeutic effect.
Name the locations in which the sites of opioid receptors regulating pain perception reside.
Name the corresponding type of opioid analgesics that is appropriate in targeting these receptors at their locations.
1) Peripheral nociceptive terminals (peripheral analgesics)
2) Spine (spinal analgesics)
3) Brain (supraspinal analgesics)
List the three major types of opioid receptors.
What type of receptors are they?
Mu, delta and kappa G-protein coupled receptors
Which major type of opioid receptor is responsible for eliciting most of the functional effects except dysphoria?
Mu
Which major type of opioid receptor is responsible for causing dysphoria upon binding with an opioid analgesic?
Kappa
At which functional effect of opioid analgesia do we suspect as a sign of overdose?
Pupil constriction
List the functional effects of opioid analgesia, starting from the lowest dose-dependent effect to the highest.
[Lowest dose] Peripheral analgesia Spinal analgesia Cough suppression Supraspinal analgesia Sedation Reduced gut motility Euphoria Pupil constriction -> sign of overdose Constipation Dysphoria Severe sedation Respiratory depression [Highest dose]
What are some therapeutic rationales to bear in mind to help guide our dosing of opioid analgesia?
Individual differences exist between drugs!
1) Elderly pt usually requires lower dose to achieve effective pain relief than younger pt.
2) Neuropathic pain (i.e. spinal analgesia & above) requires higher opioid doses than nociceptive pain.
3) Lower doses are usually required for continuous maintenance of pain relief, instead of administering reactively in response to recurrence of pain; otherwise, higher dose is required upon pain recurrence.
4) Start low, go slow & carefully titrate until adequate level of analgesia is obtained.
5) Failure of at least partial analgesia w/ incremental dosing in opioid-naive pt may indicate pain syndrome is unresponsive to opioid therapy.
6) For some pt w/ chronic pain, opioids do not exert appreciable analgesia until a threshold dose has been achieved.
