Opioid analgesics: pain Flashcards
What are the two classifications of pain?
Acute - caused by soft tissue damage, infection, inflammation
Chronic
- linked with long-term illness or disease
- may have no apparent cause
- can trigger other issues
- difficult to assess and diagnose
What is the nociception system/what does it detect?
The system that carries signals of damage and pain to the brain
These neurons have cell bodies in the dorsal root ganglia - Can detect mechanical, thermal, and chemical stimuli
How does transmission work in this system?
- bidirectional axons synapses in dorsal horn of the spinal cord
- signal continues to brain where it is processed
What are opioids capable of in the brain? what are the sources (semi-synthetic and synthetic)?
- modulate systems of pain
- mimics endogenous endorphins/enkephalins
- bind to opioid receptors: opioid agonists
From the resin of poppy seeds
Morphine, codeine, thebaine
Semi-synthetic: created from natural opioids, heroin, oxycodone, hydromorphone
Fully synthetic: derived from a lab, methadone and fentanyl
What are the three main opioid receptors? how many have been reported?
MU 123 - main physical pain suppressor
Kappa 123 - modulator
Delta 12 - helps with emotional component of pain
Up to 17 types have been reported, differential distribution in the brain
Where is MU 123 located and what is its effects?
Analgesic effects, alters respiration
- thalamus, striatum, spinal cord, periaqueductal gray, brainstem nuclei, nucleus accumbent
Where is Kappa 123 located and what is its effects?
Modest analgesia, dysphoria, little or no respiratory depression, may antagonize MU receptor activity
- basal ganglia, nucleus accumbent, hypothalamus, periaqueductal gray, deep cerebral cortex
Where is Delta 12 located and what is its effects?
Have an effect on emotional states (ad), modulate the activity of mu receptors, poor analgesics
- nucleus accumbent, limbic system, spinal cord
What are the four classifications of opioids?
Pure agonists - strong binding to receptor (ex: morphine - mu receptor)
Pure antagonists - strong binding to receptor with no activity (ex: naltrexone - mu receptor)
Mixed agonist-antagonists - agonist at one receptor, antagonist at another (ex: pentazocine)
Partial agonists - binds and has low intrinsic activity (ex: buprenorphine)
Where is morphine from/what is it more potent then?
Main derivative from opium poppy “juice” - represents 10% of the crude exudate
More potent than codeine - still more effective pain analgesic
What are the pharmacokinetics of morphine? (half-life, tolerance, and metabolites)
Usually administered via i.v injection - can also be taken orally or rectally (can be injected directly into the spinal cord)
Does not pass the BBB very well, only 20% reaches the CNS
Half-life: 3-5 hours
Liver produces active metabolites (morphine-6-glucuronide), metabolites are 10-29 times more potent analgesic than morphine
Tolerance is developed very quickly, pills increase in potency in large leaps to correct for tolerance (mostly used for end of life care)
What are the reward pathway/pharmacodynamics of morphine?
Morphine activates a receptor that blocks the GABA receptors, causes an increase of dopamine release
What are the pharmacological effects of morphine?
Analgesia, euphoria, sedation/anxiolysis Sense of tranquility/well-being Respiratory depression Suppression of the cough reflex GI symptoms - constipation Pupillary constriction
What are the withdrawal symptoms of morphine? how can this be treated?
Restlessness, dysphoria, anxiety, insomnia, diarrhea (explosive)
- can be addressed using RAAD (rapid anesthetic-aided detoxification)
- pt is given a pure opioid antagonist (naloxone) and sympathetic blocker (clonidine)
- pt remains asleep under anesthesia, upon awakening, oral dose of naltrexone
- continue with psychotherapy
Describe four pure opioid agonists that do not include morphine?
Codeine - combined with other agents for mild/moderate pain, 40% dependence, CYP-2D6 metabolized to morphine, may be ineffective if taken with SSRI
Heroin - three times more potent than morphine, high lipid solubility
Oxycodone - semi-synthetic opioid similar in action to morphine, short-acting (percodan), long-acting (oxytocin), high abuse liability, highest rate of increase
Fentanyl - 80 to 500 times are potent as morphine, depresses respiration, several routes of administration (oral, patch, IV)
What is the opioid crisis?
16 average deaths from opioid poisoning resulting in hospitalization each day in Canada
