Opiate analgesics Flashcards
opium extracted from poppy seeds was used to…
produce euphoria, analgesia, sedation, relief from diarrhea, cough suppression
Mu1 (μ1)
locatd outside spinal cord
- resonsible for central interpretation of pain
SUPRASPINAL ANALGESIA
Mu2 (μ2)
- located throughout CNS (brainstem and spinal cord
- responsible for supraspinal and spinal analgesia, respiratory depression, constipation, physical dependence and euphoria
Kappa (κ)
- modest supraspinal and spinal analgesia
- little or no respiratory depression
- little or no dependence
- dysphoric and general psychomimetic effects
Delta (δ)
modest supraspinal and spinal analgesia and little addictive potential
- modulation of hormone and neurotransmitter release
- may regulate Mu receptor activity
describe asborption and metabolism of opioids
- Absorption
–> well absorbed from GI tract; FIRST PASS EFFECT (morphine)
–> low oral bioavailability
–> FENTANYL –> because of its potency is administere by transdermal patch
- Metabolism
–> Hepatic; primary process = glucuronidation (converted to polar metabolites)
- Morphine –> morephine-6-glucuronide (M6G)
- Heroin and codeine both emtabolized to morphine
describe teh mechanism of analgesia at the receptor level
- upon opioid receptor activation the Gi/Go coupling results in large number of intracellular events:
1) inhibiton of adenylyl cyclase activity and decrease cAMP
2) reduced opening of presynaptic voltage-gated Ca channels resulting in LOSS OF INTRACELLULAR Ca AND DECREASED RELEASE OF NT
3) INCREASE POSTSYNAPTIC OPENING OF K+ CHANNELS resulting in loss of intracellular K+ and neuronal hyperpolarization (decreased firing)
describe teh mecahnsims of analgesia on Ascending pain pathway
1) Inhibiton of afferent pain transmission (blockade of pain impulses from the periphery to the brain)
- peripheral effects = activation of opioid receptors on distal ends of primary afferent (sensory) neurons decreasing their activation and excitatibility
- dorsal horn of spinal cord
–> presynaptic: opioids block release of pain-mediating neurotransmitters from primary afferent nruons via Ca++ channels (REDUCTION in INCOMING PAIN SIGNALING
–> postsynatpic: opioids inhibit actiation of secondary afferent neurons via K+ conductance (reduction in pain signaling up the spinal cord)
describe the mechanims of analgesia on descending pain pathways
- OPIOIDS BLOCK INHIBITORY GABAERGIC INTERNEURONS (disinhibiton) that lead to enahnced inhibiton of nociceptive processing
- Sites of action of opioids:
–> periaqueductal gray area = midbrain
–> rostral ventral medulla = brainstem
–> locus coeruleus = pons in brainstem
Analgesia effect
- reduce both SENSORY and AFFECTIVE aspects (components) of pain
–> acts at both spinal and supraspinal (µ, δ, ĸ) sites
–> quite effective for acute somatic and visceral pai, but much less effective in chronic neuropathic pain syndromes
Euphoria effect
- Pleasant floating sensation with reduced anxiety and distress
- more common in drug abuse situations, not typically obsvered in patients experiencing pain
- dysphoria, anxiety, restlessness, more commonly observed with mixed agonists-antagonists
Sedation effect
- drosiness and lethargy, cognitive impairement, sense of tranquility
- more prominant in elderly
- less frequent with synthetic opioids
respiratory depression effects
- Inhibiton of brainstem respiratory mechanisms (reduced sensitivity to pCO2 tension)
- dose-related, main cause of death from opioid overdose
- increased pCO2 –> reflexice cerebral vasodialtion
–> caution: use of opioids in head trauma
Miosis
- pin-point pupils
- constctions of pupils
- occurs with all opioids
- resistant to tolerance and can be use for diagnosis of overdose
cough suppression effect
- opioids suppress the cough center in the brain
- action is predominately via the brainstem chemoreceptor trigger zone –> not associated with analgesia
