Analgesics Flashcards
Analgesia and Pain pathway

- Noiceptors are stimulated by pain and originate in the periphery
- They send action potential to the dorsal horn of the spinal cord
- Synapses with secondary neuron via glutamate and neuropeptide transmitters send action potential to brain where we “sense pain”
Basically, there are opioid receptors at all these locations which can inhibit pain

What are the four different opiod receptors?
mu, kappa, delta, sigma
What are engogenous agonists of Mu receptors?
Beta endorphin
Met-encephalin
Example drugs that act on Mu receptors?
Morphine
Fentanyl
Clinical effects of Mu receptor agonists?
Supraspinal analgesia µ1
Respiratory depression µ2
Physical dependence
Muscle rigidity
What are the clinical effects of Kappa (K) agonists?
Sedation
Spinal analgesia
Example of Kappa endogenous agonists?
Dynorphin
Example Kappa agonist drugs?
Morphine
Nalbuphine
Butorphanol
Oxycodone
Example delta receptor clinical effects?
Analgesia
Behavioral
Epileptogenic
What are endogenous agonists of delta receptors?
Leu-enkephaline
Beta endorphin
Clinical effects of sigma activation?
Dysphoria
Hallucinations
Respiratory stimulation
Example sigma receptor agonists?
Pentazocine
Nalorphine
What is the mechanism of action of opioids binding to thier receptors?
Opioid receptors inhibit the presynaptic release of excitatory neurotransmitters (Ach, Substance P, NE, 5HT) which are normally released by noiceptive neurons (pain receptors)
-

Where are opioid receptors located?
Peripheral and CNS tissue
How can opioids be delivered?
Systemically or directly (spinal analgesia)
What is the benefit of direct spinal analgesia with opioids?
This spinal action provides a regional analgesic effect while reducing the unwanted respiratory depression, nausea and vomiting, and sedation that may occur from the supraspinal actions of systemically administered opioids.
Upon activated opioid G-proteins at the membrane, what are the two main ways in which opioids stop the transmission of the pain signal (Action potential)
- MOR (Mu opioid receptors) are activated and close voltage gated Ca2+ channels on presynaptic nerve terminals, inhibiting NT release
- They open K+ channels and hyperpolarize the cell, inhibiting postsynaptic neurons

Sites of opioid action of ascending pathways?
- They can act directly at the noiceptor terminals
- The Dorsal Root Ganglion (DRG) and spinal cord (Dorsal horn)
- Also possible sites in the amygdala (Anterior cingulate gyrus, ventral posterolateral nucleus of the thalamus)

Sites of opioid action of descending pathways?
In the descending (modullatory) pathway, opioids inhibit neurons by activating descending “inhibitory neurons” that send processes to the spinal cord and inhibit pain transmission neurons. The Inhibtion of inhibitory neurons acts at many different sites as shown below:
- Pain-modulating neurons in the midbrain and medulla including the midbrain aqueductal gray area
- Rostral ventral medulla
- Locus coeruleus

Part of tolerance and withdrawal from opioids involves the NMDA-receptor ion channel complex, what drug would antagonize this receptor and block tolerance development?
Ketamine (NMDA antagonist)
What is opioid-induced hyperalgesia?
Chronic use can increase the sensation of pain, including morphine, fentanyl, and remifentanil. This is why chronic opioid use for treating pain is controversial.
What are the central nervous system effects of opioids?
u (Mu) receptors in the CNS cause:
- Analgesia (Emotional and physical)
- Euphoria
- Sedation (Amplified with sedatives, deep sleep)
- Respiratory depression (Increases alveolar PC02, and apneic threshold)
- Supression of the cough reflex, especially codeine
- Miosis (constriction of pupils)
- Truncal rigidity
- Nausea and vomitting
- Homeostatic regulation of temperature (u agonist=hyperthermia; k agonist=hypothermia)
- Reduce stage 3 and 4 sleep paterns
- Tolerance (with heavy use)
What are the peripheral nervous system effects of opioids?
- Constipation
- Contract biliary smooth muscle
- Depression of renal function
- May prolong labor, inhibiting uterine contraction
- Stimulate the release of ADH, prolactin, and somatotropin
- Inhibit the release of luteinizing hormone
- Pruritus, flushing of the skin (peripheral histamine release)
What are the endogenous opioid peptides?
Endorphins
Pentapeptide enkephalins (met-enkephalin)
Leucine-enkephalin (leu-enkephalin)
Dynorphins

