Opioid receptors and basics of drugs Flashcards
How do opioid agonist work?
Produce analgesia by activating receptors located primarily in the brain and spinal cord regions involved in transmission and modulation of pain
What are the three major receptors that have been identified in various nervous system sites and other tissues?
Mu
Delta
Kappa
–G protein linked receptors, coupled to inhibition of adenylyl cyclase activation of receptor operated K channels and suppression of voltage operated Ca channels
Analgesia, euphoria, respiratory depression and physiological dependence result mainly from activation of what receptors?
Mu
Delta and Kappa receptors also contribute to analgesia, particularly at what level?
Spinal level
Mixed agonist-antagonist compounds, with agonist selectivity for the kappa receptor, were developed in the hope that?
Less addictive potential and respiratory depression than morphine and other related drugs
However,
A ceiling effect occurs that limits the amount of analgesia attainable with these drugs
Some mixed agonist-antagonist drugs such as what?
Pentazocine, butorphanol and nalbuphine
-cause severe psychotomimetic effects that are not reversible with naloxone
These drugs also can precipitate withdrawal in opioid tolerant patients
What are the functional effects and their associated receptor?
Supraspinal Analgesia: mu, kappa and delta Spinal Analgesia: mu, kappa, delta Respiratory depression: mu Reduced GI motility: mu and delta Psychotomimesis: kappa Sedation: mu and kappa
Opioids have two well established actions on neurons, what are they?
- Close voltage gated channels on presynaptic nerve terminals and therefore reduce neurotransmitter release
- Open K+ channels thus hyperpolarizing and inhibiting postsynpatic neurons
- -both reduce neurotransmitters like: glutamate, AcH, NE, serotonin and substance P.
First up lets discuss spinal analgesia. Mu, delta and Kappa receptors are present in the dorsal horn of the spinal cord. Receptors are present on both spinal cord pain transmission and presynaptically on the primary afferents that relay the pain message to them. How do opioids work then?
- Opioids inhibit release of excitatory neurotransmitters (substance P and glutamate) from these primary afferents
- Opioids also directly inhibit the dorsal horn pain transmission neuron.
Next is supraspinal analgesia. How does supraspinal pain work?
Pain-inhibitory descending neurons send processes to the spinal cord and inhibit pain transmission neurons
Pain inhibitor descending neurons are activated by opioids
–this activation results from the inhibition of inhibitory neuron by opioids
How are opioids given?
Systemically
- -so to act concurrently at both spinal and supraspinal sites
- -interaction at these sites tends to increase their overall analgesic effect
Last is Peripheral Analgesia, there are opioid mu receptors on the peripheral terminals of sensory neurons. How do opioids work on these receptors?
Stimulation of peripheral mu receptors by opioids decreases sensory neuron activity and transmitter release
–peripheral administration of opioids has shown some benefit
What are the classifications of opioid analgesics?
- Pure agonist: most of the typical morphine like drugs, all have high affinity for mu receptors
- Partial and mixed agonist-antagonist: combine a degree of agonist and antagonist activity
- Antagonist: naloxone and naltrexone
What are the pure agonist drugs?
Morphine (mu = strong and delta/kappa= weak) Fentanyl (mu = strong) Meperidine (mu=strong) Methadone (mu=strong) Codeine (mu = weak and delta = weak)
What are the mixed agonist-antagonist?
Pentazocine (mu = partial or antagonist and kappa = agonist)
Butorphanol (mu = partial or antagonist and kappa = agonist)
Nalbuphine (mu = antagonist and kappa = agonist)
Buprenorphine (mu = partial and kappa = antagonist)
