Chapter 11: The Opioids Flashcards
What are narcotic analgesics?
A class of drugs that reduce pain without causing unconsciousness. Opiates are natural narcotics derived from the opium poppy (e.g. morphine, codeine). Other narcotics are semisynthetic (heroin) or totally synthetic (demerol).
What effects do opioids have?
- relieve pain
- produce drowsiness and sleep
- euphoria or dysphoria
- pinpoint pupils
- vomiting
- suppression of the cough reflex
- reduced body temperature
- reduced appetite
- constipation
- effects on hormones
- respiratory depression (high doses)
- cardiac depression (high doses)
What are the opioid receptors?
- mu
- delta
- kappa
- NOP-R (nociceptin/orphanin FQ receptor)
How do the opioid receptors work?
They are metabotropic and coupled to G proteins. They work by opening potassium ion channels and closing calcium ion channels. This causes cell hyperpolarization, inhibition of neurotransmitter release, and inhibition of adenylyl cyclase. Opioids and opioid neuropeptides bind to the 3 classical receptors but not NOP-R. Nociceptin/orphanin FQ binds to NOP-R and not the other receptors.
Where are opioid receptors found?
They are widely and unevenly distributed in the central and peripheral nervous systems.
What are endogenous opioids?
They are also called endorphins. Larger propeptides are manufactured in the soma and cleaved into smaller active peptides/opioids by enzymes. Then they are stored in vesicles and further processed as they travel to the synapse for release. After release they bind to opioid receptors. They are not selective but show a relative preference for receptor type.
What are the types of endogenous opioids?
- prodynorphin
- POMC
- proenkephalin
- pronociceptin/orphanin FQ
How do opioids work?
They reduce synaptic transmission in three ways:
- Postsynaptic inhibition by opening K+ channels, hyperpolarizing the cell and reducing the rate of firing.
- Axoaxonic inhibition by closing Ca2+ channels and reducing neurotransmitter release.
- Via presynaptic autoreceptors closing Ca2+ channels or opening K+ channels to hyperpolarize the cell and reduce the release of co-localized neurotransmitter.
What are nociceptors?
Free nerve endings that are sensitive to a variety of stimuli.
What are the components of pain.
- Early pain is the immediate sensory component. It signals the onset of a noxious stimuli and its precise location causing immediate withdrawal and escape.
- Late pain is the emotional component. It motivates adoption of behaviours that limit damage and promote recovery.
How does early pain transmission work?
Pain is carried by myelinated A-delta neurons and transmitted from the spinal cord via the spinothalamic tract to the posteroventrolateral nucleus of the thalamus. From there it goes to the primary then secondary somatosensory cortex.
How does late pain transmission work?
Pain is carried by C fibres and transmitted to the thalamus with collaterals to limbic areas, including the anterior cingulate. Late pain occurs more slowly than early pain because the C fibre are unmyelinated.
How do opioids relieve pain?
- endorphin neurons in the spinal cord decrease the conduction of pain signals to higher brain centres
- descending neurons from the periaqueductal gray activate pathways that impede pain signals in the spinal cord
- opioid receptors in the neocortex and limbic regions modulate the emotional component of pain to relieve the sense of suffering
How do the reinforcing effects of opioids work?
Opioids have reinforcing effects through dopaminergic and nondopaminergic mechanisms. Opioid drugs inhibit inhibitory GABA cells which has the effect of increasing mesolimbic cell firing and increasing dopamine release in the nucleus accumbens.
Describe opioid tolerance.
Opioid drugs demonstrate tolerance to many of the drug effects, physical dependence, and cross-tolerance with drugs in the same class. Mechanisms for the development of tolerance include increased rate of metabolism with repeated use, classical conditioning processes, and compensation of nerve cells.
