Opioid Analgesics Part I (Mechanisms/General Information) Flashcards
(30 cards)
Placebo Meta-analytic Review
- Placebo associated with decrease in self=reported pain
- Hidden/blind injection of naloxone reverse placebo-induced analgesia
- Nucleus accumbens DA release account for 25% of placebo analgesic effects
- Placebos may NOT be an adequate negative control
Opium
Dried powdered mixture of 20 alkaloids obtained from unripe seed capsules of the poppy plant
Opiate
- Drugs from opium
- Morphine (10%) and codeine (0.5%)
Opioid
- All substances with morphine-like properties
- Exogenous or endogenous
- Generic term for this class of drugs
Analgesia
Without pain
Allodynia
Feels pain from non-painful stimuli (ex: touch)
Hypoalgesia
Reduced pain perception
Hyperalgesia
Increased pain perception
Narcotic
Induces sleep (narcosis)
Endorphins
- Endogenous opioid peptide
- In spinal cord interneurons produce analgesia
Enkephalins
- Endogenous opioid peptide
- In spinal cord interneurons produce analgesia
Nociceptive Pain
Pain receptors and transmission over intact nerves
Neuropathic Pain
Caused by damaged neural structures, doesn’t respond well to opioids
Integumental Pain
- Skin, mucosa, muscles/joints, headache
- Controlled by NSAIDs and may be combined with narcotics
General NSAID MoA
- Decrease synthesis of prostaglandins and release of bradykinin
- Peripheral MoA
Visceral Pain
- Within body cavities (thorax, abdomen)
- Diffuse, hard to localize, referred to other sites
- Best treated with opioids
- Main action is on spinal cord and in upper CNS
- NSAIDs aren’t as effective unless pain is associated with inflammation
Pain/Neurogenic Inflammation
- Components of tissue injury lower pain threshold by producing inflammation and hyperalgesia
- Serotonin, histamine, bradykinin, and prostaglandins all contribute to inflammation
Local Anesthetics MoA
- Inhibit axonal action potential propagation
- Peripheral MoA
Opioid Analgesics MoA
- Work on CNS
- Raise pain perception threshold and alter emotional response
- No other sense are affected
Ascending Pain Pathways
- Perception
- Localization and discrimination of pain
Descending Pain Pathways
- Upper brain and brainstem
- Use descending serotonin and NE neruons to reduce pain transmission through dorsal horn of the spinal cord
Opioid Site of Action
- Glutamate and neuropeptides trasmit pain signal in dorsal horn of spine’
- Mu opioid receptors are activated by enkephalins to decrease Ca++ influx in presynaptic neuron, which decreases glutamate release
- Also causes an increase in K+ efflux to hyperpolarize the postsynaptic neuron
- NE and 5HT activate presynaptic alpha2 and 5HT1A receptors to decrease calcium influx
Specific Opioid Peptides
- Leu-/Met-enkephalins: amino acids found in brain, spinal cord, and adrenal medulla with NE and EPI
- Beta endorphin: amino acids found in pituitary and hypothalamus, released with ACTH in response to stress
- Dynorphins: amino acids found in neurons with diffuse projects (neuromodulators)
- Nociceptin/Orphanin FQ: amino acids resembling dynorphin, doesn’t act at classic opioid receptors
Opioid Peptides Characteristics
- Stores in vesicles and release by exocytosis
- Requires energy, calcium, and an intact cytoskeleton to release
- Polar, soluble in aqueous solvents
- Circulate unbound in blood and tend to have a short half life
- Can’t be given orally, only injection or through a mucous membrane if the peptides are small
- Interacts with cell membrane receptors (can’t cross membranes)
