What are the 10 narcotic analgesics you’re have to know?
Morphine Codeine Fentanyl Meperidine Methadone Naloxone Naltrexone Buprenorphine Butorphanol Tramadol
Which of the 10 drugs are:
Natural agonists- morphine, codeine
Synthetic agonists- meperidine, methadone, tramadol, fentanyl
Opioid antagonists- naloxone, naltrexone
What do endogenous opioid peptides (EOPs) do?
EOPs modulate pain sensory transmission in the spinal cord, limbic structures, hypothalamus and medial thalamus
EOPs also modulate GI function (stim of opioid receptors on the intestinal increases random contractions of the circular muscles
Results in constipation
What are the 3 classes of EOP receptors with subtypes?
μ (mu): μ1 and μ2
κ (kappa): κ1, κ2, κ3
δ (delta): δ1, δ2
What are the 3 endogenous opioid peptides genes and their products?
- Pro-opiomelanocortin- produces β-endorphin, adrenocorticotropic hormone (ACTH), and melanocyte stimulating hormone
- Pro-enkephalin- produces met-enkephalin and leu-enkephalin
- Pro-dynorphin produces dynorphin
Enkephalin/endorphin/dynorphin are endogenous opioids
What are G-coupled opioid receptors?
Coupled negatively to adenylyl cyclase by G proteins
Activation decreases activity of adenylyl cyclase, decreases production of cAMP
Increases efflux of K and cellular hyperpolarization
Decreases influx of Ca and lower intracellular concentrations of free Ca, which decreases release of neurotransmitters
Which inhibit pain sensation
What are the opioid pharmacokinetics?
Opioids are metabolized by hepatic glucuronidation
Highly polar glucuronides are then extracted by the kidneys
Beware of toxicity in renal failure
Metabolites are readily detected in urine up to one week after consumption
What are the adverse effects of opioid analgesics?
Constipation- reduced GI motility
Nausea and vomiting- chemoreceptive triggers zone
Increased release of prolactin and growth hormone
Drowsiness- reduced reticular activating system in brain
Respiratory depression- reduced responsiveness of carbon dioxide sensing neurons in brain stem
What is μ receptor stimulation?
What is κ receptor stimulation?
What is δ receptor stimulation?
μ- produces analgesia in spinal cord and brain, produces euphoria in limbic system
κ- produces analgesia in the spinal cord and brain with less euphoria
δ- produces analgesia in the spinal cord and brain
What is the pain sensory system?
Primary pain sensory afferent fibres one the dorsal horn of the spinal cord release excitatory neurotransmitters (glutamate and substance P)
This stims neurons to project up to thalamus and limbic system then to somatosensory cortex
What are the descending pain inhibitory systems?
Originate in periaqueductal gray region of the midbrain and nucleus raphe Magnus
Some descending tracts are serotonin some are NE
Project to dorsal horn and inhibit activity of the ascending pathways