Term
| how long back does the use of opium go? |
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Definition
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Term
| what are past examples of recreational opium use? |
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Definition
| smoking it or drinking laudanum |
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Term
| what are past examples of medicinal opium use? |
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Definition
| Egypt 1500 BC, Greeks in the Odyssey, and Hippocrates (cathartic, hypnotic, styptic, narcotic) |
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Term
| who first isolated morphine? |
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Definition
| a german scientist named serturner in 1803 |
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Term
| when was heroin first isolated? |
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Definition
| 1893, after which it started to be used by the medical community (who had ignored morphine) to treat pain - but was found to be extremely addictive. |
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Term
| where were endogenous receptors for morphine found in 1973? what is the implication of this finding? |
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Definition
| endogenous receptors for morphine were found in the brain and spinal cord - which means that the body must produce a morphine-like substance (wouldn't have receptors for a substance not endogenously produced). |
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Term
| what were the first endogenous opioids isolated? |
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Definition
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Term
| what were the second endogenous opioids isolated? |
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Definition
| (beta) endorphins in 1976 |
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Term
| what were the third endogenous opioids isolated? |
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Definition
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Term
| where do endogenous opioids come from? |
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Definition
| precursor peptides from the neurohypophysis (posterior pituitary) |
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Term
| what is the precursor peptide for endorphin? |
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Definition
| pro-opiomelanocortin (which is also the precursor for: ACTH, beta-lipotropin [which actually includes endorphin], MSH, etc) |
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Term
| what is the precursor peptide for enkephalin? |
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Definition
| pro-enkephalin, each one of which yields 5 met-enkephalins and 1 leu-enkephalin (slightly different distributions). |
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Term
| what is the precursor peptide for dynorphin? |
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Definition
| pro-dynorphin, which becomes dynorphin, which becomes dynorphin A and dynorphin B. each of the peptides formed along this process do begin w/tyrosine which is essential for receptor-binding. the first 5 residues of both dynorphin A+B are leu-enkephalin. |
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Term
| what are the 2 peptidases most involved in metabolism of endogenous opioids? |
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Definition
| enkephalinase and angiotensin-converting enzyme - which act very rapidly. |
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Term
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Definition
| an enkephalinase inhibitor which allows a better look at endogenous opioids be preventing their catabolism |
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Term
| where are high concentrations of beta-endorphins found? |
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Definition
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Term
| where are high concentrations of enkephalins/dynorphins found? |
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Definition
| limbic areas, periaqueductal gray, rostroventral medulla, and spinal cord dorsal horn (laminae I+II - substance gelatinosa) |
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Term
| what are the 3 main opioid receptors? |
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Definition
| mu (beta endorphin), delta (enkephalins [or beta endorphin]) and kappa (dynorphin) |
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Term
| what is the distribution of opioid receptors |
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Definition
| CNS +heart, kidneys, placenta, GI organs, pancreas, and male reproductive tract. (local opioids can be injected to joints for sx). |
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Term
| what are the physiologic roles of opioids? |
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Definition
| neurotransmitters/neuromodulators, hormone modulation, and pain transmission |
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Term
| how do opioids function as neurotransmitters/neuromodulators? |
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Definition
| inhibitory (decreases firing of neurons - suppressing activity) and disinhibitory (increases firing of neurons which were previously suppressed by neurons now inhibited - mainly seen w/dynorphin) |
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Term
| how do opioids function as hormone modulators? |
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Definition
| opioids can either increase or decrease hormone release via modulation of synthesis (increasing/decreasing) or feedback mechanisms (depressing/enhancing). |
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Term
| what are some examples there endogenous opioids have been proven to be involved in modulation of pain transmission? |
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Definition
| with electrical stimulation, stress-induced analgesia and acupuncture |
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Term
| what physiological functions are associated w/mu receptors? |
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Definition
| **analgesia, body temp (hypothermia), cardiovascular (baroreceptor reflex inhibition/bradycardia), prolactin release, and respiratory depression |
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Term
| what physiological functions are associated w/delta receptors? |
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Definition
| analgesia, body temperature (hyperthermia), *cardiovascular (pts w/endotoxemic hypotension - cannot give narcotics to tx as they will cause worse hypotension), growth hormone release, inhibition of LH/testosterone, and respiratory depression |
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Term
| what physiological functions are associated w/kappa receptors? |
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Definition
| *visceral analgesia, *appetite suppression, endotoxemic hypotension, inhibition of ADH secretion, and spinal cord injury (due to decreased blood flow which affects specific reflexes). |
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Term
| why is there interest in cloning opioid receptors? |
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Definition
| in order to keep the good effects of opioids (analgesia) and lose the bad (respiratory depression, GI motility effects) |
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