Term
| what are the agonist phenanthrenes? |
|
Definition
| *naturally-occurring opium alkaloids: codeine, morphine. *semisynthetic derivatives of morphine: hydromorphone, oxymorphone. *semisynthetic derivatives of codeine: hydrocodone, oxycodone. |
|
|
Term
| what is the partial agonist phenanthrene? |
|
Definition
| buprenorphine (will activate the receptor, but w/a limited safety feature) |
|
|
Term
| what is the agonist-antagonist phenanthrene? |
|
Definition
| nalbuphine (goal was to create a non-addicting drug) |
|
|
Term
| what are the phenylheptanes? |
|
Definition
| levomethadyl, methadone and propoxyphene (off market) |
|
|
Term
| what are the 2 types of morphinans? |
|
Definition
| agonist: levorphanol, agonist-antagonist: butorphanol |
|
|
Term
| what are the phenylpiperidines? |
|
Definition
| alfentanil, fentanyl (potent), remifentanil, meperidine (weak), and sufentanil |
|
|
Term
| what is the benzomorphan agonist-antagonist? |
|
Definition
| pentazocine (prevents complete activation of the receptor) |
|
|
Term
| what is the aminotetralin agonist-antagonist? |
|
Definition
|
|
Term
| what is the difference between morphine and codeine? |
|
Definition
| codeine has a methyl group which is metabolized off (morphine in bloodstream) |
|
|
Term
|
Definition
| di-acetyl-morphine - made by the Bayer company in the late 1800s to develop a better analgesic - good drug, rapidly deacetylated & crosses BBB. if a drug test is done on this patient, won’t find heroin, but will find mono-acetylated morphine or morphine itself. |
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|
Term
| what is the most potent PO analgesic? |
|
Definition
|
|
Term
| what are the opioid antagonists? |
|
Definition
| naloxone (short acting) and naltrexone (longer acting) |
|
|
Term
| what are the IM/PO equianalgesic doses for morphine, codeine, heroin, hydromorphone, levorphanol, meperidine, methadone, and oxycodone? |
|
Definition
| hydromorphone (IM/PO: 1.5/7.5), levorphanol (2/4), heroin (5/60), methadone (10/20), morphine (10/60), oxycodone (15/30), meperidine (75/300), codeine (130/200), hydrocodone (--/30) |
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|
Term
| what is the primary action at the opioid receptor subtype mu-1? |
|
Definition
| supraspinal analgesia, euphoria |
|
|
Term
| what is the primary action at the opioid receptor subtype mu-2? |
|
Definition
| spinal analgesia, respiratory depression, constipation |
|
|
Term
| what is the primary action at the opioid receptor subtype kappa? |
|
Definition
| spinal analgesia, diuresis, dysphoria |
|
|
Term
| what is the primary action at the opioid receptor subtype delta? |
|
Definition
| supraspinal analgesia, spinal analgesia |
|
|
Term
| what is the primary action at the opioid receptor subtype sigma? |
|
Definition
| dysphoria, hallucinations, cardiac stimulation |
|
|
Term
| what opioid receptors does morphine interact with? |
|
Definition
| mu: agonist, kappa: agonist, delta: agonist |
|
|
Term
| what opioid receptors does buprenorphine interact with? |
|
Definition
|
|
Term
| what opioid receptors does butorphanol interact with? |
|
Definition
| mu: antagonist, kappa: agonist |
|
|
Term
| what opioid receptors does pentazocine interact with? |
|
Definition
| mu: antagonist, kappa: agonist |
|
|
Term
| what opioid receptors does nalbuphine interact with? |
|
Definition
| mu: antagonist, kappa: agonist |
|
|
Term
| what opioid receptors do naloxone and naltrexone interact with? |
|
Definition
| mu: antagonist, kappa: antagonist, delta: antagonist |
|
|
Term
| what will cause release of endogenous opioids? |
|
Definition
| electrical stimulation of specific CNS areas (periaqueductal gray) - which will produce strong analgesia and can be blocked by narcotic antagonists. |
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|
Term
|
Definition
| beta-endorphin, a 31 AA peptide (split from a larger peptide which also yields ACTH) which is found primarily in the pituitary and binds predominantly on mu/delta sites. precursor: propiomelanocortin. beta-endorphin produces various behavioral and physiological responses to pain. |
|
|
Term
| what are the enkephalins? |
|
Definition
either methionine-enkephalin (met-enkephalin - amino acid # 61-65 of beta-endorphin) or leucine-enkephalin (leu-enkephalin), these are located in the nerve endings throughout the CNS (esp brainstem,
dorsal horn - spinal cord, basal ganglia, portions of limbic sys.). the enkephalins appear to bind equally to delta and mu1 sites. probable mechanism: bind to opioid receptor, decrease substance P release, and reduction of pain signal transmission. precursor: proenkephalin. synthetic enkephalins have been produced; are being evaluated. |
|
|
Term
|
Definition
| these are located in neurons throughout the brain and bind primarily to kappa sites. |
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|
Term
| what defines a "narcotic" (opioids)? |
|
Definition
| requirements: ring structure, a carbon chain connected to it, an oxygen, and a nitrogen. |
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|
Term
| what are the narcotic effects in the CNS leading to supraspinal analgesia? |
|
Definition
| action at the opioid receptors in the periaqueductal gray (PAG) and related areas to simulate descending pathways of inhibition = decreased transmission of pain signals from the spinal cord to higher sites. |
|
|
Term
| what are the narcotic effects in the CNS leading to spinal analgesia? |
|
Definition
| stimulation of pre-synaptic enkephalin receptors (delta and mu1: K+ efflux) and reducing availability of Ca++ (kappa) = consequent reduction in release of pain NTs (sub P). |
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|
Term
| what characterizes the sedation effect of opioids? |
|
Definition
| not as powerful as CNS depressants/barbiturates/alcohol |
|
|
Term
| what characterizes the emesis effect of opioids? |
|
Definition
| narcotics increase sensitivity to motion |
|
|
Term
| how do narcotics affect the cough reflex? |
|
Definition
|
|
Term
| what characterizes the respiratory depression effect of opioids? |
|
Definition
| this is the primary cause of death in OD, but therapeutic doses should have a minimal effect on respiration. |
|
|
Term
| what characterizes the CV effect of opioids? |
|
Definition
| hypotension. directly: depression of vasomotor center. indirectly: histamine release (peripheral vasodilation - mostly w/morphine). |
|
|
Term
| what characterizes the GI effect of opioids? |
|
Definition
| hypomotility via decreased peristalsis and delayed gastric emptying |
|
|
Term
| what characterizes the opthalamic effect of opioids? |
|
Definition
|
|
Term
| what characterizes the smooth muscle effects of opioids? |
|
Definition
| increased tone - primarily in the GI, biliary tract (possible gall bladder attack), and urinary |
|
|
Term
| what characterizes the endocrine effects of opioids? |
|
Definition
| pts receiving daily opioid therapy for > 1 a month may undergo reductions in cortisol, sex hormones & DHEA. |
|
|
Term
| what characterizes the use of opioids for analgesia? |
|
Definition
| opioid are used for relief of moderate to severe pain (e.g., cancer, myocardial infarction, burns, fractures, postsurgical trauma). |
|
|
Term
| what characterizes legitimate chronic use of opioids for pts in pain? |
|
Definition
| chronic use does not cause addiction (psychological dependence) but physical dependence does develop after ~1 wk of daily use (determined by amount used and duration). |
|
|
Term
| what is the most effective opioid dosing schedule chronic pain, esp. cancer? |
|
Definition
| fixed (as opposed to PRN0 |
|
|
Term
| does regular analgesia improve sleep? |
|
Definition
| yes - mood is also elevated which leads to better appetite and improved social interaction. pain control may also lead to less medication necessary. |
|
|
Term
|
Definition
| this is due to fear of addiction, decreased cognition (less able to prepare for death), and decreased suffering (less spiritual growth). this leads to more restrictive narcotic regulations and less use of narcotics. |
|
|
Term
| what was found in the preop obstetrical analgesia study run by goldstein? |
|
Definition
| preop morphine has a synergistic effect w/GA, improved pain relief postop, decreased postop n/v, earlier ambulation/comfort however pts reported feeling the same degree of analgesia (pts who had OMT postop did the very best). |
|
|
Term
| what are other uses for opioids? |
|
Definition
| relief of non-productive cough (codeine), relief of severe diarrhea, immediate (short term) relief of dyspnea associated w/pulmonary edema and left ventricular failure (decreases workload), and improved respiration in pts on mechanical ventilators (pts less likely to fight). |
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|
Term
| what CNS ADRs are associated w/narcotics? |
|
Definition
| h/a, nausea, dizziness, sedation, disorientation, delirium, incoordination, transient hallucinations, agitation, tremor, seizures, and euphoria/dysphoria |
|
|
Term
| what CV ADRs are associated w/narcotics? |
|
Definition
| bradycardia, hypotension, flushing, syncope, phelbitis |
|
|
Term
| what GI ADRs are associated w/narcotics? |
|
Definition
| dry mouth, anorexia, constipation (significant effect even w/therapeutic doses, tolerance does not develop - may require increased fluid/fiber/ambulation/laxatives), biliary tract spasm, and vomiting |
|
|
Term
| what pulm ADRs are associated w/narcotics? |
|
Definition
| respiratory depression (major cause of death in OD) which is observed in newborns after dose to mother |
|
|
Term
| what GU ADRs are associated w/narcotics? |
|
Definition
| urinary hesitancy/retention, dysuria, and reduced sexual desire/performance |
|
|
Term
| what hypersensitivity ADRs are associated w/narcotics? |
|
Definition
| urticaria (possibly hemorrhagic), pruritis, wheal/flare at injection site, sneezing, and edema |
|
|
Term
| what other ADRs are associated w/narcotics? |
|
Definition
|
|
Term
| what narcotic ADRs do pts develop tolerance to? |
|
Definition
| n/v, sedation, respiratory depression |
|
|
Term
| what characterizes narcotic OD? |
|
Definition
| miosis, hypotension, bradycardia, cardiac arrest, hypothermia, oliguria, pulmonary edema, severe respiratory depression, coma |
|
|
Term
| what are opioid contraindications? |
|
Definition
| convulsive states, ICP (w/reduction in respiration, you get CO2 buildup in the blood -> can increase cerebral vasodilation), and undiagnosed acute abdominal conditions |
|
|
Term
| what characterizes narcotic drug interactions? |
|
Definition
| CNS depression enhanced by concurrent alcohol, BZD etc use. muscle relaxation & respiratory depression increased by skeletal muscle relaxants. symptoms of acute narcotic OD (& possibly death) when *meperidine used within 14 days of D/C of MAO inhibitor. anticholinergic effects of *meperidine may be enhanced by other drugs with anticholinergic activity (e.g., TCAs). phenytoin or rifampin may reduce blood level of methadone and induce withdrawal. orthostatic hypotension may be intensified by any other drugs which can lower blood pressure. analgesia can be enhanced by simultaneous use of clonidine (alpha-2 adrenergic agonist), TCAs, anticonvulsants, NSAIDs. |
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|
Term
| what characterizes opioid withdrawal after ~12 hours? |
|
Definition
| lacrimation, rhinorrhea, sweating, yawning, chills, and piloerection |
|
|
Term
| what characterizes opioid withdrawal after ~36 hours? |
|
Definition
| abdominal cramping, muscle aching, nausea, vomiting, diarrhea, hyperthermia, and hyperventilation. most effects end w/in 3-5 days. |
|
|
Term
| what characterizes morphine? |
|
Definition
| this phenanthrene is the most widely used narcotic, taken orally or by pump often for CA pain. |
|
|
Term
| what characterizes biotransformation of morphine? |
|
Definition
| there is significant first pass effect, morphine is biotransformed into glucuronides, one of which is: morphine-6-glucuronide (m-6-g) which has a high affinity for the mu receptor, analgetic activity, higher potency than morphine, is highly polar and has CSF levels after chronic administration higher than a single dose (does not readily exit blood). m-3-g is the other metabolite which may cause seizures w/high dose morphine (200 mg/hr IV) |
|
|
Term
| what may explain the difference in potency ration between acute and chronic morphine administrations? |
|
Definition
| accumulation of m-6-g. therefore acute PO doses are usually 60 mg and chronic doses are 20-30 mg. |
|
|
Term
| how should switching between opioid in a chronic pt be handled? |
|
Definition
| calculate dose based on acute potency difference, then reduce dose and make upward dosage adjustments as needed. this is b/c cross-tolerance is incomplete. |
|
|
Term
| do anti-histamines work on the histamine release which occurs w/epidural or intrathecal morphine administration? |
|
Definition
| not really. naloxone can help, but it will reduce the analgesia. |
|
|
Term
| what is the risk w/sustained-release forms of morphine and related opioids? |
|
Definition
| if taken w/alcohol it can act as a solvent and cause an OD (drugs released at once). |
|
|
Term
| what characterizes fentanyl? |
|
Definition
| this phenylpiperidine has the same pharmacological profile as morphine, but is 100x more potent. it has significantly greater lipid solubility as well - shorter acting: 30-60 min (extended action available as a skin patch). 22% of pts will develop pruritus. |
|
|
Term
| what are contraindications for fentanyl? |
|
Definition
| acute pain, post-op pain, mild/intermittent pain responsive to prn/non-opioids, and doses > 25 mcg/hr at the start of opioid therapy. |
|
|
Term
| what characterizes meperidine? |
|
Definition
| this phenylpiperidine is less potent than morphine (only 25% PO and 13% IM) and is short acting. the major problem w/chronic administration is accumulation of normeperidine which has a longer t1/2 (15-30 hrs) than meperidine (3-4 hrs) and acts as a CNS stimulant: tremor, muscle twitches, seizures. toxicity is more frequent w/renal failure pts and it is not readily reversed w/naloxone. |
|
|
Term
|
Definition
| this partial agonist phenanthrene is a strong agonist at the mu receptor (hard to reverse w/naloxone) and antagonist at the kappa receptor. similar to morphine, it has a dose-related depression of respiration. it is now used as tx for narcotic addiction usually sublingually. it can also be used w/naloxone so if addicts try to break it down to inject the naloxone will counter the effect IM (PO - not enough to counter buprenorphine’s binding effects). |
|
|
Term
| what characterizes methadone? |
|
Definition
| this phenylheptane has good PO absorption and limited biotransformation. t1/2 in most pts: 15 hrs. t1/2 in narcotic addicts: 24 hrs (increased plasma proteins; albumin & globulins). *danger: duration of respir. depression > duration of analgesia. |
|
|
Term
| what are the uses for methadone? |
|
Definition
| CA pain tx: only in compliant pts who will not deviate from dosage (should have shorter acting rescue opioid for episodic or breakthrough pain). narcotic addiction tx: PO efficacy decreases focus on injection process and long t1/2 decreases need for frequent dosing. mechanism for addiction tx: >18 y/o, >2 years of addiction, failed other modalities, and volunteer. |
|
|
Term
| what characterizes levomethadyl? |
|
Definition
| this phenylheptane is a long-acting methadone derivative w/a t1/2 of 48-72 hrs. it is only FDA-approved for addiction tx and maintenance doses are given 3x/week. |
|
|
Term
| what characterizes tramadol? |
|
Definition
| this centrally-acting analgesic is a synthetic codeine analog w/less affinity for opioid receptors. it is a mu receptor agonist and 5-HT uptake inhibitor - providing analgesia equal to codeine but less than acetaminophen. it has reduced chance for abuse/respiratory depression than other opiate agonists and is only partially reversed by naloxone. |
|
|
Term
| what generally characterizes the narcotic agonist-antagonists? |
|
Definition
| these activate the kappa receptors, have antagonistic activity at mu receptors, less respiratory depression than w/pure narcotic agonists (mu), and can precipitate withdrawal in pts mu-opioid agonists. |
|
|
Term
| what is pentazocine (benzomorphan agonist-antagonist)? |
|
Definition
| originally developed as a 'non-addictive' opioid but both psychological and physical dependence can develop. adverse psychological reactions: nightmares/hallucinations can occur, esp in hepatic/renal pts. this has more recently been combined w/naloxone which doesn't reduce analgesia PO - but will if injected (then may cause withdrawal rxn - similar to buprenorphine combination). |
|
|
Term
| what is butorphanol (morphinan agonist-antagonist)? |
|
Definition
| this is 5x more potent than morphine, is now available as a nasal spray and increase in respiratory depression is not parallel to dose increased (depression at 4 mg = 2 mg). |
|
|
Term
| what is nalbuphine (agonist-antagonist phenanthrene)? |
|
Definition
| similar to butorphanol in regard to lack of parallelism between analgetic dose and degree of respiratory depression. |
|
|
Term
| what is dezocine (aminotetralin agonist-antagonist)? |
|
Definition
| unlike the others, there is a correlation between analgetic doses and degree of respiratory depression |
|
|
Term
|
Definition
| a derivative of oxymorphone which blocks opioid receptors, has a higher affinity for opioid receptors than narcotics, and does not activate receptors. short acting (t1/2 = 60 min). |
|
|
Term
| what is naloxone used for? |
|
Definition
| tx of narcotic OD and narcan (trade name) challenge test (give a suspected addict a small dose - should precipitate a minor drug withdrawal reaction = positive test). caution: too rapid a reversal of opioid influence can produce N, V, increase in BP. |
|
|
Term
|
Definition
| a naltrexone derivative, only IV and has a longer t1/2: 8-10 hours. |
|
|
Term
|
Definition
| similar to naloxone (oxymorphone derivative) which is used in narcotic addiction tx. it is longer acting than naloxone and dose dependent. |
|
|
Term
| what characterizes naltrexone initiation? |
|
Definition
| the pt needs to be opioid-free for 7-10 days before they can start naltrexone (need negative narcan challenge test) |
|
|
Term
| what ADRs are associated w/naltrexone? |
|
Definition
| hepatoxicity (esp at doses of 300 mg+, narrow therapeutic index), confusion, and hallucinations |
|
|
Term
| what are contraindications for naltrexone? |
|
Definition
| pts recieving or physically dependent upon opioids, pts in withdrawal, pts w/a positive opioid urine test, and acute hepatitis/liver failure. |
|
|
Term
| can naltrexone help tx alcoholism? |
|
Definition
| yes, alcohol may cause endogenous endorphin release which naltrexone would then block the effects of. |
|
|
Term
| what are the reported effects of naltrexone on alcoholics? |
|
Definition
| fewer drinks per day, alcoholic beverages tasted less pleasant, experienced less of a 'high' from alcohol, improved compliance, reduced relapse, lower dropout rate, longer time to relapse, more successful in coping with relapse when it occurred |
|
|
Term
| what are other reported effects of naltrexone? |
|
Definition
| dysphoria, anorexia, and wt loss (during chronic use) |
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|
