Term
| what medically relevant alkaloids come from the papaver somniferum plant? |
|
Definition
| morphine, codeine, papaverine |
|
|
Term
| how does papaverine work and what is it used for? |
|
Definition
direct SM cell relaxant
used to treat pain due to spasms (intestinal, etc) |
|
|
Term
| drugs derived from opium are known as |
|
Definition
|
|
Term
| what are oiopid (opium-like) analgesics? |
|
Definition
| narcotic analgesics like morphine that produce analgesia without loss of consciousness |
|
|
Term
| what are the receptors for opioids? |
|
Definition
3 classic - MOP (mu), DOP (delta), KOP (kappa)
1 novel - NOP (orphanin FQ/nociceptin) |
|
|
Term
| which receptor do opioid drugs act mostly on? |
|
Definition
|
|
Term
| location of opioid receptors involved in pain? |
|
Definition
| dorsal horn, PAG, thalamus |
|
|
Term
| location of opioid receptors for respiration, coughing, vomiting, myosis? |
|
Definition
|
|
Term
| what is a good sign of opioid toxicity? |
|
Definition
pinpoint pupils
CN 3 Edinger-Westfall nucleus that controls pupil diameter has opioid receptors |
|
|
Term
| unconscious patient with pinpoint pupils. almost always due to what? |
|
Definition
| opioid overdose - heroin or morphine |
|
|
Term
| location of opioid receptors involved in neuroendocrine effects? |
|
Definition
|
|
Term
| location of opioid receptors mediating mood and behavior? |
|
Definition
|
|
Term
| which opioid receptor is the only one responsible for sedation and respiratory depression? |
|
Definition
|
|
Term
| which receptor(s) cause spinal and supraspinal analgesia? |
|
Definition
|
|
Term
| what is the most important side effect clinically of opioid use? |
|
Definition
|
|
Term
| what are the 3 endogenous ligand for opioid receptors? |
|
Definition
endorphins
enkephalins
dynorphins |
|
|
Term
| endogenous ligand affinity for MOP? |
|
Definition
| endorphins > enkephalins > dynorphins |
|
|
Term
| endogenous ligand affinity for DOP? |
|
Definition
| enkephalins > endorphins and dynorphins |
|
|
Term
| endogenous ligand affinity for KOP? |
|
Definition
| dynorphins >> endorphins and enkephalins |
|
|
Term
| historically, morphine has been used to treat? |
|
Definition
| diarrhea - causes constipation |
|
|
Term
| opioid receptors are what type? |
|
Definition
| G protein coupled receptors |
|
|
Term
| effect of activation of opioid receptors on adenylyl cyclase and cAMP? |
|
Definition
|
|
Term
| effect of activation of opioid receptors on receptor-operated K channels? |
|
Definition
activated/opened
hyperpolarizes the cell - blocks NT release and pain transmission |
|
|
Term
| 2 effects of activating opioid receptors that leads to the final blockade of NT release and pain transmission? |
|
Definition
1. activation of receptor operated K channels
2. suppression of voltage gated Ca channels |
|
|
Term
| what is the mechanism of acute tolerance at the molecular level? |
|
Definition
1. agonist binding to opioid receptors (GPCR)
2. phophorylation by GPCR kinases
*3. binding of B-arrestins to receptors
4. interference with G-protein binding
5. receptor internalization
6. decrease in effectiveness (Acute tolerance) |
|
|
Term
| what protein stops the actions of morphine? |
|
Definition
|
|
Term
| how does B-arrestin cause acute tolerance? |
|
Definition
internalizes the receptor; stops signal production
requires more and more drug for effect = tolerance |
|
|
Term
| are all symptoms of opioids subject to mechanism of tolerance? |
|
Definition
|
|
Term
| what effects have no tolerance development to opioid use? |
|
Definition
1. miosis
2. constipation
3. convulsions |
|
|
Term
| what evidence is there for an endogenous ligand for the morphine receptor? |
|
Definition
| analgesia induced by electrical stimulation of brain was blocked by naloxone (morphine antagonist) |
|
|
Term
| what are the 3 families of endogenous opioid peptides? |
|
Definition
| endorphins, enkephalins, dynorphins |
|
|
Term
| what is the smallest endogenous opioid peptide? |
|
Definition
|
|
Term
| pro-opiomelanocortin (POMC) is a precursor of what? |
|
Definition
| *b-endorphin (endogenous peptide) |
|
|
Term
| what can be made from POMC? |
|
Definition
| MSH, ACTH, lipotropin, CLIP, endorphin and enkephalin |
|
|
Term
| where does the descending endogenous analgesic anti-nociceptive pathway originate? |
|
Definition
| aquductal sylvia (PAG) with enkephalin neurons |
|
|
Term
| in the descending endogenous anti-nociceptive system, first order neurons from the PAG go where? |
|
Definition
raphe magnus nucleus in the brain stem
enkephalin neurons stimulate 2nd order neuron (serotonergic) |
|
|
Term
| NT of 3rd order neuron of descending endogenous anti-nociceptive system? |
|
Definition
|
|
Term
| what type of synapse is the final synapse in descending endogenous anti-nociceptive path? |
|
Definition
| axo-axonic in the spinal cord; secretes enkephalin in response to a stimulus |
|
|
Term
| how does the endogenous anti-nociceptive pathway affect the perception of pain? |
|
Definition
inhibitory enkephalin interneurons have axoaxonic synapse with DRG nociceptor neuron terminal fibril and block the release of NT to second order neuron
blockade is caused by hyperpolarization from opening K channels |
|
|
Term
| why is effect of pain different from person to person? |
|
Definition
| due to endogenous analgesic systems - hard to predict how much will be activated and its effect in blocking pain pathways |
|
|
Term
| which receptors does morphine act on at normal doses? |
|
Definition
mostly MOP, some KOP
no DOP |
|
|
Term
| sustained release morphine? |
|
Definition
|
|
Term
| what MOP strong agonist is most potent? |
|
Definition
|
|
Term
| what MOP strong agonist is short acting? |
|
Definition
|
|
Term
| how is fentanyl administered? |
|
Definition
patch or parenteral
not oral |
|
|
Term
|
Definition
1. morphine sulfate
2. hydromorphone
3. meperidine
4. fentanyl |
|
|
Term
| what is important to remember when you switch from IM to tablet form of morphine in a post-operative patient? |
|
Definition
| the dose must be increased |
|
|
Term
| what is important to remember about partial agonists? |
|
Definition
| even with a good dose of drug, never achieve full effect |
|
|
Term
| what are partial MOP agonists? |
|
Definition
codeine
oxycodone
hydrocodone
propoxyphene |
|
|
Term
| what is important to remember in dosing with morphine vs. a partial agonist? |
|
Definition
| partial agonist is not as potent and requires a much higher dose |
|
|
Term
| what is the mechanism of a mixed strong analgesic? |
|
Definition
| it is an agonist for one receptor type and an antagonist for another |
|
|
Term
| example of mixed strong analgesic? |
|
Definition
buprenorphin
*potent; partial MOP agonist; DOP and KOP antagonist |
|
|
Term
| mixed analgesics are used to treat? |
|
Definition
| opioid dependence - treat withdrawal effects |
|
|
Term
| morphine administration form(s)? |
|
Definition
|
|
Term
|
Definition
|
|
Term
| what is the mechanism of opioid and NSAID synergy? |
|
Definition
1. NSAIDs block COX
2. more AA available for lipoxygenase
3. lipoxygenase products facilitate opening of K channels by opioids |
|
|
Term
| benefit of adding NSAID to post-op treatment with opioid? |
|
Definition
| synergism allows for less frequent dosing |
|
|
Term
| why do you need 30 mg orally after 10 mg IM dose of morphine in the post-op period? |
|
Definition
| oral has first pass in the liver and therefore needs higher doses to be as effective |
|
|
Term
| morphine is converted to what in liver? |
|
Definition
| morphine-6-glucuronide (twice as potent as morphine) and morphine-3-glucuronide |
|
|
Term
| why is morphine 2-6 fold less potent orally than parenterally? |
|
Definition
| due to first pass metabolism |
|
|
Term
| when must be done to the dose when switching patients from parenteral to oral morphine? |
|
Definition
|
|
Term
| individual response to morphine is ____ |
|
Definition
|
|
Term
| standard dose of morphine is effective in how many patients? |
|
Definition
|
|
Term
| what is the standard dose of morphine? |
|
Definition
| morphine sulfate 10 mg IM Q3h |
|
|
Term
| when a higher dose of morphine is required what should be done? |
|
Definition
| a more potent drug should be used |
|
|
Term
| when should long acting drugs be used in place of morphine? |
|
Definition
when less frequent dosing required
methadone |
|
|
Term
| quick acting, fast dissipating drugs (remifentanil) are used for what? |
|
Definition
| short, painful procedures |
|
|
Term
| what are additional routes of admin of opioid analgesics? |
|
Definition
1. rectal transmucosal
2. epidural
3. subarachnoid
4. oral transmucosal
5. transdermal patch
6. iontophoresis
7. inhalation |
|
|
Term
| epidural access for admin of opioid analgesics |
|
Definition
direct access to DRG neurons using very low doses
usually admin as an infusion |
|
|
Term
| subarachnoid route of admin of opioid analgesics |
|
Definition
spinal or CSF
direct access to dorsal horn neurons and brain structures
much longer acting by direct access |
|
|
Term
| fentanyl patch for cancer pain mechanism |
|
Definition
after permeation, drug forms a depot in stratum corneum
unlike scopolamine patches for nausea which permeates best over the mastoid process, fentanyl patches can be applied anywhere on the skin
12 hour onset |
|
|
Term
|
Definition
| transport of soluble ions through the skin by using mild electric current |
|
|
Term
| what are the modes of control of infusion analgesia? |
|
Definition
1. patient controlled analgesia (PCA)
2. computer-assisted continuous infusion (CACI) |
|
|
Term
| what is patient-controlled analgesia (PCA)? |
|
Definition
patient has limited control of dosing from infusion pump within tightly mandated parameters
short acting drugs are used
addiction does not develop
preferred over IM injections |
|
|
Term
| what is computer-assisted continuous infusion (CACI)? |
|
Definition
needs continuous measurement of plasma opioid levels with indwelling sensors
only used for patients emerging from unconsciousness in ICU |
|
|
Term
| what are the non-analgesic use of opioids? |
|
Definition
| dyspnea and central antitussives |
|
|
Term
|
Definition
| acute left ventricular failure and pulmonary edema |
|
|
Term
| what opioid is given for improvement of dyspnea? |
|
Definition
|
|
Term
| what is the mechanism of morphine treatment of dyspnea? |
|
Definition
| not entirely clear - decreased peripheral resistance and increased capacity of peripheral vascular compartments may be involved |
|
|
Term
| when is morphine contraindicated in the treatment of dyspnea? |
|
Definition
| pulmonary edema due to resp disease |
|
|
Term
| what can be used as antitussives? |
|
Definition
codeine - 10-20 mg - ineffective as analgesic; also hydrocodone
dextromethorphan - isomer of codeine analog methorphan; no analgesic or addictive properties; 10-30 mg 3-6 times daily; OTC drug |
|
|
Term
| what is a main opioid adverse effect? |
|
Definition
|
|
Term
| what is the mechanism of resp depression with opioid use? |
|
Definition
opioid directly inhibit 5HT4a receptors in the rhythm-generating respiratory center neurons in the pre-boetzinger complex of the brain stem --> leading to decreased rate and tidal volume
resp center is less sensitive to CO2 but sensitivity to O2 is unaltered |
|
|
Term
| what can happen with oxygen admin to a patient with opioid induced resp depression? |
|
Definition
| apnea because sensitivity to oxygen is unaltered |
|
|
Term
| what increases the risk of resp depression in a patient taking opioids? |
|
Definition
| drug interactions with anesthetics, tranquilizers, alcohol, sedatives |
|
|
Term
| what can be done to avert opioid induced respiratory depression without loss of analgesia? |
|
Definition
| concurrent activation of 5-HT4a receptors |
|
|
Term
| opioid adverse effects (10) |
|
Definition
1. sedation
2. cough reflex depression
3. miosis
4. truncal rigidity
5. nausea and vomiting
6. euphoria
7. convulsion
8. endocrine changes
9. constipation
10. CV effects |
|
|
Term
| what effect do opioid have on sedation? |
|
Definition
| drowsiness; loss of concentration and recent memory |
|
|
Term
| what effect do opioid have on the cough reflex? |
|
Definition
| depress the cough center in the medulla |
|
|
Term
| how do opioid cause miosis? |
|
Definition
stimulation of Edinger-Westphal nucleus of oculomotor nerve - leads to pinpoint pupils
no tolerance develops to this effect |
|
|
Term
| what is the mechanism for truncal rigidity as an adverse effect to opioid use? |
|
Definition
increased tone in the large trunk muscles from an action at supraspinal levels
reduces thoracic compliance --> interferes with ventilation
most apparent when high doses of the highly lipid-soluble opioids are rapidly administered IV |
|
|
Term
| what is an acute effect of rapidly administering highly lipid-soluble opioids (fentanyl, sufentanil, alfentanil, remifentanil) at high doses IV? |
|
Definition
|
|
Term
| how does opioid use lead to nausea and vomiting? |
|
Definition
direct stimulation of chemoreceptor trigger zone
vestibular component may be involved because ambulation increases nausea |
|
|
Term
|
Definition
| decreased anxiety and pleasant floating sensation |
|
|
Term
| which receptors do not lead to euphoria with opioid use? |
|
Definition
|
|
Term
| what is the mechanism of convulsion due to opioid use? |
|
Definition
| due to inhibition of GABA release in interneurons |
|
|
Term
| what are the endocrine effects of opioid use? |
|
Definition
1. decrease in secretion of LH, FSH
2. increased prolactin, ADH
3. decreased libido, sperm motility, ejaculate volume
4. anovulatory cycles; amenorrhea |
|
|
Term
| effects of opioid use in the GI tract? |
|
Definition
constipation
historic use of opium poppy was for diarrhea |
|
|
Term
| what are the CV effects of opioid use? |
|
Definition
decrease preload, inotropy, and chronotropy --> reduces oxygen consumption of myocardium
morphine is used in angina pectoris and acute MI |
|
|
Term
| what opioid is used in angina pectoris and acute MI? |
|
Definition
|
|
Term
| effects of opioid antagonists? |
|
Definition
| few effects unless agonists have already been administered |
|
|
Term
| what type of drug is naloxone? |
|
Definition
|
|
Term
| what is the IV 'coma cocktail'? |
|
Definition
| naloxone + thiamine + 50% dextrose |
|
|
Term
| what is the use of the 'coma cocktail'? |
|
Definition
opioid antagonism
1 mg IV blocks 25 mg IV heroine |
|
|
Term
|
Definition
ONLY parenteral admin works
completely metabolized in liver; half life = 1 hour |
|
|
Term
| what are 2 opioid antagonists? |
|
Definition
| naloxone (coma cocktail) and naltrexone |
|
|
Term
|
Definition
| ORAL admin effective (unlike naloxone) |
|
|
Term
| what tonic substance is released into the serum by clotting platelets? |
|
Definition
|
|
Term
| what is the SM stimulant contained in enterochromaffin cells of intestinal mucosa? |
|
Definition
|
|
Term
| where is 90% of 5-HT located in the body? |
|
Definition
| enterochromaffin cells of the intestine |
|
|
Term
| what is platelets role in serotonin mechanisms in the body? |
|
Definition
| platelets actively transport and store serotonin |
|
|
Term
| serotonin containing cell localization (4) |
|
Definition
1. enterochromaffin cell of intestines
2. platelets
3. raphe magnus nuclei of brainstem
4. around BV |
|
|
Term
| serotonin in the raphe magnus nuclei in the brain stem is used in? |
|
Definition
| endogenous analgesic system |
|
|
Term
| which type of pain is mostly chronic pain? |
|
Definition
|
|
Term
| examples of neuropathic pain (5) |
|
Definition
1. polyneuropathy
2. post-herpetic neuralgia
3. trigeminal neuralgia (tic doloreaux)
4. glossopharyngeal neuralgia
5. myelitis |
|
|
Term
| what 2 classes of drugs can be used to treat neuropathic pain? |
|
Definition
1. tricyclic antidepressants
2. anticonvulsants |
|
|
Term
| how do tricyclic antidepressants work to treat neuropathic pain? |
|
Definition
| block serotonin re-uptake and facilitate the action of then endogenous opioid analgesic system |
|
|
Term
| examples of tricyclic antidepressants used to treat neuropathic pain? |
|
Definition
imipramine
amitriptyline
doxepin |
|
|
Term
| how do anti-convulsants work to treat neuropathic pain? |
|
Definition
| block Na channel and prevent neuronal firing |
|
|
Term
| examples of anti-convulsant drugs used to treat neuropathic pain? |
|
Definition
phenytoin
carbamazepine
gabapentin
levetiracetam |
|
|
Term
| what 3 classes of drugs are used to treat migraines? |
|
Definition
1. 5-HT 1D/1B agonists
2. ergot alkaloids
3. NSAIDs or NSAIDs + combined opioid |
|
|
Term
| how do the triptans work in treating migraines? |
|
Definition
| agonists for 5-HT 1D/1B receptors in serotonergic pathway |
|
|
Term
| sumatriptan (all -triptans) used to treat? |
|
Definition
|
|
