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140 Cards in this Set
- Front
- Back
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opioid high efficacy agonists
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morphine
merperidine heroin fentanyl |
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opioid low-med efficacy agonists
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codeine
oxycodone propoxyphene |
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opioid mixed agonist/antagonists
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pentazocine
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opioid antagonist
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naloxene
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non-analgesic opioids
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dextromethorpan
loperimide |
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what is a narcotic?
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sleep inducing
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what is an opiate?
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compound with pharmacology similar to morphine (opiates, synthetic drugs, ligands)
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what is an analgesic?
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pain reliever
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opiod affects aside from analgesia?
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N/V, cough suppression, urinary retention, antidiarrheal/constip, resp. depression, miosis, CNS dep, altered endocrine, altered immune, biliary spasm, histamine release, mood effects, dependence
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endogenous opioid characteristics
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- mimic endogenous peptides in brain and periphery
- multiple functions - bind to opioid receptors - three families (POMC/beta-endorphin, enkephalins, dynoprhins) |
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three families of endogenous opioids?
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- POMC/beta-endorphin
- enkephalins - dynorphins |
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-gene product of POMC?
-hormones synthesized from POMC? -where is it? - receptors? |
gene product = POMC
hormones = ACTH, b-lipotropin, MSH where = hormonal(pituitary), brain receptors = mu, kappa, delta |
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-gene product of pro-enk?
-charac? -where is it? - receptors? |
gene product = pro-enk
charac = multiple opioid active peptides, small size (5-8aa) where = brain rec = delta, mu agonist |
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-gene product of pro-dynoprhin?
-charac? -where is it? - receptors? |
gene product = pro-dynorphin
charac = multiple opiod peptides, small-med where = brain receps = kappa, delta, mu |
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opioid receptors
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mu
kappa delta |
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non opioid receptors
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sigma
DM |
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effects of Mu receptor
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- major receptor
- classic effects analgesia resp. depression euphoria dependence |
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effects of kappa receptor
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few drugs are kappa agonist
analgesia (spinal) sedation endocrine dysphoria psychomimetic |
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effects of delta receptor
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unclear clinical significance
- analgesia |
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effects of sigma receptor
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agitation
hallucination dysphoria |
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what are the major cellular effects of opioids?
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inhibitory
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activation of opioid receptor will?
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inhibit cAMP production - decreased phosphorylation
inhibit Ca channels- on prejunctional neurons (inhibit NT release) activate K channels - increase K conduction --> hyperpolarize postjunctional cells |
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response of neuron to opioid activation?
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decreased spontaneous firing
decreased evoked firing inhibited transmitter (NT) release |
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example of cellular effects of opioids?
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inhibition of pain message from periphery (image in notes) - via inhibitory, enkephalin interneuron
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sites of opioid analgesia?
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spinal = dorsal horn
supraspinal = central gray thalamus limbic system sensory cortex |
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general effects of opioid analgesia?
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increased pain threshold
increased pain tolerance selective for analgesia (little effect on other senses) |
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types of pain treated with opioids
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good =
slow, dull pain (C fiber) not fast, sharp (A/delta) nociceptive pain not neuropathic pain |
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primary afferent pain fibers
Aalpha/Abeta |
Aalpha/Abeta
myelinated large propioception, light touch |
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primary afferent pain fibers
Adelta fibers |
lightly myelinated
medium diameter nociception (thermal, mechanical, chemical) |
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primary afferent pain fibers
C fibers |
unmyelinated
small diameter innocuous temperature, itch nociception |
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what phase of pain are opioids better for?
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2nd pain
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where do opioids produce analgesic effects?
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sites of synaptic transmission along pain pathway
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are opioid receptors stereoselective? if so, how?
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yes.
active isomers = d no - opioid effects (no analgesia, no resp dep or euphoria) yes - antitussive effects active isomers = l (natural) yes - opiod effects yes - antitussive effects |
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what are the anti-diarrheal (constipating) effects of opioids?
what are the results? where? tolerance? |
organ effects =
dec propulsive movements (inc tone,peristalsis) dec secretions result= delayed gastric emptying inc transit time inc water abs. where? peripheral/CNS tol? little tol. |
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what is the significance of the opioid caused delay in gastric emptying?
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transit of the drug is shut down...less drug appears in blood
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main therapeutic effects of opioids?
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analgesia
antitussive antidiarrheal - constipation mood enhancement - abuse |
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common adverse effects of opioids?
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constipation
N/V sedation miosis tolerance itch |
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less common adverse effects of opioids?
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resp. depression
dysphoria uriniary retention postural hypotension truncal rigidity dependence |
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what is the most dangerous adverse effect?
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resp depression
- ***dec response of medullary resp. center to pCO2 - dec in rate, depth, irregular rhythm, pCO2 incs. - monitor = parenteral ex) COPD (not in normal use patients) - additive to depressive/sedative hypnotics - cause of death = opiod overdose |
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triad of opioid overdose
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coma
resp dep pinpoint pupils |
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sedation caused by opioids
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additive with other drugs
interferes with sleep patterns, REM |
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N/V caused by opioids
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20-40% patients
CTZ and vestibular components |
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miosis caused by opioids
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no tolerance
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urinary retention and opioids
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inc. urgency and diff. voiding
autonomic effects inc. ADH |
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cardiovascular effects of opioids
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no direct heart effects
histamine release beneficial in pulm. edema postural hypo. avoid with shock |
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opioid induced biliary tract spasm
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but..used to tx biliary colic
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truncal rigidity and opioids
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prob = fentanyls
more resp. depression |
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neuroendocrine effects of opioids
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inc - GH, ADH, prolactin
dec - FSH, LH, CRF, ACTH |
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inc. intracranial pressure and opioids
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secondary to inc. pCO2
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labor and delivery and opioids
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dec uterine tone
neonatal intoxication |
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altered immune function?
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secondary to altered stress hormones
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opioid cautions/CIs
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head injuries (inc. intrac. press)
pregnancy imp. pulm fxn (COPD) imp. renal fxn (exc) addisions, hypothyr. (bc of dec. CRH, ACTH) substance abuse hx MAOIs - dangerous drug intxns. |
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discuss the significance of opioids and first pass elim.
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oral dose = must be higher than parenteral (though same effect results)
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routes of admin of opioids?
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oral
buccal sublingual transdermal nasal suppository parenteral (IM, SC, IV) intrathecal (labor) |
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duration of opioids?
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most = 3-4 hrs
meperidine - less methadone - more |
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which opioids have increased duration with slow release oral preps?
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morphine
oxycodone oxymorphone |
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what is another preparation method to increase opioid action?
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transdermal prep.
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what enhances opioid abuse potential?
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fast CNS penetration!
heroin vs. morphine |
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how are opioids metabolized and excreted?
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- liver oxidation/glucuronidation
RAPID! - renal excretion - morphine- 6- glucuronide active at receptor (but doesnt penetrate BBB) |
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does morphine -6- glucuronide opioid cross the BBB?
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no!
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do opioids exhibit tolerance?
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yes! likely with repeated use
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when does a pt. experience tolerance?
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not clinically significant at first...become extreme when doses are pushed and administration is repeated
- a larger dose will be needed to result in the same effect |
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discuss opioid tolerance and safety.
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tolerance does not affect safety
- TI is unchanged |
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which effects exhibit tolerance to opioid actions?
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all but constipation and mioisis
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is there cross tolerance?
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tolerance can be conferred from one agonist to another
- when substituting a new drug, start with .5 of the equi-analgesic dose and build back up as needed for successful analgesia |
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how can the same effect of an opioid maintain itself over time?
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dose must be increased due to tolerance development
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what are the two kinds of opioid dependence? what kind of use causes this?
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physical - chronic
psychological - addictive |
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describe physical dependence.
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abstinence syndrome - drug removal
- some likely to occur, readily managed - intensity and time course = function of dose, kinetcis of drug - cross dependence is seen with other drugs |
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describe psychological dependence.
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- addiction
- altered behavior (drug seeking) - rare occurrence with normal clinical use |
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do physical and psychological dependence always occur together?
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no! they are different
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what is used to measure the intensity of opioid withdrawl?
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sum of withdrawl symptoms!
resp rate bp temp sleep caloric intake weight sum = intensity of abstinence syndrome |
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what drug characteristic is used to measure intensity and duration of withdrawl symptoms?
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kinetics!
ex) morphine (fast onset) vs. methodone (slow onset) |
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significance of the oral:parenteral ratio?
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decreased ratio = decreased first pass effect.
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what are the classes of opioid drugs?
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high efficacy analgesics
low-medium efficacy oral analgesics mixed ag-antagonists (misc) antags. non-analgesic opioids |
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what are the first line high efficacy opioid analgesics?
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morphine
methadone fentanyl |
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what are the second line high efficacy opioid analgesics?
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merperidine
heroin |
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what is the prototype high efficacy opioid analgesic? how is it administered?
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morphine - slow release, oral
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what drug is more potent and soluble than morphine?
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hydromorphone
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which drug is short acting and often used in anesthesia?
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fentanyl
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what routes of admin. apply to fentanyl?
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parenteral
transdermal oral lozenge buccal tablet |
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when is methadone used? why?
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heroin tx
- good oral:parenteral ratio - long acting |
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what is unique about oxymorphone?
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new extended release preps.
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which high efficacy opioid analgesic drug is a pro-drug?
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heroin = converted to morphine
- not legal |
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which drug is often compared to morphine?
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meperidine
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which effects of meperidine are considered similar to morphine?
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analgesia
resp. dep dependence likelihood |
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are the following effects of meperidine greater or lesser than morphine?
- N/V - dizziness - toxicity |
greater than morphine!
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are the following effects of merperidine greater or lesser than morphine?
- constip/urin. ret. - delay of labor - biliary spasm - cough supp - miosis - duration |
less than morphine!
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what is normeperidine?
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toxic metabolite of meperidine
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what does normeperdine cause?
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CNS stim and convulsions
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under what conditions does normeperdine accumulate?
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- chronic dosing
- esp : oral dosing impaired kidney fxn. |
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when is normeperidine used?
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short term!!! less than 48 hrs.
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what does normeperidine interact with? is it fatal?
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MAOIs...YES!
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what are the first line low-med efficacy opioid analgesics? what is there route of admin?
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codeine
oxycodone proproxyphene oral! |
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what are the first line low-med efficacy drugs?
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codeine
oxycodone propoxyphene |
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what is the most efficacious low-med eff. opioid? how is it admin?
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oxycodone
- often classified as high eff. - slow release prep. (often abused) |
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which drug is low efficacy, req. metabolic activation (deficient in 10% of pts), and a good antitussive at lower doses than analgesia?
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codeine
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describe propoxyphene.
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- low efficacy
- high toxicity |
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which low-med opioid is very toxic and often avoided?
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propoxyphene
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how are low-med efficacy opioids analgs. admin?
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oral!
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what is often given in combo with low-med effic. opioid analgs?
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ASA
APAP NSAIDS |
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describe the receptor activity of pentazocine. what category?
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kappa = agonist
mu = antagonist, partial agonist (mixed ag/antag) |
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what are the benefits of mixed ag/antags?
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lower dependence
overdoes toxicity is uncommon! |
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what are the drawbacks of mixed ag/antags?
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dose rel. psychomimetic effects
other adv.effects ceiling on analgesia ppt withdrawl in pts on full agonists |
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describe opioid antagonists.
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competitive at all opioid receptors.
not competitive at non-opioid rec (DM) |
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what is naloxene? how is it administered? describe its effect pattern?
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opioid antagonist! parenteral only. rapid action, slow duration.
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what are the categories of non-analgesic opioids?
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antitussives
antidiarrheals |
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what is dextromethorpan? where does it act?
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antitussive
acts at = DM R. doesnt act at = opioid R. |
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which non-analgesic opioid has little BBB penetration?
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loperamide (active in immodium)
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what are the main assessments in pain tx?
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1) assess type of pain
2) assess intensity of pain |
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what are the diff. types of pain?
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acute vs. chronic
nociceptive vs. neuropathic |
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is pain subjective or objective?
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subjective..it must be evaluated. continual re-eval assesses reponse to drug and disease progress
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are drug efficacies important is pain assessment?
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yes. diff drug efficacies det. pain intensities.
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what is the three step approach to pain tx?
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mild pain
moderate pain severe pain |
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how to tx mild? mod? severe?
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mild = nonopioid analgs.(ASA, NSAIDS, APAP)
mod = oral opioids (mild tx + oral op of low-med effic) sev = high effic opioids par/oral, alone or with adjuncts |
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what term describes the fact that high efficacy opioids differ in potency, but the same relief is attainable via dose adjustment?
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equi- analgesia
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what are two other principles of pain tx?
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equi-analgesia
use approp. route! |
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which route of admin is preferred in pain tx?
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oral. though, dose must be inc. to attain effect of parenteral potency
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is there a wide variety of admin. routes available for opioids?
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yes. even for some specialty situations.
- parenteral NSAID = ketorlac. |
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describe the relationship between drug duration and pain duration.
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match them!
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how long is opioid duration generally?
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3-4 hrs
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name some uses for opioid pain relief
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brief surgical procedures
fractures post-op pain recurrent severe pain (sickle cell) terminal cancer |
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which opioid has longer duration?
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methadone
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describe the duration of fentanyls.
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short action.
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why are patch and slow release. oral preps of fentanyl available?
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they are longer acting formulations of the drug
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how is breakthrough pain treated?
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combine long and short acting opioids.
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what causes the cycle of pain?
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prn administration
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what type of dosing is appropriate for opioids?
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regular dosing schedule (not prn)
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what kind of pumps are an option?
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PCA pumps (pt. controlled analgesia)
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does oral administration result in higher or lower concentrations than parenteral? does it peak earlier or later?
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oral peaks lower and later than parenteral.
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is easier to maintain pain free or to remove existing pain?
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pain free.
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describe the 4 characteristics of opioid tolerance.
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- may not see it with normal use, but it can occur when pushing dose.
- cross tolerance occurs when switching meds - saftety margin doesnt change with tolerance - no tolerance to constipation (it will occur) |
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what side effect will occur with tolerance?
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constipation
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should opioids be witheld due to a fear of addiction?
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no.
- iatrogenic addiction is rare - opioid dep. pts. require pain relief - addiction is irrelevant with terminally ill pts. |
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what types of pain are difficult to tx? why?
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diabetic neuropathy
postherpetic neuralgia fibromyalgia phantom limb why? bc not inflamm. or tissue damage - path is in sensory nerve or CNS processing |
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what drugs are successful with diff. pain tx?
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antidepressants
anticonvulsants |
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what is ziconitide?
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n-type Ca channel blocker used to tx neuropathic pain
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how is ziconitide administered?
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intrathecal ($$$)
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what kind of side effects does ziconitide have?
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severe
- CNS dep. - psychiatric |
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describe antidepressants and neuropathic pain tx.
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most common - tricyclics
= SSRIs are less efficacious = newer drugs are better - SNRIS - duloxetine (FDA approved for diabetic neuropathy) |
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describe anticonvulsants and neuropathic pain tx.
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- widely used off label
- phenytoin, sodium valproate, clonazepam, lamotrigine, topiramate = FDA App - carbamezipine = diabetic - gabapentin = postherpetic - pregabalin = both |
