Opioids (Exam 2) Flashcards
T/F
anaphylaxis is possible from opioids
True
T/F
SEs can be beneficial.
True
depends on patient and situation. These effects could be good for some pts and bad for others
Respiratory depression d/t
decreased SNS outflow and direct effect in respiratory parts of the brain
effects on cerebral blood flow & ICP
Decreased CBF
increased ICP
occurrence of N/v
30-40% of pts esp on first dose
Effects on body temp
Hypothermia
T/F
tolerance cannot be built against opioid SEs
False
Constipation
direct effect of Mu receptors in GIT to decrease peristaltic activity
Histamine release MoA
innate allergy reaction to morphine causing histamine release
can be life threatening or minimal (pruritis)
Your pt states he got itchy when receiving morphine in the past. What should you do?
caution when giving an opioid
second exposure can enhance/worsen the allergic rxn on subsequent exposures
Muscular rigidity effects
due to inhibition of dopamine release in the striatum (Parkinson-like)
risk ventilation difficulty d/t laryngeal contraction & chest wall rigidity
Striatum
area in brain that controls motion
Parkinsons: decrease in dopamine in striatum
Bradycardia due to
increased vagal outflow
Orthostatic hypotension/syncope due to
decreased sympathetic outflow from the CNS
Are opioids absorbed well in the GIT?
most are
T/F
PO opioids are susceptible to first pass metab
True
undergo large first pass metab
Which type of agents reach higher CNS conc. faster?
more lipid soluble
T/F
most opioids distribute well in circulation
True
T/F
↑ lipid solubility agents are more likely to be abused
True
higher lipid solubility crosses into brain faster, which creates the euphoria
Which has greater euphoria?
heroin
morphine
heroin
more lipid soluble
Fetal effects
Most cross placenta well, but fetus can not metabolize much, so conc. is high.
T/F
all opioids are metabolized to some extent
True
Excretion mainly via
renal and biliary mechanisms of metabolized forms
Two chemical classes of Opium Alkaloids: (resin from poppy)
Phenanthrenes:
Morphine
Codeine
Thebain
Benzylisoquinolines:
Papaverine
Noscapine
Morphine structure
4 ring-system w/ an overring (“5” rings)
tertiary amine
pKa of >8.0 (bases), so mostly ionized at physiologic pH
very lipid soluble on its own bc of its rings despite OH group
T/F
The benzylisoquinolines family has a structural resemblance to morphine.
False
Phenanthrenes
1/10 of morphine’s potency
codeine
(Phenanthrenes)
(Phenanthrenes)
Thebain
paramorphine
CNS stimulant, can cause convulsions
“Thebain of my existence”
most Phenanthrenes have a pka of ___, so at body pH, what happens?
> 8.0 (base)
body pH is more acidic (more H+)
drug will pick up H’s
becomes ionized
Phenanthrenes
Which isomer is more active?
Levo
lack standard opioid activity
Benzylisoquinolines
(Benzylisoquinolines)
Papaverine
a smooth muscle relaxant
phosphodiesterase inhibitor (PEDI) = ↑ cAMP
“relax, papa”(verine)
(Benzylisoquinolines)
Noscapine
antitussive and anticancer(?)
Similar effect to codeine
“NOsCA= no cough/cancer”
possess similar effects to codeine
Noscapine
phosphodiesterase inhibitor (PDEI)
inhibit breakdown of cAMP
(cAMP usually metabolized by PDE)
With papaverine (PDEI):↑cAMP = smooth muscle relaxation (esp GIT)
Note: diff cells have diff rxn to cAMP
T/F
cAMP produces consistent effects regardless of cell type
False
cells differ in their response to cAMP and what type of PDE they contain
T/F
Papaverine is a highly specific PDEI
False
fairly non specific
Heroin is also known as
diacetylmorphine
acetylate morphine’s 2 OH (remove H) groups –> 2 new -COCH3
increases lipid solubility
enters CNS faster
dont memorize, but what are these?
opioid antagonists
naltrexone
MoA
Vs morphine
opioid antagonist
similar structure to morphine but binds stronger and does not have same agonist activity
Alkaloids (natural compounds) & semi-synthetics
Synthetics
Meperidine, the fentanyls, lomotil, imodium
base structure for synthetics
Space between 3, 6, 17 positions have same angles as morphine nucleus
fits in morphine receptors
First synthetic compound
Meperidine
“MEPeridine = ME Pirst”
compound in Lomotil
Diphenoxylate
(for GI spasms; drrha)
compound in Imodium
Loperamide
(for GI spasms; drrha)
T/F
Fentanyl is a potent morphine agonist.
True
Which synthetics do not fit the expected synthetic nucleus
dont memorize, just know its different
Methadone
addict recovery (heroin)
“Turn a heroin addict into a methadone addict”
-Ron Dick
Which of these is no longer on the market?
Propoxyphene
DC’ed due to efficacy; no more effective than the Tylenol it was mixed with
PO morphine
MS contin
We often mix this opioid with other because its weak
codeine
Levorphanol is an opioid (agonist/antagonist)
agonist
T/F
Dextro structures have pain relief properties.
True
require large amounts tho
addicts try to purchase tons of Dextromethorphan
Morphine
Natural alkaloid from
Papaver somniferum
Morphine MoA
primarily at m receptors
(some k)
Agent by which all other opioid agonists are judged
morphine
(activity set at “1”)
T/F
Morphine induces its own metabolism.
true
leads to its rapid tolerance development
Why does the use of Morphine rise and fall through the years?
Dont want to create addicts vs treating pts pain
T/F
Heroin is a naturally occurring opioid, known as an alkaloid.
False
semi-synthetic
To make heroin, we acetylate which positions on morphine?
hydroxyl groups on positions 3 & 6
Heroin is ___ as potent as morphine
twice
(and more lipid soluble)
T/F
Heroin in general is not approved for clinical use.
True
d/t high addiction liability
(Some states allow for intractable cancer pain; inpatient only)
What gives codeine its potency?
10% of it is converted to morphine
does not have any notable potency at the receptor!
T/F
Codeine does not have an analgesic effects.
False
Partially converted (10%) to morphine in the body, which is thought to account for the analgesic component
Codeine MoA
Potent antitussive in the parent form.
CTZ cough control center in the brainstem
Oxycodone (Oxycontin)
~2x potent > morphine (as an analgesic)
High euphoric liability
T/F
You can crush ER Oxycodone
False
Many deaths d/t chewing ER form.
turns it into rapid release (by breaking down “beads” meant to be slowly removed by GIT)
Fatal dose if no tolerance
Very potent synthetic morphine analgesic congener (5X)
Levorphanol
Levorphanol
pros and cons
longer lasting
Less constipating (d/t the way it binds to GIT Mu)
potency restricts use (5x morphine)
Dextromethorphan
dextro-rotary isomer (“no” analgesia)
effective antitussive
This isomer has “no” analgesia
dextro-rotary
Most widely used synthetic congener.
Meperidine
Meperidine potency
Only one-tenth the mg. potency of morphine as an analgesic
(this doesn’t mean its more potent than codeine)
T/F
Meperidine is more potent than codeine.
False
Frequently abused since it does not cause miosis
Meperidine
Hard to detect abuse
Which opioids’s metabolite can cause seizures?
Meperidine
Normeperidine: CNS stimulant ↓renal fxn = build-up → seizure risk
Normeperidine lacks which group?
methyl
“nor” = without methyl group
Contraindicated with MAOI therapy
meperidine
Your pt is on certain drugs that lower seizure threshold. What should you NOT give for pain?
Meperidine
metabolite Normeperidine can cause seizures, risk is higher w/ concomitant use of drugs that lower seizure threshold
monoamine oxidase inhibitors (MAOI)
Inhibit metabolism of Norepi
pt will have higher degree of CNS stimulation
DO NOT give with Meperidine
equipotent to morphine
Methadone (Dolophine)
Methadone (Dolophine)
same potency as morphine but less sedation
longer doA (slower elimination & can counter w/drawl symptoms
Heroin addict Tx
Methadone (Dolophine)
metabolizes Norepi
MAO monoamine oxidase
Recovery/withdrawl
MoA
tolerance leads to oversensitive/overactive systems
increased CNS output (sweating)
cramping, N/V, diarrhea
Methadone (Dolophine)
for addiction treatment
longer doA = dose less often
minimal sedation = addict can fxn
tightly controlled d/t difficult manufctrg
Structurally related to Methadone, but less than one-tenth as potent per mg.
Propoxyphene (Darvon)
T/F
Propoxyphene (Darvon)
lacks analgesic effects d/t its lack of similar properties to other opioId analgesics.
False
yes it sucks as pain relief
but
it has properties similar to other Opioid analgesics
Fentanyl (Sublimaze)
chemically r/t ___
meperidine
Fentanyl = piperidine = similar to meperidine
Fentanyl is __x as potent an analgesic as Morphine
80
T/F
Fentanyl’s main advantage is its higher potency compared to morphine.
False
Main advantage is it’s short half-life of redistribution (12.5 min.).
Fentanyl
half-life of redistribution
12.5 min
Fentanyl’s …. is partially responsible for its abuse potential.
short half-life of redistribution (12.5 mins)
fast recovery
Fentanyl distribution after administration
Very lipid soluble so redistribute brain to fat fast
Piperidines vs morphine
relative potencies
Sufentanil 800x
Fentanyl 80x
Remifentanil 80x
Alfentanil 20x
Fentanyl routes
IV, epidural, transdermal
Fent vs remifent
remi is selective m-receptor agonist. (vs fentanyl)
T/F
esterases are solely found in blood.
False
all over the place
liver
Differs from other fentanyl derivatives by having an ester-linkage
remifent
T/F
Remifentanil has a short duration of action due to hydrolysis by tissue esterases.
False
non-specific esterases
Remi vs. fent
benefits
Remi:
shorter duration
more exact titration
rapid recovery
even faster than fentanyl!
What makes remifent a good adjunct for induction and/or maintenance in pediatric patients?
Peds & neonates have esterases
vs liver enzymes which take time
Etorphine (Immobilon, M99)
Veterinary-use only
1000X morphine potency
large animal immobilizer
Toxic to humans, one drop on skin can be fatal
d/t ↑↑↑↑ L. sol
Dihydroetorphine (less L sol) used in China as a painkiller, it appears to be less addictive(??)
Opioid Antagonists
affinity
intrinsic activity
Have receptor affinity but “no” intrinsic activity.
Opioid Antagonists
MoA
mainly block m receptors
(some k blockade also).
affinity but lesser degree of intrinsic activity
partial agonist/antagonist
What effects do Opioid Antagonists counter?
analgesic
respiratory
euphoric
miosis
hypotension
smooth muscle fx
…of opioids AND endogenous b-endorphin and enkephalins
T/F
Opioid Antagonists are unable to counter effects from endogenous opioids.
False
Opioid Antagonists elicit (excitatory/inhibitory) effects.
excitatory
could cause seizure in someone who is seizure prone and not in opioid OD
Naloxone
pure antagonist (mostly m)
usually IV
Complete reversal
Nalaxone vs Naltrexone
Naltrexone:
similar, but longer half-life
can be given orally
mainly for alcoholics (↓ ethanol intoxication pleasure)
not true 100% antagonist
Naltrexone (Revia)
similar to naloxone, but longer half-life
can be given orally
mainly for alcoholics (↓ ethanol intoxication pleasure)
not true 100% antagonist
Use is to control N&V from opioid agonists
Methylnaltrexone (Relistor)
Methylnaltrexone (Relistor
quat = ionized
**peripheral opioid antagonism
No CNS withdrawal effects**
Use is to control N&V from opioid agonists
treat alcoholics by decreasing ethanol intoxication pleasure
Naltrexone (Revia)
Almivopan (Entereg)
oral
m selective peripheral antagonist
approved for post-op ileus
Nalmefene (Opvee)
analog of naltrexone
nasal spray opioid antagonist
rescue agent for opioid OD
↓ ETOH pleasure
µ and δ antagonist
κ receptor partial agonist
Nalmefene (Opvee)
MoA
µ and δ antagonist
κ receptor partial agonist
Opioid OD rescue
decrease ETOH pleasure
Buprenorphine (Buprenex) shares structural components of …
Codeine and Naltrexone
Buprenorphine (Buprenex)
partial agonist/antagonist
High affinity: mu
weaker max response than other agonists
T/F
As a partial agonist/antagonist, Buprenorphine (Buprenex) elicits a weaker maximal response than other agonists and thus cannot relieve pain.
False
still has good analgesia, just not as much
T/F
Buprenorphine elicits a weaker maximal response than other agonists, so addicts take more of it to get the same effect as stronger substances”
FALSE
Partial agonist will never give full effect
Can we use Buprenorphine (Buprenex) to counteract addiction?
yes
less abuse potential
counteracts Heroin & Morphine addiction w/o causing full-blown withdrawal symptoms
limits ability of Naloxone to reverse
Buprenorphine (Buprenex)
Slow dissociation from receptors increases duration (8 hrs)
Naloxone has to “wait” for free receptors
T/F
Buprenorphine (Buprenex) can precipitate a withdrawal reaction.
True
Can displace other mu agonists (antagonistic action)
prevent agonist from beinding = w/drawl
Buprenorphine (Buprenex)
uses
Heroin & Morphine addictn
moderates severe pain
epidural
Mixed Opioid Agonist/Antagonists
Nalorphine (Nalline)
Pentazocine
Nalbuphine
Nalorphine (Nalline)
Veterinary use only
mu antagonist
K weak agonist
blocks m receptor analgesia & euphoria
stimulates k analgesia & sedation
Large doses: ~dysphoria & hallucinations
Pentazocine used with ___ to limit abuse
Naloxone
have similar actions, but are stronger k mediated analgesics than nalorphine
Pentazocine
Nalbuphine
Tramadol (Ultram)
structural similarities to Opioids and NSAIDs
Racemic: diff enantiomers cause each action
Less addiction liability
Tramadol (Ultram)
MoA
parent compound & active metabolite have:
moderate mu affinity
weak k & d affinity
block re-uptake of serotonin & norepi in central synapses
↓
decreases pain info transmission in brain
its analgesic effect is not entirely reversed by Naloxone
Tramadol
parent compound & active metabolite have:
moderate mu affinity
weak k & d affinity
naloxone = primarily mu
Tramadol SEs
dizziness, sedation, seizures and hallucinations
N/V common = limited periop use
increased risk of bleeding if taken with Warfarin
epileptogenic effects
T/F
Like other opioids, tramadol is a controlled substance d/t its potency.
False
d/t abuse potential
Naloxone acts primarily at __ receptors.
mu
Tramadol’s analgesic strength is comparable to which agent?
Codeine-Acetaminophen agents
limited periop use d/t N/V
tramadol
body synthesizes __% of norepi; __% is reused
make 20%
reuse 80%
Blocking reuptake
blocks carrier that brings it back in
compound builds up & stimulates post-synaptic neuron
initial increased stimulation
eventual depletion (b/c we only synthesize 20%)
serotonin is also known as
5HT
5-hydroxytryptamine
*Note: 5HT3 is a type of serotonin receptor)
increased risk of bleeding if taken with Warfarin
tramadol
possibly d/t NSAID component
causes abuse potential
euphoria and sedative effects
T/F
Tachyphylaxis develops as higher and higher doses are required to achieve the same euphoria
False
Rapid tolerance develops
T/F
Many “addicts” only continue to take the opioids to avoid the uncomfortable withdrawal symptoms.
True
T/F
More prescription abuse than illicit substances.
True
single largest cause of prescription deaths in US, 2011 -2012.
Opana (oxymorphone) ER
Rapid Detox
Anesthesia + Potent Opioid Antagonist for 6-8 H
Unconscious during w/drawl SEs
T/F
Opioids can be used alone or as an adjuvant to anesthesia.
True
neuroleptic anesthesia
butyrophenone (droperidol:
D2 blocker; antiemetic properties)
+
opioid (fentanyl)
+
nitrous oxide, etc.
peptide-type opioid receptor agonists
pain relief
target receptor sub-types
cant give PO (denatured in stomach)
Transplantation of adrenal medullary chromaffin cells
chromaffin cells (secrete opioid peptides) into subarachnoid space
long-term pain relief to chronic sufferers w/o exogenous opioid SE’s.
C cells survive for a certain time
No major SE bc endogenous
