Opioids Analgesics and Antagonists Flashcards
Oxymorphone
very similar to morphine but 10 times more potent. it is also more expensive
Post surgical pain relief lasts two to six hours although some clinicians claim it has a slightly shorter duration of action than morphine
lesser tendency to induce vomiting
does not cause histamine release
less depressant effect on the respiratory center
What should be administered with Oxymorphone
an Anti Ach to avoid/prevent severe bradycardia
Meperidine mechainsm of action
mu opioid receptor in CNS and PNS of the bowels
meperidine clinical effects
analgesia - about 1/3 the potency of morphine
post-anesthetic shivering
adverse effects and side effects equivalent to morphine
CNS excitation - normeperidine
Meperidine absorption
50% excapes first pass effect after oral admin
BBB - crosses more readily than morphine
Meperidine congeners - Dipheoxylate
constipation - treatment of diarrhea
high doses - typical opioid effects
Meperidine congeners - Loperamide
Antidiarrheal - slows gastric motility, decreases GI secretion, poor BBB penetration
Fentanyl
75 to 200 times more potent than morphine
short duration of action (45-60 minutes)***
minimal CV effects except for bradyarrhythmias
respiratory center depression can be more severe than with morphine and apnea may occur
Alfentanyl
new synthetic compound with ultrashort half life
Sufentanyl
half life shorter than fentanyl but with fewer side effects
Fentanyl congeners - Sufentanil
profile like fentanyl, but 500 to 1000 times more potent than morphine
Fentanyl congeners - Alfentanil
~20-30 less than fentanyl
broken down by plasma esterases - 1/2 life is about 8-20 min
Fentanyl congeners - Remifentanil
equipotent with fentanyl
metabolized by the liver - 1/2 life is about 1 to 2 hrs
piperidines: therapeutics
alfentanil and remifentanil
short, painful procedures
-intense analgesia and suppressing stress response
Absorption of opiates
most opiates are rapidly absorbed in the GI tract
undergo a high rate of first pass metabolism
highly lipophilic opiates can be absorbed transdermally
distribution of opiates
all opiates bind to plasma proteins at varying affinities
will rapidly leave the blood to concentrate in other body tissues
metabolism of opiates
first pass effect
most opiates are converted to more polar metabolites via hepatic conjugation to glucuronides or N-demethylated
6-glucuronide is more potent and the 3-glucuronide is inactive and is the highest concentration metabolite found in the urine.
certain opiates like fentanyl are metabolized by cyto P450
excretion of opiates
occurs primarily through the kidneys
morphine metabolism
conjugation with glucuronide acid
morphine-6-glucuronide is the active metabolite which is 2x as potent as morphine
First pass effect is significant
about 2 hr half life
most is metabolized and excreted by kidneys
Acute morphine poisoning
triad: coma, miosis, cyanosis (affect respiration)
asphyxia, pupils dilate, biliary spasms, GI smooth muscle spasm, pulmonary edema, muscle twitches, peripheral vasodilation, hypotension results in shock
Respiratory failure results in death in 2-4 hours
Oralet
intrabuccal fentanyl
administered to kids and adults that are about to undergo a surgical procedure (raspberry flavored :9 )
Actiq
used or cancer patients for breakthrough pain (higher dose/ no raspberry flavor)
intrabuccal fentanyl
intrabuccal fentanyl
takes effect within 15-20 minutes and lasts ~1-2 hrs
For chronic malignant pain, use this patch
fentanyl
duration of action of 72 hours
LA morphine
provides sustained serum leves of active morphine
Q8-12 hrs (MS contin)
Q12-24 hrs (Kadian)
Q24 hr(avinza)
LA oxycodone (oxycontin)
Q8-12 hrs
Methadone
Q6-12 hrs
also has NMDA effect specific for neuropathic pain
Transdermal fentanyl patch
Q 48-72hrs
Oxycodone CR (oxycontin)
pure oxycodone inside a polymer/acrylic matrix that allows for controlled release
Abusers crush the tablet to destroy the matrix and disable the controlled release
what is oxycodone metabolized to
oxymorphone, then noroxymorphone and noroxycodone
Codeine
Used for moderate pain and as an antitussive***
at high doses causes CNS stimulation
max. analgesia = 12-15%that of morphine
what is codeine converted to?
about 10% of codeine (methylmorphine) to morphine
improvements in codeine over morphine
less respiratory depression, less dependence and less euphoria than morphine
higher oral efficiency and slower development of tolerance than morphine
Tramadol
codeine analog
weak mu agonist
racemic mixture - enantiomers have different acions
mild to moderate pain
68% bioavailability oral vs. parenteral
N&V, dizziness, sedation and headache
seizures
tramadol mechanism of action
Norepi reuptake blocker
5HT reuptake blocker
Tramadol metabolism
liver - O methylation, metabolite more potent
half life is six hrs
tramadol elimination
Renal
Hydrocodone
synthetic drug similar in structure to codeine
more potent than codeine comparable to morphine
available in combination with other drugs such as NSAIDs and acetaminophen
single highest prescribed drug in USA
highly abused
Pentazocine (Talwin)
1/3 as potent as morphine as analgesic
k agonist, and delta partial agonist
effective orally, shorter duration and faster onset of action than morphine
Buprenophine
potent, long acting phenanthrene derivation
m partial agonist
mu and delta antagonist
Naloxone hydrochloride
reverse the effects of opioids (including analgesia)
no agonist properties
does not produce respiratory or CV depression. it can be used to reverse the effects (respiratory depression) of any of the opioid agoinst/antagonist group
Nalmefene
opioid antagonists
Naloxone
antagonizes most opioid receptor agonists
high doses antagonize barbiturates
almost a pure antagonist
used to reverse coma and respiratory depression in opioid overdose (within 30 sec) but short duration of action
Naltrexone (Trexan-Dupont)
pure antagonist
orally effective
longer duration of action than naloxone
Methylnaltrexone (Relistor)
opioid induced constipation in pts with advanced illness having a inadequate response to traditional laxatives
Methylnaltrexone (Relistor) contraindications
mechanical bowel obstruction
stop drug if opioids are discontinued
may cause dizziness
concomitant use with SSRIs, Li, carbamazepine, or valproic acid may produce additive effects
Methylnaltrexone (Relistor) contraindicated in patients with …
severe renal failure (
morphine and naltrexone
extended release opioid with sequestered core of the antagonist, naltrexone, in single dosage form
when taken as directed, naltrexone remains sequestered
if capsule is tampered with by crushing, chewing or dissolving then naltrexone negates effects of the opioid
What has been found to help enhance the effects of opioids?
addition of low doses of opioid antagonists, like naltrexone or naloxone, in combination with opiates, do not inhibit the analgesia effect but enhance it
reduce withdrawal syndrome, reversed tolerance and restored potency of opiates
Buprenorphine pharma
ceiling effect on respiratory depression
less physical dependence capacity
blocks withdrawal in mildy dep ppl
BUT precipitates withdrawal in mod to severe dep ppl
Buprenorphine (suboxone, subutex)
20-50 times potency of morphine
schedule III drug
sublingual
Suboxone - bup an Naloxone (4:1)
Sufentanil
works on all three opioid receptors
Nalbuphine
only kappa receptor
Contraindications for mu opioid receptors agonists
impaired pulmonary function
asthma
hepatic or renal disease
hypotension
Phenothiazines (enhanced respiratory depression, sedation)
Antidepressants (enhanced analgesia)
MAO inhibitors (contraindicated with meperidine)
side effects/ toxicity of mu opioid receptor agonists
respiratory depression constipation N and V sedation euphoria peripheral vasodilation urinary retention spasm- sphincter of oddi prutitus physical dependance tolerance miosis
signs and symptoms of opium overdose
sedation confusion miosis respiratory rate hypoxia cyanosis
Treatment of opium overdose
immediate - resuscitation by maintaining airway, oxygen and naloxone and reversal with IV naloxone or another opioid antagonist
Naltrexone
reduces pleasure from opiates
doesnt seem to reduce cravings
best for motivated pts or pregnant pts
adverse effects of chronic opiate use
hypogonadism immunosuppression increased feeding increased growth hormone secretion withdrawal effects tolerance, dependence abuse, addiction hyperalgesia impairment while driving
Opioid withdrawal symptoms stage 1 up to 8 hours
anxiety and drug craving
opioid withdrawal symptoms stage 2 8-24 hours
anxiety, insomnia, GI disturbance, rhinorrhea, mydriasis, diaphoresis
opioids withdrawal symptoms up to 3 days
tachycardia, N&V, hypertension, diarrhea, fever, chills, tremors, seizure, muscle spasms
Treatments for opiate dependence
methadone
buprenorphine
naltrexone
Methadone
main action: full opioid agoinst on mu receptor
inhibit adenyl cyclase = decreases cAMP
increases K channel opening
decreases Ca channel opening
inhibits serotonin reuptake
non competitive antagonist of NMDA receptor
Steps when detoxing
wait until opiate withdrawal starts when give first dose (30-60min until effect)
maintanence with 16-24 mg qd
max: 32 mg qd
opioids and MAOIs
absolute contraindications to meperidine and relative contraindication to other opioids because of high incidence of hyperpyrexic coma
opioids and sedative-hypnotics
increased CNS depression, particularly respiratory depression
opioids and tricyclic anti-depressants
increased sedation
variable effects on respiratory depression
opioids and antipsychotic drugs
increased sedation
variable effects on respiratory depression
___________ is used in opiate detox because it has a less severe and shorter duration of withdrawal symptoms compared to ___________
Buprenorphine
methadone
symptoms last longest with __________ but are less severe than those of __________ withdrawal
methadone
heroin
