Opioids II Flashcards
List the clinical uses of opioids
- analgesia
- acute pulmonary edema
- relief of cough
- diarrhea
- anesthesia
drug interaction: opioid + sedative hypnotics
- increased CNS and respiratory depression
drug interaction: opioid + MAO inhibitors
- high incidence of hyperpyrexic coma
- meperidine and dextromethorphan are the worst
drug interaction: codeine, oxycodone, and hydrocodone + CYP2D6 inhibitors
inhibit metabolism of these compounds to thier active state
- Fluoxetine is the worst for inhibition
contraindications to using opioids
-
use of partial agonist with full agonist
- can impair analgesia and cause withdrawal
- head injuries
-
pregnancy: especially at delivery
- cross placenta barrier -> respiratory depression or drug dependence of fetus
- impaired pulmonary function
- impaired hepatic or renal function
MOA of Morphine
- stimulates all opioid receptors: prototype
- strong agonist : useful in severe pain
why is morphine more effective when injected than taken oraly
- high first pass metabolism
where is morphine metabolized
- liver by CYP2D6
Why should morphine not be given to patients with renal dysfunction
- a major metabolite of morphine can cause adverse effects if it accumulates
Why is Hydromorphone better to use than morphine in patients with renal dysfunction
its metabolites don’t accumulate
Why is methadone traditionally used for maintenance treatment for addicts
- long lasting, more slowly absorbed
- low doses used to prevent withdrawal
MOA of methadone
- stimulates mu receptors
- block NMDA receptors
- now commonly used in long term control of pain
MOA of Meperidine
-
Mu agonist
- causes euphoria
- inhibits NE/5-HT reuptake -> serotonin syndrome with MAOIs
- blocks muscarinic receptors
adverse effects of Meperidine
- should not be used for more than 48 hours, in high doses, or in renal failure due to accumulation of metabolite normeperidine
- normeperidine -> seizures
- tachycardia
- pupil dilation
- no cough suppression
MOA of Fentanyl
- lipid soluble
- Very potent
adverse effects of Fentanyl
- high abuse potential
- truncal rigitidy -> if given rapidly IV
- metabolized by CYP3A4
oxycodone + acetaminophen =
percoset
oxycodone is metabolized by
- CYP2D6
- needed to be completely effective
MOA of Oxymorphone
- active metabolite of oxycodone, used for moderate to severe pain
- does not need to be metabolized by CYP2D6
hydrocodone + acetaminophen =
vicodin
hydrocodone requires metabolism by what enzyme for full effect
CYP2D6
codeine must be metabolized by what to be active
- CYP2D6
- codeine -> morphine
codeine is used mainly for
- cough suppressant
- doses lower than for analgesia
- shouldn’t be used in small children
MOA of Pentazocine
- kappa receptor agonist
- Mu receptor partial agonist
what is Pentazocine used for
- moderate pain
- may be less sedating than other opioids
- Low abuse potential, may be good for addicts
adverse effects of Pentazocine
- dysphoria (kappa)
- may cause withdrawal in patients dependent on opioids
MOA of Buprenorphine
-
partial agonist on mu and maybe on kappa
- ceiling to effect-doesn’t cause much euphoria
- low abuse potential
what is Buprenorphine used for
- maintenance treatment of opioid addiction - decreases craving for drug
why is Buprenorphine commonly combined with Naloxone
- tablets are formulated together with naloxone (Suboxone), which is not absorbed sublingually; prevents dissolving the tablets in water and injecting the solution IV
MOA of Tramadol
- Weak Mu agonist -> mild to moderate pain
- inhibits NE/5-HT reuptake -> contributes to analgesic effect
tramadol + antidepressants lead to
seizures
tramadol + MAOIs, TCAs, SSRIs may cause
serotonin syndrome
MOA of Dextramethorphan
- blocks NMDA receptors
- decreases 5-HT reuptake
- cough suppressant
- not an analgesic
Dextramethorphan + MAOIs will cause
serotonin syndrome
DOC for opioid overdose
- Naloxone (Narcan)
- must be injected -> give until pupils dilate
- short duration of action (2 hrs)
use of Naltrexone
- oral and long acting
- used in tx of opioid addicts
- if addict takes opioids, won’t have any effect
- decreases craving in recovering alcoholics
Route of admin Naltrexone
PO
