opioids in the clinic (Barker) Flashcards
administration routes and PK
- ___ - rapid rise, greater risk for side effects
- ___ / ___ - fast rise and fall
- ___ - stays within therapeutic window without crossing CNS SE line
t1/2 will dictate how they are used clinically
IV
SC/IM
PO
metabolism
- readily absorbed
- ___ pass metabolism (morphine bioavailability 25%)
hepatic
- CYP ___ and ___
- genetic differences
- elimination t1/2 ___ with liver disease
glucuronidation at 3’ and 6’ position
- morphine-6-glucuronide (MG6) - still potent
excretion
- glomerular filtration
- 90% excreted in 24 hrs
- first
- 2D6, 3A4
- increased
some opioid metabolites are still active
prodrugs: (3)
fentanyl and methadone do NOT produce active metabolites
onset/duration influenced b lipophilicity
- morphine: ___ lipophiicity, slower passage accross BB, prolonged duration of action
- fentanyl: ___ lipophilicity, rapid onset, short duration
heroin , tramadol, codeine
- low
- high
CYP2D6 ___ codeine to morphine
CYP3A4 (four) makes opioids staring with ___
- inactivates
- activates
- Nor
CYPD6 - genes impact opioid management
UM = ___ concentration of morphine than EM when given codeine
- high relevance world wide
- 40% in North Africa
PM = no therapeutic effect from codeine; not activated
- 10% of caucasians
higher
fentanyl is a very potent opioid
- synthetic
- significant respiratory depression
- 100x more potent than ___
- 50x more potent than ___
- used in palliative care for breakthrough pain
- morphine
- heroin
many opioid are used surrounding a hospital procedure
sufentanil, femifentanil, alfentanil
- anesthesia/sedation
- breakdown by plasma ___ due to ester linkage
Fentanyl (i.v. , patch, lollipop)
hydromorphone (Dilaudid, oxymorphone (Opana)
- no opioid-active metabolites
- IV oral liquid - ___
morphine (IV, PO - ___ )
- covered by medicare, preferred over oxycontin
- ER (MScontin) - long acting, lower ‘rush,’ ___ contribution to pain relief, risk for abuse if IV injected at once
Hydrocodone
- Zohydro (ER), Lortab/Vicodin/Norco (contains ___ )
oxycodone
- (Oxycontin, Percocet = contains ___ )
- esterases
- PCA
- PCA
- M6G
- acetaminophen
- acetaminophen
Non-phenanthrene opioids are a special subclass of opioids
___ (Ultram), tapentadol (Nucynta)
- mild opiate analgesia
- has ___ properties (5HT/NE reuptake inhibitor, stimulate 5HT release)
- management of ___ pain
- schedule ___
___ (Demerol)
- used to treat rigors ( ___)
- has toxic metabolite, normeperidine (CYP ___ )
- metabolite devoid of anagesic activity
- neurotoxic = nervousness, tremors, muscle twitches, and seizures
- renally excreted; not reccommended without good justification, dangerous in patients with decreased ___ function (accumulation)
tramadol
- SNRI
- neuropathic
- IV
meperidine
- shivering
- 3A4
- renal
certain opioids can block NDMA receptors
why would antagonism at NDMA receptors be useful?
methadone (non-phenanthrene)
- primarily used fo opioid ___
- ___ duration of action, t1/2 (15-60 hrs), fat solubility
- prolonged ___
- NMDA ___
- ___ pain
- dependence
- long
- QTc
- antagonist
- chronic
clinically used opioids (non-analgesic)
cough/antitussive
- usually codeine (schedule __ , but schedule __ in certain formulation)
- dextromethorphan: enantiomer of ___ (opioid). ___ opioid activity, at high doses acts as an ___ and ___ antagonists
- II, V
- levomethophan, limited, SSRI, NMDA
clinically used opioids (non-analgesic)
anti-diarrheal
- diphenoxylate with atropine ( ___ )
- ____ (Imodium) - strong Pgp substrate
- eluxadoline ( ___ ) irritable bowel syndrome with diarrhea, mu/kappa ___ , delta ___
- enteric nervous system localization
- schedule IV
- lomotil
- loperamide
- Viberzi
- agonist, antagonist
some opioids ct at Mu and Kappa and are used for moderate pain
pentazocin (Talwin) and butophanol (Stadol)
- ___ agonist, partial agonists/antagonism at ___
- SE: less ___ , hallucinations, increase in BP and HR
nalbuphine (Nubain)
- full agonist at ___ , antagonist at ___
- antagonism produces ___ (to those who have an addition to mu agonists)
buprenorphine (Buprenex)
- partial ___ agonist, weak ___ agonist, ___ antagonist
- primarily use in opioid ___ therapy
- kappa, mu
- dysphoria
- kappa, mu
- withdrawal
- mu, kappa, delta
- replacement
therapeutic tolerance and SE tolerance
opioid tolerance
- ___ effects
- nausea
- urinary retention
- ___ depression - biggest risk of death in withdrawn patients/users
- euphoria
opioid induced hyperalgesia
- upregulated ___ pain pathway
- linked to changes in glutamte signaling
limited/no tolerance
- ___
- itch
- miosis
- analgesic
- respiratory
- secondary
- constipation
management of ileus and constipation
senna - irritates colon - causes fluid secretion and colonic ___
polyethylene glycol (Miralax) - stool softener - osmotic increase in GI ___ content
docusate - stool softener, peristalsis > 400 mg/day
- contraction
- water
methadone
- full ___ receptor agonist
- provide relief from ___
- ___ potency than morphine
- ___ acting (2-4 hours)
slow PK - ___ with repeated doses
- elimination t1/2 (8-50hrs)
racemic mixture
- + = ___ antagonist
- structurally different than morphine
- mu
- withdrawal
- slow
- accumulation
- NMDA
buprenorphine
___ opioid receptor partial agonist
- ceiling effect
- blocks full agonist effect (heroin, oxycodone)
- antagonist - use 4 hrs after last heroin use
- agonist - provides some activation, less withdrawal
Subutex
- abuse potential
Suboxone (4:1 bup:Nx)
- partially blocked agonist effects when taken IV
Mu
Naltrexone
naltrexone (Vivitrol), the ___
- IM, ER = once monthly
- PO = Revia, daily dose
- decent oral bioavailability
- medium t1/2 (4 hours)
- will cause ___
- works better if patient has been drug free for 1 ___ or more
- antagonist
- withdrawal
- month
naloxone and naltrexone are not interchangeable
naloxone
- IV or intranasal
- limited oral bioavailability
- ___ onset (1-2 min)
- short t1/2 (30-90 min)
- viewed more as the ___ to overdose
- repeat every 2-5 min if not conscious, 1 shot not enough
naltrexone
- decent oral bioavailability
- PO adminitered
- medium t1/2 (4 hrs) - “longer word than naloxone”
- blocks the high, course of treatment to reduce withdrawal
- rapid
- antidote
neonatal abstinence syndrome - drug dependent
- symptoms: tremors, yawning, poor feeding, sweating
- onset of symtoms may begin 24-48 hours after birth or as late as 5-10 days
- some symptoms can last 4-6 months
- ___ may also occur in babies born to methadone users
- opioids can be present in breast milk
seizures
neonatal abstinence syndrome - drug dependent
Non-PCOL
- swaddling, feedings, rehydration
PCOL
- ___ and ___ linked with shorter hospital stays than methadone
- oral morphine sulfate diluted to 0.4 mg/mL
- sublingual buprenorphine
- methadone 0.05-0.1 mg/kg/dose every 6 hours
- ___ may also be useful - reduces withdrawal
- buprenorphine, morphine
- clonidine
summary for opioid receptors - Mu
effects of activation
- analgesia, ___ and mood effects, ___ depression, miosis, neuroendocrine regulation, decreased GI ___ , autonomic regulation, tolerance and withdrawal
endogenous peptide affinity
___ > enkephalins > dynorphins
- euphoria, respiratory, motility
- endorphins
summary for opioid receptors - kappa
effects of activation
- analgesia, diuresis, sedation, ___ and psychotomimetic, less miosis, less respiratory depression, little dependence
endogenous peptide affinity
___»_space; endorphins and enkephalins
- dysphoria
- dynorphins
summary for opioid receptors -dellta
effects of activation
- analgesia, mood, reduced ___ , ischemic protection, little dependence
endogenous peptide affinity
___ > endorphins and dynorphins
- anxiety
- enkephalins
summary for opioid receptors - nociceptin
effects of activation
- controversy actions opposes class ___ effects, mediate pain
endogenous peptide affinity
- ___ / ___ FQ
- mu
- nociceptin, orphanin FQ
