opioids in the clinic (Barker) Flashcards

1
Q

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

A

IV
SC/IM
PO

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

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

A
  • first
  • 2D6, 3A4
  • increased
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

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

A

heroin , tramadol, codeine
- low
- high

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

CYP2D6 ___ codeine to morphine

CYP3A4 (four) makes opioids staring with ___
- inactivates

A
  • activates
  • Nor
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

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

A

higher

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

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
A
  • morphine
  • heroin
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

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 ___ )

A
  • esterases
  • PCA
  • PCA
  • M6G
  • acetaminophen
  • acetaminophen
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

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)

A

tramadol
- SNRI
- neuropathic
- IV

meperidine
- shivering
- 3A4
- renal

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

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

A
  • dependence
  • long
  • QTc
  • antagonist
  • chronic
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

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

A
  • II, V
  • levomethophan, limited, SSRI, NMDA
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

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

A
  • lomotil
  • loperamide
  • Viberzi
  • agonist, antagonist
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

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

A
  • kappa, mu
  • dysphoria
  • kappa, mu
  • withdrawal
  • mu, kappa, delta
  • replacement
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

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

A
  • analgesic
  • respiratory
  • secondary
  • constipation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

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

A
  • contraction
  • water
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

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

A
  • mu
  • withdrawal
  • slow
  • accumulation
  • NMDA
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

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

A

Mu

17
Q

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

A
  • antagonist
  • withdrawal
  • month
18
Q

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

A
  • rapid
  • antidote
19
Q

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
A

seizures

20
Q

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

A
  • buprenorphine, morphine
  • clonidine
21
Q

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

A
  • euphoria, respiratory, motility
  • endorphins
22
Q

summary for opioid receptors - kappa

effects of activation
- analgesia, diuresis, sedation, ___ and psychotomimetic, less miosis, less respiratory depression, little dependence

endogenous peptide affinity
___&raquo_space; endorphins and enkephalins

A
  • dysphoria
  • dynorphins
23
Q

summary for opioid receptors -dellta

effects of activation
- analgesia, mood, reduced ___ , ischemic protection, little dependence

endogenous peptide affinity
___ > endorphins and dynorphins

A
  • anxiety
  • enkephalins
24
Q

summary for opioid receptors - nociceptin

effects of activation
- controversy actions opposes class ___ effects, mediate pain

endogenous peptide affinity
- ___ / ___ FQ

A
  • mu
  • nociceptin, orphanin FQ