Flashcards in Addiction Pharmacotherapy Deck (34):
What is the DSM 5's definition of an opioid use disorder?
- a problematic pattern of opioid use leading to clinically significant impairment or distress, as manifested by at least 2 of the 11 criteria, occurring within a 12 month period
What constitutes mild opioid use disorder? Moderate? Severe?
Mild: presence of 2-3 symptoms
Moderate: presence of 4-5 symptoms
Severe: presence of 6+ symptoms
What are the criteria to constitute opioid use disorder?
1. opioids are often taken in larger amounts or over a longer period than was intended
2. there is a persistent desire or unsuccessful efforts to cut down or control opioid use
3. a great deal of time is spent in activities necessary to obtain the opioid, use the opioid or recover from its effects
4. craving, or a strong desire or urge to use opioids
5. recurrent use resulting in a failure to full major role obligations at work, school or home
6. Continued opioid use despite having persistent or recurrent social problems caused by effect of opioids
7. important actives are given up or reduced because of opioid use
8. recurrent opioid use in situations where it is physically dangerous
9. continued opioid use despite the knowledge of having a persistent or recurrent physical or psychological problem that is likely to have been caused or exacerbated by the substance
What is tolerance defined by?
- a need for markedly increased amounts of opioids to achieve intoxication or desired effect
- a markedly diminished effect with continued use of the same amount of an opioid
What is withdrawal defined by?
- the characteristic opioid withdrawal syndrome
-opioids are taken to relive or avoid withdrawal symptoms
(not met for those taking opioids under medical supervision)
What is the goal of hard reduction?
- attempts to decrease the harmful consequences of illicit drug use to the individual, family, community and society
- goals to reduce illicit opioid use, needle charing, criminal activity and mortality
What is the pharmacological action of methadone?
- agonist of the mu-opioid receptor and is a weak NMDA antagonist
What is the main use of methadone?
analgesia and withdrawal management in opioid dependent individuals
- no rush or euphoria in stabilized patients, blocks euphoria from heroin and other opioids
What makes methadone so useful over the long term?
- has a long duration of action that allows for once daily dosing in methadone and maintenance therapy
- duration of analgesia is similar to morphine
Why does methadone have such a good street value?
- used on the street to reduce the withdrawal symptoms of opioids -> have diarrhea, vomiting, bone aches and pains
What is the absorption of methadone? How long until detected in the plasma? What is the peak plasma levels? Bioavailability?
- methadone is detected in the plasma within 30 minutes
- peak plasma levels are detected 2-4 hours after ingestion (we care about this because at the peak plasma level is the time that someone will stop breathing following a dose)
-po bioavailability is 90%
What is the distribution of methadone? The half life? How many days does it take to reach a steady state with repeated dosing?
The drug is highly protein bound to both plasma proteins and tissue proteins
- the Vd is 4-5 L/kg
- the T1/2 is 22 hours (15-40 hours)
- 5-7 days to reach steady state with repeated dosing
- withdrawal typically is suppressed for 24- 36 hours with therapeutic doses
What is methadone mainly metabolized by? What does this mean for the drug?
- primarily metabolized by cytochrome P450 3A4 to the inactive metabolite EDDP
- means that there will be a lot of observed drug interactions
- also weakly inhibits 2D6
How does pH affect the amount of methadone excreted in the urine?
- amount of methadone excreted in the urine increases as pH decreases
What are the most common side effects associated with methadone?
- constipation. dental, insomnia, neuroendocrine, sexual changes, sweating
- drowsiness, nausea, psychoactive effects, weight gain
What are some of the major adverse effects associated with methadone?
QT interval prolongation with high doses
- ECG recommended for patients on high doses
What are the drug interactions associated with methadone?
associated with the metabolism via CYP P450 3A4
- most often just have to monitor for signs of toxicity or withdrawal and adjust dose accordingly
- pharmacokinetic: induction/inhibitition
-pharmacodynamic: drugs with similar SE profiles
What is the typical dosing regimen of methadone?
- 10-30 mg to start
- high risk patients 10-20 mg to start
- remember it takes 5 days for plasma levels to reach a steady state
- increase by 5-10 mg every 3-5 days as tolerated. Avoid prescriptions that have dose increases without patients assessment
- >60-80 mg increase by 10 mg every 1 to 2 weeks
What are dose adjustments of methadone made based on?
- adjustments based on patients reported symptoms. how long they last for, what the symptoms are and when
What is the usual therapeutic dose of methadone?
What are some common methadone withdrawal symptoms?
- intense anxiety/dysphoria
- opioid cravings
- muscle aches
- diarrhea/abdominal cramping
(think of everything that has to do with horrible flu symptoms)
What are the symptoms associated with methadone overdose?
- lack of coordination
- respiratory depression
- emotional lability
- circulatory collapse/cardiac arrest
In what situations is split dosing appropriate to do for patients?
for RAPID METABOLIZERS
- drowsy in the afternoon but withdrawal in the evening
- measurable methadone peak and trough
- peak: through ratio should be under 2
- if > 2 then may be a rapid metabolizer- should split the dose BID
- metabolism changes in the 3rd trimester
- may require dose increase and split dosing
- methadone is standart of care for pregnant women dependent on opioids
- opioid withdrawal in pregnancy is associated with fetal complications and stillbirths
-must replace doses in the event of emesis
What is the general treatment for those undergoing an overdose on methadone?
- treat with naloxone for a minimum of 24 hours with an additional 12 hours of monitoring
- can run an infusion or give small bolus doses hourly
How does buprenorphine/naloxone work with addiction?
- buprenorphine: acts as a partial mu-opioid agonist that is absorbed sublingually
- naloxone: acts as a pure opioid antagonist (not absorbed sublingually - there for the SOLE purpose to prevent an effect if it is injected)
Buprenorphine has good SL bioavailability but has low PO bioavailability due to very high _____
first pass metabolism
Naloxone has poor ___ and ___ bioavailability
PO and SL
Buprenorphine has a very high affinity for what opioid receptor? What action does this cause it to have?
- has a very high affinity for the mu-opioid receptor (will displace morphine, methadone and other full agonists)
- slow dissociation from the mu-opioid receptor
- low intrinsic activity at the mu-opioid receptors-ceiling effect
- antagonist at the kappa opioid receptor
What is unique about buprenorphine in regards to its ability to precipitate withdrawal?
- will cause precipitated withdrawal in a person who has the taken a full opioid agonist and is physically dependent on opioids
- person must be experiencing withdrawal at the start of induction
What is the adverse effect profile like in buprenorphine?
less adverse effects than other opioids (less sedation, less constipation)
What is the onset of action of buprenorphine? When does peak effect occur?
- 30-60 minutes
-peak effect occurs 1-4 hours
- duration of action is dose dependent (4 hours to 3 days)
What is buprenorphine metabolized by? Eliminated by?
metabolized by: CYP 450 3A4 and glucuronidation
eliminated in feces
What are some of the most common interactions with buprenorphine?
- interacts with other 3A4 inducers/inhibitors
- other sedating drugs
- bezos combination produces additive respiratory depression - no plateau
- blocks analgesic effect of full opioid agonists- pain management can be difficult
- can cause QT prolongation