Lecture 15: Addiction pharmacotherapy Flashcards
(42 cards)
Characteristics of addiction
Inability to consistently Abstain
Impairment in Behavioral control
Craving; or increased “hunger” for drugs or rewarding experiences;
Diminished recognition of significant problems with one’s behaviors and
interpersonal relationships; and
A dysfunctional Emotional response
Diagnostic criteria for DSM V opioid use disorder
A problematic pattern of opioid use leading to clinically significant impairment or distress, as manifested by at least two of the 11 criteria, occurring within a 12-month period.
How to distinguish between mild, moderate and severe opioid use disorder (DSM V)
Mild: Presence of 2–3 symptoms.
Moderate: Presence of 4–5 symptoms.
Severe: Presence of 6 or more symptoms.
Other characteristics of opioid abuse
- Opioids are often taken in larger amounts or over a longer period than was intended.
- There is a persistent desire or unsuccessful efforts to cut down or control opioid use.
- A great deal of time is spent in activities necessary to obtain the opioid, use the opioid, or recover from its effects.
- Craving, or a strong desire or urge to use opioids.
- Recurrent opioid use resulting in a failure to fulfill major role obligations at work, school, or home.
- Continued opioid use despite having persistent or recurrent social or interpersonal problems caused or exacerbated by the effects of opioids.
- Important social, occupational, or recreational activities are given up or reduced because of opioid use.
- Recurrent opioid use in situations in which it is physically hazardous.
- Continued opioid use despite knowledge of having a persistent or recurrent physical or psychological problem that is likely to have been caused or exacerbated by the substance.
- Tolerance
- Withdrawal
What is tolerance?
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?
The characteristic opioid withdrawal syndrome (refer to Criteria A and B of the criteria set for opioid withdrawal, pp. 547–548).
Opioids (or a closely related substance) are taken to relieve or avoid withdrawal symptoms.
What is the harm reduction philosophy?
Harm reduction attempts to decrease the harmful consequences of illicit drug use to the individual, family, community and society.
The goals of the program are to reduce illicit opioid use, needle sharing, criminal activity and mortality associated with addiction.
What are the pharmacotherapy options for opioid use disorder?
Methadone
Buprenorphine/naloxone or buprenorphine alone
Methadone structure
Synthetic opioid
Structurally unrelated to opiates
See figure
What receptors does methadone target?
Agonist at the μ-opioid receptor
NMDA antagonist
Uses of methadone
analgesia and withdrawal management in
opioid dependent individuals
No rush/euphoria in stabilized patients
Blocks euphoria from heroin and other opioids
Duration of action of methadone and dosing
Long duration of action
allows once daily dosing in methadone maintenance therapy (MMT)
Why does methadone have a street value?
Keeps people out of withdrawal when they can’t get the opioids they want (treats “junk sickness”)
Absorption of methadone
Following oral dosing methadone is detected in the plasma within about 30 minutes
Peak plasma levels 2-4 hours after ingestion
PO bioavailability is 90 %
Distribution of methadone - VD, t1/2, steady state, withdrawal suppression
Highly protein bound to both plasma proteins and tissue proteins
VD (volume of distribution) = 4-5L/kg
t1⁄2 = 22 hours (15-40 hours)
5-7 days to reach steady state with repeated dosing
Withdrawal typically suppressed for 24-36 hours with therapeutic doses
Metabolism of methadone
Primarily metabolized by cytochrome P450 3A4 to the inactive metabolite EDDP
Also metabolized to a lesser extent by CYP 1A2, 2B6, 2C8, 2C9, 2C19, and 2D6
Weak inhibitor of 2D6
Adverse effects of methadone
Generally well tolerated
Common (persistent): constipation, dental, insomnia, neuroendocrine, sexual changes, sweating
Common (develop tolerance): drowsiness, nausea, psycoactive effects, weight gain
QT interval- QT interval prolongation with high doses.
ECG recommended for patients on high doses.
Drug interactions of methadone
CYP P450 3A4
Most often just have to monitor for signs of toxicity or withdrawal and adjust dose accordingly
Pharmacokinetic: Induction/inhibition
Pharmacodynamic: drugs with similar side effect
profile
Excretion of methadone
Methadone is excreted both as unchanged drug and as metabolites in urine and feces.
Amount of methadone excreted in urine increases as pH decreases.
How to start dosing methadone
Start low and go slow
10-30 mg to start
High risk patients (COPD, elderly) 10-20 mg to start
**Reminder: takes 5 days for plasma levels to reach steady state
Increase by 5-10 mg every 3-5 days as tolerated.
Avoid prescriptions that have dose increases without patient assessment.
> 60-80 mg increase by 10 mg q1-2weeks
How to adjust doses of methadone?
Adjustments made based on patient’s reported symptoms
How long does dose last?
What withdrawal symptoms are they experiencing and when?
Are they drowsy 2 hours after their dose? (rapid metabolizers need 2 daily doses)
Usual therapeutic dose is 50-120mg
Dose increase/decrease is not reward/punishment
Withdrawal signs and symptoms
Agitation
Sweating
Nausea/Vomiting
Chills
Goosebumps
Tachycardia
Rhinorrhea
Intense anxiety/dysphoria
Insomnia
Opioid cravings
Muscle aches
Diarrhea/abdominal cramping
Lacrimation
Methadone overdose signs and symptoms
Sedation
Lack of coordination
Respiratory depression
Emotional lability
Circulatory collapse / cardiac arrest
Sweating
Pinpoint pupils
Death
Split dosing in rapid metabolizers
Drowsy in afternoon but withdrawal by evening
Measure methadone peak and trough
Peak:trough ratio should be ≤ 2
If > 2 then may be rapid metabolizer
Consider splitting into BID dosing
