Drugs Used to Treat

Substance Use Disorders

Alysandra Rae R. Luis, Level I Resident
Opioid Receptor Agonists
Opioid Receptor Agonists
• Methadone
• Pure agonist at μ-receptors
• Peak plasma concentrations: 2-6
hours
• Plasma half-life: 4-6 hours or 24-
36 hours
• Buprenorphine
• Partial agonist at μ-receptors
• Potent antagonist at κ-receptors
• Almost wholly affected by first
pass effect
• Plasma half-life: 3-5 hours
initially, >24 hours terminally
Opioid Receptor Agonists
• Methadone
• Short-, long-term detoxification, maintenance
• Schedule II drug
Opioid Receptor Agonists
• Buprenorphine
• Milder withdrawal syndrome
• Ceiling effect
• May cause precipitated withdrawal
• Start with 2-4 mg, then give as needed in 1-2 hours
• Doses of 6-16 mg/day are associated with improved outcomes
Opioid Receptor Agonists
• Tramadol
• Weak μ-opioid receptor agonist
• Structurally similar to venlafaxine
• Long half-life
Opioid Receptor Agonists
• Precautions and Adverse Reactions
• Lightheadedness, dizziness, sedation, nausea, constipation, vomiting,
perspiration, weight gain, decreased libido, inhibition of orgasm, and insomnia
or sleep irregularities
• Tolerance
• Risk of overdosage during induction stage
• Abrupt cessation triggers withdrawal
• Methadone > buprenorphine
Opioid Receptor Agonists
• Methadone • Buprenorphine
• 5-, 10-, and 40-mg dispersible • 0.3-mg/mL solution in 1- mL
scored tablets; 40-mg scored ampules
wafers; 5-mg/5-mL, 10-mg/5-mL,
and 10-mg/mL solutions; and a 10-
mg/mL parenteral form • Tramadol
• Initial: 15-20 mg • Capsules/tablets
• Max: 120 mg/day • For depression or OCD: 50-200
mg/day
Opioid Receptor Antagonists
• Naltrexone
• Most widely used
• Naloxone
• nalmefene
Opioid Receptor Antagonists
• Naltrexone • Nalmefene
• 60% • 40-50%
• Peaks within 1 hour • Peaks in 1-2 hours
• Half-life 1-3 hours • Half-life 8-10 hours
Opioid Receptor Antagonists
• Therapeutic Indications • Precautions and Adverse
• Opioid dependence Reactions
• Rapid detoxification • Acute opioid withdrawal: drug
• Alcohol use disorder craving, a feeling of temperature
change, musculoskeletal pain, and
GI distress, confusion, drowsiness,
vomiting, and diarrhea
Opioid Receptor Antagonists
• Potentially hepatotoxic when used with disulfiram
• Potentiate sedation with thioridazine
• Flumazenil and nalmefene may induce seizures
Opioid Receptor Antagonists
• Naltrexone
• Initial: 50 mg/day
• 5, 10, 12.5, or 25 mg and titrate up to the 50- mg dosage over 1 hour to 2 weeks
• Nalmefene
• Corresponding therapeutic dosage is 20 mg/day in two equal doses
Disulfiram and Acamprosate
• Disulfiram • 250- and 500- mg tablets
• Disulfiram-alcohol reaction: • Initial: 500 mg/day
• respiratory depression, • Maintenance 125-500 mg/day
cardiovascular collapse, acute heart • Max: 500 mg/day
failure, convulsions, loss of
consciousness, and death
• More often used in inpatient
settings
• Half-life: 60-120 hours
• Increases concentration of other
drugs
Disulfiram and Acamprosate
• Acamprosate
• headache, diarrhea, flatulence, abdominal pain, paresthesias, and various skin
reactions
• Creatinine clearance <30 mL/min should not use
• Recommended dosage: two 333-mg/tablets TID
Clonidine and Guanfacine
• Presynaptic α2-receptor agonists
• inhibit sympathetic outflow
• Therapeutic indications:
• Withdrawal from opioids, alcohol, benzodiazepines, nicotine
• Tourette disorder
• Other tic disorders
• Hyperactivity and aggression in children
• PTSD
Clonidine and Guanfacine
• Precautions and Adverse Effects
• Dry mouth and eyes, fatigue, sedation, dizziness, nausea, hypotension, and
constipation
• Caution in BP <90/60 and in cardiac arrhythmias
• Overdose of clonidine: coma and constricted pupils; decreased BP, pulse, and
respiratory rate
• Abrupt discontinuation: anxiety, restlessness, perspiration, tremor, abdominal
pain, palpitations, headache, and a dramatic increase in BP
Clonidine and Guanfacine
• Clonidine • Guanfacine
• 0.1-, 0.2-, and 0.3-mg tablets • 1- and 2-mg tablets
• Initial: 0.1 mg BID • Initial: 1 mg before sleep
Case Vignette
• Susan
• 20-year-old female college student
• Alcohol use disorder
• Recently charged with driving under the
influence (DUI).
• Blacked out on five separate occasions.
• Began drinking beer at the age of 15.
• Alcohol use has escalated from two to
three bottles of beer on one or two
occasions per month to two to three
glasses of distilled spirits 5 days per
week.
• Her drink of choice is currently
whiskey.
• Oversleeps and misses class
• Attended class while intoxicated.
• Drinks before going out with friends
• Wants to stop using alcohol
• Her last drink ~18 hours ago
• Urine drug testing is unremarkable
for other substances.
• Liver function tests are within
normal limits, her creatinine is 1.0,
and her glomerular filtration rate is
>60 mL/min.
• Lives alone
Case Vignette
• What medications would you consider prescribing to Susan for
alcohol use disorder?
• Which medication is the most appropriate at this time?