Pharmacotherapy of Substance Use Disorders Flashcards
DSM-5, TR Substance Use Disorders
A problematic pattern of substance use leading to clinically significant impairment or distress, as manifested by two of the following, occurring in a 12-month period:
Taken in larger amounts or over a longer period than intended
Persistent desire or unsuccessful efforts to cut down or control use
Great deal of time spent in activities necessary to obtain substance or recover from use
Craving, strong desire, or urge to use
Recurrent use results in failure to fulfill major role obligations
DSM-5, TR CONTINUED
Continued use despite consistent or recurrent social or interpersonal problems caused or exacerbated by use or effects of use
Important activities are given up or reduced
Recurrent use in situations in which it is physically
hazardous
Continued use despite knowledge of having a persistent or recurrent physical or psychological problem related to use
Tolerance (needing increased amounts to achieve effect or diminished effect with continued use of the same amount)
Withdrawal (characteristic syndrome OR substance is used to relieve or avoid withdrawal symptoms
Blood Alcohol Concentration
50 mg/dL (0.05mg%): Motor function impairment observable
80 mg/dL (0.08mg%): Moderate impairment, legal definition of intoxication in most states
450 mg/dL: Respiratory depression
500 mg/dL: LD50 for ethanol
STAGES OF ALCOHOL WITHDRAWAL
1-4
Stage 1:
Time of Onset after Withdrawal: ~6-8 hrs
Clinical Features: Moderate autonomic hyperactivity (anxiety, tremulousness, tachycardia, insomnia, nausea, vomiting, diaphoresis) and a craving for alcohol
Stage 2:
Time of Onset after Withdrawal: ~24 hrs
Clinical Features: Autonomic hyperactivity with auditory or visual hallucinations lasting ~ 1 – 3 days – most remain lucid and oriented
Stage 3:
Time of Onset after Withdrawal: ~1-2 days
Clinical Features: ~ 4% of those untreated develop grand mal seizures ~ 7 – 48 hours after drop in BAC
Stage 4:
Time of Onset after Withdrawal: 3-5 days
Clinical Features: Delirium tremens (DTs) in ~5% of patients (confusion, illusions, hallucinations, agitation, tachycardia, hyperthermia)
Mortality associated with DTs ~5 – 15% attributable to arrhythmias, shock, infection, trauma or aspiration
RISK FACTORS FOR DELIRIUM TREMENS
Prior history of DTs
* #1 predictor of future DTs
* Kindling – repeated withdrawal episodes increase the severity of subsequent withdrawal syndromes
Number of detoxifications
Consuming the equivalent of 1 pint of whiskey per day for 10 of 14 days prior to admission
Early symptoms of withdrawal
Hepatic dysfunction
TREATING ALCOHOL WITHDRAWAL
Prohphylaxis/Fixed Dosing
Individualized Dosing
Prophylaxis/Fixed Dosing
Advantage: prevent withdrawal
Disadvantage: unnecessary BZD dosing
Example:
Chlordiazepoxide 25mg TID x 2 days, BID x 2 days, daily x 2 days, then d/c
May also see PRN use of lorazepam to supplement
Individualized Dosing
Use BZD if symptoms warrant: Use CIWA-Ar Scale
CIWA < 8-10: Nonpharmacologic tx
CIWA 8 – 15: Medicate
CIWA > 15: Risk of complications if untreated
Reduces treatment duration, decreased benzodiazepine dosing
Benzodiazepines for treating alcohol withdrawal
No liver dysfunction:
diazepam/chlordiazepoxide; Long t1/2 & ↓ risk of breakthrough symptoms; May also use lorazepam and oxazepam without liver dysfunction
Liver dysfunction: lorazepam, oxazepam
Thiamine
- Always recommend if any suspicion of alcohol use
- Dose: 100mg daily, usually for duration of hospital stay, may be given after discharge, not considered long-term treatment
Phenytoin
not effective to treat withdrawal seizures
Wernicke’s encephalopathy
- Result of thiamine deficiency
- Give before dextrose-containing fluids
- Thiamine is co-factor in glucose metabolism, Wernicke’s can be precipitated by high glucose loads
Disulfiram
Aversive therapy
Unpleasant effects if alcohol is used (flushing, nausea, vomiting, tachycardia)
Potential for cardiovascular collapse, death
Must have highly motivated person
Monitor LFTs
250 mg daily usual maintenance dose
Disulfiram reaction for up to 14 days after d/c
Acamprosate
Maintenance of abstinence
Renal elimination, monitor renal function, avoid in severe renal impairment
Suicidality warning, side effects also include diarrhea, nausea, depression, anxiety
333 mg tablets – 2 tablets (666 mg) three times daily
Is safe to take if the person uses alcohol
Clinical effectiveness is limited by the number of tablets and doses per day
Naltrexone
Decreases binge drinking, helps to increase time between drinking days
Elevated LFTs common, must monitor at baseline and routinely
Need to evaluate pain management needs, patient should have wallet card or be able to tell emergency providers that they are taking this
Warning for injection site reactions
Symptoms of Opioid Withdrawal
Muscle Aches/Tension
Agitation/Anxiety/Insomnia
Diarrhea
Abdominal Cramping/Nausea/Vomiting
Sweating/yawning/increased tearing/runny nose
Short-term tapering doses of opioids or buprenorphine may be used in the withdrawal period
Symptoms of Opioid Withdrawal: muscle aches/tension treatment
acetaminophen or NSAID
Symptoms of Opioid Withdrawal: agitation/anxiety/insomnia treatment
hydroxyzine/benzodiazepines
Symptoms of Opioid Withdrawal: abdominal cramping/nausea/vomiting treatment
ondansetron
Symptoms of Opioid Withdrawal: diarrhea treatment
loperamide
Symptoms of Opioid Withdrawal: sweating/yawning/increased tearing/runny nose treatment
clonidine or lofexidine
USE OF ALPHA-2 AGONISTS FOR OPIOID WITHDRAWAL SYMPTOMS
Treating noradrenergic symptoms can serve as an entry to longer-term treatment with MOUD and psychosocial treatment
clonidine and lofexidine
Clonidine
0.3 – 0.6 mg/day (mild withdrawal)
Up to 1.2 mg/day (severe withdrawal)
Divided doses (0.1 – 0.2 mg/dose given up to hourly
Lofexidine
Dosing (0.18 mg tablets)
0.54 mg (3 tablets) four time daily x 5 – 7 days Maximum dose = 2.88 mg/day (16 tablets)
No single dose > 0.72 mg (4 tablets)
May continue for up to 14 days
Dosing adjustments in renal and hepatic impairment
Alpha-2 agonists SEs
Hypotension is the most common side effect;
Less likely with lofexidine; lofexidine is more expensive
AMERICAN SOCIETY OF ADDICTION MEDICINE (ASAM) GUIDANCE – UPDATE 2020
Patients should be offered all forms of MOUD where possible and available
Psychotherapy should be offered, but prescribing MOUD should not be contingent on the patient agreeing to psychotherapy or other types of therapy
Pregnant women should be screened for OUD in prenatal care and offered either buprenorphine or methadone; limited data regarding use of naltrexone in pregnancy; if a pregnant woman is taking naltrexone, provide education about risks/benefits
Incarcerated people with OUD should be screened for OUD and offered treatment in the jail/prison setting; should NOT be required to switch medications if entering incarceration on medication; opioid withdrawal should be treated medically
Combination treatment with opioids and benzodiazepines is not recommended due to increased risk of fatal overdose
MAINTENANCE TREATMENT OF OPIOID USE DISORDERS
Methadone must be given in a licensed treatment program
Buprenorphine is usually given in combination with naloxone in a sublingual tablet or film strip dosage form; poor bioavailability when swallowed, must be sublingual
METHADONE TREATMENT PEARLS
P450 2B6, 3A4, 2C19, 2D6 substrate – use with caution in patients also taking moderate to strong inhibitors or inducers
QTc prolongation is a serious concern – ECG monitoring is recommended
BUPRENORPHINE CLINICAL PEARLS
Given with naloxone in the same dosage form to decrease misuse – naloxone is not absorbed through the GI tract, so no effect if taken sublingually; but if injected, will block opiate effect of buprenorphine
To avoid precipitating withdrawal, initiate therapy when there are clear signs of withdrawal; administer in divided doses on day 1
Available in sublingual films and tablets, must be dosed sublingually due to lack of gastric absorption
3A4 substrate – monitor closely when used with 3A4 inducers or inhibitors
Monitor LFTs; use with serotonergic drugs may cause serotonin syndrome - monitor
Risk of respiratory depression in overdose is much less than with opioids, including methadone, due to partial agonist effect
BUPRENORPHINE EXTENDED-RELEASE INJECTION
Extended-Release Injection (Sublocade®, Brixadi®)
Moderate-severe opioid use disorder, patients initiated on sublingual buprenorphine and dose adjustment for at least 7 days prior to first injection
Monitor for use with serotonergic drugs – risk for serotonin syndrome
WHICH TO CHOOSE? - Methadone
Clinical proof of efficacy
FDA-approved for use in pregnancy
Treatment program requires daily attendance unless patient graduates to “take-home” bottles
Must give urine samples and attend programming
Indiana Medicaid covers under medical billing
Stigma of program
Is there a program in the area?
Transportation?
WHICH TO CHOOSE? - Buprenorphine
Effective treatment over short-term, longer- term clinical trials lacking
Office-based, can get 30-day Rx
Less stigma
Less misuse potential over methadone
Indiana Medicaid covers
Removal of X-waiver prescribing requirement may increase access
NALTREXONE LONG-ACTING INJECTION (VIVITROL)
Given in same dose as that used for alcohol use disorder
Is the “abstinence” treatment, patients must be ready for this, discuss with patient about readiness to encourage adherence with ongoing dosing.
Risk for overdose if patient discontinues treatment, must tell patient of this risk
NALOXONE KITS
March 30, 2023 – FDA approved OTC naloxone nasal spray (Narcan, 4 mg)
