Pharmacotherapy of Substance Use Disorders

Question 1

DSM-5, TR Substance Use Disorders

Answer 1

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

Question 2

DSM-5, TR CONTINUED

Answer 2

 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

Question 3

Blood Alcohol Concentration

Answer 3

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

Question 4

STAGES OF ALCOHOL WITHDRAWAL

Answer 4

1-4

Question 5

Stage 1:

Answer 5

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

Question 6

Stage 2:

Answer 6

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

Question 7

Stage 3:

Answer 7

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

Question 8

Stage 4:

Answer 8

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

Question 9

RISK FACTORS FOR DELIRIUM TREMENS

Answer 9

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

Question 10

TREATING ALCOHOL WITHDRAWAL

Answer 10

Prohphylaxis/Fixed Dosing
Individualized Dosing

Question 11

Prophylaxis/Fixed Dosing

Answer 11

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

Question 12

Individualized Dosing

Answer 12

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

Question 13

Benzodiazepines for treating alcohol withdrawal

Answer 13

 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

Question 14

Thiamine

Answer 14

• 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

Question 15

Phenytoin

Answer 15

not effective to treat withdrawal seizures

Question 16

Wernicke’s encephalopathy

Answer 16

• 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

Question 17

Disulfiram

Answer 17

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

Question 18

Acamprosate

Answer 18

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

Question 19

Naltrexone

Answer 19

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

Question 20

Symptoms of Opioid Withdrawal

Answer 20

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

Question 21

Symptoms of Opioid Withdrawal: muscle aches/tension treatment

Answer 21

acetaminophen or NSAID

Question 22

Symptoms of Opioid Withdrawal: agitation/anxiety/insomnia treatment

Answer 22

hydroxyzine/benzodiazepines

Question 23

Symptoms of Opioid Withdrawal: abdominal cramping/nausea/vomiting treatment

Answer 23

ondansetron

Question 24

Symptoms of Opioid Withdrawal: diarrhea treatment

Answer 24

loperamide

Question 25

Symptoms of Opioid Withdrawal: sweating/yawning/increased tearing/runny nose treatment

Answer 25

clonidine or lofexidine

Question 26

USE OF ALPHA-2 AGONISTS FOR OPIOID WITHDRAWAL SYMPTOMS

Answer 26

 Treating noradrenergic symptoms can serve as an entry to longer-term treatment with MOUD and psychosocial treatment
clonidine and lofexidine

Question 27

Clonidine

Answer 27

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

Question 28

Lofexidine

Answer 28

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

Question 29

Alpha-2 agonists SEs

Answer 29

Hypotension is the most common side effect;
Less likely with lofexidine; lofexidine is more expensive

Question 30

AMERICAN SOCIETY OF ADDICTION MEDICINE (ASAM) GUIDANCE – UPDATE 2020

Answer 30

 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

Question 31

MAINTENANCE TREATMENT OF OPIOID USE DISORDERS

Answer 31

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

Question 32

METHADONE TREATMENT PEARLS

Answer 32

 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

Question 33

BUPRENORPHINE CLINICAL PEARLS

Answer 33

 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

Question 34

BUPRENORPHINE EXTENDED-RELEASE INJECTION

Answer 34

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

Question 35

WHICH TO CHOOSE? - Methadone

Answer 35

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?

Question 36

WHICH TO CHOOSE? - Buprenorphine

Answer 36

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

Question 37

NALTREXONE LONG-ACTING INJECTION (VIVITROL)

Answer 37

 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

Question 38

NALOXONE KITS

Answer 38

 March 30, 2023 – FDA approved OTC naloxone nasal spray (Narcan, 4 mg)