Ott Pharmacotherapy of Substance Use Disorders

Question 1

DSM-5 definition of substance use disorder

Answer 1

Two of the following is true in a 12-month period:
-Taken in larger amounts or over a longer period of time
-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
-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 which it is physically hazardous
-Continued use despite knowledge of having 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 2

Clinical presentation of people with a blood alcohol concentration of 80mg/dL or 0.08mg%

Answer 2

-Moderate impairment
-Legal definition of intoxication in most states

Question 3

Stage 1 alcohol withdrawal clinical features

Answer 3

-Onset ~6-8hrs
-Moderate autonomic hyperactivity
-Anxiety
-tachycardia
-Insomnia
-Nausea
-Vomiting
-Diaphoresis
-Craving for alcohol

Question 4

Stage 2 alcohol withdrawal clinical features

Answer 4

-Onset ~24hrs
-Autonomic hyperactivity with auditory or visual hallucinations lasting ~1-3 days - most remain lucid and oriented

Question 5

Stage 3 alcohol withdrawal clinical features

Answer 5

-Onset ~1-2 days
-~4% of those untreated develop grand mal seizures ~7-48 hours after drop in BAC

Question 6

Stage 4 alcohol withdrawal clinical features

Answer 6

-Onset 96 hours
-Delirium tremens in ~5% of patients
-Confusion
-Illusions
-Hallucinations
-Agitation
-Tachycardia
-Hyperthermia

Question 7

What attributes to mortality in delirium tremens?

Answer 7

-~5-15% mortality rate
-Arrhythmias
-SHock
-Infection
-Trauma
-Aspiration

Question 8

Risk factors for delirium tremens

Answer 8

-Prior history of DTs (#1 predictor) (kindling - repeated withdrawal episodes increases the severity of subsequent withdrawal symptoms)
-Number of detoxifications
-Consuming the equivalent of 1 pint of whiskey per day for 10 of 14 days before admission
-Early symptoms of withdrawal
-Hepatic dysfunction

Question 9

How do you treat alcohol withdrawal when there is no liver dysfunction?

Answer 9

-Diazepam/chlordiazepoxide
-Long half-life and decreased risk of breakthrough symptoms
-May also use lorazepam and oxazepam

Question 10

How do you treat alcohol withdrawal when there is liver dysfunction

Answer 10

Lorazepam and oxazepam

Question 11

What are the advantages of prophylaxis/fixed dosing when treating alcohol withdrawal?

Answer 11

Prevents withdrawal

Question 12

What are the disadvantages of prophylaxis/fixed dosing when treating alcohol withdrawal?

Answer 12

Unnecessary BZD dosing

Question 13

How do you treat alcohol withdrawal using individualized dosing?

Answer 13

Use CIWA-Ar Scale

Question 14

How do you treat alcohol withdrawal with a CIWA of less than 8-10?

Answer 14

Nonpharmacologic

Question 15

How do you treat alcohol withdrawal with a CIWA of 8-15?

Answer 15

Medicate

Question 16

How do you treat alcohol withdrawal with a CIWA of over 15?

Answer 16

Risk of complications if untreated

Question 17

Advantages of individualized dosing for the treatment of alcohol withdrawal

Answer 17

-Reduces treatment duration
-Decreased benzodiazepine dosing

Question 18

What are other commonly seen treatment options for alcohol withdrawal besides benzodiazepines?

Answer 18

-Thiamine
-Phenytoin - Not effective in treating withdrawal seizures, but many patients are on it anyway, possibly dc

Question 19

What causes Wernicke’s encephalopathy?

Answer 19

Thiamine deficiency

Question 20

Why should thiamine be given before dextrose-containing fluids?

Answer 20

Thiamine is a co-factor in glucose metabolism, Wernicke’s can be precipitated by high glucose loads

Question 21

What two drugs are used to treat alcohol use disorder?

Answer 21

-Disulfiram
-Acamprosate
-Naltrexone

Question 22

Acamprosate clinical pearls

Answer 22

-Renal elimination, monitor renal function, avoid in severe renal impairment
-Suicidality warning, side effects also include diarrhea, nausea, depression, anxiety

Question 23

Naltrexone clinical pearls

Answer 23

-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 or card available to tell emergency providers that they are taking this
-Warning for injection site reactions

Question 24

Symptoms of opioid withdrawal

Answer 24

-Muscle aches/tension
-Agitation/anxiety/insomnia
-Abdominal cramping/nausea/vomiting
-Diarrhea
-Sweating/yawning/increased tearing/runny nose

Question 25

How to treat muscle aches/tension associated with opioid withdrawal

Answer 25

Acetaminophen or NSAID

Question 26

How to treat agitation/anxiety/insomnia associated with opioid withdrawal

Answer 26

Hydroxyzine/benzodiazepines

Question 27

How to treat abdominal cramping/nausea/vomiting associated with opioid withdrawal

Answer 27

Ondansetron

Question 28

How to treat diarrhea associated with opioid withdrawal

Answer 28

Loperamide

Question 29

How to treat Sweating/yawning/increased tearing/runny nose associated with opioid withdrawal

Answer 29

Clonidine or lofexidine

Question 30

Clonidine dosing

Answer 30

-0.3-0.6mg/day (mild withdrawal)
-Up to 1.2mg/day (severe withdrawal)
-Divided doses (0.1-0.2mg/dose given up to hourly)

Question 31

Clonidine side effects

Answer 31

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

Question 32

Lofexidine dosing

Answer 32

-0.18mg tablets
-0.54mg (3 tablets) four times daily x 5-7 days
-Maximum dose = 2.88mg/day (16 tablets)
-No single dose > 0.72mg (4 tablets)
-May continue for up to 14 days
-Dosing adjustments in renal and hepatic impairment

Question 33

Why are alpha-2 agonists used for opioid withdrawal symptoms?

Answer 33

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

Question 34

American society of addiction medicine guidance

Answer 34

-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 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 35

Maintenance treatment of opioid use disorders

Answer 35

-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 36

Methadone clinical pearls

Answer 36

-P450 2B6, 2C19, 3A4, 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 37

Buprenorphine clinical pearls

Answer 37

-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 opioids, including methadone, due to partial agonist effect

Question 38

When can patients be started on buprenorphine extended-release injection?

Answer 38

Moderate-severe opioid use disorder, patients initiated on sublingual buprenorphine and dose adjustment for at least 7 days before first injection

Question 39

Buprenorphine extended-release injection side effects

Answer 39

Monitor for use with serotonergic drugs - risk for serotonin syndrome

Question 40

Considerations for methadone prescribing

Answer 40

-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 41

Considerations for buprenorphine prescribing

Answer 41

-Effective treatment over short-term, long-term clinical trials lacking
-Office-based, can get 30-day Rx
-Less stigma than methadone
-Less misuse potential over methadone
-Indiana Medicaid covers
-Removal of X-waiver prescribing requirement may increase access

Question 42

Naltrexone long-acting injection clinical pearls

Answer 42

-Given 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 43

When was naloxone approved for OTC spray

Answer 43

March 30, 2023

Question 44

What is a common withdrawal symptom of cocaine?

Answer 44

Depression