Substance dependence

Question 1

Alcohol withdrawal syndrome can lead to what?

Answer 1

Seizures, delirium, and death

Question 2

What can be used to treat acute alcohol withdrawal?

Answer 2

Long-acting benzodiazepines - Chlordiazepoxide or Diazepam

When benzodiazepines are contraindicated/not tolerated:
- Carbamazepine (off-label)

Alternative to benzodiazepines and carbamazepine:
- Clomethiazole
- Only as inpatient (risk of overdose and misuse)
- Not to be prescribed if patient is likely to continue drinking (respiratory depression)

Question 3

Patients with marked agitation/hallucinations secondary to alcohol (delirium tremens) may be prescribed what medication?

Answer 3

Lorazepam

If symptoms persist or oral medication is declined offer parenteral lorazepam or haloperidol (off-label)

Question 4

If alcohol withdrawal seizures occur, how are they treated?

Answer 4

Medical emergency
- 1st line: oral lorazepam (a fast-acting benzodiazepine, off-label)

If symptoms persist/oral medication declined:
- Parenteral lorazepam (off-label) or haloperidol (off-label)

Review withdrawal regimen

Do not offer phenytoin to treat alcohol withdrawal seizures

Question 5

What is Wernicke’s encephalopathy? Who is at risk of developing it?

Answer 5

Wernicke’s encephalopathy is a neurological emergency resulting from thiamine deficiency
- Typically involving mental status changes and gait and oculomotor dysfunction

High risk:
- Malnourishment or liver disease

Question 6

Who should be offered prophylactic oral thiamine?

Answer 6

Offer prophylactic oral thiamine to harmful or dependent drinkers:
* if they are malnourished or at risk of malnourishment or
* if they have decompensated liver disease or
* if they are in acute withdrawal or
* before and during a planned medically assisted alcohol withdrawal

Question 7

Who should be offered prophylactic parenteral thiamine?

How long should this be given for?

Answer 7

Offer prophylactic parenteral thiamine followed by oral thiamine to harmful or dependent drinkers:
* if they are malnourished or at risk of malnourishment or
* if they have decompensated liver disease

AND in addition:
* they attend an emergency department or
* are admitted to hospital with an acute illness or injury

Given for minimum 5 days unless Wernicke’s encephalopathy is excluded

Question 8

How are patients with alcohol-related hepatitis managed?

Answer 8

Corticosteroids e.g. prednisolone
- Has been shown to improve survival in the short term (1 month)
- Has not been shown to improve survival over a longer term (3 months to 1 year) and increases risk of serious infection in first 3 months

Only offer if severe alcohol related hepatitis with a discriminant function of 32 or more AFTER:
* Effectively treating any active infection or gastrointestinal bleeding
* Controlling any renal impairment
* Discussing the potential benefits and risks

Question 9

Pancreatic enzyme supplements should be given to patients with alcohol-related pancreatitis who meet what criteria?

Answer 9

Those with steatorrhea or who have poor nutritional status due to exocrine pancreatic insuffiency

Question 10

A comprehensive assessment should be offered to all adults who score above what on the Alcohol Use Disorders Identification Test (AUDIT)?

Answer 10

More than 15

Question 11

Assisted alcohol withdrawal should be offered to who?

Answer 11

Users who typically drink over 15 units of alcohol per day, and/or who score 20 or more on the AUDIT

Question 12

Inpatient or residential assisted withdrawal should be offered if the user meets one or more of what criteria?

Answer 12

• Drink over 30 units of alcohol per day
• Have a score of more than 30 on the SADQ
• Have a history of epilepsy, or experience of withdrawal-related seizures or delirium tremens during previous assisted withdrawal programmes
• Need concurrent withdrawal from benzodiazepines
• Regularly drink between 15 and 30 units of alcohol per day and have: significant psychiatric or physical comorbidities or a significant learning disability or cognitive impairment

Consider a lower threshold for vulnerable groups, for example, homeless and older people

Question 13

What should be offered after a successful withdrawal for people with moderate and severe alcohol dependence?

Answer 13

Acamprosate or oral naltrexone in combination with an individual psychological intervention (e.g. CBT)

Can also be used in mild alcohol dependence for those who have not responded to psychological interventions alone, or who have specifically
requested a pharmacological intervention
- Evidence for acamprosate less robust than naltrexone in mild dependence (off-label use)

Question 14

What regimen is used to treat alcohol withdrawal in primary care? What about in secondary care?

Answer 14

Primary care:

• Fixed-dose reducing regimens
• Standard, initial dose followed by dose reduction to zero, usually over 7–10 days

Secondary care:
Fixed-dose regimen or a symptom-triggered regimen
- Symptom-triggered approach = tailoring the drug regimen according to the severity of withdrawal and any complications in an individual patient

Question 15

When managing alcohol withdrawal in the community, what is the maximum quantity of benzodiazepines that can be supplied as take home?

Answer 15

2 days as installment dispensing,

Question 16

How are people with both benzodiazepine and alcohol addiction managed during a withdrawal programme?

Answer 16

Increase the dose of benzodiazepine medication used for withdrawal

Calculate the initial daily dose based on the requirements for alcohol withdrawal plus the equivalent regularly used daily dose of benzodiazepine

Then convert to one benzodiazepine (chlordiazepoxide or diazepam)

Inpatient withdrawal regimens should last for 2 to
3 weeks or longer (3 weeks+ in community)

Question 17

How is Acamprosate calcium used in alcohol dependence?

Answer 17

• Start treatment as soon as possible after assisted withdrawal
• In combination with psychological intervention
• 666 mg three times a day if ≥60kg, 666mg/333mg/333mg if <60kg
• Do not take indigestion remedies 2 hours before/after taking acamprosate
• Usually be prescribed for up to 6 months, or longer if benefiting from the drug and want to continue with it (>12 months = off-label use)
• Stop if drinking persists 4 to 6 weeks after starting the drug
• Supervise patients for at least monthly, for 6 months, and at reduced but regular intervals if the drug is continued after 6 months
• Do not use blood tests routinely, but consider them to monitor for recovery of liver function and as a motivational aid

Question 18

What is the interaction between alcohol and clomethiazole?

Answer 18

Alcohol with clomethiazole, particularly in patients with cirrhosis, can lead to fatal respiratory depression even with short use

Question 19

How is Naltrexone used in alcohol dependence?

Answer 19

• Start treatment after assisted withdrawal
• In combination with psychological intervention
• Initially 25 mg per day and aim for a maintenance dose of 50 mg per day
• Usually be prescribed for up to 6 months, or longer for those benefiting from the drug who want to continue with it
• Stop if drinking persists 4 to 6 weeks after starting
• Opioid receptor antagonist. Inform users re: impact on opioid-based analgesics (reduced effect)
• Supervise patients for at least monthly, for 6 months, and at reduced but regular intervals if the drug is continued after 6 months.
• Do not use blood tests routinely, but consider them to monitor for recovery of liver function, in obesity, in older people, and as a motivational aid
• If the service user feels unwell advise them to stop the oral naltrexone immediately

Question 20

How is Disulfram used in alcohol dependence?

Answer 20

For patients with a goal of abstinence but for whom acamprosate and oral naltrexone are not suitable
- Can be used if patient understands risks

Start treatment at least 24 hours after the last alcoholic drink
- Usually 200 mg per day
- For service users who continue to drink, if a dose of 200 mg (taken regularly for at least 1 week) does not cause a sufficiently unpleasant reaction to deter drinking, consider increasing the dose

MONITORING
- Baseline: liver function, urea and electrolytes
to assess for liver or renal impairment
- Rapid and unpredictable onset of the rare complication of hepatotoxicity;
advise service users that if they feel unwell or develop a fever or jaundice that they should stop taking disulfiram and seek urgent medical attention
- Supervise users at least every 2 weeks for the first 2 months, then monthly for the following 4 months. Then every 6 months thereafter
- if possible, have a family member or carer, who is properly informed about the use of disulfiram, oversee the administration of the drug

INTERACTION WITH ALCOHOL:

• Even a small amount of alcohol (e.g. in medicines, mouthwashes, toiletries)
• Symptoms: flushing, respiratory depression, hypotension, nausea, arrhythmia, collapse

Question 21

Naltrexone and acamprosate can be used in children at what age?

Answer 21

Aged 16 and 17 years who have not engaged with or benefited from a multicomponent treatment programme.

Question 22

What are the most commonly used illicit drugs in the UK?

Answer 22

1. Cannabis
2. Cocaine
3. Other stimulants such as amphetamine

Opioids, although presenting the most significant health problem, are less commonly used

Question 23

Contigency management aims at reducing illicit drug use for people receiving methadone. This often involves the use of incentives/rewards for sustained abstinence.

True or False?

Answer 23

True

Incentives need to be provided consistently and as soon as possible after the positive behaviour
- Should be continued for up to 3-6 months after detoxification

Usually vouchers that can be exchanged for
goods or services of the service user’s choice, or privileges such as take-home methadone dose
- Vouchers worth min. £2 and increasing in value with each negative drug test

Urinalysis should be the preferred method of testing but oral fluid tests may be considered as an alternative
- 3 tests per week for the first 3 weeks, 2 tests per week for the next 3 weeks, and 1 per week thereafter until stability is achieved

Question 24

What are the first-line treatment for opioid detoxification? What is an alternative?
How is treatment chosen?

Answer 24

Methadone and Buprenorphine
- Chose depends on patient preference and if the user has previously had detoxification (normally maintain on one)

Lofexidine may be considered for people:
- Who have made an informed and clinically appropriate decision not to use methadone or buprenorphine
- Who have made an informed and clinically appropriate decision to detoxify in a short time
- With mild or uncertain dependence (including young people)

Question 25

Staff should routinely offer a community-based programme to all service users considering opioid detoxification.

What are the exceptions to this?

Answer 25

People who:
- Have not benefited from previous formal community-based detoxification
- Need medical and/or nursing care because of significant physical or mental health problems
- Require complex polydrug detoxification (e.g. concurrent detoxification from alcohol or benzodiazepines)
- Are experiencing significant social problems that will limit the benefit of community-based detoxification

Question 26

How long is opioid detoxification expected to take?

Answer 26

Normally be up to 4 weeks in an inpatient or residential setting

Up to 12 weeks in a community setting

(Do not confuse with stabilisation which will last longer. Detoxification = the process by which the effects of opioid drugs are eliminated from dependent opioid users in a safe and effective manner)

Question 27

Define:
1. Ultra-rapid detoxification
2. Rapid detoxification
3. Accelerated detoxification

Answer 27

Ultra-rapid detoxification
- 24-hour period, typically under general anaesthesia or heavy sedation

Rapid detoxification
- May take 1 to 5 days, with a moderate level of sedation

Accelerated detoxification
- Use of limited doses of an opioid antagonist (e.g. naltrexone) after the start of detoxification to
shorten the process, without precipitating full withdrawal
- Typically does not involve the use of heavy or moderate sedation

All of these methods may help to establish the person on a maintenance dose of naltrexone for preventing relapse

Question 28

Ultra-rapid detoxification under general anaesthesia or heavy sedation (where the airway needs to be supported) must not be offered.

True or False?

Answer 28

True
Risk of serious adverse events, including death

Question 29

Rapid detoxification should only be considered for people who specifically request it, clearly understand the associated risks and are able to manage the
adjunctive medication.

True or False?

Answer 29

True

Healthcare professionals should ensure during detoxification that:
- The service user is able to respond to verbal stimulation and maintain a patent airway
- Adequate medical and nursing support is available to regularly monitor the service user’s level of sedation and vital signs
- Staff have the competence to support airways.

Question 30

Accelerated detoxification, using opioid antagonists at lower doses to shorten detoxification, should not be routinely offered.

True or False?

Answer 30

True

Increased severity of withdrawal symptoms and the risks associated with the increased use
of adjunctive medications

Question 31

If a patient is both opioid and alcohol dependent, which should be detoxed first?

Answer 31

Alcohol detoxification if in a community or prison setting

Both may be done concurrently in an inpatient setting

Question 32

What type of drug is methadone? What is its half-life?

Answer 32

Long-acting opioid agonist

Half-life of 20–37 hours, which allows for a once-daily
dosing schedule

Because of the long half-life, plasma concentrations progressively rise during treatment even if the patient remains on the same daily dose (it takes 3-10 days for plasma concentrations to reach steady state)

Question 33

What is the dosing regimen for methadone? (initial dose and usual maintenance)

Answer 33

Initial dose of 10–40 mg daily
- Increased by up to 10 mg daily (with a maximum weekly increase of 30 mg) until no signs of withdrawal or intoxication are seen

The usual maintenance dose range is 60–120 mg daily
- Higher doses of MMT (for example, 60 mg or more) were found to be more effective than doses of less than 50 mg for improving retention on
treatment

Question 34

Methadone appears to have no serious long-term side effects associated with chronic administration.

True or False?

Answer 34

True

Does not have the pronounced narcotic effects seen with shorter-acting opioids such as illicit diamorphine

Question 35

Name some drugs which speed up the elimination of methadone?

Answer 35

Rifampicin, phenytoin,
phenobarbital and some antiviral drugs

Question 36

Name some drugs which slow down the elimination of methadone?

Answer 36

Fluvoxamine and fluoxetine

Question 37

What type of drug is buprenorphine? How does this differ with methadone?

Answer 37

Buprenorphine has both partial opioid agonist and
opioid antagonist activity

High affinity for opioid receptors
- Reduces the impact of illicit opioid use by preventing these drugs from occupying the opioid receptors
- Results in prolonged duration of action at higher doses, which can allow alternate-day dosing regimens

Whereas methadone is an agonist, buprenorphine is an antagonist at the receptor subtype involved in mood (kappa)
- Results in milder, less euphoric and less sedating effect than full opioid agonists such as diamorphine or methadone

Question 38

Buprenorphine has a relatively good safety profile.

True or False?

Answer 38

True

Higher than normal therapeutic doses rarely result in clinically significant respiratory depression because of its partial agonist activity at the opioid receptor involved (mu).

However, the safety of buprenorphine mixed with high doses of other sedative drugs such as alcohol or benzodiazepines remains unclear
- Although thought to be safer than methadone when used with other sedating drugs

Question 39

Starting buprenorphine treatment in opioid-dependent people may precipitate symptoms of withdrawal.

True or False?

Answer 39

True

Buprenorphine has a high affinity for opioid receptors and displaces any residual illicit opioid agonists

Question 40

What is the dosing regimen for buprenorphine? (initial dose and usual maintenance)

Answer 40

Initial recommended once-daily dose of 0.8–4 mg, adjusted according to response
- In practice, a starting dose of more than 4 mg/day is often used

Maintenance dose = 12–24 mg/day. Maximum daily dose is 32 mg

Question 41

Buprenorphine is more sedating than Methadone.
True or False?

Answer 41

False
Methadone is more sedating than buprenorphine

Patients who abuse a variety of sedative drugs, alcohol and those who experience increased anxiety during withdrawal may prefer methadone because it is more sedating

Buprenorphine may be preferred in people who perform skilled tasks for a living

Question 42

Similar fixed doses of methadone are associated with higher rates of retention than similar fixed doses of buprenorphine.

True or False?

Answer 42

True

In addition, high fixed doses of methadone are more effective than lower-fixed-dose buprenorphine at preventing illicit opioid use

Results are mixed for lower-fixed-dose methadone and higher-fixed-dose buprenorphine.

Question 43

What is the missed dose protocol for opioid maintenance therapy? (e.g. methadone and buprenorphine)

Answer 43

At risk of overdose because of loss of tolerance

Patients who miss 3 days or more:
- Consider reducing dose in these patients

If patient misses 5 or more days:
- An assessment of illicit drug use is recommended before restarting substitution therapy
- This is especially important for patients taking Buprenorphine due to the risk of withdrawal

Question 44

Adjunctive therapy and symptomatic treatment for withdrawal symptoms: diarrhoea

Answer 44

Loperamide

Question 45

Adjunctive therapy and symptomatic treatment for withdrawal symptoms: stomach cramps

Answer 45

Mebeverine

Question 46

Adjunctive therapy and symptomatic treatment for withdrawal symptoms: muscular pains and headaches

Answer 46

Paracetamol and NSAIDs

Question 47

Adjunctive therapy and symptomatic treatment for withdrawal symptoms: for nausea and vomiting

Answer 47

Metoclopramide/Prochlorperazine

Question 48

Adjunctive therapy and symptomatic treatment for withdrawal symptoms: insomnia (short-courses only)

Answer 48

Short acting Benzodiazepines/Zopiclone

Question 49

Adjunctive therapy and symptomatic treatment for withdrawal symptoms: to alleviate physical symptoms of withdrawal

Answer 49

Lofexidine
(monitor BP and pulse rate on initiation for 72hours)

Question 50

Adjunctive therapy and symptomatic treatment for withdrawal symptoms: accidental overdose

Answer 50

Naloxone

Question 51

Adjunctive therapy and symptomatic treatment for withdrawal symptoms: as an aid to prevent relapse.

Answer 51

Naltrexone (opioid antagonist)

Question 52

After successful opioid detoxification, and irrespective of the setting in which it was delivered, all service users should be offered continued treatment, support and monitoring designed to maintain abstinence.

How long should this last?

Answer 52

At least 6 months