Substance dependence

Question 1

Alcohol dependence

Answer 1

Excessive drinking of alcohol beverages over a prolonged period of time can result in an alcohol withdrawal syndrome on abrupt cessation of, or marked reduction in, drinking.

Question 2

Acute alcohol withdrawal

Answer 2

• Long-acting benzodiazepines usually Chlordiazepoxide hydrochloride or Diazepam are used to attenuate alcohol withdrawal symptoms.
• When benzodiazepines are contraindicated/not tolerated… Carbamazepine (unlicensed) is used.

Question 3

Alcohol with clomethiazole

Answer 3

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

Question 4

Drugs used in alcohol dependence

Answer 4

1. Acamprosate calcium
2. Naltrexone
3. Disulfiram
4. Nalmefene

Question 5

1. Acamprosate calcium

Answer 5

This drug in combination with counselling is helpful for maintaining abstinence (restraining) in alcohol-dependent patients. It should be initiated as soon as possible after abstinence has been achieved and continued for 1 year… treatment should be maintained if the patient has a temporary relapse but STOPPED if there is regular/excessive drinking.
- Do not take indigestion remedies 2h before/after taking acamprosate

Question 6

Naltrexone

Answer 6

This is an opioid receptor antagonist but is useful as an adjunct in the treatment of alcohol dependence after successful withdrawal. It should be STOPPED if drinking continues 4-6 weeks after starting treatment.

Question 7

Disulfiram

Answer 7

An alternative to the above two drugs. It gives an extremely unpleasant reaction after ingestion of even a small amount of alcohol (e.g. in medicines, mouthwashes, toiletries), only effective if taken daily! Symptoms: flushing, respiratory depression, hypotension, nausea, palpitations + coma.

Question 8

Nalmefene

Answer 8

This drug is licensed for reduction of alcohol consumption in patients with alcohol dependence without physical withdrawal symptoms and who do not require immediate detoxification. It is not recommended for patients aiming to achieve immediate abstinence.

Question 9

Patients with alcohol dependence are at risk of developing

Answer 9

Wernicke’s encephalopathy. Those at high risk include those who are malnourished or have liver disease. Parenteral Thiamine should be prescribed for suspected Wernicke’s encephalopathy and for prophylaxis in alcohol-dependent patients attending hospital for acute treatment.

• Following parenteral treatment, high-dose oral thiamine should be given until cognitive function is maximised.
• Prophylactic high-dose oral thiamine should be given during acute withdrawal of alcohol, before planned withdrawal and for those at high-risk of developing Wernicke’s encephalopathy.

Question 10

alcohol-related pancreatitis

Answer 10

• Pancreatic enzyme supplements should be given to patients with alcohol-related pancreatitis who have symptoms of steatorrhea or who have poor nutritional status due to exocrine pancreatic insuffiency.

Question 11

Nicotine dependence

Answer 11

Nicotine replacement therapy, Bupropion + Varenicline are effective aids to smoking cessation.

 Some patients benefit from the combination of Nicotine replacement therapy, but the combination of NRT with varenicline or bupropion is not recommended.

Question 12

Smoking increases metabolism of drugs by

Answer 12

by stimulating the hepatic enzyme CYP1A2. When smoking is discontinued the dose of certain drugs (theophylline, ropinirole, cinacalcet and some antipsychotics) may need to be reduced.

Question 13

Nicotine withdrawal effects:

Answer 13

malaise, headache, dizziness, sleep disturbance, coughing, flu-like symptoms, depression, irritability, increased appetite + weight gain, restlessness, anxiety, drowsiness, aphthous ulcers, decreased heart rate + impaired concentration

Question 14

Varenicline

Important safety information:

Answer 14

patients should be advised to discontinue treatment if they develop agitation, depressed mood or suicidal thoughts

Question 15

Choice of NRT

Answer 15

 Nicotine patches are a prolonged-release formulation and are applied for 16 hours (with patch removed overnight) or for 24 hours. If patients experience strong cravings for cigarettes on waking, a 24-hour patch may be suitable.
 Immediate release preparations (gum, lozenges, sublingual tablets, inhalator, nasal spray and oral spray) are used whenever the urge to smoke occurs or to prevent cravings.
 Oral preparations + Inhalation cartridges can cause irritation of the throat. Gum, lozenges and oral sprays can cause increased salvation. Patches can cause minor skin irritation. Nasal spray causes nasal irritation, sneezing and watery eyes. Oral spray can cause taste disturbance and flatulence
 G.I. disturbances are common (e.g. nausea, hiccups, dyspepsia and vomiting) and may be caused by swallowed nicotine

Question 16

Cardiovascular effects of NRT

Answer 16

1. Chest pain: caused by patches, lozenges + PO spray

2. Palpitations

Question 17

Opioid dependence

Answer 17

Methadone and Buprenorphine are used as substitution therapy in opioid dependence. Substitute medication should be commenced with a short period of stabilisation, followed by either a withdrawal regime or maintenance regime.

• Maintenance treatment enables patients to achieve stability, reduce drug use + crime and improve health. Signs of toxicity should be monitored by both the patient + prescriber.
• Complete withdrawal from opioids usually takes 4 weeks in an inpatient or residential setting, and up to 12 weeks in a community setting.
• If abstinence is not achieved, illicit drug use is resumed or patient cannot tolerate withdrawal, the withdrawal regimen should be stopped and maintenance therapy resumed at the optimal dose.

Question 18

MISSED DOSES of opioid

Answer 18

• Patients who miss 3 days or more of their regular prescribed dose of opioid maintenance therapy are at risk of overdose because of loss of tolerance. Consider reducing dose in these patients
• If patient misses 5 or more days of treatment, an assessment of illicit drug use is recommended before restarting substitution therapy  this is important for patients taking Buprenorphine due to the risk of withdrawal.

Question 19

Buprenorphine

Answer 19

• It is less sedating than Methadone so more suitable for patients undergoing skilled tasks (driving)
• It is safer than methadone when used with other sedating drugs and has fewer drug interactions
• Dose reductions may be easier than methadone because withdrawal symptoms are milder
• There is a lower risk of overdose. It can be given on alternate days in higher doses and requires a shorter drug-free period before induction with naltrexone for prevention of relapse.

Question 20

Patients dependent on high-doses of opioids may be

Answer 20

at increased risk of precipitated withdrawal. Precipitated withdrawal can occur in any patient if Buprenorphine is administered when other opioid agonist drugs are in circulation. Opioid withdrawal if it occurs, starts within 1-3 hours of the first buprenorphine dose and peaks at 6 hours.
- Non-opioid adjunctive therapy such as Lofexidine Hydrochloride may be required if symptoms are severe.

Question 21

To reduce the risk of precipitated withdrawal, Buprenorphine

Answer 21

To reduce the risk of precipitated withdrawal, the first dose of Buprenorphine should be given when the patient is exhibiting signs of withdrawal or 6-12 hours after the last dose of Heroin (or other short-acting opioid), or 24-48 hours after the last dose of Methadone.

Question 22

Methadone

Answer 22

• Methadone is a long-acting opioid agonist and is administered as single daily dose 1mg/mL.
• Patients with a history of opioid misuse, those who abuse a variety of sedative drugs + alcohol and those who experience increased anxiety during withdrawal may prefer methadone to Buprenorphine because it is more sedating.
• Methadone is initiated atleast 8 hours after the last heroin use, provided that there is evidence of withdrawal symptoms.
• 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). Thus, titration to the optimal dose in maintenance treatment may take several weeks.

Question 23

Opioid substitution during pregnancy

Answer 23

Opioid substitution therapy is recommended during pregnancy because it carries a lower risk to the fetus, than continued use of illicit drugs.
• If a woman who is stabilised on methadone/buprenorphine becomes pregnant, therapy should be continued (buprenorphine is not licensed for use in pregnancy)
• Withdrawal during the 1st trimester should be avoided, because it is associated with an increased risk of miscarriage. Withdrawal should be undertaken gradually during the 2nd trimester, with dose reductions made every 3-5 days.
• If illicit drug use occurs, the patient should be re-stabilised at the optimal maintenance dose and consider stopping the withdrawal regime.
• Withdrawal during the 3rd trimester is not recommended because maternal withdrawal is associated with Fetal distress, stillbirth and risk of neonatal mortality.
• Drug metabolism may be increased during the 3rd trimester, hence the dose of methadone may need to be increased or change to twice-daily consumption to prevent withdrawal symptoms.
• Signs of neonatal withdrawal from opioids usually develop 24-72 hours after delivery but symptoms may be delayed for up to 2 weeks: high pitched cry, rapid breathing, hungry but ineffective suckling, excessive wakefulness; severe but rare symptoms include hypertonicity + convulsions.
• Doses should be kept as low as possible when breastfeeding. Report increased sleepiness, breathing difficulties or limpness in breast-fed babies

Question 24

Adjunctive therapy and symptomatic treatment for withdrawal symptoms: for diarrhoea, mebeverine for stomach cramps

Answer 24

 Loperamide

Question 25

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

Answer 25

 Paracetamol and NSAIDs

Question 26

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

Answer 26

 Metoclopramide/Prochlorperazine

Question 27

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

Answer 27

 Short acting Benzodiazepines/Zopiclone

Question 28

Adjunctive therapy and symptomatic treatment for withdrawal symptoms: to alleviate physical symptoms of withdrawal (monitor BP and pulse rate on initiation for 72h)

Answer 28

 Lofexidine

Question 29

Adjunctive therapy and symptomatic treatment for withdrawal symptoms: for accidental overdose

Answer 29

 Naloxone

Question 30

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

Answer 30

 Naltrexone (opioid antagonist)

Question 31

patients with alcohol-related hepatitis

Answer 31

• Corticosteroids (short-term: 1 month) can be given to patients with alcohol-related hepatitis

Question 32

Patients with marked agitation/hallucinations and those at risk of delirium tremens may be prescribed

Answer 32

• antipsychotic drugs such as Haloperidol or Olanzapine (unlicensed) as an adjunctive to benzodiazepines (they should not be used alone as they do not treat alcohol withdrawal + may lower seizure threshold)

Question 33

If a patient taking a benzodiazepine as part of withdrawal regimen develops alcohol withdrawal seizures

Answer 33

• a fast-acting benzodiazepine (e.g. I.V. Lorazepam or Rectal Diazepam) should be given. Thereafter… an increase in dose of oral benzodiazepine should be considered to prevent further seizures.