NS: Substance dependence

Question 1

What are the three effective aids to smoking cessation?

Answer 1

NRT
Bupropion hydrochloride.
Varenicline.

Question 2

Bupropion treatment should be discontinued if abstinence is not achieved at what number of weeks?

Answer 2

7 weeks.

Question 3

How many weeks before target stop date should bupropion treatment be started?

Answer 3

1-2 weeks before the target stop date.

Question 4

How does bupropion work?

Answer 4

Dual inhibition of norepinephrine and dopamine reuptake.

Question 5

How does varenicline work?

Answer 5

A selective nicotine-receptor partial agonist.

Question 6

Patients taking varenicline should be advised to discontinue treatment and seek prompt medical advice if they develop what?

Answer 6

MHRA/CHM advice: Suicidal behaviour and varenicline
Patients should be advised to discontinue treatment and seek prompt medical advice if they develop agitation, depressed mood, or suicidal thoughts. Patients with a history of psychiatric illness should be monitored closely while taking varenicline.

Question 7

How should varenicline treatment be discontinued?

Answer 7

There is a risk of relapse, irritability, depression and insomnia on discontinuation; consider dose tapering on completion of 12-week course.

Question 8

Can someone taking varenicline breastfeed?

Answer 8

Avoid- present in milk in animal studies.

Avoid- toxicity in animal pregnancy studies.

Question 9

Varenicline is a selective nicotine-receptor agonist used to aid smoking cessation. It is usually started 1-2 weeks before target stop date but can be started up to a maximum of how many weeks before the stop date?

Answer 9

5 weeks before.

Question 10

Smoking increases the metabolism of some medicines by stimulating what hepatic enzyme?

Answer 10

CYP1A2.

Question 11

When smoking is discontinued the dose of some drugs may need to be reduced due to smoking stimulation of CYP1A2. What are these drugs?

Answer 11

1. Theophylline
2. Cinacalcet - acts as calcimimetic via allosteric modulation of the calcium-sensing receptor. (Mimpara)
3. Ropinirole
4. Antipsychotics (clozapine, olanzapine, chlorpromazine hydrochloride, haloperidol)

Question 12

Is risperidone impacted by cigarette smoking induction of CYP1A2?

Answer 12

Nope. Drugs which are:
. Theophylline 
2. Cinacalcet
3. Ropinirole 
4.  Antipsychotics (clozapine, olanzapine, chlorpromazine hydrochloride, haloperidol)

Question 13

What is cinacalcet used? what is the relevance of its use with regard to smoking cessation?

Answer 13

Cincalcet acts as a calcimimetic via allosteric modulation of the calcium-sensing receptor.

It reduces parathyroid hormone which leads to a decrease in serum calcium concentrations.

Indications are:
Secondary hyperparathyroidism in patients with end-stage renal disease on dialysis, Treatment of hypercalcaemia in parathyroid carcinoma, Primary hyperparathyroidism in patients where parathyroidectomy is inappropriate.

Cigarette smoking leads to induction of CYP1A2 meaning that doses of Cinacalcet may need to be reduced on smoking cessation.

Question 14

What is the mechanism of action of clozapine?

What impact does smoking cessation have on clozapine?

Answer 14

Cloxapine is a dopamine D1, dopamine D2, 5-HT2A, alpha-adrenocepter and muscarinc receptor antagonist.

Levels may need to be reduced upon smoking cessation due to cigarette induction of CYP1A2:

1, Theophylline

2. Cinacalcet
3. Ropinirole
4. Antipsychotics (clozapine, olanzapine, chlorpromazine hydrochloride, haloperidol)

Question 15

Bupropion hydrochloride has also been used as what type of medicine other than in smoking cessation?

Answer 15

Antidepressant.

Question 16

What side-effects are associated with nicotine replacement therapy?

Answer 16

Oral preps and inhalation cartridges can cause irritation of the throat, gum, lozenges, and oral spray can cause increased increased salivation, and patches can cause minor skin irriation.

The nasal spray commonly causes coughing, nasal irritation, epistaxis, sneezing and watery eyes; the oral spray can cause watery eyes and blurred vision.

Question 17

Untreated heroin dependence shows early withdrawal symptoms within how long?

When do symptoms peak?

When do symptoms subside substantially after?

Answer 17

Untreated heroin dependence shows early withdrawal symptoms within 8 hours, with peak symptoms at 36–72 hours; symptoms subside substantially after 5 days. Methadone hydrochloride or buprenorphine withdrawal occurs later, with longer-lasting symptoms.

Question 18

Complete withdrawal from opioids usually takes up to 4 weeks in an inpatient or residential setting and up to how long in the community setting?

Answer 18

12 weeks.

Question 19

Following successful withdrawal treatment, further support and monitoring to maintain abstinence should be provided for a period of at least how long?

Answer 19

6 months

Question 20

Peope who miss who many days of their regular prescribed dose of opioid maintenance therapy are at risk of overdose because of a loss of tolerance?

Answer 20

3 or more days.

Question 21

If a patient misses 5 or more days of treatment, an assessment of what is recommended before restarting substitution therapy?

Answer 21

illicit drug use - particulalry important for patients taking buprenorphine because of the risk of precipitated withdrawal.

Question 22

Buprenorphine is preferred by some patients why?

Answer 22

It is less sedating than methadone - skilled tasks easier to accomplish.

Also buprenorphine is safer than methadone when used in conjuction with other sedating drugs and has fewer drug interactions.

Question 23

Why may dose reductions with buprenorphine be easier than with methadone?

Answer 23

The withdrawal symptoms are milder, and patients generally require fewer adjunctive medications; there is also a lower risk of overdose

Question 24

Which has a shorter drug-free period before induction with naltrexone hydrochloride for prevention of relapse: methadone or buprenorphine?

Answer 24

Buprenorphine

Question 25

Patients who are dependent on high doses of opioids may be at increased risk of precipitated withdrawal. Precipitated withdrawal can occur in any patient if buprenorphine is administered when?

Answer 25

Other opioid agonist drugs are in circulation.

Question 26

Precipitated opioid withdrawal, if it occurs, starts within how many hours of the first buprenorphine dose and peaks at around what time period?

Answer 26

Precipitated opioid withdrawal, if it occurs, starts within 1–3 hours of the first buprenorphine dose and peaks at around 6 hours. Non-opioid adjunctive therapy, such as lofexidine hydrochloride, may be required if symptoms are severe.

Question 27

If symptoms of precipitated opioid withdrawal are severe, non-opioid adjunctive therapy with what may be required?

Answer 27

Precipitated opioid withdrawal, if it occurs, starts within 1–3 hours of the first buprenorphine dose and peaks at around 6 hours. Non-opioid adjunctive therapy, such as lofexidine hydrochloride, may be required if symptoms are severe.

Lofexidine is an a2alpha adrenergic receptor agonist, historically used as an antihypertensive but commonly used to alleviate the physical symptoms of heroin and other types of opioid withdrawal.

Question 28

To reduce the risk of precipitated withdrawal, the first dose of buprenorpine should be given when the patient is exhibiting signs of withdrawal, or how long after the last use of heroin (or other short-acting opioid)?

Answer 28

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 use of heroin (or other short-acting opioid), or 24–48 hours after the last dose of methadone hydrochloride. It is possible to titrate the dose of buprenorphine within one week—more rapidly than with methadone hydrochloride therapy—but care is still needed to avoid toxicity or precipitated withdrawal; dividing the dose on the first day may be useful.

Question 29

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 use of heroin (or other short-acting opioid), or __-__ hours after the last dose of methadone hydrochloride?

Answer 29

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 use of heroin (or other short-acting opioid), or 24–48 hours after the last dose of methadone hydrochloride. It is possible to titrate the dose of buprenorphine within one week—more rapidly than with methadone hydrochloride therapy—but care is still needed to avoid toxicity or precipitated withdrawal; dividing the dose on the first day may be useful.

Question 30

Titration of which type of opioid substitution therapy is possible fastest?

Answer 30

It is possible to titrate the dose of buprenorphine within one week—more rapidly than with methadone hydrochloride therapy—but care is still needed to avoid toxicity or precipitated withdrawal; dividing the dose on the first day may be useful.

Question 31

What is Suboxone?

Answer 31

A combination preparation containing buprenorphine with naloxone (Suboxone) can be prescribed for patients when there is a risk of dose diversion for parenteral administration.

The naloxone hydrochloride component precipitates withdrawal if the prepatation is injected but has little effect when the preparation is taken sublingually.

Question 32

What type or patient may prefer methadone over buprenorphine? Why?

Answer 32

1. Patients with a long history of opioid misuse.
2. Those who typically abuse a variety of sedative drugs and alcohol.
3. Those who experience increased anxiety during withdrawal

May prefer methadone over buprenorphine because it has a more pronounced sedative effect.

Question 33

Methadone is initiated at least how many hours after the last heroin dose?

Answer 33

8 hours

Question 34

How long does it take for methadone plasma concentrations to reach steady-state in patients on a stable dose?

Answer 34

3-10 days ( a dose tolerated on the first day of treatment may become a toxic dose on the third day as cumulative toxicity develops).

Question 35

Why is opioid substitution therapy recommended during pregnancy?

Answer 35

It carries a lower risk to the fetus than continued use of illicit drugs.

Question 36

If a woman who is stabilised on methadone hydrochloride or buprenorphine for treatment for opioid dependence becomes pregnant, therapy should be continued. Are both licensed for this use?

Answer 36

Methadone = yes
Buprenorphine = no

Question 37

Many pregnant patients choose a withdrawal regimen, but withdrawal during which trimester should be avoided because it is associated with a risk of spontaneous miscarriage?

Answer 37

First trimester

Question 38

Withdrawal of methadone hydrochloride or buprenorphine should be undertaken gradually during the second trimester, with dose reductions made every how many days?

Answer 38

3-5

Question 39

Is withdrawal of methadone or buprenorphine in the third trimester recommended?

Answer 39

No, because even if mild, is associated with fetal distress, stillbirth, and the risk of neonatal mortality.

Question 40

Why may dose increases of methadone be needed in the third trimester?

Answer 40

Drug metabolism can be increased in the third trimester; it may be necessary to either increase the dose of methadone or change to twice-daily consumption to prevent withdrawal symptoms from developing.

Question 41

Signs of neonatal withdrawal from opioids usually develops how long after delivery?

Answer 41

Signs of neonatal withdrawal from opioids usually develop 24–72 hours after delivery but symptoms may be delayed for up to 14 days, so monitoring may be required for several weeks. Symptoms include a high-pitched cry, rapid breathing, hungry but ineffective suckling, and excessive wakefulness; severe, but rare symptoms include hypertonicity and convulsions.

Question 42

Can people on methadone or buprenorphine breast feed?

Answer 42

Doses of methadone and buprenorphine should be kept as low as possible in breast-feeding mothers. Increased sleepiness, breathing difficulties, or limpness in breast-fed babies of mothers taking opioid substitutes should be reported urgently to a healthcare professional.

Question 43

What common drugs are used in the adjunctive therapy of opioid withdrawal symptoms?

Answer 43

Loperamide = diarrhoea.
Mebeverine = stomach cramps.
Paracetamol and NSAIDs = muscular pains and headaches.
Metoclopramide HCL or prochlorperazine = nausea or vomiting.

Question 44

What is a rubefacients?

Answer 44

Rubefacients are drugs that cause irritation and reddening of the skin due to increased blood flow. They are believed to relieve pain in various musculoskeletal conditions and are available on prescription and in over-the-counter remedies. Salicylate is a commonly used rubefacient.

Question 45

What is the place of rubefacients in managing opioid withdrawal symptoms?

Answer 45

Topical rubefacients can be helpful for relieving muscle pain associated with methadone hydrochloride withdrawal.

Question 46

If a patient is experiencing insomnia because of opioid withdrawal how can this be managed?

Answer 46

If a patient is suffering from insomnia, short-acting benzodiazepines or zopiclone may be prescribed, but because of the potential for abuse, prescriptions should be limited to a short course of a few days only. If anxiety or agitation is severe, specialist advice should be sought.

Question 47

What are the uses of lofexidine i.e. opioid abuse etc?

Answer 47

Lofexidine hydrochloride may alleviate some of the physical symptoms of opioid withdrawal by attenuating the increase in adrenergic neurotransmission that occurs during opioid withdrawal. Lofexidine hydrochloride can be prescribed as an adjuvant to opioid substitution therapy, initiated either at the same time as the opioid substitute or during withdrawal of the opioid substitute. Alternatively, lofexidine hydrochloride may be prescribed instead of an opioid substitute in patients who have mild or uncertain dependence (including young people), and those with a short history of illicit drug use.