Phil was recently burgled in his digs. He has become anxious and has been lying awake for much of the night. A 5-day supply of a benzodiazepine hypnotic has been prescribed to help him cope with the insomnia. Which of the following pieces of advice would be appropriate for Phil:
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Take this medicine for 3–4 days to establish sleep pattern and then stop
You must not share this medicine with anybody else and you should store it in a safe place
Make sure you read the leaflet that accompanies your medicine, especially the section on how to take your medicine
You must complete the course prescribed for you
It is alright to drink alcohol socially with this medicine
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1. Take this medicine for 3–4 days to establish sleep pattern and then stop
Long-term use of a benzodiazepine for insomnia must be avoided. Benzodiazepine dose for 3–4 days may be sufficient to re-establish a sleep pattern.
2. You must not share this medicine with anybody else and you should store it in a safe place
There is considerable potential for diversion of benzodiazepines—ending up being used for illicit or recreational purposes. Phil should take responsibility for safe use and secure storage of the medicine.
3. Make sure you read the leaflet that accompanies your medicine, especially the section on how to take your medicine
The patient information leaflet reinforces the advice on how to take the medicine and the warnings about avoiding prolonged use and concomitant use of alcohol.
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4. You must complete the course prescribed for you
The benzodiazepine should be stopped as soon as normal sleep pattern is established (usually about 3–4 days) and further doses should not be taken even if some of the medicine remains unused. Phil should be advised to return all unwanted medicines promptly to a pharmacy for safe disposal.
5. It is alright to drink alcohol socially with this medicine
Alcohol should not be taken while on benzodiazepine treatment. Benzodiazepines and alcohol both depress the CNS—the combination may increase sedation and depress cardiovascular and respiratory function. Alcohol consumption during ‘social drinking’ can vary considerably and present a potential for dangerous effects when a benzodiazepine is also taken.
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Which of the following statements about benzodiazepine withdrawal effects is true?
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This is not true. Withdrawal effects occur more readily with benzodiazepines that are eliminated rapidly from the body. Withdrawing such benzodiazepines may require switching to a benzodiazepine which persists in the body for longer.
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No. Withdrawal effects comprise psychiatric features (with many effects resembling the original complaint—anxiety states and insomnia) as well as other features such as convulsions, tremor, sensory hypersensitivity and abdominal cramps.
Correct
In established dependence, benzodiazepine treatment is stopped by decreasing the dose gradually over about 8 weeks (much longer in some cases). Switching from a short-acting benzodiazepine to a long-acting one allows smoother reduction in the plasma concentration, thereby facilitating withdrawal.
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This is not correct. Withdrawal symptoms can begin within a few hours of stopping a short-acting benzodiazepine, but may not appear for up to 3 weeks after stopping a longer-acting benzodiazepine!
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Physical and psychological dependence can occur with therapeutic doses of benzodiazepines and can become established within weeks. As such, the duration of benzodiazepine treatment should be kept as short as possible; for anxiety or insomnia, benzodiazepine treatment should not exceed 4 weeks. Those prescribed a benzodiazepine should be warned of its potential for dependence.
Ali has been taking lorazepam 7.5 mg daily (generally 2.5 mg twice during the day and 2.5 mg at bedtime) for the last 9 months. Ali says that the ‘pills don’t seem to be doing any good but I just can’t seem to cut them out’. Which of the following seem the best options for moving forwards:
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Ask Ali to try harder (and ‘work through the pain’) to cut out the benzodiazepines
Agree a withdrawal plan with Ali, involving a switch to diazepam
Ask Ali to cut out the middle dose and just continue on lorazepam 2.5 mg midmorning and 2.5 mg at bedtime
Give Ali a leaflet on benzodiazepine withdrawal and involve the family in supporting Ali through the withdrawal effects
Substitute the benzodiazepine for another class of anxiolytics
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2. Agree a withdrawal plan with Ali involving a switch to diazepam
The management of withdrawal can be difficult and it is best attempted by switching to a longer-acting benzodiazepine such as diazepam, with a gradual dose reduction to avoid serious withdrawal effects such as convulsions or acute psychosis.
4. Give Ali a leaflet on benzodiazepine withdrawal and involve the family in supporting Ali through the withdrawal effects
An information sheet on withdrawal can be effective in encouraging reduction or cessation of benzodiazepine use. The management of withdrawal can be difficult and is best attempted in the context of support from family and health professionals, and with access to psychological therapy. Withdrawal may need to be conducted in a specialist centre for particularly difficult cases such as long-term dependence on a high-dose or multiple-substance abuse.
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1. Ask Ali to try harder (and ‘work through the pain’) to cut out the benzodiazepines
It is important to understand Ali’s challenge. The best way forward would be to discuss a mutually agreed plan for withdrawing the benzodiazepines as it is more likely to be effective through better education and commitment from the patient. It is more difficult to manage withdrawal in an individual on a short-acting or intermediate-acting benzodiazepine such as lorazepam.
3. Ask Ali to cut out the middle dose and just continue on lorazepam 2.5 mg midmorning and 2.5 mg at bedtime
Dose reduction needs to gradual (reduced by around one-eighth of the daily dose each fortnight) to avoid serious withdrawal effects such as convulsions and psychosis. The benzodiazepine first needs to be switched to the equivalent dose of a longer-acting one such as diazepam.
5. Substitute the benzodiazepine for another class of anxiolytics
The benzodiazepine should not be replaced with another class of anxiolytic, which may also cause dependence and withdrawal reactions. Benzodiazepine dose reduction needs to be gradual to avoid serious withdrawal effects. Switching to an equivalent dose of a longer-acting benzodiazepine such as diazepam allows smoother dose reduction.
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A benzodiazepine usually impairs recall of events that occurred before starting benzodiazepine treatment
With prolonged use of a benzodiazepine, the effects on memory are reversed as the sedative effect wears off
A CNS stimulant can reverse benzodiazepine-induced memory loss
Memory is repaired within about a fortnight of discontinuing a prolonged course of a benzodiazepine
A single dose of a benzodiazepine can interfere with recall of events that happen while clinically significant amount remains in the body
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5. A single dose of a benzodiazepine can interfere with recall of events that happen while clinically significant amount remains in the body
Benzodiazepines can induce sedation and anterograde amnesia ie loss of memory of events occurring after the first dose is taken. This effect is of benefit in surgery and when faced with unpleasant medical procedures.
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1. A benzodiazepine usually impairs recall of events that occurred before starting benzodiazepine treatment
Benzodiazepines can induce sedation and anterograde amnesia ie events occurring after the first dose is taken, not retrograde effects.
2. With prolonged use of a benzodiazepine, the effects on memory are reversed as the sedative effect wears off
Benzodiazepines seem to have specific amnesic effects and memory impairment cannot be fully explained by the sedative effects. Over time, tolerance develops to benzodiazepine sedative effects but memory impairment may persist even after discontinuation.
3. A CNS stimulant can reverse benzodiazepine-induced memory loss
There is no specific treatment to reverse benzodiazepine-induced memory loss. The benzodiazepine should be stopped as soon as possible, but memory may be impaired for a long time after discontinuation.
4. Memory is repaired within about a fortnight of discontinuing a prolonged course of a benzodiazepine
Memory impairment may persist for months or years after discontinuation.
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Sophie takes clonazepam for epilepsy. She has rushed into the late clinic very concerned that her 7-year-old son Louis swallowed the last 2-mg clonazepam tablet from the blister pack soon after he got back from school around 3:30 pm. Louis had his meal before Sophie noticed that the tablet was missing. It’s now 7:30 pm. Louis is quiet and a little sleepy. His colour is good and his blood pressure, pulse and respiratory rate are unremarkable. What do you do? Choose the single best answer
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Louis has taken a moderate amount of benzodiazepine by mouth and he has stable vital signs. Individuals without significant features of benzodiazepine toxicity four hours after an overdose are not likely to come to harm from the overdose.
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If a large dose of benzodiazepine has been taken by mouth in the previous hour then it may be possible to reduce absorption by giving activated charcoal. Giving a single dose of activated charcoal about four hours after ingestion of the benzodiazepine (followed by a meal!) is unlikely to be of much value. Individuals without significant features of benzodiazepine toxicity 4 hours after an overdose are not likely to come to harm from the overdose.
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Overdose with a benzodiazepine can cause drowsiness, dysarthria and nystagmus; very large overdose may cause hypothermia and rhabdomyolysis. Louis has taken a moderate amount of benzodiazepine by mouth and his vital signs are stable. Individuals without significant features of benzodiazepine toxicity four hours after an overdose are not likely to come to harm from the overdose. Urgent transfer to hospital is not warranted in the absence of worrying features of poisoning.
Correct
Overdose with a benzodiazepine can cause drowsiness, dysarthria and nystagmus. Louis has stable vital signs and given the time lapsed since the dose was taken, he is not likely to come to harm from the benzodiazepine. Deterioration is very unlikely—observing Louis at home for the next hour or so would pick up any untoward features.
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Louis has taken a moderate amount of benzodiazepine by mouth and his vital signs are stable. Adults and children without significant features of benzodiazepine toxicity four hours after an overdose are not likely to come to harm from the overdose.
Which of the following can increase the risk of adverse respiratory effects of benzodiazepines?
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Chronic obstructive pulmonary disease
Sleep apnoea
Fentanyl transdermal patches
Nicotine transdermal patches
Beta-lactam allergy
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1. Chronic obstructive pulmonary disease
Factors that increase the risk of respiratory adverse effects include respiratory disease, CNS depression from another cause, coma, neuromuscular disorders such as myasthenia gravis, sleep apnoea syndrome, and co-administration of a benzodiazepine with another CNS depressant such as opioid analgesics.
2. Sleep apnoea
Factors that increase the risk of respiratory adverse effects include respiratory disease, CNS depression from another cause, coma, neuromuscular disorders such as myasthenia gravis, sleep apnoea syndrome, and co-administration of a benzodiazepine with another CNS depressant such as opioid analgesics.
3. Fentanyl transdermal patches
Fentanyl is a potent opioid. Factors that increase the risk of respiratory adverse effects include respiratory disease, CNS depression from another cause, coma, neuromuscular disorders such as myasthenia gravis, sleep apnoea syndrome, and co-administration of a benzodiazepine with another CNS depressant such as opioid analgesics.
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4. Nicotine transdermal patches
Nicotine does not generally have a sedative effect nor does it affect respiratory function. It does not have a potential for interaction with benzodiazepines. Factors that increase the risk of respiratory adverse effects include respiratory disease, CNS depression from another cause, coma, neuromuscular disorders such as myasthenia gravis, sleep apnoea syndrome, and co-administration of a benzodiazepine with another CNS depressant such as opioid analgesics.
5. Beta-lactam allergy
Beta-lactam allergy should not cause adverse respiratory effects of benzodiazepines. There is no cross-sensitivity between beta-lactams and benzodiazepines. Factors that increase the risk of respiratory adverse effects include respiratory disease, CNS depression from another cause, coma, neuromuscular disorders such as myasthenia gravis, sleep apnoea syndrome, and co-administration of a benzodiazepine with another CNS depressant such as opioid analgesics.
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Cardiovascular side effects are rare with benzodiazepines. Benzodiazepines may rarely cause symptomatic hypotension in patients in shock or who suffer from postural hypotension.
Correct
A benzodiazepine may increase the risk of symptomatic hypotension in individuals whose blood pressure is low or are prone to postural hypotension. Care should be taken when a benzodiazepine is given intravenously or in high doses. Resuscitation facilities should be available during intravenous use of a benzodiazepine.
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There is no need to avoid the combination. Concomitant use of a benzodiazepines with an antihypertensive drug may increase hypotensive effect but benzodiazepine-induced symptomatic hypotension is relatively rare. There is no specific interaction between calcium-channel blockers and benzodiazepines. Blood pressure should be monitored to guard against the small possibility of excessive blood pressure reduction when the benzodiazepine is introduced or a rebound effect when it is withdrawn.
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Cardiovascular side effects are rare from benzodiazepines. Benzodiazepines rarely cause symptomatic hypotension and, in the absence of risk factors, blood pressure monitoring is not required during benzodiazepine treatment.
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Cardiovascular side effects are rare from benzodiazepines; symptomatic hypotension may occur in overdose. QT-interval prolongation and torsade de pointes are not typical features of benzodiazepine toxicity.
Which of the following circumstances represents appropriate use of a benzodiazepine?
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Diazepam is absorbed only slowly and erratically into the blood from the intramuscular injection site and is therefore less suitable than tablets for rapid effect. If necessary, diazepam can be given intravenously to relieve severe acute anxiety. NICE advises that a benzodiazepine should not be prescribed for the treatment of panic disorder; NICE recommends psychological treatment or drug treatment with an antidepressant—selective serotonin reuptake inhibitor (SSRI) or imipramine or clomipramine.
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A benzodiazepine, best taken the night before, can induce sedation and a period of amnesia in preparation for the dental procedure.
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A benzodiazepine is not suitable in these circumstances because its amnesic effects can interfere with appropriate psychological adjustment to loss or bereavement. In any case, it is unwise to prescribe a 4-week course of a hypnotic. If therapy is required, psychological treatment should be explored first.
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Oxazepam is indicated for anxiety which is disabling or subjecting the individual to unacceptable distress. A benzodiazepine should not be the first-choice treatment in this case. Further, benzodiazepines should generally be avoided in those with a history of drug or substance abuse.
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Benzodiazepines can worsen sleep-related breathing disorders and lormetazepam is contraindicated in sleep apnoea syndrome. Sleep apnoea occurs during deep sleep; use of a hypnotic could prevent the individual from going into a lighter state of sleep or wakefulness to restore breathing during an apnoeic episode.
Lizzie, a 58-year-old married woman was recently knocked off her bike and sustained a compound fracture to her arm. She takes up to 8 tablets of co-codamol 15/500 daily (in 4 divided doses). Lizzie was prescribed a 2-week course of a benzodiazepine hypnotic to help her sleep at night. However, she now says that she is having awful nightmares and has outbursts over quite trivial matters. What is the best course of action? (Select the single best answer.)
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The opioid in the analgesic tablets and the hypnotic can interact, but the interaction is likely to result in CNS depression rather than the symptoms Lizzie reports. Nightmares and outbursts after starting the hypnotic could be due to ‘paradoxical’ effects of benzodiazepines. Though paradoxical effects are rare, children and the elderly are more prone to them as are those with a history of alcohol abuse or of psychiatric disorder, and those taking a high dose.
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Increasing the dose could cause further difficulty since nightmares and outbursts after starting the hypnotic could be due to ‘paradoxical’ effects of benzodiazepines. Though paradoxical effects are rare, children and the elderly are more prone to them as are those with a history of alcohol abuse or of psychiatric disorder, and those taking a high dose.
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While complications following head injury cannot be fully ruled out, nightmares and outbursts after starting the hypnotic could be due to ‘paradoxical’ effects of benzodiazepines. Though paradoxical effects are rare, children and the elderly are more prone to them as are those with a history of alcohol abuse or of psychiatric disorder, and those taking a high dose.
Correct
Nightmares and outbursts after starting the hypnotic could be due to ‘paradoxical’ effects of benzodiazepines. Though paradoxical effects are rare, children and the elderly are more prone to them as are those with a history of alcohol abuse or of psychiatric disorder, and those taking a high dose.
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Lizzie’s report of these effects, which occurred after starting the hypnotic, should lead to the discontinuation of the benzodiazepine because their use is occasionally associated with ‘paradoxical’ effects which include aggression with rages and nightmares.
Which of the following sets of effects are associated with the long-term use of a benzodiazepine:
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Depression and disinhibition are recognised long-term effects of benzodiazepines but osteoporosis and pathological gambling are not characteristic effects.
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Amnesia is a recognised long-term effect of benzodiazepines and muscle relaxation and muscle weakness, which occur on short-term use, may also be present with continued use. However, parkinsonism is not a characteristic benzodiazepines effect. Though benzodiazepines have the potential for reducing blood pressure, clinically significant hypotension is unlikely.
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Depression (which, when accompanied by disinhibition, can lead to suicidality), blunting of emotions, amnesia, and poor concentration are all characteristic long-term adverse effects of benzodiazepines.
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Tolerance develops to the various effects of benzodiazepines. However, constipation, glaucoma and tardive dyskinesia are not characteristic effects of benzodiazepines.
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Ataxia can occur early during benzodiazepine use, but psychomotor impairment can also be a feature of long-term use, as is depression. Convulsions can occur on sudden withdrawal of a benzodiazepine. ECG changes are not characteristic benzodiazepine effects.
Susie, an 82-year-old lady, has been in hospital receiving treatment for community-acquired pneumonia. In hospital, three days before she was discharged, Susie was put on temazepam 10 mg at bedtime to help her sleep in the busy acute ward. On discharge, she brought home a 5-day supply of temazepam, together with some antibiotics. When you see her on the first day back, she is ‘feeling miles better’ except for ‘wooziness’ in the mornings over the last day or two. Beyond encouraging Susie to complete the course of antibiotics, how would you continue her care?
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It is necessary to switch to diazepam for managing withdrawal from a potent or short-acting benzodiazepine. With just three days’ use of temazepam, discontinuing the hypnotic treatment abruptly is not likely to cause significant difficulty. As Susie is no longer in an unfamiliar, noisy environment, she does not need to continue with a sedative.
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Susie’s ‘wooziness’ is likely to be a consequence of benzodiazepine ‘hangover’, which should resolve on stopping the drug. Adding a new medicine, without proper justification, especially in an elderly individual, is inappropriate and can lead to complications.
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Susie has been taking a benzodiazepine for only a short period—it can be discontinued without tapering the dose. If she does not require further doses, she should dispose of her unused tablets by handing them to her local pharmacy.
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Now that she is out of the unfamiliar, noisy environment, she probably doesn't need a hypnotic. Good sleep hygiene measures such as regular sleeping hours, a light meal in the evening, being active during the day, no alcohol last thing at night, comfortable sleeping environments and, a warm milky drink should do the trick!
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Susie does not require any further treatment with a benzodiazepine hypnotic and her unsteadiness should improve upon stopping the benzodiazepine.
Which of the following statements is correct about benzodiazepine-related withdrawal symptoms?
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These symptoms, together with yawning, mydriasis, gooseflesh, insomnia, sweating, anxiety, restlessness, lacrimaion, and abdominal cramp are typical of opioid withdrawal, not benzodiazepine withdrawal.
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Many symptoms of withdrawal are indistinguishable from those that led the benzodiazepine to be prescribed in the first place; rebound insomnia rather than drowsiness is likely on stopping a benzodiazepine.
Correct
Specific effects of benzodiazepine withdrawal include perceptual distortion and increased sensitivity to sensory stimuli and psychosis; other specific symptoms include depersonalisation, derealisation, hallucinations, paranoia and paraesthesia. Many features of benzodiazepine withdrawal resemble complaints that might have led to benzodiazepine prescribing in the first place—rebound insomnia and anxiety, which may be accompanied by other related and specific effects.
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A withdrawal symptom is mild systolic hypertension rather than hypotension.
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In some cases, especially following use of a long-acting benzodiazepine, withdrawal symptoms may not appear for up to 3 weeks after stopping the drug (but may appear within hours when a short-acting benzodiazepine is discontinued abruptly).