Alcohol withdrawal

Question 1

Benzodiazepines

Common indications

Answer 1

1. In the first-line management of seizures and status epilepticus
2. In the first-line management of alcohol withdrawal reactions
3. As common choice for sedation for interventional procedures, in general anaesthesia is unnecessary or undesirable
4. For short-term treatment of severe, disabling or distressing anxiety
5. For short-term treatment of severe, disabling or distressing insomnia

Question 2

Benzodiazepines

MOA

Answer 2

• Target GABA-a receptors
• GABA-a receptors is a Cl channel that opens in response to binding by GABA, the main inhibitory neurotransmitter in the brain
• Opening the channel allows chloride to flow into the cell, making the cell more resistant to depolarisation
• BZ facilitate and enhance the binding of GABA to the GABAa receptor
• This has a widespread depressant effect on synaptic transmission
• The clinical manifestations of this include reduced anxiety, sleepiness, sedation and anticonvulsive effects
• Ethanol also acts on GABAa, and in chronic excessive use the patient becomes tolerant to its presence
• Abrupt cessation then provokes the excitatory state of alcohol withdrawal
• This can be treated by introducing a BZ, which can then be withdrawn in a gradual and more controlled way

Question 3

BZ

Adverse effects

Answer 3

• Predictably, BZ cause dose-dependent drowsiness, sedation and coma
• There is relatively little cardiorespiratory depression in BZ overdose (in contrast to opioid overdose), but the loss of airway reflexes can lead to airway obstruction and death
• If used repeatedly for more than a few weeks, a state of dependence can d.evelop
• Abrupt cessation then produces a withdrawal reaction similar to that seen with a.lcohol

Question 4

BZ

Warnings

Answer 4

• The elderly are more susceptible to the effects of BZs so should receive lower doses
• BZ is best avoided in patients with significant respiratory impairment or neuromuscular disease (myasthenia gravis)
• They should also be avoided in liver failure as they may precipitate hepatic encephalopathy; if their use is essential (e.g. for alcohol withdrawal)
• Lorazepam may be the best choice, as it depends less on the liver for its elimination

Question 5

BZ

Interactions

Answer 5

• The effects of BZs are additive to those of other sedating drugs, including alcohol and opioids
• Most depend on CYP P450 enzymes for elimination, so concurrent use with CYP P450 inhibitors (e.g. amiodarone, diltiazem, macrolides, fluconazole, protease inhibitor) may increase their effects

Question 6

BZ

Communication

Answer 6

• When treating insomnia and anxiety, advise your patient that pharmacological therapy is only a short-term measure
• Discuss the risks of dependence, advising that this can be minimised by avoiding daily use if possible and taking them for no longer than four weeks
• Advise patients that they should not drive or operate complex or heavy machinery after taking the drug, and caution them that sometimes sleepiness may persist the following day