The Benzos

Question 1

What should patient be educated on?

Answer 1

Patients should be educated to have realistic sleep expectations and should be advised to find and treat the underlying cause of insomnia. This includes considering alcohol, drug and caffeine use. However, pharmacological interventions can be made

Question 2

What do hypnotics do?

Answer 2

Hypnotics induce sleep by modulating the effects of GABA at the GABAa receptor, causing sedation.

Question 3

What are benzodiazipines?

Answer 3

Benzodiazepines should be used to treat insomnia only when it is severe, disabling, or causing the patient extreme distress.Acting on GABAa chloride channels (on the gamma subunit), they induce Cl- conduction, inhibiting the AP. This enhances the action of the inhibitory neurotransmitter, GABA, causing sedation. BDZ induce and increase the duration of sleep.Benzodiazepine-derivatives are not traditional BDZ but have BDZ activity.

Question 4

Example of 2 BDZ?

Answer 4

Diazepam 5–15 mg ON,Temazepam 10–20 mg ON

Question 5

What are the side- effects of BDZ?

Answer 5

BDZ depress REM and slow-wave sleep, so quality of sleep and memory formation is negatively affected. As a result, continuous use can cause amnesia, ataxia (movement disorders) and impaired memory/ cognition. In the elderly, hypnotic use is attributed to an increased risk of falls and confused state. Hypnotics should be used for a maximum of two weeks, so REM deprivation does not occur.

Question 6

Paradoxical effects occur in < 1% of patients

Answer 6

It causes increased excitement, excessive talking, restlessness, agitation and aggression. If these occur, flumazenil, a competitive benzodiazepine antagonist at GABAa, can be given.

Question 7

There are various factors which may predispose one to these effects, including:

Answer 7

• Very young/ very old – varying pharmacokinetics
• Alcoholism – effect on GABA
• Psychiatric disorders
• Genetic polymorphism affects response

Question 8

What are the councelling points for BDZ?

Answer 8

Counselling points
Patients should be advised not to drive, because the sedative effects of BDZs can impair concentration. As of 2015, “driving, attempting to drive, or being in charge of a vehicle, with certain specified controlled drugs in excess of specified limits” is an offence. One can be prosecuted unless the drugs was prescribed and there is no effect of impairment on driving.

Question 9

Patients should be warned of the risks of dependence-

Answer 9

it can occur within a 7-10 days and. If suspected, the patient should begin gradual withdrawal. Withdrawal symptoms include confusion, psychosis, convulsions or tremors

Question 10

Withdrawal syndrome occurs more rapidly for short acting DBZ

Answer 10

withdrawal may occur up to three weeks after abrupt withdrawal in longer-acting agents.
1. Transfer patient stepwise, one dose at a time over about a week, to an equivalent daily dose of diazepam preferably taken at night.
2. Reduce diazepam dose, usually by 1–2 mg every 2– 4 weeks. If uncomfortable withdrawal symptoms occur, maintain this dose until symptoms lessen.
3. Reduce diazepam dose further, if necessary, in smaller steps of 500 micrograms. Then stop completely.
For long-term patients, the period needed for complete withdrawal may vary from
several months to a year or more

Question 11

What are Non-benzodiazepine hypnotics – Z-drugs?

Answer 11

Zolpidem tartrate and zopiclone
are non-benzodiazepine hypnotics (sometimes referred to as Z-drugs), but they act at the benzodiazepine receptor. They are not licensed for long-term use; dependence has been reported in a small number of patients. Both zolpidem tartrate and zopiclone have a short duration of action.

Question 12

What are Anti-cholinergic agents?

Answer 12

Diphenhydramine is an anti-histamine with anti- muscarinic activity (antagonist at H and M receptors). It crosses the blood-brain- barrier that blocking the arousing influence of central histamine causing drowsiness and promoting sleep. It may have effects on 5-HT1 receptor

Question 13

CNS-acting dopamine antagonists (SGA antipsychotics)

Answer 13

have a sedative action due to histamine receptor occupancy

Question 14

What are Barbiturates?

Answer 14

The intermediate-acting barbiturates should only be used in the treatment of severe intractable insomnia, in patients already taking barbiturates. They should be avoided in the elderly

Question 15

What are Melatonin receptor agonists?

Answer 15

A potential new treatment (still in clinical trials) involves enhancing the activity of melatonin

Question 16

How does alcohol work?

Answer 16

Alcohol depresses neuronal activity – it is an agonist at GABAa receptors and a antagonist at NMDA receptors (for electrical signals to pass, the NMDA receptor must be open and to remain open, glutamate and glycine must bind to the NMDA receptor – antagonist action prevents NMDA activation). Alcohol is a poor hypnotic because the diuretic action interferes with sleep during the latter part of the night. Alcohol also disturbs sleep patterns, and so can worsen sleep disorders. Using alcohol with hypnotics may cause respiratory depression due to CNS toxicity