Psychiatry - Anxiolytics and hypnotics

Question 1

Anxiolytics and hypnotics

Answer 1

Anxiolytics = drugs designed to reduce anxiety

Hypnotics = drugs used to induce sleep

BDZs are the most common drug used in these conditions - they will induce sleep when given in high doses at night and reduce anxiety when given at low doses during the day

Question 2

How long should hypnotics/ anxiolytics be prescribed for?

Answer 2

Short term relief of severe anxiety and insomnia - 2-4wks

This is because long term use can lead to physical and psychological dependance

Question 3

What receptor do BDZs work on?

Answer 3

GABA(A) receptors - 5 subunits (gamma important for BDZ sensitivity)
GABA = inhibitory neurotransmitter linked to Cl- channels
Binding of GABA to its receptor increases the permeability of the channel to Cl- which hyper polarises neurones and reduces excitatory transmission

Question 4

Different BDZs are used as hypnotics and anxiolytics. What determines this choice and give some examples?

Answer 4

Duration of action is the main choice

Many BDZs are metabolised in the liver into active metabolites which may have longer elimination half lives than the parent drug - e.g. diazepam

Hypnotics - temazepam, nitrazepam, lormetazepam
Anxiolytics - lorazepam, diazepam

Question 5

What is the mechanism of action of benzodiazepines?

Answer 5

Act on GABA(A) receptors - bind to specific benzodiazepine modulatory receptors and potentiate the effects of GABA

NB - barbiturates act at a separate binding site

Question 6

Is the dose different for BDZs used for anxiety compared to insomnia?

Answer 6

Yes

BDZs used for insomnia are prescribed at a higher dose than anxiety owing to shorter elimination half lives

Question 7

Examples of BDZs

Answer 7

Diazepam (epilepsy + anxiety)
Lorazepam (epilepsy + acute attacks of panic disorders)
Chlordiazepoxide (usually used for alcohol withdrawal syndrome)
Nitrazepam (hypnotic)
Midazolam (preoperative sedation)

Question 8

Contraindications to using BDZs

Answer 8

Absolute:
- respiratory depression or failure

Relative:

• Muscle weakness
• Hepatic or renal impairment

Question 9

What are common side effects of BDZs?

Answer 9

Impaired judgement and increased reaction time
Hangover effect next day: drowsiness 
Confusion: especially in elderly
Ataxia
Respiratory depression (at high doses)

Question 10

Features of BDZ withdrawal

Answer 10

Rebound increase in agitation/ insomnia
Hallucinations
Epileptic seizures 
Nausea
Depression

Question 11

Significant interactions of BDZs

Answer 11

1) Increase sedative effect with alcohol, barbiturates and antihistamines
2) Enhanced hypotensive effect when given with all classes of antihypertensive

Question 12

When should beta blockers be considered for anxiety?

Answer 12

Beta blockers - e.g. propranolol - have little value in treating morbid anxiety

They are more suitable for patients with performance anxiety

Standard dose is 40mg of propranolol before a predictably anxiety provoking situation

Question 13

Zopiclone and zolpidem

Answer 13

= short acting non benzodiazepine hypnotics (cyclopyrrolone)

Molecular structure does not resemble BDZs they are thought to act through a similar mechanism

Used for short term relief of insomnia

Question 14

Do BDZs up regulate liver enzymes?

Answer 14

BDZs are active orally and metabolised in the liver by oxidation but do not up regulate liver enzymes

Question 15

Are BDZs dangerous in overdose?

Answer 15

BDZs are central depressants but their maximum effect when given orally does not normally cause fatal or even severe respiratory depression

Respiratory depression may occur in patients with existing pulmonary disease

Question 16

When are intravenous BDZs used?

Answer 16

IV BDZs (e.g. diazepam, lorazepam) are used in status epileptics

They can be used in severe panic attacks but oral alprazolam is probably safer

Midazolam (unlike other BDZs) forms water soluble salts and is used as an IV sedative during endoscopic or dental procedures

Question 17

Are there different types of hypnotic BDZs?

Answer 17

Yes - hypnotics can be divided into short and long acting

Short acting agents (e.g. temazepam) are rapidly eliminated and are usually preferred to avoid daytime sedation

Long acting agents (e.g. nitrazepam) may be better if early morning waking is a problem and when a daytime anxiolytic effect is needed

Question 18

Why are barbiturates more dangerous than BDZs?

Answer 18

Barbiturates are far more depressive than BDZ because at high doses they directly increase Cl- conductance and decrease the sensitivity of postsynaptic membrane to excitatory neurotransmitters

They are more likely to cause dependance, induce enzymes and can be fatal in OD so they are no longer used as anxiolytics or hypnotics

Question 19

What antidepressants can be used as anxiolytics?

Answer 19

Tricyclic antidepressants - e.g. amitriptyline
- useful in patients who have anxiety and depression or require long term anxiolytic drugs where BDZs would result in dependence

MAOis - e.g. Moclobemide may be useful in phobic anxiety

SSRi’s - e.g. citalopram may be useful in panic disorder