Psychiatry - Anxiolytics and hypnotics Flashcards
Anxiolytics and hypnotics
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
How long should hypnotics/ anxiolytics be prescribed for?
Short term relief of severe anxiety and insomnia - 2-4wks
This is because long term use can lead to physical and psychological dependance
What receptor do BDZs work on?
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
Different BDZs are used as hypnotics and anxiolytics. What determines this choice and give some examples?
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
What is the mechanism of action of benzodiazepines?
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
Is the dose different for BDZs used for anxiety compared to insomnia?
Yes
BDZs used for insomnia are prescribed at a higher dose than anxiety owing to shorter elimination half lives
Examples of BDZs
Diazepam (epilepsy + anxiety)
Lorazepam (epilepsy + acute attacks of panic disorders)
Chlordiazepoxide (usually used for alcohol withdrawal syndrome)
Nitrazepam (hypnotic)
Midazolam (preoperative sedation)
Contraindications to using BDZs
Absolute:
- respiratory depression or failure
Relative:
- Muscle weakness
- Hepatic or renal impairment
What are common side effects of BDZs?
Impaired judgement and increased reaction time Hangover effect next day: drowsiness Confusion: especially in elderly Ataxia Respiratory depression (at high doses)
Features of BDZ withdrawal
Rebound increase in agitation/ insomnia Hallucinations Epileptic seizures Nausea Depression
Significant interactions of BDZs
1) Increase sedative effect with alcohol, barbiturates and antihistamines
2) Enhanced hypotensive effect when given with all classes of antihypertensive
When should beta blockers be considered for anxiety?
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
Zopiclone and zolpidem
= 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
Do BDZs up regulate liver enzymes?
BDZs are active orally and metabolised in the liver by oxidation but do not up regulate liver enzymes
Are BDZs dangerous in overdose?
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
When are intravenous BDZs used?
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
Are there different types of hypnotic BDZs?
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
Why are barbiturates more dangerous than BDZs?
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
What antidepressants can be used as anxiolytics?
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
