Anxiolytics and Sedatives

Question 1

What are barbituates used for?

Answer 1

Still used as IV induction agents and anticonvulsive

Question 2

What are the classes of drugs used for anxiety?

Answer 2

• ANtidepression,
• Benzodiazapines,
• Z-drugs,
• B-blockers,
• Others (melatonin or sedating antihistamines)

Question 3

In what condition are beta blockers contrainticated?

Answer 3

Asthma

Question 4

Describe chemical features of benzodiazepine?

Answer 4

Highly lipophilic (get into the brain quickly) which is absorbed orally.
Highly protein bound (long half life), Hepatic metabolism into active metabolites.
Excreted as glucoronide conjugate.

Question 5

What are the pharmcokinetics of benzodiazepine?

Answer 5

Allosteric agonists of GABA receptors (selectively permeable to chloride ions).
Because they are highly protein bound, they have a big reservoir so tend to be long acting.
Peak effects from 30mins-2hours.
Has renal excretion

Question 6

Describe features of GABA receptors

Answer 6

• Pentameric arrangement (two alpha, two beta and one gamma subunits) with central chloride ion channel.
  Anaesthetics and benzos allosterically activate the receptor, increasing the frequency of opening

Question 7

What are the 5 major effects of benzodiazepines?

Answer 7

1) Anxiolytics (reduced anxiety),
2) Hypnotic (induced sleep),
3) Reduce muscle tone,
4) Anterograde amnesia,
5) Anticonvulsant effect

Question 8

What are the routes of administration of Benzodiazepines?

Answer 8

• Normally given orally or intravenously (can be intranasal or rectal route),
• Not advised to be given IM because it is painful

Question 9

The sedative/anxiolysis effects of drugs is via what part of the GABA receptor?

Answer 9

Sedation mediated via alpha 1 subunit.

Anxiolysis mediated via GABA(A) with alpha2 and alpha3 subunits.

Question 10

Name the competitive antagonist of benzodiazepines

Answer 10

Flumazenil however may precipitate to agitation and seizures. It is given IV in 100mcg increments. Side effects of nausea and vomiting.

Question 11

Describe features of Z drugs

Answer 11

They act via benxodiazepine receptors and while they have similar pharmacodynamic profile, they are structurally different. Shorter half life so less of hangover.

Question 12

Name examples of Z drugs

Answer 12

• Zopiclone,
• Zaleplon,
• Zolpidem

Question 13

What is tolerance?

Answer 13

Physiological reaction characterized by a decrease in the effects of drug with chronic administeration

Question 14

Describe tolerance of Benzodiazepines

Answer 14

• Tolerance develops quickly for sedative effects but slower for anxiolytics and anticonvulsive.
• Occurs due to desensitisation of inhibitory GABA receptors but causes sensitisation of NMDA receptors

Question 15

What are the concerns of benzodiazepines?

Answer 15

The drug induces a rewarding experience and so taking the drug becomes compulsive.
They enhance highs of other drugs and blunts the lows of other drugs so used as part of polydrug misuse.

Question 16

Describe features of benzodiazepine withdrawal

Answer 16

• Occurs as a result of physical dependence (can occur after short course of treatment) and causes;
• Increased anxiety,
• Disturbed sleep,
• Pain, stiffness and muscular aches,
• Convulsions

Question 17

When is it common to prescribe benzodiazepines

Answer 17

• Management of acute alcohol withdrawal,
• Terminal care pathway,
• Enable potentially uncomfortable diagnostic and theraputic procedures to be carried out,
• Anticonvulsive.

Question 18

Explain the management of alcohol withdrawal

Answer 18

• Take alcohol history, use severity of alcohol dependence questionnaire and assess withdrawal symptoms then use chlordiazepoxide 1-2 week reducing regime

Question 19

What are the symptoms of alcohol withdrawal?

Answer 19

• Insomnia, anxiety, restlessness or agitation,
  Tremor,
• Nausea and vomiting,
• Sweating,
• Palpitations,
• Hallucinations (auditory/visual/tactile)
• Seziures

Question 20

What are investigations suggestive of chronic alcohol consumption?

Answer 20

• Raised MCV,
• Pancytopenia (as a result of alcohol induced bone marrow suppression),
• Folate Deficiency,
• Prolonged prothrombin time

Question 21

Describe some sleep hygiene measures

Answer 21

• Establish regular pattern of going to bed,
• Exercise,
• Keep bedroom cool, dark and quiet,
• Don’t have caffine, alcohol or smoke within 6 hours of bedtime,
• Avoid screen time for at least 30mins before bed,
• Avoid naps during day,
• Bed is for sleep and sex.

Question 22

If you MUST prescribe for insomnia then?

Answer 22

Use short acting benzo or z-drugs at the lowest effective dose for shortest time. No repeat prescriptions

Question 23

Describe the use of benzodiazepines in anticipatory care plans

Answer 23

• Used for management of follow;
• anxiety,
• Massive terminal haemorrhage,
• Agitated delirium,
• Breathlessness or respiratory diseases (alongside opioids)
  Often midazolam

Question 24

Describe the management of prolonged seziures?

Answer 24

Protect patient from injury,

• Provide oxygen if available,
• Consider or exclude of hypoglycaemia,
• If seizures last longer than 5 mins then IV lorazepam but if you can give IV then consider rectal diazepam or intranasal/buccal midazolam.

Question 25

Describe the management of acute anxiety

Answer 25

Guided self help (reduced caffeine, reduced alcohol, mantras, mindfulness, worry time or CBT),
- Don’t use benzodiazepines!

Question 26

When are gabapentin and pregabalin used?

Answer 26

Used to management chronic pain and has an inhibitory modulation of excitatory neurotransmitters (glutamate)

Question 27

Describe features of melatonin?

Answer 27

It is a naturally occurring hormone synthesised in the pineal gland which increases at night. It is secreted in response to input from retina (often used in children with sleep disturbances)