30-10-23 - Sedatives anxiolytics

Question 1

Learning outcomes

Answer 1

• Define the terms anxiolysis and sedation
• Outline the pharmacodynamics & pharmacokinetics of benzodiazepines & z-drugs
• Identify other classes of drugs used in the management of anxiety
• Define the terms tolerance, dependence & withdrawal
• Be aware of the clinical indications to prescribe anxiolytics
• Understand the role of B blockers in managing anxiety
• Discuss the therapeutic role of melatonin
• Be able to provide practical sleep hygiene advice

Question 2

Describe the 4 levels for sedation sleep depth.

Describe their effects on the body (in picture)

Answer 2

• 4 levels for sedation sleep depth

1) Minimal
* Also called anxiolysis
* The patient remains awake but relaxed, able to interact.

2) Moderate
* Also called conscious sedation
* The patient has depressed consciousness but will respond to verbal requests or react to touch.
* Breathing remains intact, and no support is needed.

3) Deep:
* The patient cannot be easily aroused but will respond to repeated or painful stimuli.
* Breathing may be impaired and may need to be supported.

4) Dissociative
* A trance-like state wherein the patient remains awake but unaware of the pain and retains no memory of the event.
* They can follow commands, and airway reflexes remain intact.

• Sedation depth effects on body (in picture)

Question 3

What can anxiolysis be used for?

Answer 3

• Anxiolysis can be used for therapeutic procedures where the patient needs to be conscious e.g endoscopy

Question 4

What medications can be used to treat prolonged epileptic seizures?

What is IV access is not available?

Answer 4

• For prolonged epileptic seizures lasting longer than 5 minutes, we can use intravenous lorazepam
• If IV access is not available consider rectal diazepam or intranasal / buccal midazolam

Question 5

What medications are often used in the Anticipatory Care Plan (ACP) for End Of Life (EOL) care?

Answer 5

• In the Anticipatory Care Plan (ACP) for End Of Life (EOL) care, Benzodiazepines often used in the last days or weeks of life
• Midazolam IV is usually drug of choice in order to manage anxiety

Question 6

NHS Fife Alcohol Withdrawal guideline

Answer 6

Question 7

What medication used in alcohol withdrawal?

Answer 7

• Chlordiazepoxide is often used to treat alcohol withdrawal

Question 8

NICE Clinical Guidelines Feb 2010 Chlordiazepoxide dosing regimes in alcohol withdrawal (in picture)

Answer 8

Question 9

What is anxiety a response to?

What 5 factors make up anxiety?

What are anxiety states?

What is the difference between ‘pathological’ and ‘normal’ state of anxiety?

Answer 9

• Anxiety is a normal fear response to threatening stimuli:
• 5 factors make up anxiety:
  1) Defensive behaviours
  2) Autonomic reflexes
  3) Arousal and alertness
  4) Corticosteroid secretion
  5) Negative emotions.
• Anxiety states are reactions that occur in an anticipatory manner with no apparent stimuli.
• Difference between ‘pathological’ and ‘normal’ state of anxiety is not clear-cut.
• Defined at the point at which the symptoms interfere with normal productive activitie

Question 10

What are 7 symptoms of anxiety?

Answer 10

• 7 symptoms of anxiety:
  1) Apprehension
  2) Cued Panic Attacks
  3) Spontaneous Panic Attacks
  4) Irritability
  5) Poor sleeping
  6) Avoidance
  7) Poor concentration

Question 11

What are 3 classifications of anxiety disorders?

Answer 11

• 3 classifications of anxiety disorders:

1) Generalised Anxiety Disorder (GAD)
* Over-arousal, irritability, poor concentration, poor sleeping and worry over several areas most of the time

2) Panic disorder
* Intermittent episodes of panic or anxiety and taking / avoiding action to prevent these feelings.
* Panic disorder may be with or without agoraphobia (a fear of being in situations where escape might be difficult or that help wouldn’t be available if things go wrong.)
* Marked somatic symptoms, such as sweating, tachycardia, chest pains, trembling and choking

3) Other anxiety disorders
* Includes:
* Phobias (episodes of anxiety triggered by external stimuli)
* Obsessive Compulsive Disorders (distressing, intrusive thought ands and related compulsions “rituals”)
* Post Traumatic Stress Disorder (delayed and / or protracted response to a stressful event or situation).

Question 12

What are 3 non-pharmacological treatments for anxiety?

Answer 12

• 3 non-pharmacological treatments for anxiety?

1) Reassurance and Lifestyle Advice
* Anxiety is normal.
* No “quick fix”.

2) Guided self help
* Mantras, mindfulness, worry time
* www.moodcafe.co.uk

3) Psychological Therapy
* Cognitive behaviour therapy

Question 13

What are 6 types of Pharmacological treatments for anxiety?

Question 14

What are 3 types of anti-depressants? What are examples of each?

Answer 14

• 3 types of anti-depressants? What are examples of each:

1) Selective serotonin (5-HT) reuptake inhibitors (SSRIs)
* e.g. escitalopram , sertraline and paroxetine )

2) Serotonin/noradrenaline reuptake inhibitors (SNRIs
* e.g. venlafaxine and duloxetine

3) Older antidepressants
* Tricyclic antidepressants e.g. amitriptyline
* Monoamine oxidase inhibitors (MAOIs) are also effective

Question 15

What are 3 examples of benzodiazepines?

What are they effective for?

How quickly do they act?

Describe the tolerance and dependence of benzodiazepines?

What is a potential adverse effect of benzodiazepines?

Answer 15

• 3 examples of benzodiazepines:
  1) Diazepam
  2) Lorazepam
  3) Temazepam
• Benzodiazepines are effective anxiolytic drugs
• Act within 30 minutes, - useful for patients who need acute treatment, and can be taken on an ‘as needed’ basis.
• Induce tolerance
• Dependence – both physical and psychological
• Benzodiazepines can be drugs of abuse and can also have unwanted side effects e.g. amnesia

Question 16

When can benzodiazepines be used for anxiety?

Answer 16

• The use of benzodiazepines to treat short term ‘mild’ anxiety is inappropriate
• Benzodiazepines are indicated for the short-term relief (two to four weeks only) of anxiety that is severe, disabling, or causing the patient unacceptable distress, occurring alone or in association with insomnia or short-term psychosomatic, organic, or psychotic illness

Question 17

What is one of the fist benzodiazepines?

What was it used for?

Answer 17

• Chlordiazepoxide/Librium is one of the first benzodiazepines
• It is used in the treatment of alcohol withdrawal

Question 18

Where are benzodiazepines well absorbed?

How long does it take until their peak effects?

What are chemical properties of benzodiazepines?

How are they metabolised?

How are they secreted?

Answer 18

• Benzodiazepines are well absorbed orally
• Peak effects 30mins – 2 hours
• Beznodiaepines are Highly lipophilic (absorbed fast and enter CNS quickly) and Highly protein bound (Big reservoir tend to be long acting)
• Hepatic metabolism (cytochrome p450)
• Renal excretion in urine

Question 19

Benzodiazepines Pharmacodynamics (what the drug does to the body)

What are 5 major effects of benzodiazepines?

How many benzodiazepines are there?

Answer 19

• Benzodiazepines Pharmacodynamics (what the drug does to the body)
• 5 major effects of benzodiazepines:
  1) Anxiolytic - reduce anxiety (α2 & α3 )
  2) Hypnotic - induce sleep (α1)
  3) Reduce muscle tone
  4) Anterograde amnesia (pros & cons)
  5) Anticonvulsant effect
• Large number of benzodiazepine - all similar actions, main difference duration of action.

Question 20

What receptors do benzodiazepines affect?

How is sedation and anxiolysis mediates through GABAA receptors?

Answer 20

• Benzodiazepines act allosterically on GABAA receptors
• Allosteric binding is the process of an effector binding to an enzyme to modify its activity
• Sedation mediated via GABAA with α1 subunit
• Anxiolysis mediated via GABAA with α2 & α3 subun

Question 21

Benzodiazepines half-life, speed of onset, and use (in picture)

Answer 21

Question 22

What are 2 examples of antiepileptics?

What are they used to treat?

What other antiepileptics might be used for generalised anxiety disorder.?

Answer 22

• 2 examples of antiepileptics:
  1) Gabapentin
  2) Pregabalin
• These antiepileptics are used to treat general anxiety disorder, although trial data on gabapentin are limited.
• Other antiepileptic drugs such as tiagabine, valproate and levetiracetam, may also be effective in treating generalised anxiety disorder

Question 23

What is an example of a 5-HT 1A receptor agonist?

What is it effective and ineffective in treating?

Answer 23

• Buspirone is a 5-HT 1A receptor agonist
• It is effective in Generalised Anxiety Disorder
• Ineffective in the treatment of phobias or severe anxiety states.

Question 24

What are 3 examples of atypical antipsychotics?

What are they effective in treating?

Answer 24

• 3 examples of atypical antipsychotics:
  1) Olanzapine
  2) Risperidone
  3) Quetiapine
• They are effective in Generalised Anxiety Disorder and posttraumatic stress disorder

Question 25

What is an example of β-Adrenoceptor antagonists?

What groups of people is it used by?

What does the effectiveness of the block depend on?

Answer 25

• Propranolol is a β-Adrenoceptor antagonists (beta-blocker)
• Sometimes used by actors and musicians to reduce the symptoms of stage fright, but their use by snooker players to minimise tremor is banned as unsportsmanlike
• Effectiveness depends on block of peripheral sympathetic responses rather than on any central effects

Question 26

What is tolerance?

Describe the 4 parts in development of tolerance for benzodiazepines?

Answer 26

• Tolerance is a physiological reaction (neuroadaption) characterised by a decrease in the effects of a drug with chronic administration requiring increasing dose to attain same effect.
• 4 parts in development of tolerance for benzodiazepines:

1) Tolerance develops quickly for sedative effects

2) More slowly for anxiolytic & anticonvulsant effects

3) Neuroadaptive due to desensitisation of inhibitory GABA receptors

4) Sensitisation of (excitatory) NMDA receptors

Question 27

How does drug dependence develop?

What are the 2 types of dependence?

What can influence dependence?

Describe the criteria for dependence (in picture)

Answer 27

• Drug dependence develops when a drug induces a rewarding experience, leading to drug taking becomes compulsive
• There is psychological and physical dependence
• Genetic factors can influence dependence
• Criteria for dependence (in picture)

Question 28

What is withdrawal a result of?

How quickly can it occur?

What are 5 symptoms/signs of withdrawal?

Answer 28

• Withdrawal is a result of physical dependence
• It can occur after relatively short courses of treatment (4 weeks)
• 5 Symptoms/signs of withdrawal:
  1) Increased anxiety
  2) Onset / exacerbation of depression
  3) Disturbed sleep
  4) Pain, stiffness, muscular aches
  5) Convulsions (seizures)

Question 29

What drugs are commonly used in abuse?

How does it alter highs and crashes?

How can it be driven?

Answer 29

• Common drugs of misuse / abuse e.g Rohypnol
• Usually, part of polydrug misuse
• Enhances “highs”
• Attenuates (reduces) “crashes”
• In part, drug abuse is iatrogenically driven (induced unintentionally by a physician or surgeon or by medical treatment or diagnostic procedures)

Question 30

What is insomnia?

Why is assessment surrounding insomnia important?

What is important in avoiding insomnia?

What group are hypnotics reserved for?

What group should be cautious using hypnotics?

Answer 30

• Insomnia is difficulty getting to sleep or staying asleep for long enough to feel refreshed the next morning
• Assessment around insomnia is important, as factors such as pain/breathlessness that cause insomnia should be treated instead of using a sleeping tablet
• Good sleep hygiene is important in avoiding insomnia
• Hypnotics reserved for the acutely distressed
• Caution in the elderly for hypnotics:
  1) Confusion
  2) Falls
  3) Slower metabolism

Question 31

What are 3 rules for prescribing in insomnia if we must prescribe?

Answer 31

• 3 rules for prescribing in insomnia if we must prescribe:

1) Short acting benzo or z-drug

2) Lowest effective dose for shortest time

3) Inform patient no repeat prescriptions & explain why
* With benzodiazepines, tolerances develop, and drugs stop working

Question 32

What is the aim of sleep hygiene?

What are 6 parts of good sleep hygiene?

Answer 32

• 6 parts of good sleep hygiene:

1) Establish a regular pattern of going to bed & getting up

2) Get regular exercise preferably in the morning but not within 4 hours of going to bed

3) Keep your bedroom cool, dark & quiet

4) Don’t have caffeine, alcohol or smoke within 6 hours of bedtime

5) Avoid screen time for at least 30mins before bed

6) Avoid naps during the day

Question 33

What are 3 examples of Z drugs?

What is their mechanism of action?

How do they compare to benzodiazepines?

When should we consider Z drugs?

What is their a risk of?

Answer 33

• 3 examples of Z drugs:
  1) Zopiclone
  2) Zolpidem
  3) Zaleplon
• Z drugs act via benzodiazepine receptors (GABAA receptors)
• Z drugs are structurally different, but have a very similar pharmacodynamic profile to benzodiazepines
• Consider in elderly shorter half-life means less hangover
• Consider if risk of misuse
• With Z drugs, there is a fall risk

Question 34

What is melatonin?

What is it synthesised by?

When are melatonin levels high and low?

What conditions it is licensed for?

Answer 34

• Melatonin is a naturally occurring hormone
• It is synthesized in pineal gland
• There are high levels at night, low during day
• Serotonin is licensed for insomnia > 55yrs – not SMC (Scottish medical consortium) approved, lack of evidence?
• Can have specialists use it in children with sleep disturbance.

Question 35

Describe the Law on driving (October 2019).

What 3 types of medications does this law cover?

Answer 35

• Law on driving (October 2019)
• This law states that it is an offence to drive with certain drugs above specified levels in the body, whether your driving is impaired or not
• If you are taking these medicines as directed and your driving is not impaired, then you are not breaking the law
• This law covers:
  1) Benzodiazepines
  2) Opioids
  3) Amphetamines