2. Sedatives anxiolytics

Question 1

Why were barbiturates discontinued?

Answer 1

Dependence / addiction / misuse narrow therapeutic index

Suicide easily done e.g. marylyn munroe and jimmy henricks

Also used as IV induction agents and anti convulsant

So…
Become obsolete as anxiolytics

Question 2

Classess of sedatives and anxiolytics?

Answer 2

• Antidepressants
• Benzodiazepines (1960s)
• Z-drugs (1990)
• B-blockers
• Other
– Melatonin
– Sedating antihistamine

Question 3

Properties/formulation of benzodiazepine?

Answer 3

Serendipity? (librium)
Highly lipophilic: so easily absorbed
Well absorbed orally
Highly protein bound (95%) Hepatic metabolism
Active metabolites, so can last for hours
Excreted as glucoronide conjugate.

Question 4

5 major effects of benzodiazepines?

Answer 4

1. Anxiolytic: reduce anxiety (α2 & α3 )
2. Hypnotic: induce sleep (α1)
3. Reduce muscle t§one
4. Anterograde amnesia (pros&cons)
5. Anticonvulsant effect

Question 5

Administration of benzodiazepines?

Answer 5

• Normally given orally or intravenously – (can be given by intranasal or rectal route)
Not advised to be given intramuscular route

Question 6

Categorisation of benzodiazepines?

Answer 6

SHORT ACTING
Lorazepam, temazepam t1/2 8-12 hours intermediate

LONG ACTING
Diazepam t1/2 20-100

Question 7

Structure of GABAa receptor?

Answer 7

• Pentameric arrangement
• Central ion channel pore
• 18 possible subunits
• Approx 30 forms of receptor
• Some subunits location specific

Question 8

Role of GABAa receptor?

Answer 8

• Anaesthetics and benzos allosterically activate the receptor
• Increase the frequency of opening

Act allosterically on GABAa receptors
Sedation mediated via GABAa with α1 subunit
– Anxiolysis mediated via GABAA with α2 & α3 subunits

Question 9

Flumazenil:
Class?
Half life?
Precipitates?
Administration?
SE?

Answer 9

Class: Competitive benzo antagonist
Half life: Short
Precipitates: Agitation and seizures
Administration: IV in 100mcg increments
SE: N/V

Question 10

Z drugs:
Act where?
Eg?

Answer 10

Act via benzodiazepine receptors
– Zopiclone
– Zaleplon
– Zolpidem

No benefit over z drugs and short acting benzo

Question 11

What is tolerance

Answer 11

Is a physiological state characterized by a decrease in the effects of a drug with chronic administration.

Question 12

Tolerance of benzo?

Answer 12

Tolerance develops quickly for sedative effects

more slowly for anxiolytic & anticonvulsant effects.

Question 13

Mechanism for tolerance?

Answer 13

• Neuro-adaptive process
• Desensitisation of inhibitory GABA receptors • Sensitisation of (excitatory) NMDA receptors • Adaptions take place on different time scale

Question 14

What is dependance?

Answer 14

• The drug induces a rewarding experience
• Drug taking becomes compulsive

Genetic component*

Question 15

Two forms of dependence?

Answer 15

Psychological and physical

Question 16

Withdrawl is a result of…

Answer 16

dependence

Question 17

Symptoms of withdrawal?

Answer 17

• Increased anxiety, onset / exacerbation of
depression
• Disturbed sleep
• Pain, stiffness , muscular aches
• Convulsions
• Can occur after relatively short courses of treatment (4 weeks)

Question 18

Clinical role of sedative and anxiolytic agents?

Answer 18

Enable potentially uncomfortable diagnostic and therapeutic procedures to be carried out
Management of acute alcohol withdrawn
Management of insomnia
Management of generalised anxiety states
Other: Anticonvulsants

Question 19

How to manage acute alcohol withdrawl?

Answer 19

• Acute admissions to hospital
• Supply of alcohol interrupted
• Index of suspicion…
– Alcohol history
– Severity of alcohol dependence questionnaire
– Assessment of withdrawal symptoms
Chlordiazepoxide 1-2 week reducing regime

Question 20

What are the 4 questions of the CAGE questionnaire when approaching potential alcohol withdrawal cases?

Answer 20

C• Have you ever felt you should Cut down your drinking?
A• Have you ever been Annoyed by other people criticizing your drinking?
G• Have you ever felt Guilty about drinking?
E• Have you ever taken a drink in the morning to steady your nerves or ease a hangover (Eye- opener)?

Question 21

Alcohol withdrawal symptoms?

Answer 21

**May start 8 hours after drop in alcohol levels (peak day 2) **
Insomnia / anxiety/ restlessness/ agitation
Tremor
Nausea & vomiting
Sweating
Palpitations
Hallucinations auditory / visual/tactile
Seizures

Question 22

Investigation results that suggest chronic alcohol consumption?

Answer 22

• Raised MCV
• Pancytopenia (result of alcohol induced bone
marrow suppression
• Folate deficiency
• Prolonged prothrombin time

Question 23

How to treat alcohol withdrawl?

Answer 23

Chlordiazepoxide dosing regimes in alcohol withdrawal

Question 24

How to manage insomnia?

Answer 24

Try not to lol

Assess the source FIRST
Hypnotics reserved for the acutely distressed

Avoid benzo administration for insomnia in elderly bc

1. Confusion
2. Falls
3. Slower metabolism

Question 25

What is sleep hygiene?

Answer 25

Sleep hygiene aims to make people more aware of behavioural, environmental & temporal factors that may be detrimental or beneficial to sleep

Question 26

How to encourage good sleep hygiene?

Answer 26

Get into routine Exercise in morning, not within 4 hrs of sleep Bedroom = cool, dark, quiet No caffiene, alcohol or smoke within 6 hrs Screen time not 30 mins before bed No day naps

Question 27

Drug treatment for insomnia?

Answer 27

TO BE AVOIDED Short acting benzo or z-drug Lowest dose for shortest period no repeat prescriptions. Explain? Tolerance makes it ineffective

Question 28

Considerations when managing prolonged seizures?

Answer 28

DO IT, need to protect patient from injury Provide 02 is available Consider/exclude hypoglycaemia Lorazapam: For seizures 5 mins ++ Route: IV access. If not possibile, then rector diazepam or intranasal/buccal midazolam

Question 29

``` Minimal sedation (anxiolysis) definition? Responsiveness Airway Spontaneous ventilation CV function ```

Answer 29

Responsiveness: Normal response to verbal stimulation Airway: Unaffected Spontaneous ventilation: Unaffected CV function: Unaffected

Question 30

``` Moderate sedation/analgesia (conscious sedation) definition? Responsiveness Airway Spontaneous ventilation CV function ```

Answer 30

Responsiveness: Purposeful* response to verbal or tactile stimulation Airway: No intervention required Spontaneous ventilation: Adequate CV function: Usually maintained

Question 31

``` Deep sedation/analgesia? Responsiveness Airway Spontaneous ventilation CV function ```

Answer 31

Responsiveness: Purposeful response after repeated or painful stimulation Airway: Intervention may be required Spontaneous ventilation: May be inadequate CV function: Usually maintained

Question 32

``` General analgesia? Responsiveness Airway Spontaneous ventilation CV function ```

Answer 32

Responsiveness: Unarousable, even w/painful stimulus Airway: Intervention often required Spontaneous ventilation: Frequently inadequate CV function: May be impaired

Question 33

Acute anxiety management?

Answer 33

Anxiety is a normal. It becomes a problem if it starts to interfere with your everyday life. No “quick fix” Guided self help: • reduce caffeine, reduce alcohol • Mantras, mindfulness, worrytime Cognitive behaviour therapy

Question 34

Use of benzo in acute anxiety management?

Answer 34

Just don't! “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 35

Use of b-blockers in acute anxiety treatment?

Answer 35

Helps with tachycardia, palpitations, tremor and sweating Blocks sympathetic system Usually: Propranolol Advantages: non-sedative, no dependence or abuse

Question 36

SSRI withdrawal profile?

Answer 36

– Nausea / diarrhoea – Insomnia – Sexual dysfunction – Suicidal behaviour (is it toxic in OD)

Question 37

Use of gabapentin and pregabalin?

Answer 37

Management of chronic pain

Question 38

Melatonin: What is it? Fluctuation of level? Use?

Answer 38

What is it? Naturally occurring hormone Synthesized in pineal gland Secreted in response to input from retina. Level change: High levels at night, low during day Use: Clinically often used in children with sleep disturbance.

Question 39

Law on driving (March 2015)

Answer 39

* 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 * Benzos, opioids, amphetamines