Sedatives anxiolytics

Question 1

Barbituants

Answer 1

• narrow therapeutic index
• Obsolete as anxiolytics
• Still used as IV induction agents
• Anti convulsants

Question 2

Properties of benzodiazepines

Answer 2

• Highly lipophilic
• Well absorbed orally
• Highly protein bound
• Hepatic metabolism
• Active metabolites

Question 3

What are Benzodiazepines excreted as?

Answer 3

Gluconoride conjugate

Question 4

What are the major effects of benzodiazepines?

Answer 4

• Anxiolytic: reduce anxiety
• Hypnotic: induce sleep
• Reduce muscle tone
• Anterograde amnesia (pros and cons)
• Anticonvulsant effects

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

Describe the structure of GABA a receptors

Answer 6

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

Question 7

What allosterically activates the GABA a receptor

Answer 7

• Anaesthetics

* Benzodiazepines

Question 8

What is flumazenil

Answer 8

Competitive bezodiazipine antagonist

Question 9

What are the side effects of flumazenil?

Answer 9

• nausea
• Vomiting
• may precipitate agitation and seizures

Question 10

How is flumazenil given?

Answer 10

IV in 100microgram increments

Question 11

What are Z drugs?

Answer 11

• Act via benzodiazepine receptors
• Zopiclone
• Zalepam
• Zolpidem

Question 12

What is tolerance?

Answer 12

Physiological state characterised by a decrease in the effects of a drug with chronic administration

Question 13

Describe the tolerance of benzodiazepines

Answer 13

• Tolerance develops quickly for sedative effects

* More slowly for anxiolytic and anticonvulsant effects

Question 14

What is the mechanism for tolerance?

Answer 14

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

Question 15

Describe dependence

Answer 15

• Drug induces a rewarding experience
• Drug taking becomes compulsive
• Psychological dependence
• Physical dependence
• Genetic factors

Question 16

Describe withdrawal

Answer 16

• A result of physical dependence
• Increased anxiety, onset/exacerbation of depression
• Disturbed sleep
• Pain, stiffness, muscular aches
• Convulsions
• Can occur after relatively short courses of treatment

Question 17

What are the clinical roles for sedatives and anxiolytic agents?

Answer 17

• enable potentially uncomfortable diagnostic and therapeutic procedures to be carried out
• management of acute alcohol withdrawal
• Management of insomnia
• Management of generalised anxiety states
• other: anticonvulsant

Question 18

Index of suspicious of alcohol dependence

Answer 18

• Alcohol history
• Severity of alcohol dependence questionnaire
• Assessment of withdrawal symptoms

Question 19

CAGE questionnaire

Answer 19

• Have you ever felt you should cut down on your drinking?
• Have you ever been annoyed by other people criticising your drinking?
• Have you ever felt guilty about drinking
• Have you ever taken a drink in the morning to steady your nerves or ease a hangover

Question 20

What are the symptoms of alcohol withdrawal?

Answer 20

• Insomnia/anxiety/ restlessness/ agitation
• Tremor
• Nausea and vomiting
• Sweating
• Palpitations
• Hallucinations auditory/visual/tactile
• Seizures

Question 21

When do symptoms of alcohol withdrawal start and when do they peak?

Answer 21

• May start 8 hours after drop in alcohol levels

* Peak day 2

Question 22

What investigations are suggestive of chronic alcohol consumption?

Answer 22

• Raised MCV
• Pancytopenia
• Folate deficiency
• Prolonged prothrombin time

Question 23

why may someone with chronic alcohol consumption have pancytopenia?

Answer 23

Alcohol induced bone marrow suppression

Question 24

What drug can be given in alcohol withdrawal?

Answer 24

Chlordiazepoxide

Question 25

What is sleep hygiene?

Answer 25

Aims to make people more aware of behavioural, environmental and temporal factors that may be detrimental or beneficial to sleep

Question 26

Good sleep hygiene

Answer 26

* establish a regular pattern of going to bed and getting up * Get regular exercise preferably in the morning but not within 4 hours of going to bed * Keep your bedroom cool, dark and quiet * Don't have caffeine, alcohol or smoke within 6 hours of bedtime * Avoid screen time for at least 30 minutes before bed * Avoid naps during the day * Bed is for sleep and for sex

Question 27

If you must prescribe for insomnia, what should you do?

Answer 27

* Short acting benzodiazepine or z-drug * Lowest effective dose for shortest time * Inform patient no repeat prescriptions and explain why

Question 28

Management of prolonged seizures

Answer 28

* Protect the patient from injury * Provide oxygen if available * Consider/exclude hypoglycaemia * Seizures lasting longer than 5 minutes: IV lorazepam * If intravenous access not available, consider rectal diazepam or intranasal or buccal midazolam

Question 29

What is melatonin?

Answer 29

* Naturally occurring hormone synthesised in the pineal gland * high levels at night, low during the day * Secreted in response to input from the retina