BP.17 Anxiolytics, sedatives and hypnotics

Question 1

What is the function of anxiolytics?

Answer 1

alleviate fear and anxiety

Question 2

What is the function of sedatives?

Answer 2

alleviate fear and anxiety

produce a degree of amnesia and analgesia

Question 3

What is the function of hypnotics?

Answer 3

induce sleep

Question 4

Names sadations in dentistry taken:

1) inhalation
2) oral (2)
3) intravenous
b) do you need local anaesthetics?

Answer 4

1) nitrous oxide
2) benzodiazepines and H1 antagonists (side effect – drowsiness)
3) benzodiazepines
b) yes

Question 5

sedation vs general anaesthesia

Answer 5

general is last resort, it is like deep sedation.

Question 6

Go from lowest sedative dose upwards

Answer 6

1. anxiety relief
2. sedation
3. hypnosis
4. general anaesthetisa

Question 7

What are barbituates?

1b) How do they work?
2) WHat replaced them?
3) Why?

Answer 7

general anaesthetic

1b) inhibit excitatory neurotransmitter, increase GABA transmission,
2) benzodiazepines
3) barbituates have toxic side effects and easy to overdose.

Question 8

What pychological traits do benzodiazepines reduce?

2) What else can they do?

Answer 8

reduction of anxiety and aggresssion

2) sedation and induction of sleep (if sleeping for less than 6hrs)
3) muscle relaxation (
4) some have anticonvulsant effect
5) induces amnesia
6) induces amnesia

Question 9

1) Are benzodiazepines pos or neg, allosteric or orthosteric modulators?
2) Describe mode of action:
3) Would their effect be seen on their own?

Answer 9

Positive allosteric modulators

2) GABA and BDZ bind to independent sites of the same receptor-Cl-ion channel complex, by binding to a specific regulatory site on the GABAa receptor= conformational change= therapeutic effect
3) no, BDZ do not open the Cl- ion channel by themselves, they increase the affinity of the receptor for GABA

Question 10

What effect ooes benzodiazepines have on GABA?

Answer 10

BDZ binding enhances neuronal inhibitory effect of GABA

Question 11

Describe absorbtion and route of administration of benzodiazepines:

Answer 11

Well absorbed when given orally

Question 12

Describe distribution of benzodiazepines:

Answer 12

Bind strongly to plasma proteins

High lipid solubility → accumulation/sequestration in body fat

Question 13

1) are benzodiazepines activated/inactivated by metabolism?

2) What substance is it excreted as in urine?

Answer 13

1) deactivated

2) glucuronides

Question 14

Why can’t you take benzodiazepines then drive the next morning?
2) What is the difference between long acting and short acting drugs?

Answer 14

as BDZ hangover, accumulates in fat but is slowly metabolised = prolonged effect
2) long acting drugs when metabolised are activated, short drugs are deactivated by metabolism (e.g. temazepam (but special so forms oxazepam (not glucuronidated)

Question 15

What happens do all short acting drugs that are benzodiazepines?
b) which does this not happen to? what is its pathway in metabolise?

Answer 15

1. glucuronidation
2. to hydroxylated metabolites (skipped by lorazepam)
3. glucuronide
   b) temazepam to oxazepam to glucuronide

Question 16

What happens to all long acting drugs?

Answer 16

1) undergoes demethylation to nordazepam -the active agent-(medazepam goes to diazepam then nordazepam)
2) then forms oxazepam
3) then forms glucuronide

Question 17

What is the active agent formed by metabolise of long acting diazepine drugs?

Answer 17

nordazepam

Question 18

Unwanted effects of diazepines:

Answer 18

1) Reasonably safe in overdose [advantage since often used in suicide attempts]
2) Interaction with alcohol → alcohol is CNS depressant, so if taken with alcohol this results in a push in the metabolism in the drug resulting in a more than double effect→ recovered via GABA antagonists (antidote)
3) Long lasting ‘hangover effects’ e.g. drowsiness, confusion etc → larger in obese patients who have larger fat stores
4) Development of dependence
5) Sexual fantasies → patients sedated and believe they have been sexually assaulted (1:200)