anxiety/sedation/depression

Question 1

activity of benzodiazepines and barbiturates alone on GABA-A receptor complex

Answer 1

no activity alone (allosteric action as positive allosteric modulators)

Question 2

mechanism of benzodiazepines (with GABA)

Answer 2

increase frequency of openings

Question 3

mechanism of barbiturates (with GABA)

Answer 3

increase duration of openings

Question 4

relative selectivity of barbiturates and benzodiazepines

Answer 4

barbiturates are less selective than benzodiazepines

Question 5

effect of barbiturates on excitatory transmission

Answer 5

decrease, plus other membrane effects

Question 6

what may barbiturates causing a decrease in excitatory transmission explain

Answer 6

induction of surgical anaesthesia, low margin of safety

Question 7

clincal use specific to barbiturates, with example

Answer 7

anaesthetics e.g. thiopentone which induces generalised anaesthesia before switching over to gaseous anaesthetic

Question 8

4 clinical uses of barbiturates and benzodiazepines

Answer 8

anticonvulsants, anti-spastics, anxiolytics, sedatives/hypnotics

Question 9

examples of anticonvulsant drugs

Answer 9

diazepam (benzodiazepine), clonazepam (benzodiazepine), phenobarbital (barbiturate)

Question 10

example of anti-spastic drug

Answer 10

diazepam (benzodiazepine)

Question 11

define anxiolytic

Answer 11

drug which removes anxiety without impairing mental or physical activity (minor tranquillisers); typically different drugs to sedatives and hypnotics

Question 12

define sedative

Answer 12

drug which reduces mental and physical activity without producing loss of consciousness

Question 13

define hypnotic

Answer 13

drug which induces sleep (continuous spectrum so if reduce dose, can cause sedative effects)

Question 14

6 ideal properties of anxiolytics, sedatives and hypnotics

Answer 14

wide margin of safety, not depress respiration, produce natural sleep (hypnotics), not interact with other drugs, not produce ‘hangovers’, not produce dependence

Question 15

structure of barbiturates

Answer 15

6-membered ring structure of R1 (ethyl group), R2 (phenyl group) and X group: C(O)C(R1, R2)C(O)NC(X)N(H) molecule

Question 16

clinical uses of barbiturates

Answer 16

sedative, hypnotic

Question 17

example of barbiturate causing sedation and hypnosis

Answer 17

amobarbital

Question 18

what does amobarbital treat

Answer 18

severe intractable insomnia

Question 19

half-life of barbiturates

Answer 19

20-25 hours

Question 20

6 unwanted effects of barbiturates which mean they are not drug of 1st choice

Answer 20

low safety margins (depress respiration, overdosing lethal), alter natural sleep (decrease REM) which causes hangovers and irritability, enzyme inducers (co-administered drugs less effective), potentiate effect of other CNS depressants (e.g. alcohol), tolerance, dependence (withdrawal syndrome)

Question 21

5 features of withdrawal syndrome from barbiturates

Answer 21

insomnia, anxiety, tremor, convulsions, death

Question 22

structure of benzodiazepines

Answer 22

3-ring structure with small R1, 2, 3 and 4 groups

Question 23

structure of flumazenil meaning it works as antagonist

Answer 23

large R group so acts as antagonist as no efficacy

Question 24

where do benzodiazepines act

Answer 24

all act at GABA-A receptors, with all having similar potencies and profiles (pharmacokinetics largely determines use)

Question 25

describe administration of benzodiazepines

Answer 25

well absorbed orally, with a peak plasma concentration after 1 hour; can be given i.v. to treat status epilepticus (severe prolonged seizure activity)

Question 26

describe distrubution of benzodiazepines

Answer 26

bind plasma proteins strongly, and are highly lipid soluble so have a wide distribution

Question 27

describe metabolism of benzodiazepines

Answer 27

usually extensive metabolsim in liver

Question 28

describe excretion of benzodiazepines

Answer 28

urine as glucoronide conjugates

Question 29

duration of action of benzodiazepines, and hence 2 groups

Answer 29

vary greatly (short-acting or long-active with slow metabolism and/or active metabolites)

Question 30

example of long-acting benzodiazepine (can be metabolised to long e.g. nordiazepam (can also be produced by metabolism of chlordiazeproxide) or short-acting benzodiazepines)

Answer 30

diazepam

Question 31

example of short-acting benzodiazepine (which diazepam is metabolised to)

Answer 31

temazepam

Question 32

example of short-acting benzodiazepine (which diazepam is metabolised to nordiazepam, which is metabolised to this drug)

Answer 32

oxazepam

Question 33

what are long-acting benzodiazepines used as

Answer 33

anxiolytics (e.g. diazepam, chlordiazepoxide, nitrazepam)

Question 34

when would oxazepam (short-acting benzodiazepines) be used as anxiolytic

Answer 34

used if hepatic impairment (increase plasma half life as reduced metabolism)

Question 35

what are short-acting benzodiazepines used as

Answer 35

sedative/hypnotics (e.g. temazepam, oxazepam)

Question 36

when would nitrazepam (long-acting benzodiazepines) be used as sedative/hypnotic

Answer 36

if require daytime anxiolytic effect as longer plasma half life

Question 37

3 advantages of benzodiazepines over barbiturates

Answer 37

wide margin of safety (overdose causes prolonged sleep which is rousable e.g. using i.v. flumazenil), mild effect on REM sleep, do not induce liver enzymes (other co-administered drugs effective)

Question 38

4 unwanted effects of benzodiazepines as anxiolytic and/or hypnotic

Answer 38

sedation (if used as anxiolytic), confusion, amnesia, ataxia (impaired manual skills)

Question 39

other unwanted effects of benzodiazepines: other depressants, tolerance, dependence, co-administered drugs

Answer 39

potentiate other CNS depressants, tolerance (less than barbiturates and in tissue only), dependence (less intense withdrawal syndrome compared to barbiturates, but must withdraw slowly), increase in free plasma concentration by co-administered drugs (e.g. aspirin, heparin)

Question 40

example of another sedative/hypnotic

Answer 40

zopiclone

Question 41

where does zopiclone act

Answer 41

short-acting at benzodiazepine receptors to enhance GABA activity, with similar efficacy to benzodiazepines but are not benzodiazepines (cyclopyrolones)

Question 42

advantage and disadvantage of zopiclone as sedative/hypnotic

Answer 42

minimal hangover effects but dependency is a problem

Question 43

antidepressant drug class used as anxiolytics

Answer 43

SSRIs

Question 44

advantage and disadvantage of SSRIs as anxiolytics

Answer 44

less sedation and dependence, but have a delayed response but used for long term treatment

Question 45

2 examples of antiepileptic drugs used as anxiolytics

Answer 45

valproate, tiagabine (both enhance GABA activity in brain)

Question 46

2 examples of antipsychotic drugs used as anxiolytics (limited by side effects)

Answer 46

olanzapine, quetiapine

Question 47

how does propranolol improve physical symptoms of anxiolytics

Answer 47

tachycardia (B1), tremor (B2 on skeletal muscle fibres)

Question 48

example of 5HT-1A agonist used as anxiolytic

Answer 48

buspirone

Question 49

advantage of buspirone as anxiolytic compared to benzodiazepines

Answer 49

fewer side effects (less sedation)

Question 50

disadvantage of buspirone as anxiolytic compared to benzodiazepines

Answer 50

slower onset of action (days/weeks)