anxiolytics, sedatives and hypnotics

Question 1

neurotransmission of GABA and receptors for too much GABA

Answer 1

glutamate converted into GABA by GAD (decarboxylase), which binds to GABA A receptor- there are also GABA B receptors which cause -feedback ie like alpha 2 receptors if too much GABA

Question 2

metabolism of GABA

Answer 2

reuptaken and converted into succinate semialdehyde in both GLIAL CELLS AND presynaptic terminal by GABA transaminase, and then into succinic acid by succinate dehydrogenase

Question 3

drugs inhibiting metabolism of GABA

Answer 3

sodium valproate, and vigabatrin

Question 4

DIAGRAM GABAa receptor

Answer 4

made up of GABA receptor protein, benzodiazepine receptor protein, and barbibuturate receptor protein, with Cl- channel in middle- GABA, BDZ and BARB each act on their receptor protein

Question 5

effects of BDZ and BARB and differences

Answer 5

both enhance GABA action ie don’t work alone, BARB more powerful than BDZ’s, hence BARBS can cause anaesthesia and less safe unlike BDZ- BARBS also increase DURATION of opening of Cl- channels, but BDZ’s increase FREQUENCY of opening

Question 6

anatagonists of GABA receptor

Answer 6

bicuculine is a BDZ antagonist, flumazenil is a GABA antagonist

Question 7

define anxiolytics, sedatives and hypnotics

Answer 7

remove anxiety without mental/physical effect- reduce mental/physical activity without loss of conciousness- cause loss of conciousness

Question 8

use of barbiturates and eg

Answer 8

as a sedative/hypnotic= severe insomnia eg amobarbital

Question 9

side effects of barbiturates

Answer 9

low safety margin (can cause respiratory depression), affect REM sleep, potentiate CNS depressants effects eg alcohol, and can become dependent on them

Question 10

pharmacokinetics of benzodiazepines- absorption, metabolism and DOA

Answer 10

lipid soluble so well absorbed- metabolised well into glucoronide conjugates, and their duration of action varies depending on whether short or long acting

Question 11

long acting vs shorting acting examples and uses

Answer 11

diazepam is long acting- used for anxiolytics: temazepam and oxazepam are short acting- used as sedative/hypnotic ie insomnia

Question 12

BDZ advantage over barbs

Answer 12

wide margin of safety, low effect on REM sleep, and don’t induce liver enzymes unlike barbiturates ie don’t interact with other drugs

Question 13

side effects of BDZ

Answer 13

can cause sedation/confusion (if used only for anxiolytics), dependence ie withdrawal syndrome, potentiates CNS depressants

Question 14

other sedatives/hypnotics

Answer 14

ZOPICLONE - short acting on BDZ receptors (but NOT BDZ’S)

Question 15

other anxiolytics

Answer 15

SSRIS (antidepressants), antiepileptics eg valproates, PROPANOLOL (improves symptoms of anxiety), and buspirone (5HT agonist)