anxiolytics and sedative-hypnotic drugs

Question 1

3 types of anxiety disorders

Answer 1

generalised anxiety - persistent and excessive anxiety
panic disorder - attacks of overwhelmed fear with marked somatic symptoms (sweating, tachycardia, chest pains etc.)
social anxiety disorder (social phobia) - fearful and anxious about social interactions an situations that may be subject to scrutiny

Question 2

GABAa receptor

Answer 2

19 subunits
native GABAa receptors - two a subunits, two b subunits and one subunit of a third type (usually gamma)
distinct pharmacological profiles and physiological roles

Question 3

GABA

Answer 3

the primary inhibitory neurotransmitter in the brain

binds to the GABAa receptor at the interface of a/b subunits

Question 4

BZD binds at

Answer 4

interface of alpha and gamma subunit in GABAa receptor

Question 5

benzo diazepine side effects - a2 subunit mediated

Answer 5

anxiolytic effects -
short acting drugs may paradoxically increase aggression due to withdrawal syndromes
muscle relaxant effects - act through the GABAa receptor in the spinal cord, facilitates anxiolytic effects (increased muscle tone is common to anxiety)

Question 6

BZD side effects - a1 subunit mediated

Answer 6

hypnotic and sedative side effects - decrease sleep latency and increase sleep duration, short acting preferred, long acting drugs lead to drowsiness
anticonvulsant effects
anterograde amnesia - prevent memory of events experienced under influence of drugs, can also be a5-mediated

Question 7

BZD chemical structure

Answer 7

seven membered ring fused to an aromatic ring
positive allosteric modulator - binds to BZD site at interface of a/y, increasing affinity for GABA and the frequency of channel opening, producing greater inhibitory effect on the target neuron

Question 8

four BZDs

Answer 8

midazolam, alprazolam, diazepam, oxazepam

Question 9

why is BZD a PAM

Answer 9

positive allosteric modulator - binds to a different site than GABA but increases affinity for GABA

Question 10

midazolam

Answer 10

ultra short acting
produces minor active metabolites
hypnotic, anaesthetic and anticonvulsant

Question 11

short acting BZD

Answer 11

oxazepam

Question 12

oxazepam

Answer 12

short acting
no active metabolites
anxiolytic, hypnotic

Question 13

medium acting BZD

Answer 13

alprazolam

Question 14

long acting BZD

Answer 14

diazepam

Question 15

alprazolam

Answer 15

active metabolites
anxiolytic
medium acting

Question 16

diazepam

Answer 16

long actiing
active metabolites
anxiolytic, muscle relaxant, anticonvulsant

Question 17

drug administration of BZD

Answer 17

oral (common, IV or rectal
good oral absorbtion and bioavailability
fast onset (30-60 minutes) of therapeutic effects

Question 18

BZD used for

Answer 18

acute anxiety
behavioural emergencies
premedication for surgery and procedures

Question 19

undesribale effects of BZD

Answer 19

drowsiness, amnesia, and impaired coordination

Question 20

short acting drugs are

Answer 20

hypnotics

Question 21

long acting drugs are

Answer 21

anxiolytics

Question 22

diazepam in older patients

Answer 22

drug metabolism by cytochrome P450
significant impact of aging on drug metabolism
has active metabolites

Question 23

oxazepam in elderly patients

Answer 23

drug metabolism by glucuronidation, relatively minor effect of aging on drug emtabolism
does not form active metabolites

Question 24

drug drug interactions with BZD

Answer 24

eg. coadministration of diazepam and fluvoxamine (an SSRI)

diazepam uses CYP2C19 and flluvoxamine is a CYP2C19 inhibitor

Question 25

tolerance in BZD

Answer 25

develops due to continued use decrease in therapeutic effects when given the same dose use for <2 weeks

Question 26

withdrawal symptoms in BXD

Answer 26

on cessation of use rebound anxiety, tremor, sleep disturbance, loss of appetite short acting drugs are more problematic

Question 27

acute overdose of BZD

Answer 27

relatively safe treated with IV flumazenil (compete with benzodiazepines for the binding site) if combined with other CNS depressants (alcohol or opioids) - severe respiratory depression

Question 28

flumazenil

Answer 28

used to treat BZD overdose competed with BZD for binding site short duration of action for long acting BZD overuse - may require multiple flumazenil injections

Question 29

buspirone

Answer 29

5-HT1a receptor partial agonist delayed anxiolytic effect less problematic than benozdiazepines (no sedation or impaired motor control, no tolerance or withdrawal) effective for generalised anxiety

Question 30

side effects of buspirone

Answer 30

nausea, dizziness, headache and restlessness does not cause sedation or impared notor coordination does not lead to tolerance or withdrawal effects

Question 31

antidepressants

Answer 31

SSRIs are preferred due to better side effect profile delayed anxiolytic effects reduce depression associated with anxiety does not produce hypnotic effect effective for generalised and socialised anxiety disorder

Question 32

transient insomnia

Answer 32

shift work, jet lag

Question 33

short term insomnia

Answer 33

experience emotional or stressful events

Question 34

chronic insomnia

Answer 34

underlying conditions (eg. anxiety, depression, drug abuse)

Question 35

BZD for insomnia

Answer 35

a1 subunit-mediated hypnotic effects - decrease sleep latency and increase sleep duration - improved sleeping quality while on treatment but rebound worsening of sleep - short term use ( <2 weeks)

Question 36

Z-drugs

Answer 36

zolpidem, zaleplon, and eszopiclone structurally distinct from benzodiazepines but share the same binding site a1-selective - hypnotic effects, short acting lacks appreciable anxiolytic activity

Question 37

adverse effects of Z-drugs

Answer 37

similar to benzodiazepines short-term use to avoid tolerance and dependance reports of bizarre behaviours and falls - use with caution, particularly in elderly patients overdose - treated with flumazenil more dangerous when combined with other CNS depressants

Question 38

3 Z-drugs examples

Answer 38

zolpidem, zaleplon, eszopiclone