Anxiolytics and hypnotics

Question 1

Anxiolytics

Answer 1

Remove anxiety without impairing mental or physical activity

• ‘long acting’
• eg: diazepam, chlordiazepoxide
• oxazepam example used if patient has hepatic impairment

Question 2

Sedatives

Answer 2

Reduce mental and physical activity without producing loss of consciousness
-‘short acting’

Question 3

Hypnotics

Answer 3

Induce sleep

-‘short acting’

Question 4

Anxiolytic examples

Answer 4

• SSRIs (antidepressants)
• Valproate, Tiagabine (antiepileptics)
• Olanzapine, Quetiapine (antipsychotics)
• Propranolol (beta blocker)
• Buspirone (serotonin receptor agonist)

Question 5

Sedatives/hypnotics examples

Answer 5

Zopiclone

Question 6

GABA metabolism

Answer 6

1) GABA converted to succinic semialdehyde by GABA transaminase (GABA-T)
2) succinic semialdehyde converted to succinic acid by succinic semialdehyde dehydrogenase (SSDH)
- enzymes involved are mitochondrial
- inhibitors of GABA metabolism lead to increased brain GABA and more inhibition (eg: sodium valproate, vigabatrin)

Question 7

GABA neurotransmission

Answer 7

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Question 8

GABAa receptor complex

Answer 8

Made up of 4 main proteins:

• GABA modulin
• BDZ receptor protein
• Barbiturate receptor protein
• GABA receptor protein

Question 9

Ideally anxiolytics,sedatives and hyponotics should have:

Answer 9

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

Question 10

Barbiturates structure

Answer 10

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Question 11

Barbiturates side effects

Answer 11

CAUSE OF NOT BEING FIRST LINE TREATMENT

• low safety margins
• alter natural sleep (reducing REM)
• induce enzymes
• potentiates effects of other CNS depressants
• tolerance
• dependence

Question 12

Benzodiazepines structure

Answer 12

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Question 13

Benzodiazepines pharmacokinetics

Answer 13

ADMINISTRATION
-plasma concentration peaks at 1 hour
-well absorbed oral admin
DISTRIBUTION
-bind plasma proteins strongly
-high lipid solubility
METABOLISM
-extensive liver metabolism
EXCRETION
-urine as glucuronide conjugates
DURATION OF ACTION

Question 14

Benzodiazepine advantages

Answer 14

• mild effect on REM sleep
• does not induce liver enzymes
• wide margin of safety (overdose results in prolonged sleep which is rousable)

Question 15

Benzodiazepine side effects

Answer 15

• impaired manual skills (sedation, confusion, amnesia and ataxia)
• potentiates other CNS depressants
• lower tolerance than BARBs
• dependence (withdrawal syndrome similar but less intense to BARBs=withdraw drug slowly)
• free plasma concentration increases by aspirin/heparin co-administration

Question 16

Zopiclone

Answer 16

• short acting (5 hour half life)
• acts at BZ receptors
• similar efficacy to BZs
• minimal hangover effects but dependency is a problem

Question 17

Antidepressant drugs

Answer 17

SSRIs

• less sedation and dependence on drug
• delayed response
• used in long-term treatment

Question 18

Antiepileptic drug examples

Answer 18

• Valproate

- Tiagabine

Question 19

Antipsychotic drug examples

Answer 19

• Olanzapine

- Quetiapine

Question 20

Propanolol

Answer 20

-improves physical symptoms of anxiety (tachycardia, tremor etc)

Question 21

Buspirone

Answer 21

• 5HT1a agonist
• fewer side effects (less sedation)
• slow onset of action (days/weeks)

Question 22

BZs and BARBs on the GABAa receptor complex

Answer 22

• BARBs increase opening duration
• BZs increase opening frequency
• BARBs are less selective than BZs so have less excitatory transmission and other membrane effects=explains why BARBs lead to induction of surgicla anaesthesia and low margin of safety

Question 23

Clinical uses of BZs and BARBs

Answer 23

• anaesthetics
• anti-convulsants
• anti-spastics
• anxiolytics
• sedatives/hypnotics