Anxiolytics and hypnotics Flashcards
Anxiolytics
Remove anxiety without impairing mental or physical activity
- ‘long acting’
- eg: diazepam, chlordiazepoxide
- oxazepam example used if patient has hepatic impairment
Sedatives
Reduce mental and physical activity without producing loss of consciousness
-‘short acting’
Hypnotics
Induce sleep
-‘short acting’
Anxiolytic examples
- SSRIs (antidepressants)
- Valproate, Tiagabine (antiepileptics)
- Olanzapine, Quetiapine (antipsychotics)
- Propranolol (beta blocker)
- Buspirone (serotonin receptor agonist)
Sedatives/hypnotics examples
Zopiclone
GABA metabolism
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)
GABA neurotransmission
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GABAa receptor complex
Made up of 4 main proteins:
- GABA modulin
- BDZ receptor protein
- Barbiturate receptor protein
- GABA receptor protein
Ideally anxiolytics,sedatives and hyponotics should have:
- have wide margin of safety
- not depress respiration
- produce natural sleep (hypnotics)
- not interact with other drugs
- not produce ‘hangovers’
- not produce dependence
Barbiturates structure
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Barbiturates side effects
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
Benzodiazepines structure
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Benzodiazepines pharmacokinetics
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
Benzodiazepine advantages
- mild effect on REM sleep
- does not induce liver enzymes
- wide margin of safety (overdose results in prolonged sleep which is rousable)
Benzodiazepine side effects
- 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
Zopiclone
- short acting (5 hour half life)
- acts at BZ receptors
- similar efficacy to BZs
- minimal hangover effects but dependency is a problem
Antidepressant drugs
SSRIs
- less sedation and dependence on drug
- delayed response
- used in long-term treatment
Antiepileptic drug examples
- Valproate
- Tiagabine
Antipsychotic drug examples
- Olanzapine
- Quetiapine
Propanolol
-improves physical symptoms of anxiety (tachycardia, tremor etc)
Buspirone
- 5HT1a agonist
- fewer side effects (less sedation)
- slow onset of action (days/weeks)
BZs and BARBs on the GABAa receptor complex
- 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
Clinical uses of BZs and BARBs
- anaesthetics
- anti-convulsants
- anti-spastics
- anxiolytics
- sedatives/hypnotics
