Anxiolytics

1
Anxiolytics Hypnotics by Sue Henderson
2
Therapeutic actions

• Hypnotic
• Anxiolytic
• Anticonvulsant
• Amnestic
• Myorelaxant

• In what medical circumstances might the amnestic
  properties of benzodiazepines be useful?

3
Indications

• Why are benzodiazepines useful in the treatment
  of alcohol detoxification?
• Can they be used in the long term to prevent
  further alcohol abuse?

4
Anti-Anxiety Hypnotics

• Anti-Anxiety
• Benzodiazepine e.g. Diazepam
• Non Benzodiazepine e.g. Buspirone

• Hypnotics Sedatives
• Benzodiazepine e.g. Temazepam
• Non Benzodiazepine e.g. Zopiclone

5
Differentiate

• What is the difference between an anti-anxiety
  medication and a hypnotic?

6
Antidepressants for anxiety
Clomipramine (TCA) OCD
Fluvoxamine (SSRI) OCD
Paroxetine (SSRI) OCD, panic disorder, social phobia
Sertraline (SSRI) OCD, panic dis, PTSD
Venlafaxine (SNRI) GAD
Fluoxetine (SSRI) OCD
7
Benzodiazepines

• Used mostly in primary care rather than
  psychiatry.
• Often prescribed for problems that are more
  effectively managed with non-drug therapies.
• Temazepam in 10 most frequently prescribed up
  until 2001.

8
Benzodiazepines

• Should not be 1st line therapy in mental health
  sleep management.
• Limit use to less than 2 weeks.
• Only benefit of continued use is avoiding
  withdrawal effects (NPS, 1999).
• All equally effective but differ in metabolism,
  speed of onset half life

9
2004-05 National Health Survey

• 5 of Australians had used a benzodiazepine for
  anxiety management in the 2 weeks prior to the
  survey.
• Benzodiazepine use was higher in women and in
  older age groups (mostly due to sleeping
  tablets).
• Overall use has fallen since 80s but total use
  remains high (ABS, 2006).

10
(No Transcript)
11
MCQ

• Benzodiazepines can safely be prescribed during
  pregnancy.
•  
• A. True
• B. False

12
Indications Drug
Anxiolytic Diazepam, Alprazolam, Bromazepam, Lorazepam, Oxazepam, Buspirone
Muscle relaxant Diazepam
Pre-med Diazepam, Lorazepam
Alcohol withdrawal Diazepam, Oxazepam,
Panic disorder Alprazolam, Clonazepam.
Anti-convulsant Clobazam, Clonazepam, Diazepam, Lorazepam
Hypnotic Flunitrazepam, Nitrazepam Temazepam, Zolpidem, Zopiclone
13
Dose Equivalents
Drug Daily range mg Equiv 5mg diazepam. Duration (½ life)
alprazolam 1 4 0.5 - 1 Short/Intermediate
bromazepam 6 9 3 6 Short/Intermediate
clobazam 30 80 10 Intermediate
clonazepam 4 8 0.5 Intermediate
diazepam 5 20 5 Long
flunitrazepam 0.5 2 1 2 Intermediate
lorazepam 2 4 1 Short/Intermediate
nitrazepam 5 20 5 10 Intermediate
oxazepam 45 90 15 30 Short
temazepam 10 30 10 - 20 Short
triazolam 0.125 - 0.25 0.25 Short
buspirone 15 30 - Short
zopiclone 3.75 - 7.5 - Short
14
Short Acting 3 - 8 hrs

• Oxazepam
• Temazepam
• Triazolam
• Buspirone
• Zopiclone

15
Intermediate Acting 10 - 20 hours

• Alprazolam
• Bromazepam
• Clobazam
• Clonazepam
• Flunitrazepam
• Lorazepam
• Nitrazepam

16
Hypnotics

• Explain the benefit of using Temazepam over
  Nitrazepam for assisting with sleep.
• Why should hypnotics be used for a limited time
  to assist with sleep?

17
Long Acting 1- 3 days Diazepam
X
X
X
18
Addiction

• Why are short acting benzodiazepines more of a
  problem with addiction than the long acting ones?

19
Dependency cycle of benzodiazepines
Green, 1996, p. 88
20
Benzodiazepines Action

• CNS depressant
• Enhance the effect of GABA.
• GABA is a neurotransmitter that inhibits neuronal
  activity i.e. reduces the firing rate of
  neurones.

21
Agonist Facilitate

• Benzodiazepines bind to a site near the GABA
  binding site thus facilitating the action of GABA

22
Death
Increasing dose of drug
Coma General Anaesthesia Sleep Sedation Disinhibi
tion Relief from anxiety No effect

• (Julien, 2001)

23
Combination CNS depressants
24
Contra-indications

• Myasthenia gravis.
• Severe respiratory impairment e.g sleep apnoea,
  COAD.

25
Avoid (if possible)

• Pregnancy
• Lactation

26
Adverse Effects

• Physical dependence occurs in about 1 in 3
  patients.
• History substance abuse gt risk dependence
• Increased accident risk.
• Tolerance rebound insomnia.
• Alcohol CNS depressants potentiate adverse
  effects.

27
Adverse effects

• 60y gt vulnerability to confusion, memory
  impairment, over sedation (most common S/E)
  falls.
• Adverse mood effects depression, emotional
  anaesthesia, aggression, increased suicide risk
  in elderly.

28
Withdrawal from Benzodiazepines

• Abrupt cessation gt seizures
• Withdrawal symptoms may occur between doses
  during continuous use (inter-dose withdrawal).
  Patients may think these symptoms are due to the
  original problem.
• Withdrawal symptoms increased anxiety, sleep
  disorder, aching limbs, nervousness nausea.

29
Withdrawal from Benzodiazepines

• Withdrawal experienced by 45 of patients
  discontinuing low dose benzodiazepines 100
  patients on high doses.
• Short half life benzodiazepines are associated
  with more acute intense withdrawal symptoms.
• Long half life benzodiazepines - milder, more
  delayed withdrawal (NPS, 1999).

30
Withdrawal from benzodiazepines

• Benzodiazepines should not be ceased abruptly.
• Dose reduced by 10-20 per week.
• Patient allowed to stabilise between each
  reduction.
• Admission for high dose users, history of
  seizures or psychosis, or for more rapid
  withdrawal.

31
Withdrawal from benzodiazepines

• Implement relaxation/cognitive techniques.
• If necessary referral
• Drug Alcohol Services
• Self Help group TRANX www.tranx.org.au
• Psychologist (for CBT)

32
Overdose Benzodiazepines

• Generally safe in overdose unless mixed with
  alcohol/CNS depressants.
• Symptoms overdose hypotension, respiratory
  depression coma.
• Treatment Supportive
• Flumazenil rarely indicated

33
IV Flumazenil

• Dangerous to use if mixed overdose (e.g
  benzodiazepine tricyclics, amphetamines, other
  pro-convulsants) - Result in uncontrolled seizure
  
• In dependent individuals severe withdrawal
• Flumazenil has a shorter half life ( one hour)
  than all benzodiazepines Therefore, repeat doses
  of flumazenil may be required to prevent
  recurrent symptoms of overdosage once the initial
  dose of flumazenil wears off.

34
Flumazenil is a benzodiazepine Antagonist
Blocker

• Flumazenil binds to GABA receptor displacing
  benzodizepine

35
Non benzodiazepines Anxiolytic Buspirone
(Buspar)

• Different action to bzd.
• Not a CNS depressant.
• Partial agonist (stimulant) of dopaminergic
  serotoninergic receptors.
• No sedation, anti-convulsant or muscle relaxant
  properties - just anxiolytic.
• Delayed action (1-2 weeks)
• Effect reduced if benzodiazepine used in last 3/12

36
Comparison of benzodiazepine buspirone

• Buspirone
• Delayed onset (cannot be used PRN)
• Does not cause sedation
• Does not impair performance
• No additive effect with alcohol
• Non addictive
• No pharmacokinetic change with age
• Does not cause falls in elderly
• Expensive (Not on PBS)

• Benzodiazepine
• Rapid onset
• Can cause sedation
• May impair performance
• Additive effects with alcohol
• May cause dependence withdrawal
• Pharmacokinetic change with age
• Associated with falls in elderly (Keltner
  Folks, 2001)

37
Presentation Buspar

• White scored
• 5 mg 10 mg tabs

38
Buspirone Agonist Mimic

• Buspirone attaches to serotonin receptor
  mimicking serotonin.

39
Non benzo Hypnotic Zopiclone (Imovane)

• Similar action, side effects contraindications
  to benzos.

40
Benzodiazepines key points

• Should not be used in patients with liver
  disease, history of substance abuse, severe
  respiratory distress, performing hazardous tasks
• Avoid during pregnancy/lactation if possible
• Assess for over sedation
• Cease slowly
• Monitor elderly (cognition, falls)
• Be aware they raise seizure threshold, and
• Potentiate CNS depressants (alcohol)

41
Hypnotic key points

• Advise re rebound insomnia when medications
  ceased
• Should not be used in sleep apnoea
• Avoid alcohol
• Hangover effect (impairing performance)
• Monitor in elderly (falls, double dosing)

42
References

• Australian Bureau of Statistics. (2006). National
  health survey 2004-05 Summary of results.
  Canberra Australian Bureau of Statistics.
• Fortinash, K. M., Holoday-Worret, P. A. (2000).
  Psychiatric mental health nursing ( 2nd ed.). St.
  Louis Mosby.
• Galbraith, A., Bullock, S. Manias, E. (2001).
  Fundamentals of pharmacology (3rd ed.).
  Melbourne Prentice Hall.

43
References

• Julien, R. M. (2001). A primer of drug action A
  concise, non-technical guide to the actions,
  uses, and side effects of psychoactive drugs. New
  York W. H. Freeman and Co.
• Keltner, N. L., Folks, D. G. (2001).
  Psychotropic drugs (3rd ed.). St. Louis Mosby.
• National Prescribing Service. (1999). Helping
  patients withdraw. National Prescribing Service
  Newsletter, No. 4 June.
• National Prescribing Service. (1999).
  Benzodiazepines reviewing long term use A
  suggested approach. Prescribing Practice Review,
  No. 4 July.