Pharmacology of anxiolytics

Question 1

What are the main drugs used in the treatment of anxiety ?

Answer 1

1. Benzodiazepines
2. Antidepressant drugs
3. Buspirone
4. Pregabalin
5. β-blockers (propanolol)

Question 2

List some of the different types of benzopiazepines

Answer 2

• Midazolam
• Lorazepam
• Loprazolam
• Oxazepam
• Temazepam
• Alprazolam
• Nitrazepam
• Diazepam
• Chlordiazepoxide
• Flurazepam
• Clonazepam

Think basically drugs ending in ‘lam’ or ‘pam’

Question 3

Whatare the effects of benzodiazepines ?

Answer 3

• reduce anxiety and aggression
• hypnosis/sedation
• muscle relaxation
• anticonvulsant effect
• anterograde amnesia - loss of the ability to create new memories after the event that caused the amnesia, leading to a partial or complete inability to recall the recent past, while long-term memories from before the event remain intact.

Question 4

What is the function of GABA neurotransmitter ?

Answer 4

Causes hyperpolarisation of target cells by binding to the part of GABA_A which is situated outside the cell and causing a subsequent influx of Cl- into the cell (hyperpolarisation) & ==> inhibiting firing of new AP’s

Question 5

What is the mechanism of action of benzodiazepines ?

Answer 5

The all act to enhance the effect of the neurotransmitter GABA at GABA_A receptor

Question 6

What are some of the different clinical uses of benzodiazepines that they may be used in?

Answer 6

• Acute treatment of extreme anxiety
• Hypnosis
• Alcohol withdrawal
• Mania
• Delirium
• Rapid tranquillisation
• Premedication before surgery or during minor procedures
• Status epilepticus

Question 7

What are some of the problems with benzodiazepines ?

Answer 7

• Fairly safe in overdose as alone are unlikely to cause respiratory depression but if needed there is an antagonist – Flumazenil to reverse this
• Aggression
• Anterograde amnesia & impaired coordination
• Cause tolerance and dependence (addiction) (rebound anxiety on withdrawal and sometimes physical symptoms)

Question 8

What are the signs and symptoms of benzodiazepine withdrawal?

Answer 8

• Anxiety
• Convulsions/seizures
• Psychosis
• Insomnia
• Loss of appetite & body weight
• Tremor
• Sweating, palpitations
• Agitation

Question 9

How should you withdraw someone off a benzo to reduce the chances of withdrawal symptoms ?

Answer 9

1. Transfer patient to equivalent daily dose of diazepam/chlordiazepoxide, preferably taken at night
2. Reduce dose every 2–3 weeks in steps of 2 or 2.5 mg; if withdrawal symptoms occur, maintain this dose until symptoms improve
3. Reduce dose further, if necessary in smaller steps; it is better to reduce too slowly rather than too quickly
4. Stop completely; time needed for withdrawal can vary from about 4 weeks to a year or more

Question 10

What drug is esp good for palpitations and tremors in anxiety disorders ?

Answer 10

Beta blockers e.g. propanolol

Question 11

What is the mechanism of action of pregabalin and when is it used in anxiety ?

Answer 11

(Ca2+ channel blocker, GABA enhancer) - only considered if not responsive to other treatments

Question 12

What is the mechanism of action of busiprone and when is it used in anxiety ?

Answer 12

Buspirone (5-HT1A receptor partial agonist, presynaptic dopamine antagonist at the D2, D3 and D4 receptors) - effect may take weeks to develop, sometimes prescribed with SSRI in order to modify SSRI effects on libido.