Week 2 - C - Pharamacology of Anxiolytic drugs - Benzodiazepines mainly - effects and how to withdraw

Question 1

What are the different types of anxiety disorders?

What is generally considered to be the first line treatment of the anxiety disorders?

Answer 1

Different types -

• Generalised anxiety disorder
• Panic disorder
• Phobias - agoraphobia, social phobia, specific phobia
• Obsessive compulsive disorder
• Post traumatic stress disorder

Psychotherapy - specifically cognitive behavioral therapy is mainly 1st line for all these anxiety disorder

Specific phobias - it is usually behavioral therapy (graded exposure)

PTSD - 1st line - CBT or Eye movement desentisation & reprocessing (EMDR)

Question 2

In GAD, Panic disorders and social phobias, benzos can be used in the short term treatment of these

What do all benzodiazepines end in?

What is the exception to his?

Answer 2

Benzodiazepines end in the letters ‘am’ eg

• Midazolam
• Diazepam
• Lorazepam

The exception to this is the benzodiazepine chlordiazepoxide - this is a long acting benzo

Question 3

Benzodiazepines exhibit a number of different pharamcological effects hence their many different uses

What pharamcological effects do they exhibit?
What is the one effect that effects memory known as?

Answer 3

Benzodiazepines
Reduce anxiety and aggression

Hypnosis/sedation

Muscle relaxation

Anti-convulsant effects - hence 1st line for status elepticus

Also cause anterograde amnesia

Question 4

What is anterograde amnesia?

Answer 4

This is where there is the loss of ability form new memories after the onset of an illness or in this case benzo
Therefore memories there is a partial inability to recall the recent pass but recall of long term memories is not affected

Antergrade amnesia usually ccurs in short term use of high dose benzos

Question 5

What is the opposite of anterograde amnesia and describe it?

Answer 5

This retrograde amnesia

Retrograde is where memories completed prior to the event are lost with the ability to form new memories

Question 6

What is the main inhibitory neurotransmitter?

It is this that benzodiazepines potentiate the action of

Answer 6

The main inhibitory neurotransmitter is GABA
Benzodiazepines work by potentiating the inhibitory effect of gamma aminobutyric acid on neuronal activity

Benzodiazepines bind at an allosteric site to the ion channel to increase the effects of GABA

Question 7

What is the other main inhibitory neurotransmitter? It is not as widespread as GABA but where is it mainly found?

Answer 7

The other main inhibitory neurotransmitter is glycine

It is mainly found in the spinal cord and brainstem

Question 8

How does GABA work? How do benzodiazepines affect GABA?

Answer 8

GABA works by allowing the influx of chloride ions into the cells causing hyperpolarization of the cell and therefore releasing a postsynaptic inhibitory transmission

Benzos bind at an allosteric site to potentiate this effects

Question 9

Which other conditions (other than anxiety) and scenarios are benzodiazepines used?

Answer 9

Apart from the acute treatment of extreme anxiety

Hypnosis
Alcohol withdrawal
Anti-convulsant - used in status elepticus
Mania and delirium

Rapid tranquilisation and premedication before surgeries

Question 10

What choice of benzos are usually used for the management of alcohol withdrawal?

Answer 10

Chlordiazepoxide, diazepam or lorazepam

Question 11

What is another type of drug that potentiates the effects of GABA by binding to the GABAa receptor on the chloride channel?

Answer 11

This would be the barbituates

Question 12

What is the Meaning of anxiolytic?

Answer 12

This means something that causes an anxiety reducing effect

Question 13

Problems with benzodiazepines
• Fairly safe in overdose as alone are unlikely
to cause respiratory depression

What can they cause however if used in very high doses for a long period of time?

Answer 13

Paradoxical aggression
Anterograde amnesia
Tolerancy usually develops
Dependency usually also develops - a rebound anxiety on withdrawal can occur

Question 14

What are the issues with benzodiazepines and alcohol?

Answer 14

As both act on the GABA receptor, this can cause extreme effects - such as severe respiratory depression

Question 15

What issues may arise from rapid withdrawal of benzodiazepines?

Answer 15

There may be an associated benzo withdrawal phenomenona

Such as confusion, toxic psychosis, coma, anxiety, insomnia

Question 16

How does chronic treatment with benzodiazepines affect GABA?

Answer 16

In chronic treatment there is a neuroadaptation response to the benzos which results in a decreased response to GABA - tolerance
Therefore on withdrawal, because there is a decreased respoinse to GABA, can have rebound anxiety along with the other withdrawal symptoms

Question 17

How would you withdraw a patient from benzodiazepines?

What you do if withdrawal symptoms occur on withdrawing a patient from benzos?

Answer 17

The patient is transferred to the oral diazepam or chlordiazepoxide equivalent daily dose - preferably taken at night
Then every 2-3 weeks, reduce the dose by 2-2.5 mg - if withdrawal symptoms occur, maintain the dose until symptoms improve

Reduce the dose further, in smaller steps if necessary
And finally stop the dose completely

Question 18

What drug is used to treat benzodiazepine overdoses?

Answer 18

Flumazenil
It is a selective GABAA receptor antagonist administered via injection, otic insertion, or intranasally. Therapeutically, it acts as both an antagonist and antidote to benzodiazepines, through competitive inhibition

Question 19

As stated, psychotherapy is the first line treatment for all the anxiety disorders

What is the most common drug that is used first line in the anxiety disorders?

Answer 19

SSRIs are the most commonly used 1st line drug - GAD, PAnic disorder, Phobias, OCD and PTSD

Question 20

In which anixety conditions is tricyclics second line?

Answer 20

Second line drug therapy in panic disorders
and

Clompiramine can be used if SSRIs dont work in OCD

Question 21

What is the third line medication for GAD?

Used if not responsive to SSRIs/SNRIs

Answer 21

This would be pregablin

Question 22

How does pregablin work?

Answer 22

It works by blocking voltage gated calcium channels - decreases release of glutamate and substance P and therefore is a GABA analogue that doesnt actually work on the GABA channels

Question 23

Best for somatic symptoms e.g. palpitation, tremor

What drug would be best for this?

Answer 23

A non selective B blocker known as propranolol (non-selectively inhibits B1 and B2 - dont use in asthma as cause bronchoconstriction)