Week 2 - C - Pharamacology of Anxiolytic drugs - Benzodiazepines mainly - effects and how to withdraw Flashcards
What are the different types of anxiety disorders?
What is generally considered to be the first line treatment of the anxiety disorders?
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)
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?
Benzodiazepines end in the letters ‘am’ eg
- Midazolam
- Diazepam
- Lorazepam
The exception to this is the benzodiazepine chlordiazepoxide - this is a long acting benzo
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?
Benzodiazepines
Reduce anxiety and aggression
Hypnosis/sedation
Muscle relaxation
Anti-convulsant effects - hence 1st line for status elepticus
Also cause anterograde amnesia
What is anterograde amnesia?
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
What is the opposite of anterograde amnesia and describe it?
This retrograde amnesia
Retrograde is where memories completed prior to the event are lost with the ability to form new memories
What is the main inhibitory neurotransmitter?
It is this that benzodiazepines potentiate the action of
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
What is the other main inhibitory neurotransmitter? It is not as widespread as GABA but where is it mainly found?
The other main inhibitory neurotransmitter is glycine
It is mainly found in the spinal cord and brainstem
How does GABA work? How do benzodiazepines affect GABA?
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
Which other conditions (other than anxiety) and scenarios are benzodiazepines used?
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
What choice of benzos are usually used for the management of alcohol withdrawal?
Chlordiazepoxide, diazepam or lorazepam
What is another type of drug that potentiates the effects of GABA by binding to the GABAa receptor on the chloride channel?
This would be the barbituates
What is the Meaning of anxiolytic?
This means something that causes an anxiety reducing effect
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?
Paradoxical aggression
Anterograde amnesia
Tolerancy usually develops
Dependency usually also develops - a rebound anxiety on withdrawal can occur
What are the issues with benzodiazepines and alcohol?
As both act on the GABA receptor, this can cause extreme effects - such as severe respiratory depression
What issues may arise from rapid withdrawal of benzodiazepines?
There may be an associated benzo withdrawal phenomenona
Such as confusion, toxic psychosis, coma, anxiety, insomnia
How does chronic treatment with benzodiazepines affect GABA?
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
How would you withdraw a patient from benzodiazepines?
What you do if withdrawal symptoms occur on withdrawing a patient from benzos?
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
What drug is used to treat benzodiazepine overdoses?
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
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?
SSRIs are the most commonly used 1st line drug - GAD, PAnic disorder, Phobias, OCD and PTSD
In which anixety conditions is tricyclics second line?
Second line drug therapy in panic disorders
and
Clompiramine can be used if SSRIs dont work in OCD
What is the third line medication for GAD?
Used if not responsive to SSRIs/SNRIs
This would be pregablin
How does pregablin work?
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
Best for somatic symptoms e.g. palpitation, tremor
What drug would be best for this?
A non selective B blocker known as propranolol (non-selectively inhibits B1 and B2 - dont use in asthma as cause bronchoconstriction)
