21. Benzodiazepines Flashcards
On which neurotransmitter do Benzodiazepines work on?
Benzodiazepines are centrally acting medications which potentiate the actions of gamma amino butyric acid (GABA), the major inhibitory transmitter within the brain.
Give 3 examples of Benzodiazepines.
Benzodiazepines
- Diazepam
- Nitrazepam
- Temazepam
What are the 5 pharmacological and therapeutic actions of benzodiazepines?
Benzodiazepines
Pharmacological and therapeutic actions of benzodiazepines include:
- Hypnotic → puts you to sleep
- Anxiolytic → anti-anxiety
- Anticonvulsant → epileptic
- Skeletal muscle relaxation → eg. back pain due to muscular spasm
- Anterograde amnesia → Dose dependent effect = don’t lay down new memories = don’t remember what happens when under the influence of the drug
What is Gamma Amino Butyric Acid (GABA)?
Where is it found in the body?
What is its action?
Which cells release GABA?
Gamma Amino Butyric Acid (GABA)
- GABA is found primarily in the brain
- It is the major inhibitory transmitter in the CNS
- It acts as an inhibitory transmitter in many parts of the CNS
- About 20% of neurones in the CNS are GABAergic (they release GABA)
- Virtually all neurons in the CNS are sensitive to the inhibitory effects of GABA
On which 2 receptors does GABA work?
GABA acts on two different types of receptors:
1) GABAA receptors = ligand-gated ion channel receptors
* Fastest receptors in body
2) GABAB receptors = G protein-coupled receptors
- Most receptor in body are GPCRs
- Slower than ligand-gated
What happens when GABA binds to GABAA receptors?
What happens when a G-Protein Coupled Receptor (GPCR) is stimulated?
What type of receptors are GABAA Receptors?
What is the GABAA Receptor channel selectively permeable to?
What is the effect on the cell?
GABAA Receptors
- GABAA receptors are ligand-gated ion channel receptors
- The GABAA receptor channel is selectively permeable to Cl- ions
- Increasing the permeability and concentration of Cl- ions in the cell hyperpolarises the cell and reduces excitability
What is the structure of GABAA Receptors?
GABAA Receptor - Structure
- They are pentamers made up of different subunits (alpha, beta, gamma, delta, epsilon, pi and theta).
- 19 GABAA receptor subunits have been identified.
- The most common configuration is α1β2γ2 arranged as α1-β2-α1-β2-γ2
Where do Benzodiazepines bind at GABAA Receptors?
- Benzodiazepines potentiate the effects of GABA at some GABAA receptors depending on the subunit composition of the receptor
- Benzodiazepines bind to a site on the GABAA receptor distinct from the GABA binding site
- NOT agonists at the GABA binding site
- Benzodiazepines facilitate the binding of GABA and increase its effects
- Benzodiazepines increase the frequency of opening of GABA activated chloride channels
How do the following affect GABA at GABAA Receptors?
- Benzodiazepines?
- Barbiturates?
- Alcohol?
GABAA Receptors
- Benzodiazepines increase the frequency of opening.
- Barbiturates increase the duration of the opening.
- Alcohol increases both the frequency and the duration of the opening.
What is the pharmacological basis for the different therapeutic effects of Benzodiazepines?
Benzodiazepines
- 19 GABAA receptor subunits have been identified
- These are (α1-6, β1-3, γ1-3, δ, ε, θ, π and ρ1-3)
- Various combinations occur in GABAA receptors in different parts of the brain.
- Stimulation of these different receptors can produce different responses.
Which therapeutic effects of Benzodiazepines are attributed to the GABAΑ receptor subtype α1?
GABAΑ receptors containing the α1 subunit mediate the:
- Hypnotic
- Sedative
- Anticonvulsant
- Addictive effects
Which therapeutic effects of Benzodiazepines are attributed to the GABAΑ receptor subtype α2?
GABAΑreceptorscontainingthe α2 subunit mediate the anxiolytic effect.
Which therapeutic effects of Benzodiazepines are attributed to the GABAΑ receptor subtype α2, α3 and α5?
GABAΑ receptors containing the α2, α3 and α5 subunits mediate muscle relaxation.
Which GABAΑ receptor subtypes are responsible for the amnesic effects of benzodiazepines?
GABAΑ receptors containing the α1 and α5 subunits mediate the amnesic effects.
Which 2 Benzodiazepines are used in the treatment of insomnia?
Benzodiazepines
Those used in the treatment of insomnia include:
- Nitrazepam
- Temazepam
Which 3 Benzodiazepines are used in the treatment of anxiety?
Benzodiazepines
Those used in the treatment of anxiety include:
- Diazepam
- Oxazepam
- Alprazolam
Which Benzodiazepine is used in the treatment of skeletal muscle spasm?
Benzodiazepines
Those used in the treatment of skeletal muscle spasm include:
- Diazepam
Which 2 Benzodiazepines are used in the treatment of epilepsy and convulsions?
Benzodiazepines
Those used in the treatment of epilepsy and convulsions include:
- Clonazepam
- Diazepam
How long should Benzodiazepams be used for?
As a general rule benzodiazepines should only ever be used for the shortest time possible (weeks rather than months).
Which group of patients should you take care when prescribing Benzodiazepines to?
Take particular care in elderly patients who may experience excess sedation, confusion, ataxia, falls etc
What is the “hangover effect” of benzodiazepines?
How is it fixed?
“Hangover effect” (morning drowsiness) may occur with the use of benzodiazepines as hypnotics
Solution = reduce dose + use shorter t1/2
e.g. change from nitrazepam (t1/2 16 - 48 hours) to temazepam (t1/2 5 - 15 hours)
What are some of the different half lives of Benzodiazepines?
