The groggy grandmother is a scenario detailing the issues surrounding Edith, a 72 year old lady. She is suffering anxiety on account of the death of her husband leading to the prescription of 5mg of diazepam – also known as Valium – per day, owing to its anxiolytic effects (Rang, et al., 2012). However she doubled her intake due to her having problems sleeping. Following a visit to her GP she is warned of the potential dangers regarding this supratherapeutic dose of diazepam and her treatment is switched to a drug with known hypnotic (Rang, et al., 2012) effects and a safer metabolism profile – temazepam.
These two drugs fall under the class of benzodiazepines; being a group of psychotropic drugs they have an effect on and modulate brain behaviour…show more content… This surrounds the central ion pore which exists in the transmembrane domain of the ligand gated chloride channel. See figure 4.
• The endogenous ligand GABA binds at the boundary between the α and β subunits and benzodiazepines bind at the boundary between the α and γ subunits (Rang, et al., 2012). The binding sites exist in the extracellular domain. Figure 4 has been labelled to show this.
• Once bound benzodiazepines act “allosterically to increase the affinity of GABA for the receptor” (Lu, n.d.).
• In short this causes the coupled chloride ion channel to open a greater amount of times in a given time period when GABA binds to the receptor.
• chloride ions move in from the synaptic cleft into the post-synaptic neurone faster, hyperpolarizing the neuron
• This makes the neuron resistant to…show more content… Hence, specific benzodiazepines target different GABAA receptor subtype isoforms to result in their different pharmacologic actions.
The alpha subunit is deemed as the most important as it mediates most of the effects off benzodiazepines. Although all benzodiazepines bind to the alpha subunit (on the boundary between the alpha and gamma subunits), each type has different ‘affinity’ levels to the subtype isoforms (Clayton, et al., 2007). I have summarised the varying pharmacologic effects associated with each subunit and subtype isoform and the affinity levels of diazepam and temazepam to each in figure 5.
N.B I have also included affinity levels for Oxazepam and Nordazepam as the former is the final metabolic product of Temazepam and the latter is the active metabolite of Diazepam. These will be referred to in the ‘pharmacokinetics and metabolism’ section.
Not all subtype isoforms are sensitive to benzodiazepines hence why only data on γ2, β3 and α1,2,3 and 5 have been
