GABA-ergic drugs

GABA is made from glutamate using an enzyme that is only found in GABA neurones.
– It binds GABA
A receptors which are ionotropic + permeable to Clwhich hyperpolarizes neurones
– Also binds GABA
B receptors, which are metabotropic and Gi linked, which inhibits neurones.
– General anaesthetics and alcohol are all positive modulators of GABA receptors.

Barbiturates

e.g. Phenobarbital + Thiopental

These are GABA positive modulators at low doses but can also directly increase GABA receptor activity in the absence of endogenous GABA, giving low therapeutic index.
– Phenobarbital is used as an anticonvulsant
– Thiopental is used as a general anaesthetic, rapidly acting but superseded by Propofol

Side effects
  • Sedation
  • Respiratory depression
  • Porphyrin synthesis

Benzodiazepines

e.g. Diazepam + Midazolam (suffix = -am)

These drugs are allosteric modulators of GABAA receptors which bind to the alpha subunit.
– They increase the binding of GABA to its receptor, without directly activating the receptor itself unlike barbiturates.
– They are safer and have superseded the use of barbiturates and dose-dependently inhibit CNS

Short acting benzodiazepines (Temazepam) are used for insomnia and seizures
– Used for short-term management of anxiety disorders
– Diazepam is used to treat spontaneous muscle spasms
– Midazolam is used preoperatively for sedation and to
reduce anxiety in procedures that do not need analgesia e.g. endoscopy + cardiac catheterization

Side effects
  • Tolerance and dependence
  • Daytime drowsiness (hangover), and confusion (a very common cause of confusion/amnesia in elderly)
  • Respiratory and CNS depression, especially when taken in combination with alcohol
  • Overdose is treated with supportive care/flumazenil

Flumazenil

This is a benzodiazepine receptor competitive antagonist.
– It is used to treat benzodiazepine overdoses to reverse CNS side effects.
– In addition, it can be used to accelerate recovery from anaesthetics.
 

Side effects
  • Increases the risk of seizures, so must be used with extreme caution when reversing benzodiazepine overdose.

Z drugs

e.g. Zolpidem + Zopiclone + Zaleplon

These bind to the same site as the benzodiazepines but are more specific for sedative effects
– They are used for the short-term treatment of insomnia due to their rapid action
– They have weaker activity elsewhere, which means they have less potential for tolerance, dependence and rebound insomnia.

GABA-b agonists

e.g. Baclofen

This acts on the spinal cord to inhibit synaptic transmission. It is used as an antispasmodic to reduce hyperexcitability in stroke, MS and other upper motor neurone lesions.

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The intended purpose of this website is to be used as a resource for revision for exams. It should not be used as a guideline or reference for clinical practice/decision making or by patients looking for medical information or advice. In2Med takes no responsibility for any loss or damaged resulting from the use of information from this website.

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