Pharmacology of Z-Drugs

Z-drugs are used in the short-term treatment of insomnia. Up to half of people experience substantial insomnia each year, making it one of the most common symptoms and one of the most common causes of GP visits.

Because Z-drugs cause sedation, they are also known as hypnotic drugs.

Examples of Z-drugs include:

  • Zolpidem
  • Zopiclone, eszopiclone
  • Zaleplon

Though eszopiclone does not begin with ‘z’, it is still classified as a “Z-drug” – it is the S-enantiomer of zopiclone.

Z-drugs are nonbenzodiazepines, though they act in a manner similar to benzodiazepines.

Mechanism of action

Z-drugs are classified as follows:

  • Imidazopyridines – zolpidem
  • Cyclopyrrolones – zopiclone, eszopiclone
  • Pyrazolopyrimidines – zaleplon

Z-drugs pharmacology is heavily linked to the GABAA receptor – a chloride channel that opens in response to the binding of GABA to the receptor. Z-drugs bind to this receptor and facilitate the binding of GABA to the receptor.

GABA is the primary inhibitory neurotransmitter in the brain. By binding to GABAA receptors, a depressant effect permeates throughout the brain – inducing a hypnotic and anxiolytic state in patients.

Though Z-drugs bind at the same site as benzodiazepines, they are chemically distinct.

Side effects

Side effects associated with Z-drugs include:

  • Daytime sleepiness

This effect can be problematic – for example, for routine activities such as driving, using machinery or other, more challenging tasks.

  • Rebound insomnia
  • Headache
  • Confusion
  • Sleep disturbances – vivid dreams, nightmares etc.
  • Taste disturbances – with zopiclone
  • Gastrointestinal upset – particularly with zolpidem

Dependence may develop if patients take Z-drugs for more than the recommended short-term use. Immediate withdrawal may lead to effects such as anxiety, rebound insomnia, headache and muscle pains and aches.

Clinical considerations

When we talk about the clinical pharmacology of Z-drugs, we need to think about the following factors:

  • That caution is warranted before using Z-drugs in the elderly – as it increases the risk of falls. Doses should be reduced.
  • That Z-drugs should be avoided in patients with established respiratory depression or other forms of respiratory compromise.
  • That side effects of Z-drugs are increased when taken with other sedating drugs, alcohol, antihistamines or benzodiazepines.
  • That CYP450 inhibitors – such as macrolides – increase their sedative effect.
  • That CYP450 inducers – such as phenytoin – diminish their sedative effect.
  • That Z-drugs should only be used for short-term treatment – around the 4-week mark. Longer use is associated with dependence.
  • That because the medicines are sedative, the drug should be taken before bedtime.

Z-drugs are a short-term measure. The patient and their clinical team should identify the causes of insomnia and deal with those causes accordingly to resolve insomnia and prevent recurrence in the long-term.

For even more facts and pharmacology quiz questions on Z-drugs pharmacology, register with PharmaFactz today. Check back to our pharmacy blog soon for even more articles on other major hypnotic drug classes!