Z-Drugs

Products

Z-drugs – they are also called Z-substances – are usually taken in the form of film-coated tablets. In addition, other dosage forms such as sustained-release tablets and effervescent tablets are commercially available. Zolpidem (Stilnox) was the first substance from this group to be approved in many countries in 1990. In the literature, alluding to the field of application, it is also referred to as Zzz drugs. stands for the first letter of the active ingredients and for drug or active ingredient.

Structure and properties

The Z-drugs share certain structural similarities. Zaleplon is a pyrazolopyrimidine derivative, zolpidem is an imidazopyridine derivative, and zopiclone is a cyclopyrrolone derivative. They are not benzodiazepines but are pharmacologically related to them.

Effects

The Z-drugs (ATC N05CF) have primarily sleep-inducing and sedative properties. The effects are due to binding to the GABAA receptor. This increases the affinity of the receptor for the neurotransmitter GABA and promotes chloride channel opening and chloride influx, which enhances the central inhibitory effects of GABA. The γ-aminobutyric acid is the major centrally inhibitory neurotransmitter. How do Z-drugs differ from benzodiazepines? The GABAA receptors consist of five subunits that are combined differently. The Z-drugs bind mainly to the alpha1 subunit, which alters the pharmacological properties. For example, zolpidem is hardly muscle relaxant, anxiolytic, and anticonvulsant. The half-life is comparatively short, being about 5 hours for zopiclone. Zolpidem has a half-life of 2.4 hours and is therefore also offered in the form of sustained-release tablets, which release the active ingredient for 5 hours. For zaleplon, the half-life is just one hour, and the drug is therefore approved only for sleep disorders.

Indications

For short-term treatment of sleep disorders.

Dosage

According to the professional information. The film-coated tablets are taken immediately before bedtime or in bed. The duration of treatment should be kept short.

Abuse

Z-drugs, for one, are often prescribed as continuous therapy, which is contrary to the instructions in the SmPC and thus to the guidelines of drug authorities. See also under Medication Overuse. Second, Z-drugs can be used as depressant intoxicants. Because the agents make patients drowsy and cause anterograde amnesia, they can be misused for sexual assault. For this reason, Zaleplon capsules contain the dye indigocarmine, which causes a change in the color of liquids when dissolved in them.

Active ingredients

  • Zaleplon (Sonata, off-label in many countries).
  • Zolpidem (Stilnox, Stilnox CR, generic).
  • Zopiclone (Imovane, auto-generics).
  • Eszopiclone (Lunesta, USA) – the -enantiomer of zopiclone.

Contraindications

Contraindications include (selection):

  • Hypersensitivity
  • Severe hepatic insufficiency
  • Sleep apnea syndrome
  • Severe respiratory failure
  • Myasthenia gravis
  • Children and adolescents under 18 years

For complete precautions, see the drug label.

Interactions

Centrally depressant drugs, such as sedatives, anxiolytics, 1st-generation antihistamines, opioids, or antidepressants, as well as alcohol, may potentiate the adverse effects of Z-drugs. The combination of multiple depressant agents can be life-threatening. In the event of an overdose, flumazenil is injected as an antidote. Zaleplon, zolpidem, and zopiclone are substrates of CYP3A4 and susceptible to appropriate interactions with CYP inhibitors and CYP inducers. Zaleplon is primarily degraded by aldehyde oxidase.

Adverse effects

The most common possible adverse effects include:

Z-drugs can lead to habituation and physical and psychological dependence. Sudden discontinuation can trigger withdrawal symptoms.